Signaling by the B Cell Receptor (BCR) (Homo sapiens)

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6, 13, 15, 18, 19, 24...16, 29, 39, 81, 87...23, 25, 82, 12413, 52, 1404, 24, 64, 83, 84, 95...10, 33, 50, 62, 967, 53, 68, 117, 1436, 18, 56, 65, 74...88, 97, 102, 1162, 9, 14, 16, 28...15, 64, 92, 105, 110...21, 30, 8611212, 21, 30, 61, 861, 45, 90, 101, 1255, 91, 93, 98, 13431, 47, 57, 763, 22, 40, 55, 66...17, 37, 48, 120, 122...8, 23, 25, 54, 59...11, 71, 99, 104, 129...32, 36, 72, 77, 108...10, 96, 11213, 52, 14026, 27, 35, 114, 13417, 37, 48, 120, 122...33, 70, 11256, 64, 121, 135plasma membraneendoplasmic reticulum lumencytosolnucleoplasmIg lambda chain V-VIregion AR IGHV7-81(1-?) Ig kappa chain V-IIIregion HAH Ig lambda chain V-IIregion VIL Ig kappa chain V-IIIregion NG9 STIM1 Ig lambda chainV-III region SH Ig lambda chainV-III region LOI Ig lambda chain V-IIregion BOH Ig lambda chain V-IIregion WIN Ig heavy chain V-IIregion HE Ig kappa chain V-IIregion FR Ig kappa chain V-Iregion Kue IgH heavy chainV-III region VH26precursor Ig heavy chain V-IIIregion JON Ig kappa chain V-IVregion JI Ig heavy chain V-IIIregion TIL IGHD Ig kappa chain V-IIIregion SIE Ig kappa chain V-IIIregion SIE Ig heavy chain V-IIIregion TEI Ig lambda chain V-VIregion WLT Ig heavy chain V-Iregion SIE IGHV(1-?) Ig heavy chain V-Iregion Mot Ig lambda chain V-Iregion VOR IGLC1 Ig lambda chain V-Iregion BL2 IGLC6 Ig kappa chain V-Iregion Kue Ig heavy chain V-IIIregion WEA Ig heavy chain V-IIIregion HIL Ig heavy chain V-IIIregion BRO Ig kappa chain V-IIIregion VH Ig lambda chain V-IIregion BOH PSMD7 Ig kappa chain V-Iregion Hau Ig kappa chain V-Iregion WEA ADPFYNIg lambda chain V-VIregion EB4 Ig kappa chain V-IIIregion Ti Ig lambda chain V-Iregion BL2 NF-kappa-Bp50,p65,c-Rel:IKBIg heavy chain V-IIIregion KOL IGLC6 Ig heavy chain V-IIIregion POM Ig lambda chainV-III region SH Ig lambda chain V-Iregion HA Ig kappa chain V-Iregion WEA Ig heavy chain V-IIregion MCE NAD+ Ig kappa chain V-IIIregion VH IGLC3 IGKV4-1(21-?) PSMC6 IGLC6 Ig lambda chain V-IIregion BOH Ig heavy chain V-IIIregion BUR p-T187-MAP3K7 PSMB9 Ig kappa chain V-IIIregion HAH Ig lambda chain V-IIregion TRO p-Y223,Y551-BTK p-T184-RASGRP1 Ig lambda chain Vregion 4A Ig heavy chain V-IIIregion TUR Ig kappa chain V-IIIregion HAH Ig lambda chain V-IIregion NIG-84 Ig kappa chain V-IIIregion POM p-RASGRP1,3:DAGIg lambda chain V-Iregion EPS IGHD UbCalcineurin (CaN)Ig kappa chain V-IIregion GM607 IgH heavy chainV-III region VH26precursor Ig kappa chain V-Iregion BAN Ig heavy chain V-IIIregion HIL Ig kappa chain V-IVregion STH PIP3 activates AKTsignalingIg kappa chain V-IVregion STH Ig heavy chain V-IIIregion HIL Ig kappa chain V-Iregion Walker NF-kappaB:p-IkB:SCF-betaTrCPIg lambda chainV-III region LOI ADPPSMB1 Ig kappa chain V-Iregion WEA Ig lambda chain V-IIregion BOH Ig lambda chain V-IVregion Bau ITPR2 Ig lambda chain V-VIregion SUT ADPIg kappa chain V-IVregion B17 Ig heavy chain V-IIregion HE ATPIg kappa chain V-IIIregion GOL Ig lambda chain Vregion 4A Ig heavy chain V-IIIregion POM Ig lambda chain V-IIregion NIG-58 Ig kappa chain V-Iregion Hau Ig lambda chain V-Iregion NIG-64 IGKVA18(21-?) Ig kappa chain V-IIregion FR Ig lambda chain V-VIregion WLT CARD11 Ig kappa chain V-Iregion Bi p-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-IIregion NIG-84 Ig lambda chain V-Iregion HA Ig kappa chain V-Iregion Wes Ig lambda chain V-IIregion TRO Ig kappa chain V-IVregion JI Ig kappa chain V-IIIregion HIC Ig lambda chain V-IIregion BUR Ig lambda chain V-Iregion NEWM Ig kappa chain V-Iregion WAT IgH heavy chainV-III region VH26precursor IGHV(1-?) Ig lambda chain V-Vregion DEL IGHV7-81(1-?) Ig lambda chain V-Iregion BL2 Ig lambda chain V-IIregion NIG-58 NRAS Ig heavy chain V-Iregion ND Ig lambda chain V-IIregion WIN KRAS IKKA Ig heavy chain V-IIIregion POM p21 RAS:GDPHRAS Ig kappa chain V-IIIregion VH Ig heavy chain V-Iregion ND Ig kappa chain V-IIIregion POM Ig lambda chain V-IIregion MGC IGKV1-5(23-?) Calcineurin:Phosphorylated NFATC1,2,3Ig kappa chain V-Iregion DEE PSMC2 Ig heavy chain V-IIregion SESS ATPIg kappa chain V-Iregion Wes PSMC4 IKKA:IKBKB:IKBKGIg kappa chain V-IIIregion B6 PSMD1 Ig heavy chain V-IIIregion JON IGHV(1-?) Zn2+ Ig heavy chain V-IIIregion NIE Ig heavy chain V-Iregion SIE MALT1 Ig kappa chain V-IIregion FR Ig kappa chain V-Iregion Gal Ig lambda chain V-IVregion Kern Ig heavy chain V-Iregion ND Ig heavy chain V-IIregion WAH CD19 SignalosomeIg heavy chain V-IIIregion KOL Ig heavy chain V-IIIregion NIE IGLC3 PIK3CD:PIK3R1Ig kappa chain V-Iregion Roy Ig heavy chain V-IIIregion NIE PPP3CB Ig kappa chain V-Iregion WAT CyclophilinA:Cyclosporin AIg kappa chain V-IIregion TEW PPP3R1 IGLC7 PSME3 KRAS REL Ig heavy chain V-IIIregion TIL Ig kappa chain V-IIIregion SIE RELA IGLC3 Ig heavy chain V-IIIregion GA CARMA1:BCL10:MALT1:TAK1SH3KBP1 Ig lambda chain V-Iregion MEM Ig kappa chain V-IVregion B17 Ig kappa chain V-Iregion HK101 Ig lambda chain V-IVregion X p-Y194,Y195,Y272-SHC1-1(156-583) Active IKK complexIGHD AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerIg lambda chain V-IIregion NIG-58 Ig heavy chain V-IIregion ARH-77 Ig heavy chain V-IIIregion BRO Ig heavy chain V-IIregion OU p-Y771,Y783-PLCG1 Ig lambda chain V-IIregion BO Ig lambda chain V-IIregion BO Ig lambda chain V-IIregion NIG-58 Ig kappa chain V-IIIregion Ti LYNIg lambda chain V-IIregion TOG Ig lambda chain V-IVregion Hil Ig kappa chain V-Iregion DEE Ca2+Ig lambda chain V-Iregion NEW IKBKB Ig kappa chain V-Iregion Kue Ig kappa chain V-Iregion Gal CBL Ig kappa chain V-Iregion Wes Ig heavy chain V-IIregion HE Ig heavy chain V-IIIregion TRO ORAI1 Ig kappa chain V-IVregion STH Ig lambda chain V-VIregion AR Ig lambda chain V-IIregion NEI IGKC GRB2-1 Ig heavy chain V-IIregion OU Ig kappa chain V-Iregion AU PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRIg heavy chain V-IIIregion BRO Ig lambda chain V-VIregion NIG-48 PSMB8 Ig lambda chain V-IIregion BO Ig kappa chain V-IVregion B17 p-S559,S644,S652-CARD11 IGHM Ig lambda chain V-Vregion DEL Ig lambda chain V-IIregion WIN MALT1Ig lambda chain V-VIregion WLT Ig heavy chain V-IIIregion DOB ATPIg kappa chain V-IIIregion WOL Ig heavy chain V-IIregion SESS Ig kappa chain V-IIIregion NG9 IgH heavy chainV-III region VH26precursor Ig lambda chain V-Iregion NIG-64 Ig heavy chain V-IIIregion NIE Ig kappa chain V-Iregion BAN Ig kappa chain V-Iregion HK101 Ig heavy chain V-IIregion SESS Ig kappa chain V-IIIregion CLL Ig kappa chain V-Iregion Bi Ig kappa chain V-Iregion Lay Ig heavy chain V-IIregion OU Ig heavy chain V-Iregion WOL PIK3R1 PPIA Ig lambda chain V-Iregion NEW Ig lambda chain V-IIregion NIG-58 Ig heavy chain V-Iregion HG3 PI(4,5)P2Ig kappa chain V-Iregion AU DAPP1Ig heavy chain V-IIregion WAH Ig kappa chain V-IIregion Cum Ig lambda chainV-III region LOI Ig kappa chain V-IIIregion SIE IGHM Ig kappa chain V-Iregion Rei Ig heavy chain V-IIIregion DOB Ig kappa chain V-IIregion Cum PSMD8 IGHM Ig lambda chain V-Iregion EPS Ig kappa chain V-Iregion BAN Ig kappa chain V-IIregion GM607 VAV1 Ig heavy chain V-IIregion SESS ATPIg lambda chain V-IIregion NIG-84 IGHV(1-?) Ig heavy chain V-IIregion OU NF-kappa-Bp50,p65,c-Rel:p-IKBIg kappa chain V-IIregion TEW Ig kappa chain V-Iregion Scw p-Y753,Y759,Y1217-PLCG2 I(1,4,5)P3Ig heavy chain V-IIIregion GA ADPIg kappa chain V-IIIregion POM Ig kappa chain V-IIIregion VH Ig kappa chain V-IIIregion SIE Ig lambda chain Vregion 4A IGKV4-1(21-?) p-Y188,Y199-CD79A Ig lambda chain V-IVregion X Ig kappa chain V-IIIregion GOL PSMA3 STIM1 p-S32,S36-NFKBIA Ig kappa chain V-IIregion MIL Ig heavy chain V-IIregion NEWM Ig heavy chain V-IIIregion WEA NF-kappaBp50,p65,c-Rel:ub-p-IKBIg lambda chain V-Iregion NEWM Cyclosporin A Ig heavy chain V-IIIregion JON Ig kappa chain V-IIIregion IARC/BL41 Ig kappa chain V-IIIregion GOL Ig heavy chain V-IIIregion KOL IGLV(23-?) Ig heavy chain V-IIregion COR Ig heavy chain V-Iregion Mot Ig lambda chain V-Iregion HA IGHV7-81(1-?) MALT1 Ig heavy chain V-IIregion COR Ig heavy chain V-IIIregion TRO Ig heavy chain V-Iregion Mot Ig kappa chain V-Iregion AG Orai1 dimerIg kappa chain V-IIIregion HIC Ig kappa chain V-IVregion STH Ig kappa chain V-IIIregion GOL Ig kappa chain V-Iregion EU Ig heavy chain V-IIregion SESS Ig lambda chain V-IIregion TOG Ig kappa chain V-Iregion WAT Ig heavy chain V-Iregion EU Ig heavy chain V-Iregion WOL ADPZn2+ PSMA2 Ig lambda chain V-IVregion X p-S19,S23-NFKBIB Ig heavy chain V-IIIregion DOB PhosphatidylserineIg kappa chain V-IVregion STH IGLC6 Ig heavy chain V-IIIregion TUR Ig lambda chain V-Vregion DEL Ig kappa chain V-IIIregion POM Ig lambda chain V-IIregion NEI Ig kappa chain V-IVregion Len Ig kappa chain V-IIIregion B6 IGLC7 Ig heavy chain V-IIIregion TEI Ig heavy chain V-IIIregion CAM Ig heavy chain V-IIregion ARH-77 Ig heavy chain V-IIIregion DOB p-Y196,Y207-CD79B Ig heavy chain V-Iregion EU Activated PKC betaIGHD p-BCL10 IGLV(23-?) Ig kappa chain V-IVregion Len Ig heavy chain V-IIregion ARH-77 Ig lambda chainV-III region SH Ig kappa chain V-IIIregion POM Ig heavy chain V-Iregion WOL Ig heavy chain V-IIregion ARH-77 IGLC1 Ig kappa chain V-IIIregion HAH Ig lambda chain V-IIregion TRO Ig heavy chain V-IIIregion NIE Ig heavy chain V-IIIregion GA Ig kappa chain V-Iregion OU Ig lambda chain V-Iregion MEM Ig lambda chain V-IVregion Hil ATPIg kappa chain Vregion EV15 Ig kappa chain V-IVregion JI Ig kappa chain V-IIregion TEW Ig lambda chain V-VIregion SUT Ig lambda chain V-VIregion EB4 GDP AntigenIGLC7 IGLC2 BCAP SignalosomePhosphatidylserine Ig lambda chain V-IIregion VIL Ig lambda chain V-VIregion NIG-48 Ig lambda chain V-Iregion NIG-64 Ig heavy chain V-Iregion SIE Ig kappa chain V-Iregion OU Ig heavy chain V-IIIregion CAM Ig kappa chain V-IIIregion HIC STIM1 Ig kappa chain V-Iregion CAR Ig heavy chain V-IIIregion ZAP Ig kappa chain V-IIIregion Ti Ig lambda chain V-Iregion NEWM Ig heavy chain V-IIIregion CAM Ig heavy chain V-IIIregion WAS Ig kappa chain V-Iregion Gal Ig heavy chain V-IIIregion GA IGLC1 Ig kappa chain V-IIregion RPMI 6410 ORAI1 Ig kappa chain V-Iregion Scw Ig kappa chain V-IIIregion HAH Ig kappa chain V-IIregion TEW Ig kappa chain V-IIregion RPMI 6410 IGKVA18(21-?) Ig kappa chain V-Iregion EU IGHM Ig heavy chain V-IIIregion GAL Ig kappa chain V-Iregion AG Ig heavy chain V-IIIregion ZAP Ig heavy chain V-IIregion NEWM Ig heavy chain V-IIIregion TIL Ig kappa chain V-Iregion Ka Ig lambda chain V-VIregion EB4 Ig heavy chain V-Iregion Mot Ig kappa chain V-Iregion Wes CBL Antigen:BCRIg kappa chain V-Iregion Rei Ig kappa chain V-Iregion Ni Ig lambda chain V-Iregion HA IgH heavy chainV-III region VH26precursor Ig kappa chain V-Iregion HK101 p-CARMA1 OligomerIg kappa chain V-IIregion MIL PSMA7 Ig heavy chain V-IIIregion GAL Ig heavy chain V-IIregion MCE GRB2-1PSMA8 Ig lambda chain V-IIregion BUR IGKV1-5(23-?) PIK3R1 Ig kappa chain V-IIregion Cum IGHV(1-?) Ig lambda chain V-IIregion NEI Ig kappa chain V-Iregion Ka Ig kappa chain V-Iregion Mev IGHD Ig kappa chain V-IIIregion VH Ig kappa chain V-Iregion Gal Ig kappa chain V-IIIregion IARC/BL41 Ig lambda chain V-IVregion Hil IGLC3 FBXW11 Ig kappa chain V-IIIregion HIC Ig kappa chain V-IIIregion IARC/BL41 Ig heavy chain V-IIIregion GAL p-6Y-SYK Ig kappa chain V-Iregion AU IGKV4-1(21-?) IGKVA18(21-?) Ig kappa chain V-IIIregion WOL DAG ITPR3 Ig heavy chain V-IIregion OU Ig kappa chain V-IIregion TEW Ig kappa chain V-Iregion Daudi CD79A Ig lambda chain V-VIregion WLT Ig heavy chain V-IIIregion POM Ig heavy chain V-IIIregion ZAP CUL1 Ig kappa chain V-IIregion Cum CALM1Ig heavy chain V-Iregion Mot Ig lambda chain V-Iregion NEWM Ig lambda chain V-IVregion MOL Ig kappa chain V-IIregion MIL Ig kappa chain V-IIregion RPMI 6410 IGHV7-81(1-?) SOS1 I(1,4,5)P3 Ig lambda chain V-VIregion SUT PSMA6 PSMB11 Ig lambda chain V-IIregion BUR Ig lambda chain V-Vregion DEL Ig heavy chain V-IIIregion LAY IGLV(23-?) IGLC7 IGLV(23-?) Ig heavy chain V-IIregion NEWM STIM1 Ig lambda chain V-VIregion NIG-48 IGHV7-81(1-?) PPP3CA Ig kappa chain V-IIIregion IARC/BL41 Ig heavy chain V-IIIregion WAS Ig kappa chain V-Iregion BAN Ig heavy chain V-IIIregion GAL Ig heavy chain V-IIregion NEWM Ig lambda chain V-IIregion BOH IGLC2 Ig lambda chain V-Iregion NEW IGKV1-5(23-?) CD79A Ig lambda chain V-VIregion NIG-48 p-Y139-DAPP1 Ig kappa chain V-Iregion Roy Ig lambda chainV-III region SH Ig heavy chain V-IIregion ARH-77 ADPIg kappa chain V-Iregion DEE CARMA1:MALT1:BCL10Ig heavy chain V-IIIregion BRO Ig lambda chain V-IVregion Bau Ig heavy chain V-IIregion WAH Ig lambda chainV-III region LOI Ig heavy chain V-IIIregion BUR Ig heavy chain V-IIIregion HIL Ig lambda chain V-IVregion MOL Ig lambda chain V-Iregion NIG-64 Ig heavy chain V-IIIregion BRO PPP3CA Ig kappa chain V-IIIregion B6 Ig heavy chain V-IIregion WAH IGHM Ig kappa chain V-Iregion OU Ig lambda chain V-Iregion WAH IGLV(23-?) IGLC2 Ig kappa chain V-IIIregion VG Ig kappa chain Vregion EV15 Ig lambda chain V-IIregion BO Ig heavy chain V-Iregion HG3 NF-kappaBp50,p65,c-Rel dimerAntigen:p-BCRIg heavy chain V-Iregion SIE Ig kappa chain V-Iregion Hau Ig kappa chain V-IIregion RPMI 6410 Ig kappa chain V-IIIregion HIC Ig heavy chain V-IIregion DAW Ig kappa chain V-Iregion AU Ig lambda chain V-VIregion AR Ig kappa chain V-Iregion Roy Ig kappa chain V-Iregion HK101 Ig lambda chain V-Iregion VOR Ig heavy chain V-IIregion COR SOS1 Ig heavy chain V-IIIregion TUR Ig heavy chain V-IIregion MCE Ig heavy chain V-IIregion DAW Ig heavy chain V-IIIregion GAL Ig kappa chain V-Iregion BAN Ig heavy chain V-Iregion SIE IGHD Ig kappa chain V-IVregion JI Ca2+Ig heavy chain V-Iregion SIE p-12S-NFATC1 Ig kappa chain V-IIIregion WOL CARMA1 oligomerIg kappa chain V-IIIregion HAH Ig kappa chain V-IIregion GM607 IGLC1 Ig kappa chain V-IIregion RPMI 6410 IGLC7 Ig kappa chain V-IIIregion NG9 Ig heavy chain V-IIIregion TUR Ig kappa chain V-IIIregion Ti PIK3AP1p-Y188,Y199-CD79A Ig kappa chain V-Iregion Kue Ig lambda chain V-Iregion NEW Ig kappa chain V-IVregion JI Tacrolimus Ig heavy chain V-IIIregion TRO Ig heavy chain V-IIIregion TIL Ig kappa chain V-IVregion Len Ig lambda chain V-IIregion MGC Ig heavy chain V-IIIregion TUR Ig kappa chain V-IIregion Cum Ig lambda chainV-III region LOI Ig kappa chain V-IVregion B17 PSMD6 Ig lambda chain V-Iregion NEW Ig kappa chain V-IIIregion HAH Ig heavy chain V-IIregion WAH p-BCL10Ig kappa chain V-Iregion Hau Ig kappa chain V-IVregion Len Ig kappa chain V-Iregion WEA IGKV1-5(23-?) Ig heavy chain V-Iregion EU Ig heavy chain V-IIIregion GAL Ig lambda chain V-VIregion EB4 Ig lambda chain V-IIregion NEI Ig kappa chain V-Iregion Bi Ig kappa chain V-Iregion Wes Ig kappa chain V-Iregion Mev NRAS Ig kappa chain V-IIregion FR Ig kappa chain V-IIregion TEW Ig heavy chain V-IIIregion WEA HRAS Ig heavy chain V-IIIregion LAY Ig kappa chain V-Iregion Daudi Ig heavy chain V-IIIregion BUR Ig heavy chain V-IIIregion TRO Ig kappa chain V-IIIregion HIC Ig kappa chain V-IIIregion Ti Ig lambda chain V-IIregion NIG-84 Ig lambda chain V-IIregion WIN Ig heavy chain V-IIIregion JON Ig heavy chain V-IIIregion TEI Ig heavy chain V-IIIregion GAL Ig kappa chain V-IIIregion POM Ig lambda chain V-IIregion BOH Ig kappa chain V-Iregion Lay Ig heavy chain V-IIregion ARH-77 Ig kappa chain V-Iregion Bi Ig lambda chain V-Iregion HA Ig lambda chain V-IIregion NIG-84 Ig heavy chain V-IIIregion NIE Ig kappa chain V-IIregion MIL GRB2-1 Ig lambda chain V-Iregion EPS ITPR:I(1,4,5)P3tetramerIg kappa chain V-IIIregion Ti Ig heavy chain V-IIIregion ZAP p-S559,S644,S652-CARD11 Ig kappa chain V-Iregion Ni Ig kappa chain V-IIIregion CLL Ig lambda chain V-Iregion VOR IGHV(1-?) IGLC6 Ig heavy chain V-IIIregion BUT Ig lambda chain V-Iregion EPS Ig lambda chain V-IVregion Bau Ig lambda chainV-VII region MOT Ig heavy chain V-IIIregion CAM Ig kappa chain V-Iregion Gal Ig kappa chain V-Iregion Bi PSMD11 IGHV(1-?) Ig kappa chain V-IIIregion SIE p-6Y-CD19 Ig lambda chain V-Vregion DEL Ig lambda chain V-VIregion NIG-48 Ig heavy chain V-IIIregion WEA p-Y196,Y207-CD79B Ig lambda chain V-Iregion WAH Ig kappa chain V-Iregion AG Ig kappa chain V-Iregion Walker Ig lambda chainV-III region SH Ig kappa chain V-Iregion Ni IGLC3 Ig kappa chain V-Iregion DEE Ig lambda chain V-VIregion WLT PI(3,4,5)P3 IGKV4-1(21-?) Ig kappa chain V-Iregion Ka Ig kappa chain V-Iregion CAR Ig lambda chain V-IVregion X Ig lambda chain Vregion 4A IGLC6 Ig lambda chain V-IIregion VIL Ig lambda chain V-Iregion WAH Ig kappa chain V-IVregion STH Ig lambda chainV-III region SH Ig kappa chain V-Iregion CAR Ig kappa chain V-Iregion Mev PTPN6 Ig lambda chain V-IVregion Bau Ig kappa chain V-Iregion Scw Ig lambda chain V-IVregion Hil Ig kappa chain V-IVregion Len Ig heavy chain V-IIregion SESS p-5Y-BLNK IGLC3 Ig kappa chain V-Iregion Lay p-Y188,Y199-CD79A Ig kappa chain V-IVregion Len Ig kappa chain V-Iregion Kue Ig lambda chain V-Iregion MEM Ig heavy chain V-IIregion MCE Ig kappa chain V-IIregion FR Ig kappa chain V-IIIregion WOL ATPIg kappa chain V-Iregion EU SH3KBP1 Ig kappa chain V-Iregion EU Ig heavy chain V-Iregion WOL Ig heavy chain V-IIregion COR Ig heavy chain V-IIIregion GA Ig lambda chain V-VIregion AR ADPIg lambda chain V-IIregion VIL 26S proteasomeIg kappa chain V-Iregion WAT Ig lambda chain V-IVregion MOL Ig heavy chain V-IIIregion TEI BTRC Antigen:p-BCR:SYKIg heavy chain V-IIIregion CAM Ig kappa chain V-Iregion DEE Ig lambda chain V-Iregion MEM Ig lambda chain V-IVregion MOL Ca2+ Ig kappa chain V-IIIregion IARC/BL41 Ig kappa chain V-Iregion DEE Ig lambda chain V-IIregion TOG PSMC5 MALT1 DAGIg kappa chain V-Iregion Scw Ig lambda chain V-Iregion NEW p-S559,S644,S652-CARD11 Ig lambda chain V-Iregion BL2 Ig kappa chain V-Iregion Rei Ig heavy chain V-IIIregion TIL PIK3CD Ig heavy chain V-IIIregion KOL Ig lambda chain V-Iregion BL2 Ig kappa chain V-Iregion Wes Ig lambda chain V-IIregion TOG Ig lambda chain Vregion 4A IGKV4-1(21-?) p-T133-RASGRP3 Ig lambda chain V-IIregion NEI Ig heavy chain V-Iregion ND VAV1 IGLC7 Ig heavy chain V-IIIregion CAM Ig heavy chain V-IIregion NEWM p-Y196,Y207-CD79B IGKVA18(21-?) Ig heavy chain V-IIIregion TUR Ig lambda chain V-IVregion Kern ITPR2 IGLC1 IGKVA18(21-?) Ig lambda chain V-IIregion BOH STIM1:TRPC1Ig lambda chain V-VIregion SUT Ig lambda chainV-VII region MOT Ig heavy chain V-IIIregion CAM Ig kappa chain V-IIIregion WOL Ig kappa chain V-Iregion Daudi Ig kappa chain V-Iregion Walker Ig lambda chain V-VIregion AR Ig kappa chain V-IIIregion CLL Ig kappa chain V-IIIregion GOL Ig lambda chain V-IVregion Bau CALM1 Ig kappa chain V-Iregion AG Ig lambda chain V-IVregion Hil Ig kappa chain V-Iregion Lay Ig lambda chain V-IIregion MGC IKBKG Ig kappa chain V-Iregion Ka PSMB4 PSMB10 Ig lambda chain V-IIregion MGC Ig lambda chain V-Iregion NIG-64 Ig heavy chain V-IIIregion TIL ITPR1 Ig heavy chain V-IIregion HE Ig lambda chainV-VII region MOT Ig heavy chain V-Iregion EU Ig lambda chain V-IIregion MGC ITPR3 Ig kappa chain V-Iregion Ni Ig lambda chain V-Iregion WAH Ig kappa chain V-IIIregion IARC/BL41 Ig kappa chain V-IIregion MIL Ig lambda chain V-Iregion VOR Ig kappa chain V-IVregion JI STIM1:CalciumIGHV7-81(1-?) IGLC2 Ig heavy chain V-IIregion ARH-77 PIK3CD Ig lambda chain V-Vregion DEL Ig kappa chain V-Iregion WAT Ig kappa chain V-IIregion GM607 DAG Ig lambda chain V-IIregion BO Ig lambda chain V-IVregion Kern Ig lambda chain V-Iregion WAH CBLB Ig heavy chain V-Iregion WOL Ig kappa chain V-Iregion Rei Ig heavy chain V-IIregion OU Ig kappa chain V-Iregion Daudi Ig heavy chain V-IIregion COR Ig heavy chain V-IIIregion WEA Ig kappa chain V-IIregion FR Ig kappa chain V-IIregion TEW PI(3,4,5)P3Ig kappa chain V-Iregion HK101 p-6Y-SYK Ig lambda chain V-VIregion WLT IGKVA18(21-?) Ig kappa chain V-IIIregion VG Ig kappa chain V-Iregion BAN Ig kappa chain V-Iregion OU Ig kappa chain V-IIIregion WOL Ig heavy chain V-IIregion MCE PSMD3 PSMD4 VAV1 Ig heavy chain V-IIIregion POM Ig heavy chain V-IIIregion DOB Ig lambda chain V-IVregion Kern Ig heavy chain V-IIIregion BRO Ig lambda chain V-VIregion WLT PSMB7 PIK3CD Ig heavy chain V-Iregion HG3 IGLC2 PSMC3 Ig kappa chain V-IVregion STH Ig heavy chain V-Iregion WOL Ig lambda chain V-IIregion NIG-58 Ig heavy chain V-IIIregion BUR SYK Ig kappa chain V-Iregion Scw SHC1 p46,p52Ig kappa chain V-Iregion Ni Ig heavy chain V-IIregion OU BLNK:GRB2:SOS1:CIN85:CBLIg kappa chain V-Iregion Ni Ig kappa chain V-Iregion Ka p-6Y-SYK Ig kappa chain V-Iregion Walker Ig lambda chain V-Iregion WAH IGLC2 Ig lambda chain V-Iregion HA Ig lambda chain V-IIregion NEI Ig lambda chain V-Iregion MEM Ig kappa chain V-IIregion Cum Ig lambda chain V-Iregion MEM DephosphorylatedNFATC1,2,3Ig lambda chain V-VIregion SUT IGKC Ig kappa chain V-Iregion Hau Ig lambda chain V-VIregion EB4 Ig kappa chain V-Iregion Rei PRKCB Ig heavy chain V-Iregion ND CD19:VAV1CBLB Ig heavy chain V-IIIregion WAS p-BCL10 SH3KBP1 Ig lambda chain V-VIregion AR Ig heavy chain V-IIregion HE PSMA4 Ig kappa chain V-IVregion Len Ig lambda chainV-III region SH TRPC1IKBKB IGKC Ig heavy chain V-Iregion Mot Ig lambda chain V-Iregion WAH SCF-beta-TrCp1,2IGKV4-1(21-?) IGLC1 Ig lambda chain V-Iregion MEM Ig heavy chain V-IIIregion LAY Ig kappa chain V-Iregion AG Ig heavy chain V-IIregion DAW Ig lambda chain V-IVregion Kern Ig heavy chain V-IIIregion CAM Ig kappa chain V-IIIregion CLL Ig heavy chain V-IIIregion BUT p-14S-NFATC2 Ig kappa chain V-IIIregion CLL Ig kappa chain V-Iregion Lay PSMF1 IGLC7 Ig heavy chain V-IIIregion TRO Ig heavy chain V-IIIregion BUT Ig heavy chain V-IIIregion BUR Ig heavy chain V-IIIregion POM Ig kappa chain V-Iregion WAT Ig kappa chain V-IIIregion B6 NCK1Ig heavy chain V-IIregion SESS Ig heavy chain V-IIIregion BUR Ig lambda chain V-VIregion SUT Ig heavy chain V-IIIregion WAS Ig heavy chain V-IIregion OU Ig kappa chain V-Iregion CAR Ig lambda chain V-VIregion SUT Ig kappa chain V-Iregion Hau Ig lambda chain V-IIregion MGC Ig lambda chain V-IIregion TRO Ig heavy chain V-Iregion SIE Ig kappa chain V-IIIregion NG9 IGLC6 IGKV1-5(23-?) Ig heavy chain V-IIregion DAW IGKVA18(21-?) Ig kappa chain V-Iregion AU Ig lambda chain V-IIregion TRO IGLC3 PSMA5 Ig kappa chain V-IIregion MIL Ig kappa chain V-Iregion WAT Ig heavy chain V-Iregion EU Ig kappa chain V-Iregion Kue IGLC2 Ig heavy chain V-IIregion COR Ig kappa chain V-Iregion Kue p-4Y-PIK3AP1 Ig lambda chain V-IIregion NIG-84 Ig lambda chain V-Iregion NIG-64 Ig lambda chain V-IIregion MGC Ig heavy chain V-IIIregion GA Ig heavy chain V-IIIregion DOB Ig kappa chain V-Iregion AU Ig kappa chain V-IIIregion B6 Ig kappa chain V-Iregion Gal Ig kappa chain V-Iregion Daudi Ig heavy chain V-IIIregion WAS Ig kappa chain V-Iregion Rei Ig lambda chain V-VIregion SUT Ig lambda chainV-III region LOI IGLC3 PIK3R1 Ig lambda chain V-IVregion X Ig kappa chain V-IIIregion VG Ig lambda chain V-VIregion EB4 Ig heavy chain V-IIIregion LAY Ig kappa chain V-Iregion Lay IGKV1-5(23-?) IGKV4-1(21-?) Ig lambda chain V-Vregion DEL Ig lambda chain V-IIregion NEI Ig lambda chain V-IIregion TRO Ig heavy chain V-IIIregion JON IGLC1 Ig heavy chain V-IIIregion BUT Ig kappa chain V-IVregion B17 Ig heavy chain V-IIregion DAW Ig heavy chain V-IIregion WAH Ig lambda chain V-IIregion WIN Ig heavy chain V-IIregion COR Ig heavy chain V-IIregion NEWM Ig kappa chain V-Iregion HK101 Ig kappa chain V-IIIregion Ti RASGRP1,3Ig lambda chain V-VIregion EB4 Ig lambda chain V-IIregion BUR PSMD9 BLNK Ig kappa chain V-IIregion RPMI 6410 Ig heavy chain V-IIIregion HIL Ig kappa chain V-Iregion AG PSMD5 IGHD Ig heavy chain V-IIIregion ZAP Ig heavy chain V-IIregion DAW Ig lambda chain V-IIregion TRO IGLV(23-?) Ig kappa chain V-Iregion Mev Ig heavy chain V-IIIregion TRO Ig kappa chain Vregion EV15 Ig kappa chain V-IIIregion HAH Ig lambda chain V-Iregion NIG-64 Ig kappa chain V-IIIregion VG Ig lambda chain V-IVregion MOL Ig kappa chain V-Iregion Daudi Antigen:p-BCR:p-SYK:p-BLNKIg lambda chain V-Iregion BL2 Ig kappa chain V-IIregion FR Ig kappa chain V-Iregion Ka Ig heavy chain V-IIIregion JON IGKC p21 RAS:GTPIg lambda chain V-IIregion VIL Ca2+ Ca2+BCRIg lambda chain V-IIregion TOG Ig lambda chain V-Vregion DEL Ig kappa chain V-IIIregion SIE PLC gamma1,2PSMD10 PIK3CD:PIK3R1Ig lambda chain V-IVregion MOL Ig lambda chain V-Iregion BL2 p-13S-NFATC3 Ig lambda chain V-IVregion Bau PIK3CD STIM1 DimerIg kappa chain V-Iregion AG GRB2-1 Ig lambda chain V-IIregion TRO Ig lambda chain V-IIregion VIL NFKB1(1-433) Ig lambda chain V-IIregion BO NF-kappaBp50,p65,c-Rel dimerIg heavy chain V-IIIregion GA Ig lambda chain V-IIregion WIN Ig kappa chain V-IVregion JI Ig kappa chain V-Iregion Roy Ig lambda chain V-VIregion AR Ig heavy chain V-Iregion HG3 Ig lambda chain V-Iregion EPS PPP3CB BLNK (SLP-65)SignalosomeIg kappa chain V-Iregion Lay Ig kappa chain V-Iregion Hau PPP3R1 p-Y196,Y207-CD79B Ig kappa chain V-IIIregion B6 Ig lambda chainV-VII region MOT Fe3+ PSMA1 IGLV(23-?) Ig heavy chain V-IIIregion ZAP Ig kappa chain V-IIIregion NG9 Ig lambda chain V-IIregion BUR PSMD13 IGKC IKBKG CBLB Ig kappa chain V-Iregion Walker Ig heavy chain V-IIIregion BUR Ig heavy chain V-IIregion SESS Ig lambda chainV-III region LOI Ig kappa chain V-IVregion B17 Ig lambda chain V-IIregion VIL p-Y196,Y207-CD79B Ig kappa chain V-Iregion Mev Ig kappa chain V-IIIregion NG9 Ig kappa chain V-IIregion RPMI 6410 IGHD Ig kappa chain V-Iregion Roy p-Y188,Y199-CD79A Ig kappa chain V-IIIregion IARC/BL41 Ig kappa chain V-Iregion Scw Ig heavy chain V-IIIregion TIL Ig heavy chain V-Iregion EU Ig lambda chain V-Iregion EPS Ig lambda chain V-IIregion BO Ig heavy chain V-IIIregion NIE Ig kappa chain V-Iregion CAR CRAC channelIg heavy chain V-Iregion Mot Ig kappa chain V-Iregion BAN CD79B Ig heavy chain V-IIIregion LAY Ig kappa chain V-IIIregion VG Ig heavy chain V-Iregion ND Ig heavy chain V-IIIregion BRO CARMA1:BCL10:MALT1:TAK1:IKKIGKVA18(21-?) Ig lambda chain V-Iregion EPS Ig lambda chain V-IIregion NIG-58 IGLV(23-?) CD19 Ig kappa chain V-Iregion WEA Ig kappa chain V-Iregion Bi Ig lambda chain V-IVregion Hil IGHV7-81(1-?) Ig lambda chain V-IIregion WIN Ig heavy chain V-IIregion DAW Ig kappa chain V-Iregion Hau Ig lambda chain V-Iregion NEW Ig heavy chain V-Iregion HG3 Ig kappa chain V-Iregion Gal Ig heavy chain V-IIIregion HIL Ig lambda chainV-VII region MOT Ig lambda chainV-VII region MOT 4xCa2+:CaMIg lambda chain V-IIregion NIG-58 Ig heavy chain V-IIregion MCE Ig kappa chain V-IIIregion NG9 Ig kappa chain V-Iregion Ka Ig heavy chain V-IIIregion HIL Ig kappa chain V-IIIregion VH Ig heavy chain V-IIIregion GAL Ig lambda chain V-IVregion X Ig kappa chain V-IIregion FR Ig kappa chain V-Iregion EU Ig kappa chain V-Iregion HK101 Ig heavy chain V-IIregion HE Ig kappa chain V-IIIregion VG Ig lambda chain V-Iregion VOR Ig kappa chain V-Iregion Rei Ig kappa chain V-IIregion RPMI 6410 IGKV1-5(23-?) Ig kappa chain V-IIIregion SIE Ig heavy chain V-IIIregion JON CD79B Ig lambda chain V-IVregion Kern Ig lambda chain V-IVregion X Ig kappa chain V-IIregion Cum MAP3K7Ig heavy chain V-IIIregion BUT Ig lambda chain V-Iregion EPS Ig heavy chain V-IIregion COR Ig kappa chain V-IIIregion Ti Ig lambda chain V-IIregion TOG Ig kappa chain V-IIregion MIL Ig lambda chain V-IIregion BUR Ig kappa chain Vregion EV15 p-5Y-BLNK Ig kappa chain V-IVregion JI Ig lambda chain V-IIregion NEI Ig heavy chain V-Iregion HG3 ITPR1 Ig kappa chain V-Iregion EU PSME1 BLK-like proteinsPI(4,5)P2VAV1Ig kappa chain V-Iregion Roy Ig kappa chain V-Iregion CAR SYKIg lambda chain V-IIregion TOG Ig kappa chain V-Iregion Mev Ig heavy chain V-IIregion MCE Ig heavy chain V-IIIregion DOB IKBKG Ig kappa chain V-Iregion AU PSME4 ITPR1 GTP Ig lambda chain V-IVregion Kern IKKA NCK1 Ig lambda chain V-Iregion HA Ig kappa chain V-IIregion TEW Ig lambda chain V-Iregion HA IGKV1-5(23-?) Ig heavy chain V-IIIregion NIE Ig heavy chain V-IIIregion BRO Ig kappa chain V-IIIregion WOL GRB2-1 Ig kappa chain V-Iregion EU Ig kappa chain V-Iregion WEA IgH heavy chainV-III region VH26precursor Ig heavy chain V-IIIregion BUT Ig lambda chain V-IIregion BUR Ig lambda chain V-Iregion NEWM Antigen:p-BCR:p-SYKIg lambda chain V-IVregion Hil Ig kappa chain V-Iregion Daudi Ig kappa chain V-Iregion Kue PSMB2 Ig heavy chain V-IIIregion TRO Ig heavy chain V-IIIregion TRO Ig kappa chain V-Iregion Walker Ig kappa chain V-IIIregion POM Ig lambda chainV-VII region MOT Ig lambda chain V-Iregion VOR Ig lambda chain V-IVregion Bau Ig heavy chain V-IIIregion DOB Ig lambda chain V-IVregion X Ig kappa chain V-Iregion Daudi Ig heavy chain V-IIregion NEWM Ig kappa chain V-IIIregion VH Ig kappa chain V-IVregion B17 Ig kappa chain V-Iregion OU Ig heavy chain V-Iregion ND Ig heavy chain V-IIIregion HIL Ig heavy chain V-IIIregion TEI IGKC Ig lambda chain Vregion 4A PSMB5 I(1,4,5)P3 Ig kappa chain V-Iregion Wes Ig heavy chain V-IIIregion WAS PSMC1 Ig lambda chain V-Iregion NEWM IgH heavy chainV-III region VH26precursor PSMD12 Ig heavy chain V-IIIregion TUR Ig kappa chain V-Iregion CAR Ig kappa chain V-Iregion Ni Ig lambda chainV-III region LOI Ig lambda chain V-IIregion BO Ig heavy chain V-IIregion HE p-BCL10 Ig lambda chain V-Iregion MEM IGKC Ig kappa chain V-Iregion OU IGHV7-81(1-?) Ig lambda chain V-IVregion MOL Ig kappa chain V-Iregion DEE p-S559,S644,S652-CARD11 Ig kappa chain V-IIIregion POM PRKCBIg lambda chain V-Iregion NEWM Ig lambda chain V-VIregion NIG-48 Ig kappa chain V-Iregion Bi Ig kappa chain V-IIregion GM607 Ig kappa chain V-Iregion AU PSMB3 CBL Ig kappa chain V-Iregion CAR p-Y762,807,822-CD22 Ig kappa chain V-Iregion WEA Ig heavy chain V-IIIregion WAS Ig kappa chain V-IIIregion HIC Ig kappa chain V-Iregion Lay Ig kappa chain V-Iregion OU p-Y188,Y199-CD79A ITPR2 Ig heavy chain V-IIIregion ZAP Ig lambda chain V-Iregion WAH Ig lambda chainV-VII region MOT PSME2 IGLC7 Ig lambda chain V-IVregion Kern Ig lambda chain V-Iregion NEWM IGLC6 Ig heavy chain V-IIIregion TEI Ig lambda chain V-IIregion NIG-84 CHUK Ig heavy chain V-Iregion HG3 p-S157,S161-NFKBIE Ig kappa chain V-IIIregion CLL Ig kappa chain V-IVregion STH PSMB6 Ig kappa chain V-IIregion GM607 Ig kappa chain V-Iregion Scw Ig kappa chain V-IIIregion CLL Ig heavy chain V-Iregion EU Ig heavy chain V-IIIregion LAY Ig kappa chain V-IIIregion GOL p-T187-MAP3K7 p-Y196,Y207-CD79B Ig lambda chain V-Iregion NEW Ig heavy chain V-IIIregion KOL Ig kappa chain V-IIIregion IARC/BL41 Ig kappa chain V-IIIregion WOL Ig heavy chain V-IIIregion TIL Ig heavy chain V-IIregion DAW Ig kappa chain V-IIIregion CLL Ig kappa chain V-IIregion GM607 Ig kappa chain V-Iregion Mev Ig kappa chain Vregion EV15 Ig lambda chain V-IIregion WIN Ig kappa chain V-Iregion HK101 Ig heavy chain V-Iregion WOL Ig kappa chain V-Iregion Ni Ig lambda chain V-Iregion VOR Ig heavy chain V-IIIregion BUT Ig heavy chain V-IIIregion TEI Ig heavy chain V-IIIregion BUT Ig kappa chain V-Iregion Ka Ig kappa chain V-IIregion Cum Ig kappa chain V-Iregion EU Ig heavy chain V-IIregion NEWM Ig lambda chain V-VIregion EB4 FKBP1A:TacrolimusIg kappa chain Vregion EV15 Ig lambda chain V-Iregion BL2 PhosphorylatedNFATC1,2,3Ig kappa chain V-Iregion Scw Ig kappa chain V-Iregion Mev Ig heavy chain V-IIIregion WEA BLKIGLC2 Ig heavy chain V-Iregion HG3 Ig heavy chain V-IIIregion GA Ig heavy chain V-IIIregion ZAP Ig lambda chain V-IVregion Hil Ig heavy chain V-IIregion WAH ITPR3 Ig kappa chain V-IIregion GM607 Ig kappa chain V-Iregion Gal IGHM Ig kappa chain V-IVregion B17 BTKIg heavy chain V-IIIregion WAS PSMD14 Ig lambda chain V-VIregion NIG-48 PSMD2 IGLC1 Ig lambda chain V-IIregion VIL Ig kappa chain V-IIIregion GOL Ig kappa chain V-IIIregion VG Ig kappa chain V-IIIregion VG Ig kappa chain V-Iregion WAT p-Y188,Y199-CD79A Ig heavy chain V-IIIregion KOL Ig heavy chain V-IIIregion POM Ig heavy chain V-Iregion ND Ig heavy chain V-IIregion HE Ig lambda chain V-IIregion NIG-84 Ig kappa chain V-IIIregion GOL Ig kappa chain V-Iregion Walker Ig heavy chain V-IIregion ARH-77 SKP1 ATPCa2+ Ig heavy chain V-IIIregion WEA Ig heavy chain V-IIregion WAH Ig heavy chain V-IIIregion TUR p-S177,S181-IKBKB Ig kappa chain V-IIIregion VH TRPC1 Ig heavy chain V-IIIregion LAY Ig lambda chain V-IIregion BOH Ig kappa chain V-Iregion Roy Ig heavy chain V-IIIregion KOL Ig kappa chain V-IIIregion HIC Ig kappa chain Vregion EV15 Ig lambda chain V-IIregion MGC Ig kappa chain V-Iregion Roy IGHM FKBP1A CALM1 Ig heavy chain V-IIIregion JON Ig kappa chain V-IVregion Len Ig heavy chain V-Iregion WOL Ig kappa chain V-Iregion Wes Ig lambda chain V-VIregion WLT Ig kappa chain V-Iregion DEE Ig kappa chain V-Iregion WEA Ig heavy chain V-IIIregion BUR Ig kappa chain V-Iregion Rei IGKC Ig lambda chain V-IVregion MOL IP3 receptorhomotetramerIg kappa chain V-Iregion Bi Ig lambda chain V-IIregion TOG IGKV4-1(21-?) PIK3R1 Ig lambda chain V-Iregion VOR Ig lambda chain V-VIregion AR Ig heavy chain V-IIIregion LAY Ig lambda chain Vregion 4A AHCYL1 Ig kappa chain V-IIIregion NG9 Ig heavy chain V-Iregion EU Ig heavy chain V-IIIregion WEA Ig kappa chain V-IIIregion B6 Ig lambda chain V-VIregion NIG-48 SOS1 Ig lambda chain V-Iregion NIG-64 Ig kappa chain V-Iregion Walker Ca2+ Ig kappa chain V-IIregion MIL Ig lambda chainV-III region SH Ig heavy chain V-Iregion SIE Ig heavy chain V-IIIregion TEI Ig kappa chain V-Iregion BAN IGHV(1-?) PI(4,5)P2Ig lambda chain V-IIregion BUR IGHM Ig kappa chain Vregion EV15 Ig kappa chain V-IIIregion B6 IgH heavy chainV-III region VH26precursor Ig kappa chain V-Iregion AG Ig lambda chain V-IVregion Bau Ig kappa chain V-Iregion OU Ig heavy chain V-IIIregion POM Ig heavy chain V-Iregion Mot Ig heavy chain V-IIregion MCE Ig heavy chain V-IIIregion KOL Fe3+ Ig lambda chain Vregion 4A 8570, 11229, 67, 94, 14220, 38, 107, 123701, 9011813410316, 29, 94, 103, 1424142, 69, 736334146448, 23, 25, 54103804213860


Description

Mature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesel et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010).
The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Baldock et al. 2000, Irish et al. 2006, Tsang et al. 2008, reviewed in Bradshaw 2010).
Activated SYK and other kinases phosphorylate BLNK (SLP-65), BCAP, and CD19 which serve as scaffolds for the assembly of large complexes, the signalosomes, by recruiting phosphoinositol 3-kinase (PI3K), phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
PLC-gamma associated with BLNK hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of calcium ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels in the plasma membrane, resulting in an influx of extracellular calcium ions (Muik et al. 2008, Luik et al. 2008, Park et al. 2009, Mori et al. 2002). PI3K associated with BCAP and CD19 phosphorylates phosphatidylinositol 4,5-bisphosphate to yield phosphatidyinositol 3,4,5-trisphosphate.
Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidylinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS is activated via RasGRP proteins, NF-AT is activated via calcineurin, and AKT (PKB) is activated via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006). Source:Reactome.

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  55. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF.; ''NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways.''; PubMed Europe PMC Scholia
  56. Baba Y, Hashimoto S, Matsushita M, Watanabe D, Kishimoto T, Kurosaki T, Tsukada S.; ''BLNK mediates Syk-dependent Btk activation.''; PubMed Europe PMC Scholia
  57. Harwood NE, Batista FD.; ''Early events in B cell activation.''; PubMed Europe PMC Scholia
  58. Carter RH, Park DJ, Rhee SG, Fearon DT.; ''Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes.''; PubMed Europe PMC Scholia
  59. Flaswinkel H, Reth M.; ''Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor.''; PubMed Europe PMC Scholia
  60. Ghosh CC, Vu HY, Mujo T, Vancurova I.; ''Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes.''; PubMed Europe PMC Scholia
  61. Uckun FM, Burkhardt AL, Jarvis L, Jun X, Stealey B, Dibirdik I, Myers DE, Tuel-Ahlgren L, Bolen JB.; ''Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny.''; PubMed Europe PMC Scholia
  62. Shinohara H, Kurosaki T.; ''Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling.''; PubMed Europe PMC Scholia
  63. Nishizumi H, Horikawa K, Mlinaric-Rascan I, Yamamoto T.; ''A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals.''; PubMed Europe PMC Scholia
  64. Whiteside ST, Epinat JC, Rice NR, Israël A.; ''I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity.''; PubMed Europe PMC Scholia
  65. Loh C, Shaw KT, Carew J, Viola JP, Luo C, Perrino BA, Rao A.; ''Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity.''; PubMed Europe PMC Scholia
  66. Marshall AJ, Niiro H, Lerner CG, Yun TJ, Thomas S, Disteche CM, Clark EA.; ''A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase.''; PubMed Europe PMC Scholia
  67. Baeuerle PA, Baltimore D.; ''Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.''; PubMed Europe PMC Scholia
  68. Batiuk TD, Kung L, Halloran PF.; ''Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.''; PubMed Europe PMC Scholia
  69. Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, Habermann TM, Kutok JL, Shipp MA.; ''SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma.''; PubMed Europe PMC Scholia
  70. Fagerlund R, Melén K, Cao X, Julkunen I.; ''NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules.''; PubMed Europe PMC Scholia
  71. Ohba Y, Mochizuki N, Yamashita S, Chan AM, Schrader JW, Hattori S, Nagashima K, Matsuda M.; ''Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3.''; PubMed Europe PMC Scholia
  72. Dinh M, Grunberger D, Ho H, Tsing SY, Shaw D, Lee S, Barnett J, Hill RJ, Swinney DC, Bradshaw JM.; ''Activation mechanism and steady state kinetics of Bruton's tyrosine kinase.''; PubMed Europe PMC Scholia
  73. Alicia S, Angélica Z, Carlos S, Alfonso S, Vaca L.; ''STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts.''; PubMed Europe PMC Scholia
  74. Hata D, Nakamura T, Kawakami T, Kawakami Y, Herren B, Mayumi M.; ''Tyrosine phosphorylation of MB-1, B29, and HS1 proteins in human B cells following receptor crosslinking.''; PubMed Europe PMC Scholia
  75. Wesselborg S, Fruman DA, Sagoo JK, Bierer BE, Burakoff SJ.; ''Identification of a physical interaction between calcineurin and nuclear factor of activated T cells (NFATp).''; PubMed Europe PMC Scholia
  76. Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M.; ''Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
  77. Beals CR, Clipstone NA, Ho SN, Crabtree GR.; ''Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporin-sensitive intramolecular interaction.''; PubMed Europe PMC Scholia
  78. Buhl AM, Pleiman CM, Rickert RC, Cambier JC.; ''Qualitative regulation of B cell antigen receptor signaling by CD19: selective requirement for PI3-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization.''; PubMed Europe PMC Scholia
  79. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS.; ''STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.''; PubMed Europe PMC Scholia
  80. Shibasaki F, Price ER, Milan D, McKeon F.; ''Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4.''; PubMed Europe PMC Scholia
  81. Weng WK, Jarvis L, LeBien TW.; ''Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors.''; PubMed Europe PMC Scholia
  82. Irish JM, Czerwinski DK, Nolan GP, Levy R.; ''Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry.''; PubMed Europe PMC Scholia
  83. Li CC, Dai RM, Longo DL.; ''Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product.''; PubMed Europe PMC Scholia
  84. Garcia-Cozar FJ, Okamura H, Aramburu JF, Shaw KT, Pelletier L, Showalter R, Villafranca E, Rao A.; ''Two-site interaction of nuclear factor of activated T cells with activated calcineurin.''; PubMed Europe PMC Scholia
  85. Luo C, Shaw KT, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino BA, Hogan PG, Rao A.; ''Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.''; PubMed Europe PMC Scholia
  86. Papp E, Tse JK, Ho H, Wang S, Shaw D, Lee S, Barnett J, Swinney DC, Bradshaw JM.; ''Steady state kinetics of spleen tyrosine kinase investigated by a real time fluorescence assay.''; PubMed Europe PMC Scholia
  87. Valentine MA, Bursten SL, Harris WE, Draves KE, Pollok BA, Ostrowski J, Bomsztyk K, Clark EA.; ''Generation of phosphatidic acid and diacylglycerols following ligation of surface immunoglobulin in human B lymphocytes: potential role in PKC activation.''; PubMed Europe PMC Scholia
  88. Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS.; ''Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions.''; PubMed Europe PMC Scholia
  89. Kochs G, Hummel R, Fiebich B, Sarre TF, Marmé D, Hug H.; ''Activation of purified human protein kinase C alpha and beta I isoenzymes in vitro by Ca2+, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate.''; PubMed Europe PMC Scholia
  90. Park J, Yaseen NR, Hogan PG, Rao A, Sharma S.; ''Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells.''; PubMed Europe PMC Scholia
  91. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  92. Law CL, Aruffo A, Chandran KA, Doty RT, Clark EA.; ''Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind multiple sialylated ligands expressed on B and T cells.''; PubMed Europe PMC Scholia
  93. Kim YJ, Sekiya F, Poulin B, Bae YS, Rhee SG.; ''Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.''; PubMed Europe PMC Scholia
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  95. Roifman CM, Wang G.; ''Phospholipase C-gamma 1 and phospholipase C-gamma 2 are substrates of the B cell antigen receptor associated protein tyrosine kinase.''; PubMed Europe PMC Scholia
  96. Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF.; ''STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels.''; PubMed Europe PMC Scholia
  97. Fu C, Turck CW, Kurosaki T, Chan AC.; ''BLNK: a central linker protein in B cell activation.''; PubMed Europe PMC Scholia
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  101. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
  102. Tanner MJ, Hanel W, Gaffen SL, Lin X.; ''CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation.''; PubMed Europe PMC Scholia
  103. Suzuki H, Chiba T, Kobayashi M, Takeuchi M, Suzuki T, Ichiyama A, Ikenoue T, Omata M, Furuichi K, Tanaka K.; ''IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.''; PubMed Europe PMC Scholia
  104. Meller N, Elitzur Y, Isakov N.; ''Protein kinase C-theta (PKCtheta) distribution analysis in hematopoietic cells: proliferating T cells exhibit high proportions of PKCtheta in the particulate fraction.''; PubMed Europe PMC Scholia
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  106. Oellerich T, Grønborg M, Neumann K, Hsiao HH, Urlaub H, Wienands J.; ''SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins.''; PubMed Europe PMC Scholia
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  143. Li Z, Nabel GJ.; ''A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
112687view16:08, 9 October 2020ReactomeTeamReactome version 73
101604view11:47, 1 November 2018ReactomeTeamreactome version 66
101140view21:32, 31 October 2018ReactomeTeamreactome version 65
100668view20:06, 31 October 2018ReactomeTeamreactome version 64
100218view16:51, 31 October 2018ReactomeTeamreactome version 63
99769view15:17, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93934view13:46, 16 August 2017ReactomeTeamreactome version 61
93521view11:25, 9 August 2017ReactomeTeamreactome version 61
87188view08:07, 19 July 2016EgonwOntology Term : 'signaling pathway' added !
86619view09:22, 11 July 2016ReactomeTeamreactome version 56
83158view10:13, 18 November 2015ReactomeTeamVersion54
81511view13:03, 21 August 2015ReactomeTeamVersion53
76984view08:27, 17 July 2014ReactomeTeamFixed remaining interactions
76689view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76015view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75724view11:19, 10 June 2014ReactomeTeamReactome 48 Update
75074view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74860view17:46, 2 May 2014EgonwMarked two metabolites as a DataNode type="Metabolite"...
74721view08:48, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
4xCa2+:CaMComplexR-HSA-74294 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AHCYL1 ProteinO43865 (Uniprot-TrEMBL)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerComplexR-HSA-5226920 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PKC betaComplexR-HSA-139829 (Reactome)
Active IKK complexComplexR-HSA-727820 (Reactome)
Antigen:BCRComplexR-HSA-983689 (Reactome)
Antigen:p-BCR:SYKComplexR-HSA-983693 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNKComplexR-HSA-983687 (Reactome)
Antigen:p-BCR:p-SYKComplexR-HSA-983690 (Reactome)
Antigen:p-BCRComplexR-HSA-983691 (Reactome)
AntigenR-NUL-983667 (Reactome)
BCAP SignalosomeComplexR-HSA-2045909 (Reactome)
BCRComplexR-HSA-983677 (Reactome)
BLK-like proteinsR-HSA-3902518 (Reactome) This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
BLKProteinP51451 (Uniprot-TrEMBL)
BLNK (SLP-65) SignalosomeComplexR-HSA-984818 (Reactome)
BLNK ProteinQ8WV28 (Uniprot-TrEMBL)
BLNK:GRB2:SOS1:CIN85:CBLComplexR-HSA-983692 (Reactome)
BTKProteinQ06187 (Uniprot-TrEMBL)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CARD11 ProteinQ9BXL7 (Uniprot-TrEMBL)
CARMA1 oligomerComplexR-HSA-1169088 (Reactome)
CARMA1:BCL10:MALT1:TAK1:IKKComplexR-HSA-1168620 (Reactome) TAK1 and the IKK complex are observed to migrate to lipid rafts containing phosphorylated CARMA1, BCL10, and MALT1. By analogy with NF-kappaB signaling pathways in other cells, the CARMA1:BCL10MALT1:TAK1:IKK complex in B cells may also contain TAB1, TAB2 and/or TAB3, TRAF6.
CARMA1:BCL10:MALT1:TAK1ComplexR-HSA-1168619 (Reactome) TAK1 and the IKK complex are observed to migrate to lipid rafts containing phosphorylated CARMA1, BCL10, and MALT1. By analogy with NF-kappaB signaling pathways in other cells, the CARMA1:BCL10MALT1:TAK1:IKK complex in B cells may also contain TAB1, TAB2 and/or TAB3, TRAF6.
CARMA1:MALT1:BCL10ComplexR-HSA-1168622 (Reactome)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBLB ProteinQ13191 (Uniprot-TrEMBL)
CD19 ProteinP15391 (Uniprot-TrEMBL)
CD19 SignalosomeComplexR-HSA-2076233 (Reactome)
CD19:VAV1ComplexR-HSA-2076225 (Reactome)
CD79A ProteinP11912 (Uniprot-TrEMBL)
CD79B ProteinP40259 (Uniprot-TrEMBL)
CHUK ProteinO15111 (Uniprot-TrEMBL)
CRAC channelComplexR-HSA-434679 (Reactome)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcineurin (CaN)ComplexR-HSA-2025977 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3ComplexR-HSA-2025899 (Reactome)
Cyclophilin A:Cyclosporin AComplexR-HSA-2026008 (Reactome)
Cyclosporin A MetaboliteCHEBI:4031 (ChEBI)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGCHEBI:17815 (ChEBI)
DAPP1ProteinQ9UN19 (Uniprot-TrEMBL)
Dephosphorylated NFATC1,2,3R-HSA-2025852 (Reactome)
FBXW11 ProteinQ9UKB1 (Uniprot-TrEMBL)
FKBP1A ProteinP62942 (Uniprot-TrEMBL)
FKBP1A:TacrolimusComplexR-HSA-2026019 (Reactome)
FYNProteinP06241 (Uniprot-TrEMBL)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
GDP MetaboliteCHEBI:17552 (ChEBI)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
HRAS ProteinP01112 (Uniprot-TrEMBL)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IGHD ProteinP01880 (Uniprot-TrEMBL)
IGHM ProteinP01871 (Uniprot-TrEMBL)
IGHV(1-?) ProteinA2KUC3 (Uniprot-TrEMBL)
IGHV7-81(1-?) ProteinQ6PIL0 (Uniprot-TrEMBL)
IGKC ProteinP01834 (Uniprot-TrEMBL)
IGKV1-5(23-?) ProteinP01602 (Uniprot-TrEMBL)
IGKV4-1(21-?) ProteinP06312 (Uniprot-TrEMBL)
IGKVA18(21-?) ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1 ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2 ProteinP0CG05 (Uniprot-TrEMBL)
IGLC3 ProteinP0CG06 (Uniprot-TrEMBL)
IGLC6 ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7 ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV(23-?) ProteinA2NXD2 (Uniprot-TrEMBL)
IKBKB ProteinO14920 (Uniprot-TrEMBL)
IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
IKKA ProteinO15111 (Uniprot-TrEMBL)
IKKA:IKBKB:IKBKGComplexR-HSA-168113 (Reactome)
IP3 receptor homotetramerComplexR-HSA-169686 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
ITPR:I(1,4,5)P3 tetramerComplexR-HSA-169696 (Reactome)
Ig heavy chain V-I region EU ProteinP01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 ProteinP01743 (Uniprot-TrEMBL)
Ig heavy chain V-I region Mot ProteinP06326 (Uniprot-TrEMBL)
Ig heavy chain V-I region ND ProteinP01744 (Uniprot-TrEMBL)
Ig heavy chain V-I region SIE ProteinP01761 (Uniprot-TrEMBL)
Ig heavy chain V-I region WOL ProteinP01760 (Uniprot-TrEMBL)
Ig heavy chain V-II region ARH-77 ProteinP06331 (Uniprot-TrEMBL)
Ig heavy chain V-II region COR ProteinP01815 (Uniprot-TrEMBL)
Ig heavy chain V-II region DAW ProteinP01816 (Uniprot-TrEMBL)
Ig heavy chain V-II region HE ProteinP01818 (Uniprot-TrEMBL)
Ig heavy chain V-II region MCE ProteinP01817 (Uniprot-TrEMBL)
Ig heavy chain V-II region NEWM ProteinP01825 (Uniprot-TrEMBL)
Ig heavy chain V-II region OU ProteinP01814 (Uniprot-TrEMBL)
Ig heavy chain V-II region SESS ProteinP04438 (Uniprot-TrEMBL)
Ig heavy chain V-II region WAH ProteinP01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO ProteinP01766 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUR ProteinP01773 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUT ProteinP01767 (Uniprot-TrEMBL)
Ig heavy chain V-III region CAM ProteinP01768 (Uniprot-TrEMBL)
Ig heavy chain V-III region DOB ProteinP01782 (Uniprot-TrEMBL)
Ig heavy chain V-III region GA ProteinP01769 (Uniprot-TrEMBL)
Ig heavy chain V-III region GAL ProteinP01781 (Uniprot-TrEMBL)
Ig heavy chain V-III region HIL ProteinP01771 (Uniprot-TrEMBL)
Ig heavy chain V-III region JON ProteinP01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL ProteinP01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region LAY ProteinP01775 (Uniprot-TrEMBL)
Ig heavy chain V-III region NIE ProteinP01770 (Uniprot-TrEMBL)
Ig heavy chain V-III region POM ProteinP01774 (Uniprot-TrEMBL)
Ig heavy chain V-III region TEI ProteinP01777 (Uniprot-TrEMBL)
Ig heavy chain V-III region TIL ProteinP01765 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO ProteinP01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region TUR ProteinP01779 (Uniprot-TrEMBL)
Ig heavy chain V-III region WAS ProteinP01776 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA ProteinP01763 (Uniprot-TrEMBL)
Ig heavy chain V-III region ZAP ProteinP01778 (Uniprot-TrEMBL)
Ig kappa chain V region EV15 ProteinP06315 (Uniprot-TrEMBL)
Ig kappa chain V-I region AG ProteinP01593 (Uniprot-TrEMBL)
Ig kappa chain V-I region AU ProteinP01594 (Uniprot-TrEMBL)
Ig kappa chain V-I region BAN ProteinP04430 (Uniprot-TrEMBL)
Ig kappa chain V-I region Bi ProteinP01595 (Uniprot-TrEMBL)
Ig kappa chain V-I region CAR ProteinP01596 (Uniprot-TrEMBL)
Ig kappa chain V-I region DEE ProteinP01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi ProteinP04432 (Uniprot-TrEMBL)
Ig kappa chain V-I region EU ProteinP01598 (Uniprot-TrEMBL)
Ig kappa chain V-I region Gal ProteinP01599 (Uniprot-TrEMBL)
Ig kappa chain V-I region HK101 ProteinP01601 (Uniprot-TrEMBL)
Ig kappa chain V-I region Hau ProteinP01600 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ka ProteinP01603 (Uniprot-TrEMBL)
Ig kappa chain V-I region Kue ProteinP01604 (Uniprot-TrEMBL)
Ig kappa chain V-I region Lay ProteinP01605 (Uniprot-TrEMBL)
Ig kappa chain V-I region Mev ProteinP01612 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ni ProteinP01613 (Uniprot-TrEMBL)
Ig kappa chain V-I region OU ProteinP01606 (Uniprot-TrEMBL)
Ig kappa chain V-I region Rei ProteinP01607 (Uniprot-TrEMBL)
Ig kappa chain V-I region Roy ProteinP01608 (Uniprot-TrEMBL)
Ig kappa chain V-I region Scw ProteinP01609 (Uniprot-TrEMBL)
Ig kappa chain V-I region WAT ProteinP80362 (Uniprot-TrEMBL)
Ig kappa chain V-I region WEA ProteinP01610 (Uniprot-TrEMBL)
Ig kappa chain V-I region Walker ProteinP04431 (Uniprot-TrEMBL)
Ig kappa chain V-I region Wes ProteinP01611 (Uniprot-TrEMBL)
Ig kappa chain V-II region Cum ProteinP01614 (Uniprot-TrEMBL)
Ig kappa chain V-II region FR ProteinP01615 (Uniprot-TrEMBL)
Ig kappa chain V-II region GM607 ProteinP06309 (Uniprot-TrEMBL)
Ig kappa chain V-II region MIL ProteinP01616 (Uniprot-TrEMBL)
Ig kappa chain V-II region RPMI 6410 ProteinP06310 (Uniprot-TrEMBL)
Ig kappa chain V-II region TEW ProteinP01617 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 ProteinP01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region CLL ProteinP04207 (Uniprot-TrEMBL)
Ig kappa chain V-III region GOL ProteinP04206 (Uniprot-TrEMBL)
Ig kappa chain V-III region HAH ProteinP18135 (Uniprot-TrEMBL)
Ig kappa chain V-III region HIC ProteinP18136 (Uniprot-TrEMBL)
Ig kappa chain V-III region IARC/BL41 ProteinP06311 (Uniprot-TrEMBL)
Ig kappa chain V-III region NG9 ProteinP01621 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM ProteinP01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region SIE ProteinP01620 (Uniprot-TrEMBL)
Ig kappa chain V-III region Ti ProteinP01622 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG ProteinP04433 (Uniprot-TrEMBL)
Ig kappa chain V-III region VH ProteinP04434 (Uniprot-TrEMBL)
Ig kappa chain V-III region WOL ProteinP01623 (Uniprot-TrEMBL)
Ig kappa chain V-IV region B17 ProteinP06314 (Uniprot-TrEMBL)
Ig kappa chain V-IV region JI ProteinP06313 (Uniprot-TrEMBL)
Ig kappa chain V-IV region Len ProteinP01625 (Uniprot-TrEMBL)
Ig kappa chain V-IV region STH ProteinP83593 (Uniprot-TrEMBL)
Ig lambda chain V-III region LOI ProteinP80748 (Uniprot-TrEMBL)
Ig lambda chain V-III region SH ProteinP01714 (Uniprot-TrEMBL)
Ig lambda chain V-VII region MOT ProteinP01720 (Uniprot-TrEMBL)
Ig lambda chain V region 4A ProteinP04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region BL2 ProteinP06316 (Uniprot-TrEMBL)
Ig lambda chain V-I region EPS ProteinP06888 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA ProteinP01700 (Uniprot-TrEMBL)
Ig lambda chain V-I region MEM ProteinP06887 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEW ProteinP01701 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEWM ProteinP01703 (Uniprot-TrEMBL)
Ig lambda chain V-I region NIG-64 ProteinP01702 (Uniprot-TrEMBL)
Ig lambda chain V-I region VOR ProteinP01699 (Uniprot-TrEMBL)
Ig lambda chain V-I region WAH ProteinP04208 (Uniprot-TrEMBL)
Ig lambda chain V-II region BO ProteinP01710 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH ProteinP01706 (Uniprot-TrEMBL)
Ig lambda chain V-II region BUR ProteinP01708 (Uniprot-TrEMBL)
Ig lambda chain V-II region MGC ProteinP01709 (Uniprot-TrEMBL)
Ig lambda chain V-II region NEI ProteinP01705 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-58 ProteinP01713 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-84 ProteinP04209 (Uniprot-TrEMBL)
Ig lambda chain V-II region TOG ProteinP01704 (Uniprot-TrEMBL)
Ig lambda chain V-II region TRO ProteinP01707 (Uniprot-TrEMBL)
Ig lambda chain V-II region VIL ProteinP01711 (Uniprot-TrEMBL)
Ig lambda chain V-II region WIN ProteinP01712 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Bau ProteinP01715 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Hil ProteinP01717 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Kern ProteinP01718 (Uniprot-TrEMBL)
Ig lambda chain V-IV region MOL ProteinP06889 (Uniprot-TrEMBL)
Ig lambda chain V-IV region X ProteinP01716 (Uniprot-TrEMBL)
Ig lambda chain V-V region DEL ProteinP01719 (Uniprot-TrEMBL)
Ig lambda chain V-VI region AR ProteinP01721 (Uniprot-TrEMBL)
Ig lambda chain V-VI region EB4 ProteinP06319 (Uniprot-TrEMBL)
Ig lambda chain V-VI region NIG-48 ProteinP01722 (Uniprot-TrEMBL)
Ig lambda chain V-VI region SUT ProteinP06317 (Uniprot-TrEMBL)
Ig lambda chain V-VI region WLT ProteinP06318 (Uniprot-TrEMBL)
IgH heavy chain

V-III region VH26

precursor
ProteinP01764 (Uniprot-TrEMBL)
KRAS ProteinP01116 (Uniprot-TrEMBL)
LYNProteinP07948 (Uniprot-TrEMBL)
MALT1 ProteinQ9UDY8 (Uniprot-TrEMBL)
MALT1ProteinQ9UDY8 (Uniprot-TrEMBL)
MAP3K7ProteinO43318 (Uniprot-TrEMBL)
NAD+ MetaboliteCHEBI:15846 (ChEBI)
NCK1 ProteinP16333 (Uniprot-TrEMBL)
NCK1ProteinP16333 (Uniprot-TrEMBL)
NF-kappa-B p50,p65,c-Rel:IKBR-HSA-1168593 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBR-HSA-1168588 (Reactome)
NF-kappaB p50,p65,c-Rel dimerR-HSA-1168598 (Reactome)
NF-kappaB p50,p65,c-Rel dimerR-HSA-1168608 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBR-HSA-1168613 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPComplexR-HSA-1168617 (Reactome)
NFKB1(1-433) ProteinP19838 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
ORAI1 ProteinQ96D31 (Uniprot-TrEMBL)
Orai1 dimerComplexR-HSA-434696 (Reactome)
PI(3,4,5)P3 MetaboliteCHEBI:16618 (ChEBI)
PI(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PIK3AP1ProteinQ6ZUJ8 (Uniprot-TrEMBL)
PIK3CD ProteinO00329 (Uniprot-TrEMBL)
PIK3CD:PIK3R1ComplexR-HSA-1045152 (Reactome)
PIK3CD:PIK3R1ComplexR-HSA-1806213 (Reactome)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayR-HSA-1257604 (Reactome) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PLC gamma1,2R-HSA-1169089 (Reactome)
PPIA ProteinP62937 (Uniprot-TrEMBL)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CB ProteinP16298 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PRKCB ProteinP05771 (Uniprot-TrEMBL)
PRKCBProteinP05771 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
PTPN6 ProteinP29350 (Uniprot-TrEMBL)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRComplexR-HSA-5690677 (Reactome)
Phosphatidylserine MetaboliteCHEBI:18303 (ChEBI)
PhosphatidylserineCHEBI:18303 (ChEBI)
Phosphorylated NFATC1,2,3R-HSA-2025924 (Reactome)
RASGRP1,3R-HSA-1169462 (Reactome)
REL ProteinQ04864 (Uniprot-TrEMBL)
RELA ProteinQ04206 (Uniprot-TrEMBL)
SCF-beta-TrCp1,2R-HSA-1168601 (Reactome)
SH3KBP1 ProteinQ96B97 (Uniprot-TrEMBL)
SHC1 p46,p52R-HSA-1169480 (Reactome) SHC1 isoforms p46 and p52 are found in B cells (Smit et al. 1994).
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
STIM1 DimerComplexR-HSA-1168370 (Reactome)
STIM1 ProteinQ13586 (Uniprot-TrEMBL)
STIM1:CalciumComplexR-HSA-1168371 (Reactome)
STIM1:TRPC1ComplexR-HSA-2089954 (Reactome)
SYK ProteinP43405 (Uniprot-TrEMBL)
SYKProteinP43405 (Uniprot-TrEMBL)
TRPC1 ProteinP48995 (Uniprot-TrEMBL)
TRPC1ProteinP48995 (Uniprot-TrEMBL)
Tacrolimus MetaboliteCHEBI:61049 (ChEBI)
UbR-HSA-113595 (Reactome)
VAV1 ProteinP15498 (Uniprot-TrEMBL)
VAV1ProteinP15498 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
p-12S-NFATC1 ProteinO95644 (Uniprot-TrEMBL)
p-13S-NFATC3 ProteinQ12968 (Uniprot-TrEMBL)
p-14S-NFATC2 ProteinQ13469 (Uniprot-TrEMBL)
p-4Y-PIK3AP1 ProteinQ6ZUJ8 (Uniprot-TrEMBL)
p-5Y-BLNK ProteinQ8WV28 (Uniprot-TrEMBL)
p-6Y-CD19 ProteinP15391 (Uniprot-TrEMBL)
p-6Y-SYK ProteinP43405 (Uniprot-TrEMBL)
p-BCL10 ProteinO95999 (Uniprot-TrEMBL)
p-BCL10ProteinO95999 (Uniprot-TrEMBL)
p-CARMA1 OligomerComplexR-HSA-1168616 (Reactome) The coiled coil (CC) domain of CARMA1 interacts with the CC domain on other CARMA1 molecules to form oligomers of unknown stoichiometry.
p-RASGRP1,3:DAGComplexR-HSA-1168369 (Reactome) RasGRP3 binds diacylglycerol via its C1 domain.
p-S157,S161-NFKBIE ProteinO00221 (Uniprot-TrEMBL)
p-S177,S181-IKBKB ProteinO14920 (Uniprot-TrEMBL)
p-S19,S23-NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
p-S559,S644,S652-CARD11 ProteinQ9BXL7 (Uniprot-TrEMBL)
p-T133-RASGRP3 ProteinQ8IV61 (Uniprot-TrEMBL)
p-T184-RASGRP1 ProteinO95267 (Uniprot-TrEMBL)
p-T187-MAP3K7 ProteinO43318 (Uniprot-TrEMBL)
p-Y139-DAPP1 ProteinQ9UN19 (Uniprot-TrEMBL)
p-Y188,Y199-CD79A ProteinP11912 (Uniprot-TrEMBL)
p-Y194,Y195,Y272-SHC1-1(156-583) ProteinP29353-3 (Uniprot-TrEMBL)
p-Y196,Y207-CD79B ProteinP40259 (Uniprot-TrEMBL) By homology with CD79A (Ig-alpha), CD79B (Ig-beta) is presumed to be phosphorylated on tyrosines 196 and 207.
p-Y223,Y551-BTK ProteinQ06187 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2 ProteinP29353-2 (Uniprot-TrEMBL)
p-Y753,Y759,Y1217-PLCG2 ProteinP16885 (Uniprot-TrEMBL)
p-Y762,807,822-CD22 ProteinP20273 (Uniprot-TrEMBL)
p-Y771,Y783-PLCG1 ProteinP19174 (Uniprot-TrEMBL)
p21 RAS:GDPComplexR-HSA-109796 (Reactome)
p21 RAS:GTPComplexR-HSA-109783 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-1168640 (Reactome)
4xCa2+:CaMArrowR-HSA-74448 (Reactome)
4xCa2+:CaMR-HSA-2025890 (Reactome)
ADPArrowR-HSA-1168374 (Reactome)
ADPArrowR-HSA-1168635 (Reactome)
ADPArrowR-HSA-1168638 (Reactome)
ADPArrowR-HSA-1168641 (Reactome)
ADPArrowR-HSA-983703 (Reactome)
ADPArrowR-HSA-983707 (Reactome)
ADPArrowR-HSA-983709 (Reactome)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerTBarR-HSA-169683 (Reactome)
ATPR-HSA-1168374 (Reactome)
ATPR-HSA-1168635 (Reactome)
ATPR-HSA-1168638 (Reactome)
ATPR-HSA-1168641 (Reactome)
ATPR-HSA-983703 (Reactome)
ATPR-HSA-983707 (Reactome)
ATPR-HSA-983709 (Reactome)
Activated PKC betaArrowR-HSA-1168373 (Reactome)
Activated PKC betamim-catalysisR-HSA-1168635 (Reactome)
Active IKK complexArrowR-HSA-1168641 (Reactome)
Active IKK complexmim-catalysisR-HSA-1168638 (Reactome)
Antigen:BCRArrowR-HSA-983696 (Reactome)
Antigen:BCRR-HSA-983709 (Reactome)
Antigen:p-BCR:SYKArrowR-HSA-983700 (Reactome)
Antigen:p-BCR:SYKR-HSA-983707 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNKArrowR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNKR-HSA-983704 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNKmim-catalysisR-HSA-983704 (Reactome)
Antigen:p-BCR:p-SYKArrowR-HSA-983707 (Reactome)
Antigen:p-BCR:p-SYKR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYKmim-catalysisR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYKmim-catalysisR-HSA-983707 (Reactome)
Antigen:p-BCRArrowR-HSA-983709 (Reactome)
Antigen:p-BCRR-HSA-983700 (Reactome)
AntigenR-HSA-983696 (Reactome)
BCAP SignalosomeArrowR-HSA-983704 (Reactome)
BCAP Signalosomemim-catalysisR-HSA-2045911 (Reactome)
BCRR-HSA-983696 (Reactome)
BLK-like proteinsmim-catalysisR-HSA-983709 (Reactome)
BLNK (SLP-65) SignalosomeArrowR-HSA-983704 (Reactome)
BLNK (SLP-65) Signalosomemim-catalysisR-HSA-1112666 (Reactome)
BLNK:GRB2:SOS1:CIN85:CBLR-HSA-983703 (Reactome)
BTKR-HSA-983704 (Reactome)
BTKmim-catalysisR-HSA-983704 (Reactome)
CALM1R-HSA-74448 (Reactome)
CARMA1 oligomerR-HSA-1168635 (Reactome)
CARMA1:BCL10:MALT1:TAK1:IKKArrowR-HSA-1168637 (Reactome)
CARMA1:BCL10:MALT1:TAK1:IKKR-HSA-1168641 (Reactome)
CARMA1:BCL10:MALT1:TAK1:IKKmim-catalysisR-HSA-1168641 (Reactome)
CARMA1:BCL10:MALT1:TAK1ArrowR-HSA-1168641 (Reactome)
CARMA1:MALT1:BCL10ArrowR-HSA-1168644 (Reactome)
CARMA1:MALT1:BCL10R-HSA-1168637 (Reactome)
CD19 SignalosomeArrowR-HSA-983704 (Reactome)
CD19 Signalosomemim-catalysisR-HSA-2076220 (Reactome)
CD19:VAV1R-HSA-983704 (Reactome)
CRAC channelArrowR-HSA-434700 (Reactome)
CRAC channelmim-catalysisR-HSA-434798 (Reactome)
Ca2+ArrowR-HSA-1168376 (Reactome)
Ca2+ArrowR-HSA-169683 (Reactome)
Ca2+ArrowR-HSA-2089943 (Reactome)
Ca2+ArrowR-HSA-434798 (Reactome)
Ca2+R-HSA-1168373 (Reactome)
Ca2+R-HSA-169683 (Reactome)
Ca2+R-HSA-2025890 (Reactome)
Ca2+R-HSA-2089943 (Reactome)
Ca2+R-HSA-434798 (Reactome)
Ca2+R-HSA-74448 (Reactome)
Calcineurin (CaN)R-HSA-2025890 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3ArrowR-HSA-2025890 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3R-HSA-2025882 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3mim-catalysisR-HSA-2025882 (Reactome)
Cyclophilin A:Cyclosporin ATBarR-HSA-2025882 (Reactome)
DAGArrowR-HSA-1112666 (Reactome)
DAGR-HSA-1168373 (Reactome)
DAGR-HSA-1168374 (Reactome)
DAPP1R-HSA-983704 (Reactome)
Dephosphorylated NFATC1,2,3ArrowR-HSA-2025882 (Reactome)
FKBP1A:TacrolimusTBarR-HSA-2025882 (Reactome)
FYNmim-catalysisR-HSA-983709 (Reactome)
GRB2-1R-HSA-983704 (Reactome)
I(1,4,5)P3ArrowR-HSA-1112666 (Reactome)
I(1,4,5)P3ArrowR-HSA-169683 (Reactome)
I(1,4,5)P3R-HSA-169680 (Reactome)
IKKA:IKBKB:IKBKGR-HSA-1168637 (Reactome)
IP3 receptor homotetramerR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramerArrowR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-1168376 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-169683 (Reactome)
LYNmim-catalysisR-HSA-983709 (Reactome)
MALT1R-HSA-1168644 (Reactome)
MAP3K7R-HSA-1168637 (Reactome)
NCK1R-HSA-983704 (Reactome)
NF-kappa-B p50,p65,c-Rel:IKBR-HSA-1168638 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBArrowR-HSA-1168638 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBR-HSA-1168642 (Reactome)
NF-kappaB p50,p65,c-Rel dimerArrowR-HSA-1168633 (Reactome)
NF-kappaB p50,p65,c-Rel dimerArrowR-HSA-1168640 (Reactome)
NF-kappaB p50,p65,c-Rel dimerR-HSA-1168633 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBArrowR-HSA-1168643 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBR-HSA-1168640 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPArrowR-HSA-1168642 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPR-HSA-1168643 (Reactome)
Orai1 dimerR-HSA-434700 (Reactome)
PI(3,4,5)P3ArrowR-HSA-2045911 (Reactome)
PI(3,4,5)P3ArrowR-HSA-2076220 (Reactome)
PI(4,5)P2R-HSA-1112666 (Reactome)
PI(4,5)P2R-HSA-2045911 (Reactome)
PI(4,5)P2R-HSA-2076220 (Reactome)
PI(4,5)P2R-HSA-983704 (Reactome)
PIK3AP1R-HSA-983704 (Reactome)
PIK3CD:PIK3R1R-HSA-983704 (Reactome)
PIK3CD:PIK3R1mim-catalysisR-HSA-983704 (Reactome)
PLC gamma1,2R-HSA-983704 (Reactome)
PRKCBR-HSA-1168373 (Reactome)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRTBarR-HSA-983707 (Reactome)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRTBarR-HSA-983709 (Reactome)
PhosphatidylserineR-HSA-1168373 (Reactome)
Phosphorylated NFATC1,2,3R-HSA-2025890 (Reactome)
R-HSA-1112666 (Reactome) Phospholipase C gamma (PLC-gamma) is activated by phosphorylation in response to antigen-binding by the B cell receptor (Carter et al. 1991, Roitman and Wang 1992, Rodriguez et al. 2001, Kim et al. 2004, Sekiya et al. 2004). Phospholipase C gamma hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate and diacylglycerol (Carter et al. 1991, Kim et al. 2004). Human B cells contain both PLC-gamma1 and PLC-gamma2, with PLC-gamma2 predominating (Coggeshall et al. 1992).
R-HSA-1168373 (Reactome) Human Protein kinase C beta (PKC-beta) is activated by calcium ions, diacylglycerol, and binds phosphatidylserine (Kochs et al. 1991). Experiments in mice have shown that knocking out PKC-beta causes severe defects in B cells, leading to the conclusion that PKC-beta is the predominant signaling PKC in these cells (Leitges et al. 1996, Su et al. 2002, Saijo et al. 2002).
R-HSA-1168374 (Reactome) RasGRP1 and RasGRP3 translocate to the plasma membrane where they bind diacylglycerol (Lorenzo et al. 2001) and are phosphorylated (Teixeira et al. 2003, Zheng et al. 2005). Though RasGRP3 is phosphorylated in vitro and in some cell lines (e.g. Ramos cells) by protein kinase C theta (PKC-theta, Zheng et al. 2005), normal B cells do not contain PKC-theta (Meller et al. 1999). Both Rasgrp1 and Rasgrp3 participate in activating Ras in response to BCR signaling in mouse B cells (Coughlin et al. 2005).
R-HSA-1168376 (Reactome) In the resting state the luminal domain of STIM1 binds Ca2+ ions within the endoplasmic reticulum and this binding prevents dimerization of STIM1 (Luik et al. 2008). Upon depletion of Ca2+ ions from the endoplasmic reticulum, STIM1 is no longer bound to Ca2+ and forms homodimers (Muik et al. 2008, Luik et al. 2008, Park et al. 2009).
R-HSA-1168633 (Reactome) Nf-kappaB subunits contain nuclear localization sequences and, in the absence of IkB, are translocated to the nucleus (Bauerle and Baltimore 1988, Blank et al. 1991, Ghosh et al. 2008, Fagerlund et al. 2008). c-Rel binds to importins alpha5, alpha6, and alpha7; RelB binds to importins alpha5 and alpha6; p52 binds importin alpha3, alpha4, alpha5, and alpha6 (Fagerlund et al. 2008)
R-HSA-1168635 (Reactome) CARMA1 is phosphorylated at serines 559, 644, and 652 by Protein Kinase C beta (PKC-beta) (Sommer et al. 2005). CARMA1 is constitutively oligomerized (Tanner et al. 2007) and most CARMA1 in unstimulated cells is cytosolic (Sommer et al. 2005, Tanner et al. 2007), though a portion is constitutively associated with the plasma membrane (Gaide et al. 2002, Sommer et al. 2005). After phosphorylation, CARMA1 is associated with lipid rafts in the plasma membrane (Sommer et al. 2005). Note that some publications refer to CARMA1 with a different N-terminal methionine that is 7 amino acids shorter. In this case the phosphorylated serines are 552, 537, and 645.
R-HSA-1168636 (Reactome) RasGRP1 (Roose et al. 2007) and RasGRP3 (Ohba et al. 2000, Yamashita et al. 2000, Rebhun et al. 2000, Lorenzo et al. 2001) catalyze the exchange of GDP for GTP bound by RAS.
R-HSA-1168637 (Reactome) TAK1 and the IKK complex are observed to migrate from the cytosol to lipid rafts containing the CARMA1:BCL10:MALT1 (CBM) complex (Sommer et al. 2005, Shinohara et al. 2005 using chicken cells). By analogy with activation of NF-KappaB signaling in T cells, TAK1 in B cells may also be bound to TAB1 and TAB2 or TAB3, which bind K63-conjugated polyubiquitin on a TRAF protein bound to the CBM complex (reviewed in Shinohara et al. 2009).
R-HSA-1168638 (Reactome) Activated IKK complex phosphorylates the I-kappaB component of the cytoplasmic NF-kappaB complex (Zandi et al. 1998, Burke et al. 1999, Heilker et al. 1999). B cells contain I-kappaB-alpha, I-kappaB-beta, and I-kappaB-epsilon (Whiteside et al. 1997, Li and Nabel 1997).
R-HSA-1168640 (Reactome) Phosphorylated, ubiquitinated IkB is degraded by the proteasome (Miyamoto et al. 1994, Traenckner et al. 1994, Alkalay et al. 1995, DiDonato et al. 1995, Li et al. 1995, Lin et al. 1995, Scherer et al. 1995, Chen et al. 1995). IkB does not dissociate from NF-kB before it is proteolyzed (Miyamoto et al. 1994, Traenckner et al. 1994, DiDonato et al. 1995, Lin et al. 1995).
R-HSA-1168641 (Reactome) TAK1 phosphorylates IKK-beta (Wang et al. 2001). As inferred from chicken B cells, the reaction in human B cells may occur when TAK1 and the IKK complex are associated with the CARMA1:BCL10:MALT1 (CBM) complex. During T cell activation TAK1 forms a complex with TAB1 and TAB2, which binds K-63 conjugated polyubiquitin attached to TRAF6 associated with the CBM complex (Sun et al. 2004, reviewed in Shinohara et al. 2009). TRAF6 also polyubiquitinates IKK-gamma in T cells (Zhou et al. 2004). B cells contain functional TRAF6 and TRAF2 (Zhang et al. 2010) so the same mechanism may occur during activation of B cells.
R-HSA-1168642 (Reactome) SKP:Cul:F-box (SCF) complexes containing F-box factors Beta-TrCP1 (BTRCP, E3RSIkappaB) or beta-TrCP2 (BTRCP2, FBXW11, HOS) bind IkappaB (Yaron et al. 1998, Fuchs et al. 1999, Suzuki et al. 1999, Tan et al. 1999, Winston et al. 1999, Wu and Ghosh 1999).
R-HSA-1168643 (Reactome) SKP:Cul:F-box (SCF) complexes containing F-box factors Beta-TrCP1 (BTRCP, E3RSIkappaB) or beta-TrCP2 (BTRCP2, FBXW11, HOS) catalyze the polyubiquitination of IkappaB (Yaron et al. 1998, Fuchs et al. 1999, Suzuki et al. 1999, Tan et al. 1999, Winston et al. 1999, Wu and Ghosh 1999).
R-HSA-1168644 (Reactome) CARMA1 is phosphorylated and recruits BCL10 and MALT1 to the plasma membrane to form the CBM complex (Sommer et al. 2005, Tanner et al. 2007). Evidence from T cells (Jurkat cells) indicates that MALT1 and BCL10 oligomerize to activate the IKK complex (Zhou 2004).
R-HSA-169680 (Reactome) The IP3 receptor (IP3R) is an IP3-gated calcium channel. It is a large, homotetrameric protein, similar to other calcium channel proteins such as ryanodine. The four subunits form a 'four-leafed clover' structure arranged around the central calcium channel. Binding of ligands such as IP3 results in conformational changes in the receptor's structure that leads to channel opening.
R-HSA-169683 (Reactome) IP3 promotes the release of intracellular calcium.
R-HSA-2025882 (Reactome) As inferred from mouse (Okamura et al. 2000), calcineurin dephosphorylates NFATC2 at 13 serine residues (Batiuk et al. 1997, Kim et al. 2000). B lymphocytes also contain NFATC2 and NFATC3 which are inferred to undergo dephosphorylation at homologous serines. Dephosphorylation of NFATs exposes a nuclear localization signal which cause NFATs to be imported into the nucleus (Kim et al. 2000). In mouse, Calcineurin is observed to also transit into the nucleus in a complex with NFATs and may remain associated (Shibasaki et al. 1996).
R-HSA-2025890 (Reactome) Calcium activates calcineurin in two ways: binding the regulatory subunit of calcineurin directly and binding calmodulin which then interacts with the catalytic subunit of calcineurin. As inferred from mouse, B lymphocytes contain the R1 regulatory subunit (PPP3R1) and the beta catalytic subunit (PPP3CB).
In the presence of calcium and calcium:calmodulin calcineurin binds phosphorylated and unphosphorylated NFATs at 2 regions in the N-terminus (Luo et al. 1996, Garcia-Cozar et al. 1998, Park et al. 2000, evidence from mouse in Loh et al. 1996 and Wesselborg et al. 1996). Calcineurin also weakly interacts with NFATs in the absence of calcium (Garcia-Cozar et al. 1998).
R-HSA-2045911 (Reactome) PI3K generates phosphoinositol-3,4,5-trisphosphate (PIP3) from PIP2 after activation of the BCR (Gold et al. 1992, Chantry et al. 1997). Experiments in mice indicate that PI3K associated with BCAP is partly responsible for the activity (Aiba et al. 2008). (PI3K associated with CD19 is also partly responsible (Aiba et al. 2008).)
R-HSA-2076220 (Reactome) PI3K generates phosphoinositol-3,4,5-trisphosphate (PIP3) from PIP2 after activation of the BCR (Gold et al. 1992). Experiments in mice indicate that PI3K associated with CD19 is partly responsible for the activity (Buhl et al. 1997, Otero et al. 2001, Aiba et al. 2008). (PI3K associated with BCAP is also partly responsible (Aiba et al. 2008).)
R-HSA-2089927 (Reactome) The polybasic region of STIM1 interacts with 2 aspartate residues in the C-terminal region of TRPC1 (Zeng et al. 2008, Huang et al. 2006). The STIM1:TRPC1 complex can form a tenary complex with ORAI1 (Ong et al. 2007, Jardin et al. 2008) and ORAI participates in function of STIM1:TRPC1 channels (Cheng et al. 2008, Cheng et al. 2011). As inferred from chicken DT40 cells, TRPC1 (and possibly other TRP channels) participates in store-operated calcium influx during signaling by the B cell receptor (Mori et al. 2002).
R-HSA-2089943 (Reactome) TRPC1 forms a channel that transports Ca2+ across the plasma membrane. TRPC1 is gated by STIM1 (Ong et al. 2007).
R-HSA-434700 (Reactome) Sustained calcium signalling in lymphocytes and platelets requires the uptake of extracellular calcium when intracellular stores are depleted. The process whereby intracellular calcium depletion stimulates calcium uptake is often referred to as Store-operated calcium entry (SOCE). Store depletion is sensed by stromal interaction molecule 1 (STIM1), which then translocates to the plasma membrane and associates with 2 dimers of Orai1 to form a calcium-release activated calcium (CRAC) channel.
R-HSA-434798 (Reactome) Activation of Calcium-release-activated (CRAC) channels allows influx of calcium. The Orai component of CRAC is responsible for the selectivity of the channel, while the Stim component is responsible for activation.
R-HSA-74448 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
R-HSA-983696 (Reactome) Mature, unstimulated B cells express IgM and IgD immunoglobulins on their surfaces (Fu et al. 1974, Fu et al. 1975, reviewed in Kunkel 1975). The immunoglobulins form B cell receptor (BCR) complexes with disulfide-linked heterodimers of Ig-alpha (CD79A) and Ig-beta (CD79B), which have cytoplasmic tails containing immunoreceptor tyrosine-based activation motifs (ITAMs) (van Noesel et al. 1992, Saouaf et al. 1995, inferred from mouse Hombach et al. 1990, Wienands et al. 1990). Upon binding of antigen to the immunoglobulin a chain of phosphorylation events is triggered (Nel et al. 1984, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Harwood and Batista 2010).
R-HSA-983700 (Reactome) The SYK protein tyrosine kinase binds specifically to phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Law et al. 1994, Saouaf et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding activates the kinase activity of SYK (Rowley et al. 1995, Tsang et al. 2008).
R-HSA-983703 (Reactome) BLNK (SLP-65, BASH) forms a stable complex with GRB2, SOS1, and CIN85 in the cytosol. The complex is recruited to the plasma membrane where activated (phosphorylated) SYK phosphorylates BLNK at tyrosines 72, 84, 96, 178, and 189 (Fu et al. 1998, Chiu et al. 2002, inferred from mouse in Wienands et al. 1998, from chicken in Oellerich et al. 2009). Phosphorylated BLNK serves as a scaffold that binds effector molecules such as Phospholipase C. As inferred from mouse, BLNK interacts with phosphorylated tyrosines on CD79A (Ig-alpha) (Engels et al. 2001, Kabak et al. 2002).
R-HSA-983704 (Reactome) Phosphorylated SYK phosphorylates BLNK (SLP-65, Fu et al. 1998, Chiu et al. 2002) and BCAP (inferred from mouse, Okada et al. 2000). Effector molecules are then recruited: phosphoinositol 3-kinase (PI3K), Phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
As inferred from chicken DT40 cells and mouse B cells (Okada et al. 2000), phosphorylated BCAP recruits PI3K, which is phosphorylated by a SYK-dependent mechanism (Kuwahara et al. 1996) and produces phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 recruits BAM32 (Marshall et al. 2000) and BTK (de Weers et al. 1994, Baba et al. 2001) via their PH domains. PIP3 also recruits and activates PLC-gamma1 and PLC-gamma2 (Bae et al. 1998). BTK binds phosphorylated BLNK via its SH2 domain (Baba et al. 2001). BTK phosphorylates Phospholipase C gamma-2 (Rodriguez et al. 2001), which activates phospholipase activity (Carter et al. 1991, Roifman and Wang 1992, Kim et al. 2004, Sekiya et al. 2004).
Phosphorylated BLNK recruits PLC gamma, VAV, GRB2, and NCK (Fu and Chan 1997, Fu et al. 1998, Chiu et al. 2002).
SYK phosphorylates SHC which then binds GRB2 (Saxton et al. 1994, Harmer and DeFranco 1997).
CD19 in a stable complex with VAV1 is phosphorylated by Src kinases (inferred from mouse, Xu et al. 2002) and possibly by LYN (inferred from mouse, Fujimoto et al. 2000) in response to BCR activation. Phosphorylated CD19 then binds PI3K (Roifman and Ke 1993, Chalupny et al. 1993, Uckun et al. 1993, Weng et al. 1994, Brooks et al. 2000, Brooks et al. 2004) and can bind PLC-gamma2, which competes with VAV1 for the same binding site on CD19 (Brooks et al. 2000, Brooks et al. 2004).
R-HSA-983707 (Reactome) The SYK protein tyrosine kinase autophosphorylates at tyrosines 131, 323, 348, 352, 525, and 526 (Law et al. 1994, Rowley et al. 1995, Baldock et al. 2000, Irish et al. 2006, Papp et al. 2007, Chen et al. 2008, Tsang et al. 2008). The autophosphorylation increases the kinase activity of SYK. SYK is also phosporylated on additional residues in response to BCR activation (Bohnenberger et al. 2011).
R-HSA-983709 (Reactome) The B cell receptor (BCR) comprises an immunoglobulin complexed with a heterodimer of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29). After immunoglobulin IgM or IgD binds antigen the associated Ig-alpha and Ig-beta are each observed to be phosphorylated at two tyrosine residues in the cytoplasmic immunoreceptor tyrosine-activated motif (ITAM) (Sanchez et al. 1993, Hata et al. 1994, Saouaf et al. 1994, Saouaf et al. 1995). Saouaf et al. (1995) showed that the kinase Blk could phosphorylate both tyrosines of each ITAM and that the kinase SYK specifically bound phosphorylated but not unphosphorylated ITAMs. In mouse the kinase Lyn and other kinases phosphorylate one tyrosine and Syk is believed to phosphorylate the other (Yamanashi et al. 1991, Flaswinkel and Reth 1994, Rolli et al. 2002).
RASGRP1,3R-HSA-1168374 (Reactome)
SCF-beta-TrCp1,2ArrowR-HSA-1168643 (Reactome)
SCF-beta-TrCp1,2R-HSA-1168642 (Reactome)
SHC1 p46,p52R-HSA-983704 (Reactome)
STIM1 DimerArrowR-HSA-1168376 (Reactome)
STIM1 DimerR-HSA-2089927 (Reactome)
STIM1 DimerR-HSA-434700 (Reactome)
STIM1:CalciumR-HSA-1168376 (Reactome)
STIM1:TRPC1ArrowR-HSA-2089927 (Reactome)
STIM1:TRPC1mim-catalysisR-HSA-2089943 (Reactome)
SYKR-HSA-983700 (Reactome)
TRPC1R-HSA-2089927 (Reactome)
UbR-HSA-1168643 (Reactome)
VAV1R-HSA-983704 (Reactome)
p-BCL10R-HSA-1168644 (Reactome)
p-CARMA1 OligomerArrowR-HSA-1168635 (Reactome)
p-CARMA1 OligomerR-HSA-1168644 (Reactome)
p-RASGRP1,3:DAGArrowR-HSA-1168374 (Reactome)
p-RASGRP1,3:DAGmim-catalysisR-HSA-1168636 (Reactome)
p21 RAS:GDPR-HSA-1168636 (Reactome)
p21 RAS:GTPArrowR-HSA-1168636 (Reactome)
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