Semaphorin interactions (Homo sapiens)

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29, 31, 35, 37, 468193345, 4830, 392, 5, 4716, 271715, 4213, 3822221, 14, 284, 19, 44, 489, 402, 41, 432, 12, 26216, 711, 16, 18, 25321, 283, 243620, 454, 19, 482310, 34RhoA/B/CGTP Plexin-B1Met DAP12TRIM2 Sema3ANRP-1pPlexin-Afyn FARP2PIP5KIgamma SEMA4D dimer Sema3ANRP-1pPlexin-Afyn Sema3ANrp-1PlexinARac1-GTPPAK Sema3A dimer Sema3A dimer Plexin-A1-4 Sema3ANRP-1pPlexin-AFynFes PlexinA1-4FYNCDK5p-CRMPs Sema3ANrp-1pPlexinAFynFesRac-1-GTP SEMA4APLXND1 Sema4DpPlexin-B1Met R-Ras-GTP Sema3ANRP-1pPlexin-Afyn Rnd1-GTP cytosolPIP5K1gammaTalin-1 RAC1-GTP Rnd1-GTP R-Ras-GDP RAC1-GTP p-Plexin-A1-4 Sema3ANRP-1pPlexin-Afyn Sema3A dimer RhoA/B/CGTP Integrin alpha1beta1 Plexin-A1-4FYN pLIMK dimerHSP-90 SEMA4D dimer RAC1-GTP SEMA4D dimer pPlexin-B1Met Sema4DpPlexin-B1MetRnd1 Integrin alpha1beta1 Smooth muscle/non-muscle myosin II p-Plexin-A1-4 Sema3ANrp-1PlexinARac1-GTPpPAK SEMA4DPTPRC Active LIMK1 pCdk5p35 Sema4DpPlexin-B1Met NRP1p-Plexin-A1-4FYN Active LIMK1 Sema4DpPlexin-B1ErbB2Rac1Rnd1 RhoA/B/C Sema3ANrp-1PlexinAFynCdk5pCRMP's PLXNA2,PLXNA4 HSP-90 RhoA/B/C pPlexin-B1ErbB2 Rnd1-GTP pCdk5p35 Plexin-A1-4FYN Plexin-A1-4 Sema3ANRP-1pPlexin-AFynFes RAC1-GDP VAV1 Rho/Rac effectorsGTP pCRMP's tetramers Smooth muscle/non-muscle myosin 2 regulatory light chains pCdk5p35 NRP1PlexinA1-4FYN Sema3A dimer Sema3ANRP-1pPlexin-AFynFes Sema3A dimer SEMA4D dimer PAK homodimer Plexin-A1-4 Sema4DpPlexin-B1Met Sema3A dimer p-Plexin-A1-4 ROCK SEMA4D dimer Sema4DpPlexin-B1MetRnd1 Sema3ANrp-1pPlexinAFynFesRac-1-GTP FynpCdk5p53 SEMA6DPLXNA1TREM2DAP12 pPlexin-B1Met DAP12 dimer PLXNA1TREM2DAP12 pPlexin-B1ErbB2 RAC1-GTP NRP1p-Plexin-A1-4FYN Sema3A dimer SEMA4DpPlexin-B1ErbB2 complex pPlexin-B1ErbB2 Plexin-A1-4FYN Cdk5 phosphorylated CRMP1-5 Plexin-A1-4 PlexinA1-4FYNCdk5p53p-CRMP tetramers NRP1PlexinA1-4FYNCdk5p53p-CRMP tetramers Sema3A dimer FynpCdk5p53 Sema3ANrp-1pPlexinAFynFesRac-1-GTP PlexinA1-4FYNpCdk5p53 Sema4DpPlexin-B1Met RAC1-GTP Plexin-A1-4 cytosolSema3ANRP-1pPlexin-AFynFes RhoA,B,CGDP Sema3ANrp-1PlexinAFynpCdk5 SEMA4DpPlexin-B1ErbB2 complex Nrp-1PlexinAFynCdk5pCRMP's Sema3A dimer cytosolNRP1PlexinA1-4FARP2FYN Cdk5p35 R-Ras-GDP Sema3ANrp-1pPlexinAFynFesRac-1-GTPRnd1 SEMA6APLXNA2,PLXNA4 SEMA4D dimer RhoA Sema3ANRP-1pPlexin-AFynFes SEMA7AIntegrin alpha1beta1 NRP1p-Plexin-A1-4FYN FynpCdk5p53 DAP12 dimer SEMA5APLXNB3 Plexin-A1-4FYN RAC1-GTP Phospho-activated smooth muscle/non-muscle myosin 2 Sema4DpPlexin-B1ErbB2Rac1Rnd1 p-2Y-PAK SEMA4D dimer RhoA VAV1 Rho/Rac effectorsGTP cytosolSema3ANrp-1Plexin AFyn Phosphorylated smooth muscle/non-muscle myosin 2 regulatory light chains SEMA4D dimer Sema3ANrp-1pPlexinAFynFesRac-1-GTP PAK Smooth muscle/non-muscle myosin 2 heavy chains LARG and PDZ-RhoGEF Plexin-A1-4 Plexin-A1-4 Sema3A dimer Sema4DPlexin-B1p190RhoGAPRacRnd1 CRMP's tetramers Sema3A dimer Sema3ANrp-1PlexinAFyn cytosolSema3A dimer SEMA3APLXND1 Sema3A dimer CRMP's 1-5 PLXNA1TREM2DAP12 Sema3ANP-1Plexin-AFesCRMP RAC1-GTP SEMA4DCD72 Sema3ANrp-1PlexinAFynCdk5pCRMP's p-Plexin-A1-4 p-CRMP tetramers Fes phosphorylated CRMP's 1-5 NRP1Plexin-A1-4FYN Rnd1-GTP Smooth muscle/non-muscle myosin 2 heavy chains Plexin-A1-4FYNFARP2 Sema3ANRP-1pPlexin-Afyn Sema3ANRP-1pPlexin-AFynFes p-Plexin-A1-4 NRP1p-Plexin-A1-4FYN SEMA4D dimer NRP1p-Plexin-A1-4FYN GSK3beta phosphorylated CRMP's 1-5 Sema3ANRP-1pPlexin-Afyn NRP1p-Plexin-A1-4FYN pPlexin-B1Met pCRMP's tertramers Plexin-A1-4 NRP1PlexinA1-4FYNpCdk5p53 Rnd1-GTP SEMA7APLXNC1 pPlexin-B1Met Plexin-B1ErbB2 RhoA/B/C Sema4DpPlexin-B1MetRAC1-GTP pCofilin Active LIMK-1 SEMA4DpPlexin-B1ErbB2 complex Activated ROCKRhoA/B/CGTP NRP1PlexinA1-4FYN PAK DAP12TRIM2 Sema4DPlexin-B1Rac-Rnd1LARG/PDZ-RhoGEF R-Ras-GTP p-Plexin-A1-4 PLXND1SEMA7A PIP5K1C TREM2 Plexin-B1ErbB2RND1 p-S534-DPYSL5 SEMA4APLXND1PLXNA1 ATPATPERBB2 GDP MYH10 Sema4DpPlexin-B1ErbB2Rac1Rnd1PLXNA1 p-Y-PLXNA4 SEMA3Ep-Y-PLXNA1 FYNMET ERBB2 MYH11 Sema3ANrp-1PlexinAFynCdk5pCRMP'sp-Y15-CDK5 Sema3A dimerMET NRP1 GDP PLXNB1 NRP1 RND1 Sema3ANRP-1pPlexin-AFynFesSEMA5AFYNPLXNA3 PLXNA4 RHOB SEMA6D GTP p-Y-PLXNA4 ARHGEF12 SEMA4A GTPSEMA4D RAC1 p-Y15-CDK5 p-Y-PLXNA4 ARHGAP35SEMA3E ADPFYNPLXNA2CDK5R1DPYSL3 SEMA5APLXNB3p-Y-PLXNB1 p-Y-PLXNB1 p-Y-PLXNA1 Sema3ANrp-1pPlexinAFynFesRac-1-GTPSEMA4DCD72FESRND1 RhoA PLXNA4 GTP PLXNA1 p-Y-PLXNA4 PLXNA1 HSP90AB1 FES Sema3ANrp-1PlexinAFynCdk5pCRMP'sp-Y-PLXNA1 Sema3ANrp-1PlexinAFynpCdk5FES PLXNB3GTP GDP ADPMYH14 ROCKFYNADPMg2+ MYH9 RHOB PAK1 p-T509,T514,S518,S522-DPYSL3 SEMA3A ADPERBB2 p-Y-DPYSL4 NRP1FARP2PIP5KIgammaRHOA LARG and PDZ-RhoGEFDPYSL4 SEMA3APLXND1GTPRAC1-GTPGTP ATPPLXND1PiPlexin-B1Metp-S,T508-LIMK1 RAC1-GTPp-Y-PLXNA3 PAK2FYNPlexin-A1-4FYNATPFYNR-Ras-GTPPLXNA2SEMA4D RHOA SEMA4DPLXND1 ADPIntegrin alpha1beta1RHOA FYNNRP1 SEMA4D R-Ras-GTPSEMA3A GTP Pip-Y-PLXNA1 LIM Kinases, phosphorylatedNRP1 PLXNA3 p-Y-PLXNA3 p-Y-PLXNA4 SEMA3A LIM KinasesSEMA3A PLXNA2p-Y15-CDK5 NRP1 MYH10 RHOA p-S141,T402-PAK2pLIMK dimerHSP-90Sema3ANrp-1pPlexinAFynFesRac-1-GTPRnd1PLXNC1 p-S,T508-LIMK1 SEMA3A NRP1 FES p-Y-PLXNA2ATPPAKRND1 RhoA,B,CGDPPLXNA2,PLXNA4MET PLXNA2RRAS ATPPLXNA3 PAK1 ITGA1 TYROBP GDPCDK5R1RRAS Rnd1-GTPRAC1 TLN1 GTP RRAS ATPRHOC PLXND1 R-Ras-GDPp-Y-PLXNB1 Cdk5p35PLXNA2pCofilin Active LIMK-1DPYSL5 ATPSEMA3A RHOB TYROBP MYH11 PIP5K1C NRP1 SEMA4D GTP NRP1 p-Y-PLXNA1 RhoA NRP1PlexinA1-4FARP2FYNSEMA7APLXNC1MET SEMA7AGDP PLXNA2SEMA4D p-Y-PLXNB1 p-Y-PLXNA1 MYH14 Sema3ANrp-1PlexinAFynRHOC PLXNA1 CRMP1 p-Y-DPYSL2 GTP PLXNA4 FES FARP2NRP1 p-Y-PLXNA3 PLXNA1 Sema3ANrp-1PlexinARac1-GTPPAKMg2+ PAK homodimerPLXNA1 NRP1PlexinA1-4FYNPLXNA3 Sema3ANP-1Plexin-AFesCRMPSEMA3A p-T19,S20-MYL12BActive LIMK1PAK2ADPFYNADPTLN1PLXNA4 Rnd1-GTPNRP1 SEMA3A PLXNC1RRAS PLXNA2ITGB1 p-Y-PLXNA2p-T508-LIMK1RND1 SEMA4D SEMA4D dimerp-Y-PLXNB1 p-S522-DPYSL3 ATPNRP1 ADPCDK5R1GTP GTP RAC1 GTP CRMP's tetramersp-T508-LIMK1 SEMA4DpPlexin-B1ErbB2 complexSema3A dimerGTP ATPSema4DPlexin-B1p190RhoGAPRacRnd1RAC1 SEMA6A SEMA3A Sema4DpPlexin-B1MetSEMA6APLXNA2,PLXNA4FES ADPGDP GTP Sema4DpPlexin-B1MetRAC1-GTPPLXNA1 p-S534-DPYSL5 PLXNA3 SEMA3A ITGA1 LIMK1ADPR-Ras-GDPROCK2 NRP1 p-Y-DPYSL3 SEMA4D PLXNA4 ADPGTP Sema3ANrp-1PlexinARac1-GTPpPAKRAC1 p-Y-PLXNB1 SEMA4DPTPRCPLXNA4 ATPARHGAP35 p-Y-DPYSL5 RND1 p-S544-DPYSL4 p-S144,T423-PAK1 p-Y-PLXNA3 HSP-90FARP2 Phospho-activated smooth muscle/non-muscle myosin 2PLXNA2p-S522-DPYSL2 p-T19,S20-MYL9 SEMA4D p-Y-PLXNA3 FYNp-Y-PLXNA2TREM2 PTPRCPLXNA4 MYL9 SEMA4D dimerSEMA4D PLXNB3 ADPFYNGTP MYL12Bp-Y-PLXNA2PTPRC SEMA4D PLXNA3 GTP p-Y-PLXNA3 CD72 SEMA6Dp-T509,T514,S518,S522-CRMP1 FYNROCK1SEMA6APLXNA4 p-Y-PLXNA2SEMA7AIntegrin alpha1beta1FYNMET ATPPLXNA3 Activated ROCKRhoA/B/CGTPSEMA4D FYNITGB1 Sema4DPlexin-B1Rac-Rnd1LARG/PDZ-RhoGEFRND1 ADPFYNMYH9 p-Y-PLXNA4 PLXNA1 SEMA3A RAC1 PLXNA1 GTP RHOA FARP2 DPYSL2 SEMA3A MYL6 SEMA6DPLXNA1TREM2DAP12FES PIP5K1gammaTalin-1SEMA3A p-S522-CRMP1 PLXNB1 CDK5 PLXNA3 CD72ARHGEF11 p-S544-DPYSL4 RAC1 RAC1 Smooth muscle/non-muscle myosin IIRHOC CDK5R1p-Y-CRMP1 p-T509,T514,S518,S522-DPYSL2 ERBB2 HSP90AA1 PLXNA1TREM2DAP12RAC1-GDPMYL6 p-Y-PLXNB1 SEMA7A GDPSEMA5A ATPNRP1 Sema3ANrp-1Plexin AFynPLXNA4 PiGSK3Bp-S3-CFL1 Sema4DpPlexin-B1MetRnd1CFL1SEMA4AGTP p-Y-PLXNA2RhoA/B/CGTPPLXNA2


Description

Semaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphorins signal through multimeric receptor complexes that include other proteins such as plexins and neuropilins. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=373755

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Bibliography

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History

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CompareRevisionActionTimeUserComment
114896view16:41, 25 January 2021ReactomeTeamReactome version 75
113342view11:41, 2 November 2020ReactomeTeamReactome version 74
112552view15:52, 9 October 2020ReactomeTeamReactome version 73
101466view11:33, 1 November 2018ReactomeTeamreactome version 66
101004view21:12, 31 October 2018ReactomeTeamreactome version 65
100540view19:46, 31 October 2018ReactomeTeamreactome version 64
100088view16:31, 31 October 2018ReactomeTeamreactome version 63
99638view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99241view12:44, 31 October 2018ReactomeTeamreactome version 62
94051view13:54, 16 August 2017ReactomeTeamreactome version 61
93678view11:30, 9 August 2017ReactomeTeamreactome version 61
86802view09:26, 11 July 2016ReactomeTeamreactome version 56
83271view10:36, 18 November 2015ReactomeTeamVersion54
81381view12:54, 21 August 2015ReactomeTeamVersion53
76850view08:07, 17 July 2014ReactomeTeamFixed remaining interactions
76554view11:54, 16 July 2014ReactomeTeamFixed remaining interactions
75887view09:54, 11 June 2014ReactomeTeamRe-fixing comment source
75587view10:42, 10 June 2014ReactomeTeamReactome 48 Update
74942view13:47, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74586view08:38, 30 April 2014ReactomeTeamReactome46
45022view18:42, 6 October 2011ThomasOntology Term : 'signaling pathway' added !
42123view21:58, 4 March 2011MaintBotAutomatic update
39933view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
ARHGAP35 ProteinQ9NRY4 (Uniprot-TrEMBL)
ARHGAP35ProteinQ9NRY4 (Uniprot-TrEMBL)
ARHGEF11 ProteinO15085 (Uniprot-TrEMBL)
ARHGEF12 ProteinQ9NZN5 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated ROCK

RhoA/B/C

GTP		ComplexREACT_19928 (Reactome)
Active LIMK1ComplexREACT_19790 (Reactome)
CD72 ProteinP21854 (Uniprot-TrEMBL)
CD72ProteinP21854 (Uniprot-TrEMBL)
CDK5 ProteinQ00535 (Uniprot-TrEMBL)
CDK5R1ProteinQ15078 (Uniprot-TrEMBL)
CFL1ProteinP23528 (Uniprot-TrEMBL)
CRMP's tetramersComplexREACT_19835 (Reactome)
CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
Cdk5 p35ComplexREACT_19863 (Reactome)
DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
DPYSL4 ProteinO14531 (Uniprot-TrEMBL)
DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
ERBB2 ProteinP04626 (Uniprot-TrEMBL)
FARP2 PIP5KIgammaComplexREACT_19748 (Reactome)
FARP2 ProteinO94887 (Uniprot-TrEMBL)
FARP2ProteinO94887 (Uniprot-TrEMBL)
FES ProteinP07332 (Uniprot-TrEMBL)
FESProteinP07332 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GSK3BProteinP49841 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
HSP-90ProteinREACT_19960 (Reactome)
HSP90AA1 ProteinP07900 (Uniprot-TrEMBL)
HSP90AB1 ProteinP08238 (Uniprot-TrEMBL)
ITGA1 ProteinP56199 (Uniprot-TrEMBL)
ITGB1 ProteinP05556 (Uniprot-TrEMBL)
Integrin alpha1beta1ComplexREACT_14015 (Reactome)
LARG and PDZ-RhoGEFProteinREACT_20012 (Reactome)
LIM Kinases, phosphorylatedProteinREACT_19576 (Reactome)
LIM KinasesProteinREACT_20207 (Reactome)
LIMK1ProteinP53667 (Uniprot-TrEMBL)
MET ProteinP08581 (Uniprot-TrEMBL)
MYH10 ProteinP35580 (Uniprot-TrEMBL)
MYH11 ProteinP35749 (Uniprot-TrEMBL)
MYH14 ProteinQ7Z406 (Uniprot-TrEMBL)
MYH9 ProteinP35579 (Uniprot-TrEMBL)
MYL12BProteinO14950 (Uniprot-TrEMBL)
MYL6 ProteinP60660 (Uniprot-TrEMBL)
MYL9 ProteinP24844 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NRP1

PlexinA1-4 FARP2

FYN		ComplexREACT_20390 (Reactome)
NRP1

PlexinA1-4

FYN		ComplexREACT_20319 (Reactome)
NRP1 ProteinO14786 (Uniprot-TrEMBL)
NRP1ProteinO14786 (Uniprot-TrEMBL)
PAK homodimerComplexREACT_19479 (Reactome)
PAK1 ProteinQ13153 (Uniprot-TrEMBL)
PAK2ProteinQ13177 (Uniprot-TrEMBL)
PAKProteinREACT_19640 (Reactome)
PIP5K1C ProteinO60331 (Uniprot-TrEMBL)
PIP5K1gamma Talin-1ComplexREACT_19891 (Reactome)
PLXNA1

TREM2

DAP12		ComplexREACT_20126 (Reactome)
PLXNA1 ProteinQ9UIW2 (Uniprot-TrEMBL)
PLXNA2,PLXNA4ProteinREACT_20091 (Reactome)
PLXNA2ProteinO75051 (Uniprot-TrEMBL)
PLXNA3 ProteinP51805 (Uniprot-TrEMBL)
PLXNA4 ProteinQ9HCM2 (Uniprot-TrEMBL)
PLXNB1 ProteinO43157 (Uniprot-TrEMBL)
PLXNB3 ProteinQ9ULL4 (Uniprot-TrEMBL)
PLXNB3ProteinQ9ULL4 (Uniprot-TrEMBL)
PLXNC1 ProteinO60486 (Uniprot-TrEMBL)
PLXNC1ProteinO60486 (Uniprot-TrEMBL)
PLXND1 ProteinQ9Y4D7 (Uniprot-TrEMBL)
PLXND1ProteinQ9Y4D7 (Uniprot-TrEMBL)
PTPRC ProteinP08575 (Uniprot-TrEMBL)
PTPRCProteinP08575 (Uniprot-TrEMBL)
Phospho-activated smooth muscle/non-muscle myosin 2ComplexREACT_19704 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C), two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYLC2B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective. Kinases responsible for the phosphorylation include myosin light chain kinase (MLCK), ROCK kinase, citron kinase, myotonic dystrophy kinase-related CDC42-binding protein kinase, and Zipper-interacting protein (ZIP) kinase. ROCK activity has been shown to regulate MRLC phosphorylation by directly mono- (Amano et al., 1996) or di- (Ueda et al., 2002) phosphorylating MRLC.
PiMetaboliteCHEBI:18367 (ChEBI)
Plexin-A1-4 FYNComplexREACT_19507 (Reactome)
Plexin-B1 ErbB2ComplexREACT_19954 (Reactome)
Plexin-B1 MetComplexREACT_19866 (Reactome)
R-Ras-GDPComplexREACT_20329 (Reactome)
R-Ras-GTPComplexREACT_20411 (Reactome)
RAC1 ProteinP63000 (Uniprot-TrEMBL)
RAC1-GDPComplexREACT_22018 (Reactome)
RAC1-GTPComplexREACT_21594 (Reactome)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOB ProteinP62745 (Uniprot-TrEMBL)
RHOC ProteinP08134 (Uniprot-TrEMBL)
RND1 ProteinQ92730 (Uniprot-TrEMBL)
ROCK1ProteinQ13464 (Uniprot-TrEMBL)
ROCK2 ProteinO75116 (Uniprot-TrEMBL)
ROCKProteinREACT_20281 (Reactome) ROCK I (alternatively called ROK ?) and ROCK II (also known as Rho kinase or ROK ?) were originally isolated as RhoA-GTP interacting proteins. The kinase domains of ROCK I and ROCK II are 92% identical, and so far there is no evidence that they phosphorylate different substrates. RhoA, RhoB, and RhoC associate with and activate ROCK but other GTP-binding proteins can be inhibitors, e.g. RhoE, Rad and Gem. PDK1 kinase promotes ROCK I activity not through phosphorylation but by blocking RhoE association. PLK1 can phosphorylate ROCK II and this enhances the effect of RhoA. Arachidonic acid can activate ROCK independently of Rho.
RRAS ProteinP10301 (Uniprot-TrEMBL)
RhoA ComplexREACT_13852 (Reactome)
RhoA ComplexREACT_14306 (Reactome)
RhoA,B,C GDPComplexREACT_20118 (Reactome)
RhoA/B/C GTPComplexREACT_19589 (Reactome)
Rnd1-GTPComplexREACT_20300 (Reactome)
SEMA3A PLXND1ComplexREACT_20367 (Reactome)
SEMA3A ProteinQ14563 (Uniprot-TrEMBL)
SEMA3E ProteinO15041 (Uniprot-TrEMBL)
SEMA3EProteinO15041 (Uniprot-TrEMBL)
SEMA4A PLXND1ComplexREACT_19803 (Reactome)
SEMA4A ProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4AProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4D CD72ComplexREACT_20194 (Reactome)
SEMA4D PTPRCComplexREACT_19862 (Reactome)
SEMA4D

pPlexin-B1

ErbB2 complex		ComplexREACT_20256 (Reactome)
SEMA4D ProteinQ92854 (Uniprot-TrEMBL)
SEMA4D dimerComplexREACT_19817 (Reactome)
SEMA4DProteinQ92854 (Uniprot-TrEMBL)
SEMA5A PLXNB3ComplexREACT_19434 (Reactome)
SEMA5A ProteinQ13591 (Uniprot-TrEMBL)
SEMA5AProteinQ13591 (Uniprot-TrEMBL)
SEMA6A PLXNA2,PLXNA4ComplexREACT_19923 (Reactome)
SEMA6A ProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6AProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6D

PLXNA1 TREM2

DAP12		ComplexREACT_19554 (Reactome)
SEMA6D ProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA6DProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA7A Integrin alpha1beta1ComplexREACT_20443 (Reactome)
SEMA7A PLXNC1ComplexREACT_20419 (Reactome)
SEMA7A ProteinO75326 (Uniprot-TrEMBL)
SEMA7AProteinO75326 (Uniprot-TrEMBL)
Sema3A

NP-1 Plexin-A Fes

CRMP		ComplexREACT_20015 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		ComplexREACT_19958 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		ComplexREACT_19816 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ComplexREACT_19706 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ComplexREACT_20425 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		ComplexREACT_20429 (Reactome)
Sema3A

Nrp-1 PlexinA

Fyn		ComplexREACT_20413 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		ComplexREACT_20083 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		ComplexREACT_19495 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes Rac-1-GTP

Rnd1		ComplexREACT_19802 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		ComplexREACT_20187 (Reactome)
Sema3A dimerComplexREACT_19939 (Reactome)
Sema4D

Plexin-B1 Rac-Rnd1

LARG/PDZ-RhoGEF		ComplexREACT_20349 (Reactome)
Sema4D

Plexin-B1 p190RhoGAP Rac

Rnd1		ComplexREACT_19579 (Reactome)
Sema4D

pPlexin-B1 ErbB2 Rac1

Rnd1		ComplexREACT_19890 (Reactome)
Sema4D

pPlexin-B1 Met

RAC1-GTP		ComplexREACT_20028 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		ComplexREACT_19721 (Reactome)
Sema4D

pPlexin-B1

Met		ComplexREACT_19905 (Reactome)
Smooth muscle/non-muscle myosin IIComplexREACT_19969 (Reactome) Class 2 myosins are a set of protein complexes that bind actin and hydrolyse ATP, acting as molecular motors. They consist of two myosin heavy chains , two essential light chains and two regulatory light chains (MRLCs). Smooth muscle and non-muscle myosin isoforms are a subset of Class 2 myosin complexes. The nomenclature for isoforms is misleading, as non-muscle isoforms can be found in smooth muscle. The 4 smooth muscle isoforms all have heavy chains encoded by MYH11. The non-muscle isoforms have heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C). The essential light chain (LC17) common to smooth and non-muscle isoforms is encoded by MYL6. The regulatory light chain (LC20) is encoded by either MYL9, giving a slightly more basic protein that is referred to as the smooth muscle LC20 isoform, and MRLC2, giving a more acidic isoform referred to as the non-muscle LC20 isoform. Class 2 myosins play a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis.
TLN1 ProteinQ9Y490 (Uniprot-TrEMBL)
TLN1ProteinQ9Y490 (Uniprot-TrEMBL)
TREM2 ProteinQ9NZC2 (Uniprot-TrEMBL)
TYROBP ProteinO43914 (Uniprot-TrEMBL)
p-S,T508-LIMK1 ProteinP53667 (Uniprot-TrEMBL)
p-S141,T402-PAK2ProteinQ13177 (Uniprot-TrEMBL)
p-S144,T423-PAK1 ProteinQ13153 (Uniprot-TrEMBL)
p-S3-CFL1 ProteinP23528 (Uniprot-TrEMBL)
p-S522-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-S522-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-S522-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-S534-DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
p-S544-DPYSL4 ProteinO14531 (Uniprot-TrEMBL) CRMP-3 does not have the conserved serine 522 and based on similarity serine 544 may be phosphorylated upon sema3A stimulation.
p-T19,S20-MYL12BProteinO14950 (Uniprot-TrEMBL)
p-T19,S20-MYL9 ProteinP24844 (Uniprot-TrEMBL)
p-T508-LIMK1 ProteinP53667 (Uniprot-TrEMBL)
p-T508-LIMK1ProteinP53667 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-Y-CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
p-Y-DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
p-Y-DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
p-Y-DPYSL4 ProteinO14531 (Uniprot-TrEMBL) CRMP-3 does not have the conserved serine 522 and based on similarity serine 544 may be phosphorylated upon sema3A stimulation.
p-Y-DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
p-Y-PLXNA1 ProteinQ9UIW2 (Uniprot-TrEMBL)
p-Y-PLXNA2ProteinO75051 (Uniprot-TrEMBL)
p-Y-PLXNA3 ProteinP51805 (Uniprot-TrEMBL)
p-Y-PLXNA4 ProteinQ9HCM2 (Uniprot-TrEMBL)
p-Y-PLXNB1 ProteinO43157 (Uniprot-TrEMBL)
p-Y15-CDK5 ProteinQ00535 (Uniprot-TrEMBL)
pCofilin Active LIMK-1ComplexREACT_20103 (Reactome)
pLIMK dimer HSP-90ComplexREACT_19543 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_19161 (Reactome)
ADPArrowREACT_19168 (Reactome)
ADPArrowREACT_19191 (Reactome)
ADPArrowREACT_19197 (Reactome)
ADPArrowREACT_19221 (Reactome)
ADPArrowREACT_19276 (Reactome)
ADPArrowREACT_19282 (Reactome)
ADPArrowREACT_19285 (Reactome)
ADPArrowREACT_19321 (Reactome)
ADPArrowREACT_19381 (Reactome)
ADPArrowREACT_19393 (Reactome)
ADPArrowREACT_19398 (Reactome)
ADPArrowREACT_19420 (Reactome)
ARHGAP35REACT_19356 (Reactome)
ATPREACT_19161 (Reactome)
ATPREACT_19168 (Reactome)
ATPREACT_19191 (Reactome)
ATPREACT_19197 (Reactome)
ATPREACT_19221 (Reactome)
ATPREACT_19276 (Reactome)
ATPREACT_19282 (Reactome)
ATPREACT_19285 (Reactome)
ATPREACT_19321 (Reactome)
ATPREACT_19381 (Reactome)
ATPREACT_19393 (Reactome)
ATPREACT_19398 (Reactome)
ATPREACT_19420 (Reactome)
Activated ROCK

RhoA/B/C

GTP		mim-catalysisREACT_19191 (Reactome)
Activated ROCK

RhoA/B/C

GTP		mim-catalysisREACT_19282 (Reactome)
Active LIMK1ArrowREACT_19168 (Reactome)
Active LIMK1REACT_19276 (Reactome)
Active LIMK1mim-catalysisREACT_19276 (Reactome)
CD72REACT_19336 (Reactome)
CFL1REACT_19276 (Reactome)
CRMP's tetramersREACT_19161 (Reactome)
CRMP's tetramersREACT_19285 (Reactome)
Cdk5 p35REACT_19393 (Reactome)
FARP2 PIP5KIgammaArrowREACT_19403 (Reactome)
FARP2ArrowREACT_19173 (Reactome)
FARP2REACT_19128 (Reactome)
FARP2REACT_19403 (Reactome)
FARP2mim-catalysisREACT_19363 (Reactome)
FESREACT_19420 (Reactome)
GDPArrowREACT_19137 (Reactome)
GDPArrowREACT_19363 (Reactome)
GSK3Bmim-catalysisREACT_19321 (Reactome)
GTPREACT_19137 (Reactome)
GTPREACT_19363 (Reactome)
HSP-90ArrowREACT_19168 (Reactome)
HSP-90REACT_19307 (Reactome)
Integrin alpha1beta1REACT_19139 (Reactome)
LARG and PDZ-RhoGEFREACT_19153 (Reactome)
LIM Kinases, phosphorylatedArrowREACT_19282 (Reactome)
LIM KinasesREACT_19282 (Reactome)
LIMK1REACT_19221 (Reactome)
NRP1

PlexinA1-4 FARP2

FYN		REACT_19173 (Reactome)
NRP1

PlexinA1-4

FYN		REACT_19368 (Reactome)
NRP1REACT_19128 (Reactome)
PAK homodimerREACT_19269 (Reactome)
PAKArrowREACT_19269 (Reactome)
PIP5K1gamma Talin-1REACT_19403 (Reactome)
PLXNA1

TREM2

DAP12		REACT_19177 (Reactome)
PLXNA2,PLXNA4REACT_19345 (Reactome)
PLXNB3REACT_19322 (Reactome)
PLXNC1REACT_19190 (Reactome)
PLXND1REACT_19273 (Reactome)
PLXND1REACT_19408 (Reactome)
PTPRCREACT_19295 (Reactome)
Phospho-activated smooth muscle/non-muscle myosin 2ArrowREACT_19191 (Reactome)
PiArrowREACT_19117 (Reactome)
PiArrowREACT_19120 (Reactome)
PiArrowREACT_19242 (Reactome)
Plexin-A1-4 FYNREACT_19128 (Reactome)
Plexin-B1 ErbB2REACT_19381 (Reactome)
Plexin-B1 ErbB2mim-catalysisREACT_19381 (Reactome)
Plexin-B1 MetREACT_19398 (Reactome)
Plexin-B1 Metmim-catalysisREACT_19398 (Reactome)
R-Ras-GDPArrowREACT_19117 (Reactome)
R-Ras-GDPArrowREACT_19120 (Reactome)
RAC1-GDPREACT_19363 (Reactome)
RAC1-GTPArrowREACT_19363 (Reactome)
RAC1-GTPREACT_19160 (Reactome)
RAC1-GTPREACT_19354 (Reactome)
REACT_19117 (Reactome) Plexin-A's are GAPs for the Ras family GTPase R-Ras. On stimulation with Rnd-1, plexin-A directly and specifically down regulates R-Ras activity. R-Ras activity is critical for PI3K activation and ECM-mediated beta1 integrin activation and cell migration. Inactivation of R-Ras by Sema3A/Plexin-A1 reduces integrin-mediated adhesions. It has been suggested that the final step in the Sema3A repulsive signaling pathway is inhibition of integrin activity. Reduced integrin activity allows detachment from the substratum and subsequent cell retraction.
REACT_19120 (Reactome) Plexin-B1 functions as an R-Ras GTPase-activating protein (GAP) and directly and specifically down regulates R-Ras activity in response to Sema4D, inducing growth cone collapse. R-Ras inactivation promotes PI3K and Akt inactivation followed by GSK-3beta activation and CRMP inactivation. R-Ras inactivation also inhibits cell migration by regulating beta1 integrin activity.

REACT_19128 (Reactome) The best characterized receptors for mediating semaphorin signaling are members of the neuropilin and plexin families of transmembrane proteins. Neuropilins form complexes with Plexin-A which in turn can act as a signaling moiety. Also, when complexed with neuropilin-1, plexin-A1 can associate directly with the FERM domain containing guanine nucleotide exchange factor (GEF) FARP2. FARP2 exerts GEF activity for Rac but not Cdc42 and Rho.
REACT_19137 (Reactome) The RhoGEFs LARG and PDZ-RhoGEF complexed with Plexin-B1 stimulate the exchange of GDP for GTP on RhoA through their DH and PH domains.
REACT_19139 (Reactome) Sema7A has a RGD-motif in the extracellular region and interacts with alpha1beta1 integrin in both olfactory nerves and monocytes/macrophages. This interaction stimulates cytokine production in monocytes and macrophages, and is critical for the effector phase of the inflammatory immune response.
REACT_19153 (Reactome) Plexin-B1 activates RhoA and induces growth cone collapse and and cytoskeletal reorganization through Rho-specific guanine nucleotide exchange factors PDZ-RhoGEF and leukemia-associated RhoGEF (LARG). Plexin-B1 directly interacts with PDZ-RhoGEF through its c-terminal PDZ domain binding motif. It has been suggested that Rnd1, which binds to the cytoplasmic part of plexin-B1, can promote the interaction between plexin-B1 and PDZ-RhoGEF. The PDZ domain of LARG is directly involved in the interaction with the c-terminal sequence of Plexin-B1.
REACT_19160 (Reactome) Active Rac1 associates directly with Plexin-A1 in the linker region separating Plexin-A1's cytoplasmic GAP domains. Rac1 association relieves an inhibitory intramolecular interaction between the two Plexin-A1 GAP domains C1 and C2.
REACT_19161 (Reactome) Fes bound to Plexin-A is able to phosphorylate all five forms of CRMP, though neither specific sites nor the consequence of tyrosine phosphorylation in CRMP's have yet been investigated directly.
REACT_19168 (Reactome) Binding of Hsp90 to the LIMK proteins protects them from degradation and promotes their dimer formation and transphosphorylation. It is estimated that LIMK1 contains at least 5 phospho-amino acids primarily phospho-serines, in its kinase domain. The positions of these serine residues are not known. Transphosphorylation of these serine residues in LIMK1 increases its stability.
REACT_19173 (Reactome) Although neuropilin-1 is required for Sema-3A action, it is incapable of transmitting a Sema-3A signal to the growth cone interior. The function of Sema-3A is mediated by Plexins. Sema-3A binds with high affinity to Plexin when the latter is complexed with Neuropilin-1.
Plexin-A1 is known to act as an R-Ras GAP (GTPase activating protein) when bound by Sema-3A. Plexin's GAP activity is regulated by FARP2 mediated Rac1 activation. Sema-3A binding to neuropilin-1/Plexin-A1 seems to induce a conformational change of plexin-A1 necessary for releasing FARP2. This suggests that neuropilin1 is required not only for ligand binding, but also for signaling, by modulating the interaction of FARP2 with plexin-A1.
REACT_19177 (Reactome) Plexin-A1 is a receptor for the transmembrane semaphorin, Sema6D. Plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12.
REACT_19190 (Reactome) Sema7A signals through two unrelated receptors, an RGD-dependent alpha1beta1-integrin and a member of the plexin family, plexinC1. Sema7A-plexinC1 interactions have been implicated in immune system function and also participate in neuronal network formation.
REACT_19191 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10 or MYH14 (NMHC-IIA, B and C), two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYLC2B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective. Kinases responsible for the phosphorylation include myosin light chain kinase (MLCK), ROCK kinase, citron kinase, myotonic dystrophy kinase-related CDC42-binding protein kinase, and Zipper-interacting protein (ZIP) kinase. ROCK activity has been shown to regulate MRLC phosphorylation by directly mono- (Amano et al., 1996) or di- (Ueda et al., 2002) phosphorylating MRLC.
REACT_19197 (Reactome) PAK is autophosphorylated at several sites but S-144 flanking the kinase inhibitor region and T-423 (S-141/T-402 in PAK-gamma) within the catalytic domain are the two conserved sites that regulate the catalytic activity.
REACT_19221 (Reactome) LIM-kinase is responsible for the tight regulation of the activity of cofilin (a protein that depolymerizes actin filaments) and thus maintains the balance between actin assembly and disassembly. LIMK is one of the downstream targets of PAK1 and is activated through phosphorylation by PAK1 on T508 within its activation loop.
REACT_19242 (Reactome) p190RhoGAP complexed with Plexin-B1 stimulates GTP hydrolysis by RhoA. The resulting lower levels of Rho-GTP may account for F-actin depolymerization and cytoskeletal rearrangements.
REACT_19269 (Reactome) Plexin-bound Rac1 binds to and stimulates the kinase activity of PAK. PAK dimers are arranged in head-to-tail fashion, in which the catalytic domain binds the kinase inhibitory (KI) domain and is supported by associated PAK-interacting exchange factor (PIX) dimers. Upon Rac1 binding the kinase undergoes conformational change that allows autophosphorylation. Phosphorylation of serine residues disables the KI-domain-kinase interaction and thereby reduces the affinity of PIX.
REACT_19273 (Reactome) SEMA3E binds to neither neuropilin but instead binds directly to plexin-D1. This interaction controls endothelial cell positioning and the patterning of the developing vasculature.
REACT_19276 (Reactome) Cofilin is a member of the ADF (actin-depolymerizing factor) protein family, that is involved in regulating actin dynamics in the growth cone. It binds to actin in a one-to-one molar ratio, and stimulates both the severing of actin filaments and depolymerization of actin subunits from the actin filament end.
Activated LIMK phosphorylates cofilin on conserved serine 3 (Ser3/S3), located near the actin binding site. After phosphorylation cofilin is inactive and looses its affinity for actin and releases from G-actin monomers. Now the ADP-actin monomers are free and can exchange ADP with cytoplasmic ATP and they are ready for reincorporation at the barbed end of the a growing filament.
REACT_19282 (Reactome) ROCK I phosphorylates LIMK1 at Thr508 and LIMK2 at Thr505, enhancing the ability of LIMKs to phosphorylate cofilin.
REACT_19285 (Reactome) Cdk5:p35 complex is associated with Plexin-A through the actived form of Fyn. CRMPs are the downstream substrates for Cdk5. Cdk5 phosphorylates serine 522 of CRMPs. Phosphorylation of CRMPs mediates the Sema3A induced growth cone collapse.
Collapsin response mediator proteins (CRMPs) are five homologous cytosolic phosphoproteins (CRMP1–5) involved in neuronal differentiation and axonal guidance. These members oligomerize and exist as tetramers.
REACT_19295 (Reactome) SEMA4D also associates with CD45, a cell surface protein tyrosine phosphatase (PTP) considered a key molecule in the T-cell receptor (TCR) activation process.
REACT_19307 (Reactome) After phosphorylation on Thr 508, LIMK undergoes homodimerization. Homodimer formation is promoted by the binding of heat shock protein 90 (Hsp90) to a short sequence in the kinase domain of LIMKs. LIMKs are further phosphorylated after homodimer formation and transphosphorylation of the kinase domain.
REACT_19321 (Reactome) The phosphorylation of CRMPs at Ser522 allows the subsequent phosphorylation of CRMP1, CRMP2 and CRMP4 at Ser518, Thr509, and Thr514 mediated by serine/threonine kinase GSK3beta. Phosphorylation of CRMP by GSK3beta results in decreased CRMP affinity for beta-tubulin and changes in microtubule dynamics.
REACT_19322 (Reactome) Sema5s have been implicated in invasive growth, vascular patterning and axon guidance. Plexin-B3 is the specific and high-affinity receptor for Sema5A, and their interaction triggers the collapsing response.
REACT_19336 (Reactome) In the immune system, Sema4D/CD100 binds CD72 to mediate B-cell-B-cell, B-cell-T-cell and T-cell-dendritic cell interactions and there by regulates B-cell and T-cell activation. In B-cells, this interaction directs the dissociation of SHP-1 from the CD72 cytoplasmic domain and enhances their activation.

REACT_19337 (Reactome) Binding of Sema3A to the Neuropilin-1-Plexin-A receptor complex results in the recruitment of Rnd1 to the cytoplasmic linker region of Plexin-A. Rnd1 activates the cytoplasmic GTPase signaling domain of Plexin-A.
REACT_19345 (Reactome) Sema6A binds plexinA2 and plexinA4 to establish lamina-restricted axon projection in the hippocampus.
REACT_19354 (Reactome) The cytoplasmic tails of plexins have two domains, C1 and C2, which are highly conserved and act as GAP for small GTPases like Rac1. Active Rac1 binds directly to a binding domain of Plexin-B1 in the linker region between C1 and C2. The functional consequence of the plexin-B1/Rac interaction is not understood but this binding might sequester Rac1 away from p21-activated kinase (PAK). Plexin-B1 can compete with PAK for binding to active Rac and this competition results in the ability of plexin-B1 to inhibit Rac-induced PAK activation.
REACT_19356 (Reactome) Plexin-B1 can mediate inhibition of RhoA via the Sema4D-dependent recruitment of p190RhoGAP into the semaphorin receptor complex.
REACT_19363 (Reactome) Sema3A-mediated dissociation of FARP2 from Plexin-A is followed by activation of Rac1 by the GEF activity of released FARP2.
FARP2 is critical for Sema3A-mediated axonal repulsion through two independent downstream signaling pathways. Sema3A mediated disassociation of FARP2 from Plexin-A is followed by activation of Rac by GEF activity of released FARP2, binding of Rnd1 to plexin-A and down regulation of R-Ras by GAP activity of plexin-A.
REACT_19368 (Reactome) PlexinA1 and A2 are constitutively bound to the src family tyrosine kinase, Fyn. Stimulation with Sema3A causes Fyn activation and leads to the recruitment of Cdk5 into the complex.
REACT_19381 (Reactome) Sema4D binds Plexin-B1 to induce repulsive or attractive effects in neuronal and nonneuronal cells. Plexins constitute a large family of transmembrane proteins that function as receptors for semaphorins and their interaction governs cell adhesion and migration in a variety of tissues. All B-class plexins can interact with the receptor tyrosine kinases Met and ErbB2. Upon binding of Sema4D to plexin-B1, the kinase activity of ErbB2 is increased resulting in tyrosine phosphorylation of both Plexin-B1 and ErbB2. ErbB2 has been shown to mediate Sema4D-induced growth cone collapse in hippocampal neurons by the activation of RhoA via plexinB1 and PDZRhoGEF/LARG.
Sequence alignment reveals the presence of 13 conserved tyrosine residues (highly conserved sites 1918, 1953, 2038) but the specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
REACT_19382 (Reactome) Rnd1 is constitutively active and stably associates with Plexin-B1 and regulates the R-Ras GAP activity of the C1 and C2 domains of the Plexin-B1 cytoplasmic tail. These domains interact with each other and in this closed conformation cannot associate with active R-Ras-GTP. Rnd1 binds to the region between C1 and C2 domains and disrupts this interaction, allowing the receptor to associate with GTP-bound R-Ras.
REACT_19389 (Reactome) Rho-associated, coiled-coil containing protein kinases (ROCKs) are primarily known as downstream effectors of Rho, but they can also be activated by arachidonic acid, which binds to the pleckstrin homology domain, releasing an autoinhibitory loop within ROCK allowing catalytic activity. Multiple targets of ROCK contribute to the stabilization of actin filaments and the generation of actin-myosin contractile force.
REACT_19393 (Reactome) Cdk5:p53 complex is recruited to the growth cone by associating with active Fyn. Fyn promotes the kinase activity of Cdk5 by phosphorylating Cdk5 on tyrosine residue 15. Activation of Cdk5 by Fyn via Tyr15 phosphorylation might facilitate suppression of Rac-PAK signaling downstream of PlexinA.
Cyclin-dependent kinase 5 (Cdk5), a member of the serine/threonine kinase Cdk family, is complexed with p35 a neuron specific activator of Cdk5. The complex Cdk5:p35 is required for neurite outgrowth and cortical lamination.
REACT_19398 (Reactome) Sema4D binds Plexin-B1 to induce repulsive or attractive effects in neuronal and nonneuronal cells. Plexins constitute a large family of transmembrane proteins that function as receptors for semaphorins and their interaction governs cell adhesion and migration in a variety of tissues. All B-class plexins can interact with the receptor tyrosine kinases Met and ErbB2. The binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of Met, leading to the phosphorylation of both Plexin-B1 and Met. The phosphorylation of the plexin-B1/Met complex induced by Sema4D is crucial for epithelial cell migration and invasive growth. Sequence alignment reveals the presence of 13 conserved tyrosine residues (highly conserved sites 1918, 1953, 2038), but the specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
REACT_19403 (Reactome) Sema3A also mediates integrin inhibition by a mechanism involving PIPKI gamma 661, a phosphatidylinositol kinase that participates in integrin mediated focal adhesion assembly. The binding of talin to beta-integrin is required for integrin activation and is strengthened by PtdIns(4,5)P(2). PIPKI gamma 661, an enzyme that makes PtdIns(4,5)P(2), is targeted to focal adhesions by an association with talin. Sema3A induced dissociation of FARP2 from Plexin-A1 stimulates an interaction between FARP2 and PIPKI gamma 661. FARP2 inhibits PIPK gamma 661's kinase activity, and thus inhibits integrin mediated adhesion.
REACT_19408 (Reactome) Sema4A binds plexinD1 to inhibit angiogenesis. Sema4A–plexinD1 interactions modulate VEGF-mediated endothelial cell migration and proliferation at the intracellular level by suppressing VEGF–VEGFR2-induced activation of Rac1, Akt and integrins.
REACT_19420 (Reactome) Sema3A binding to Neuropilin-1:Plexin-A complex results in conformational change of plexin-A and this conformational change permits Fes nonreceptor tyrosine kinase to bind and phosphorylate Plexin-A. The specific tyrosine residues phosphorylated in the cytoplasmic domain of plexins in response to semaphorin stimulation have not yet been identified.
ROCKREACT_19389 (Reactome)
RhoA ArrowREACT_19242 (Reactome)
RhoA,B,C GDPREACT_19137 (Reactome)
RhoA/B/C GTPArrowREACT_19137 (Reactome)
RhoA/B/C GTPREACT_19389 (Reactome)
Rnd1-GTPREACT_19337 (Reactome)
Rnd1-GTPREACT_19382 (Reactome)
SEMA3EREACT_19273 (Reactome)
SEMA4AREACT_19408 (Reactome)
SEMA4D

pPlexin-B1

ErbB2 complex		ArrowREACT_19381 (Reactome)
SEMA4D dimerREACT_19381 (Reactome)
SEMA4D dimerREACT_19398 (Reactome)
SEMA4DREACT_19295 (Reactome)
SEMA4DREACT_19336 (Reactome)
SEMA5AREACT_19322 (Reactome)
SEMA6AREACT_19345 (Reactome)
SEMA6DREACT_19177 (Reactome)
SEMA7AREACT_19139 (Reactome)
SEMA7AREACT_19190 (Reactome)
Sema3A

NP-1 Plexin-A Fes

CRMP		ArrowREACT_19161 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		ArrowREACT_19420 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		REACT_19160 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		REACT_19161 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		mim-catalysisREACT_19161 (Reactome)
Sema3A

NRP-1 pPlexin-A Fyn

Fes		mim-catalysisREACT_19420 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		ArrowREACT_19173 (Reactome)
Sema3A

Nrp-1 Plexin A

Fyn		REACT_19420 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ArrowREACT_19285 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		ArrowREACT_19321 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn Cdk5

pCRMP's		REACT_19321 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		ArrowREACT_19393 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		REACT_19285 (Reactome)
Sema3A

Nrp-1 PlexinA Fyn

pCdk5		mim-catalysisREACT_19285 (Reactome)
Sema3A

Nrp-1 PlexinA

Fyn		REACT_19393 (Reactome)
Sema3A

Nrp-1 PlexinA

Fyn		mim-catalysisREACT_19393 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		ArrowREACT_19269 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		REACT_19197 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

PAK		mim-catalysisREACT_19197 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		ArrowREACT_19197 (Reactome)
Sema3A

Nrp-1 PlexinA Rac1-GTP

pPAK		mim-catalysisREACT_19221 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes Rac-1-GTP

Rnd1		mim-catalysisREACT_19117 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		REACT_19269 (Reactome)
Sema3A

Nrp-1 pPlexinA Fyn Fes

Rac-1-GTP		REACT_19337 (Reactome)
Sema3A dimerREACT_19173 (Reactome)
Sema3A dimerREACT_19368 (Reactome)
Sema4D

Plexin-B1 Rac-Rnd1

LARG/PDZ-RhoGEF		mim-catalysisREACT_19137 (Reactome)
Sema4D

Plexin-B1 p190RhoGAP Rac

Rnd1		mim-catalysisREACT_19242 (Reactome)
Sema4D

pPlexin-B1 ErbB2 Rac1

Rnd1		REACT_19153 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		REACT_19356 (Reactome)
Sema4D

pPlexin-B1 Met

Rnd1		mim-catalysisREACT_19120 (Reactome)
Sema4D

pPlexin-B1

Met		ArrowREACT_19398 (Reactome)
Sema4D

pPlexin-B1

Met		REACT_19354 (Reactome)
Sema4D

pPlexin-B1

Met		REACT_19382 (Reactome)
Smooth muscle/non-muscle myosin IIREACT_19191 (Reactome)
TLN1ArrowREACT_19403 (Reactome)
p-T508-LIMK1ArrowREACT_19221 (Reactome)
p-T508-LIMK1REACT_19307 (Reactome)
pCofilin Active LIMK-1ArrowREACT_19276 (Reactome)
pLIMK dimer HSP-90REACT_19168 (Reactome)
pLIMK dimer HSP-90mim-catalysisREACT_19168 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1907"
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