Semaphorin interactions (Homo sapiens)

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7, 11, 36, 37, 40286, 24, 5213, 26, 51, 563, 12, 47, 54, 578, 22, 441413, 51, 5643, 483827, 29, 525, 18, 33, 5315, 25, 31, 50, 554, 20, 23134910, 1921, 4135, 425839, 513216, 391, 34, 5217, 3029, 455820, 2333, 46cytosolcytosolcytosolcytosolcytosolp-T508-LIMK1 PLXNA1 Cdk5:p35p-Y-PLXNB1 PLXNA3 SEMA6AGTP TLN1 pLIMK dimer:HSP-90PLXNA2 PLXNA4 RHOA GTP PAK1 SEMA4D p-T508-LIMK1ATPSEMA3ERHOC TLN1RRAS FYN FARP2:PIP5KIgammaTREM2 NRP1 ActivatedROCK:RhoA/B/C:GTPRHOC Active LIMK1ROCK2 SEMA4D ROCK1,ROCK2ITGA1 p-Y15-CDK5 ROCK1 PTPRC PLXNA2 ATPPLXNA1 HSP90AA1 MYH10 NRP1 ERBB2 SEMA3A ATPp-Y-PLXNB1 HSP90AA1 MYL6 PLXNC1GTP p-Y-PLXNA2 SEMA4A:PLXND1SEMA4D dimerR-Ras-GDPPLXNA1 p-Y-PLXNA4 p-S,T508-LIMK1 ATPPLXNB1 MYL6 GTP RHOB RND1 GTPPLXNB1 PLXNA3 Sema3A:Nrp-1:PlexinA:FynLIMK2 p-Y-PLXNA1 Sema3A:Nrp-1:PlexinA:FynPlexin-B1:MetRND1 PLXND1SEMA3A ATPp-Y-PLXNA1 Mg2+ ATPRAC1 ADPARHGEF11 DPYSL3 ARHGEF11 SEMA3A:PLXND1SEMA7A RHOA FYN PAK1,2,3p-Y-PLXNA2 PLXNA3 GTP GSK3BFYN p-T509,T514,S518,S522-CRMP1 SEMA6A ADPADPMYH14 PLXNA2 ATPRnd1-GTPDPYSL4 PLXNA4 Plexin-B1:ErbB2Sema4D:pPlexin-B1:Metp-Y-PLXNA1 ATPMg2+ SEMA3E TREM2 Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAKRAC2 RAC1 p-Y15-CDK5 MYH9 RND1 GTP NRP1Sema3A dimerSEMA4D FYN HSP90AB1 SEMA3A CDK5 RAC1:GTPFES SEMA3A ADPGTP SEMA4D PAK1 GDPRHOA Plexin-A1-4:FYNSEMA4D p-Y15-CDK5 PLXNB3GTP RHOA RAC1 MYH11 LARG and PDZ-RhoGEFPLXNA1 PLXNA4 Sema3A dimerATPNRP1 Sema3A:NRP-1:pPlexin-A:Fyn:FesMET GTP ROCK1 Smoothmuscle/non-musclemyosin IIGTP FYN GTP p-Y-CRMP1 pCofilin: ActiveLIMK-1ADPPAK2 PLXNA2 SEMA4D:PTPRCSEMA4D PiSEMA7A p-S534-DPYSL5 ATPR-Ras-GDPATPPLXNA1 SEMA4D p-T19,S20-MRLC-smooth muscle/non-muscle myosin IISema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1Sema4D:pPlexin-B1:Met:Rnd1p-Y-PLXNB1 NRP1 PLXNA4 RAC1:GTPSEMA7A:PLXNC1PLXNA3 TYROBP SEMA4D GTP HSP90AA1,HSP90AB1p-Y-PLXNB1 RAC1 GDP ATPDPYSL2 NRP1 FARP2 GDP PLXNA4 SEMA5A R-Ras-GTPp-Y-PLXNB1 SEMA4D dimerRAC1 PLXNA3 PiSema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEFFES ARHGEF12 FYN RHOG PLXNA3 ERBB2 GDP LIMK1RHOA SEMA6DSema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1ADPRAC1 p-Y-PLXNA2 p-Y-PLXNA1 SEMA4D R-Ras-GTPPiRAC1 NRP1 MYH10 p-Y-PLXNA3 PLXNA1 RRAS p-Y-PLXNB1 RRAS RHOB SEMA3A PAK3 PAK2 ROCK2 PLXNB3 PLXNA3 p-Y-DPYSL3 GDP SEMA3A PIP5K1C PLXNA2 PLXND1FARP2 GTP p-Y-DPYSL2 p-Y-PLXNA4 FYN p-LIMKp-Y-PLXNA2 PLXNA2 PLXNA4 Sema4D:pPlexin-B1:ErbB2:Rac1:Rnd1p-S,T508-LIMK1 SEMA3A ADPFYN TYROBP p-Y-DPYSL4 PIP5K1C PLXNA4 p-Y-PLXNB1 p-S522-CRMP1 SEMA3A p-Y-PLXNA1 MYH11 CD72SEMA6D CD72 MYL12B PLXNA1:TREM2:DAP12p-Y-PLXNA1 PTPRCp-T509,T514,S518,S522-DPYSL3 PLXNA1 RHOA/B/C:GTPIntegrin alpha1beta1ADPRhoA (Mgcofactor):GDPERBB2 MYH9 NRP1:PlexinA1-4:FYNp-T19,S20-MYL9 p-S3-CFL1 CDK5R1(1-307) SEMA3A PAK3 PLXNA2 ERBB2 FYN RND1 NRP1 p-Y-PLXNA3 PAK1,2,3 dimerPLXNA1 Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sPLXNA3 RAC1 RND1 ADPGTP p-Y-PLXNA3 RND1 PAK1 p-T505-LIMK2 RHOA p-T508-LIMK1 PLXNA4 p-S154,T436-PAK3 NRP1 SEMA3A CDC42 SEMA4Ap-Y-PLXNA4 PLXNA1 p-Y-PLXNA4 NRP1:PlexinA1-4:FARP2:FYNSema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sp-Y-PLXNA4 LIMK1 NRP1 RAC1 CRMP's tetramersRHOC p-T509,T514,S518,S522-DPYSL2 RRAS p-Y-DPYSL5 PAK3 ADPRND1 SEMA6D:PLXNA1:TREM2:DAP12ITGB1 SEMA3A p-S141,T402-PAK2 RHOB CDK5R1(1-307) CDK5R1(1-307) RAC2 CFL1FYN FES p-S522-DPYSL3 GTP FARP2ADPp-S144,T423-PAK1 DPYSL5 FYN SEMA4D:pPlexin-B1:ErbB2 complexGTP RAC1 FYN p-Y-PLXNA2 FYN ADPSema3A:Nrp-1:PlexinA:Rac1-GTP:PAKp-S534-DPYSL5 SEMA7APAK2 Sema3A:Nrp-1:PlexinA:Fyn:pCdk5SEMA7A:Integrinalpha1beta1MET SEMA4D FES CDC42 PLXND1 SEMA5A:PLXNB3GTP CDK5R1(1-307) PLXNA2 ITGA1 MET PLXNA4 SEMA5AMET PLXND1 MYH14 RHOG SEMA4D:CD72ARHGAP35RhoA,B,C:GDPARHGEF12 p-S544-DPYSL4 GTPNRP1 p-Y-PLXNA3 Rnd1-GTPSEMA4DNRP1 p-T19,S20-MYL12B MET RAC1:GDPGDP Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPGDPp-Y-PLXNA3 NRP1 PLXNA2,PLXNA4p-S522-DPYSL2 SEMA6A:PLXNA2,PLXNA4PIP5K1gamma:Talin-1ARHGAP35 Sema4D:pPlexin-B1:Met:RAC1-GTPFES PLXNA2 SEMA3A p-Y-PLXNA3 SEMA3A PLXNA1 MYL9 PLXNA2 PLXNC1 ADPp-Y-PLXNA2 FES RHOA ATPGTP PLXNA4 FESNRP1 CRMP1 p-S544-DPYSL4 ITGB1 Sema3A:NP-1:Plexin-A:Fes:CRMPHSP90AB1 SEMA4A RhoA (Mgcofactor):GTPSEMA4D LIM KinasesFYN p-Y-PLXNA4


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. View original pathway at:Reactome.

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Ontology Terms

 

Bibliography

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History

View all...
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:GTPComplexR-HSA-422483 (Reactome)
Active LIMK1ComplexR-HSA-419630 (Reactome)
CD72 ProteinP21854 (Uniprot-TrEMBL)
CD72ProteinP21854 (Uniprot-TrEMBL)
CDC42 ProteinP60953 (Uniprot-TrEMBL)
CDK5 ProteinQ00535 (Uniprot-TrEMBL)
CDK5R1(1-307) ProteinQ15078 (Uniprot-TrEMBL)
CFL1ProteinP23528 (Uniprot-TrEMBL)
CRMP's tetramersComplexR-HSA-399843 (Reactome)
CRMP1 ProteinQ14194 (Uniprot-TrEMBL)
Cdk5:p35ComplexR-HSA-421107 (Reactome)
DPYSL2 ProteinQ16555 (Uniprot-TrEMBL)
DPYSL3 ProteinQ14195 (Uniprot-TrEMBL)
DPYSL4 ProteinO14531 (Uniprot-TrEMBL)
DPYSL5 ProteinQ9BPU6 (Uniprot-TrEMBL)
ERBB2 ProteinP04626 (Uniprot-TrEMBL)
FARP2 ProteinO94887 (Uniprot-TrEMBL)
FARP2:PIP5KIgammaComplexR-HSA-399839 (Reactome)
FARP2ProteinO94887 (Uniprot-TrEMBL)
FES ProteinP07332 (Uniprot-TrEMBL)
FESProteinP07332 (Uniprot-TrEMBL)
FYN ProteinP06241 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GSK3BProteinP49841 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
HSP90AA1 ProteinP07900 (Uniprot-TrEMBL)
HSP90AA1,HSP90AB1ComplexR-HSA-419619 (Reactome)
HSP90AB1 ProteinP08238 (Uniprot-TrEMBL)
ITGA1 ProteinP56199 (Uniprot-TrEMBL)
ITGB1 ProteinP05556 (Uniprot-TrEMBL)
Integrin alpha1beta1ComplexR-HSA-215982 (Reactome)
LARG and PDZ-RhoGEFComplexR-HSA-416544 (Reactome)
LIM KinasesComplexR-HSA-419708 (Reactome)
LIMK1 ProteinP53667 (Uniprot-TrEMBL)
LIMK1ProteinP53667 (Uniprot-TrEMBL)
LIMK2 ProteinP53671 (Uniprot-TrEMBL)
MET ProteinP08581 (Uniprot-TrEMBL)
MYH10 ProteinP35580 (Uniprot-TrEMBL)
MYH11 ProteinP35749 (Uniprot-TrEMBL)
MYH14 ProteinQ7Z406 (Uniprot-TrEMBL)
MYH9 ProteinP35579 (Uniprot-TrEMBL)
MYL12B ProteinO14950 (Uniprot-TrEMBL)
MYL6 ProteinP60660 (Uniprot-TrEMBL)
MYL9 ProteinP24844 (Uniprot-TrEMBL)
Mg2+ MetaboliteCHEBI:18420 (ChEBI)
NRP1 ProteinO14786 (Uniprot-TrEMBL)
NRP1:PlexinA1-4:FARP2:FYNComplexR-HSA-399837 (Reactome)
NRP1:PlexinA1-4:FYNComplexR-HSA-399846 (Reactome)
NRP1ProteinO14786 (Uniprot-TrEMBL)
PAK1 ProteinQ13153 (Uniprot-TrEMBL)
PAK1,2,3 dimerComplexR-HSA-399856 (Reactome)
PAK1,2,3ComplexR-HSA-390765 (Reactome)
PAK2 ProteinQ13177 (Uniprot-TrEMBL)
PAK3 ProteinO75914 (Uniprot-TrEMBL)
PIP5K1C ProteinO60331 (Uniprot-TrEMBL)
PIP5K1gamma:Talin-1ComplexR-HSA-398218 (Reactome)
PLXNA1 ProteinQ9UIW2 (Uniprot-TrEMBL)
PLXNA1:TREM2:DAP12ComplexR-HSA-416707 (Reactome)
PLXNA2 ProteinO75051 (Uniprot-TrEMBL)
PLXNA2,PLXNA4ComplexR-HSA-416718 (Reactome)
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)
PiMetaboliteCHEBI:18367 (ChEBI)
Plexin-A1-4:FYNComplexR-HSA-399844 (Reactome)
Plexin-B1:ErbB2ComplexR-HSA-419629 (Reactome)
Plexin-B1:MetComplexR-HSA-419634 (Reactome)
R-Ras-GDPComplexR-HSA-399866 (Reactome)
R-Ras-GTPComplexR-HSA-399865 (Reactome)
RAC1 ProteinP63000 (Uniprot-TrEMBL)
RAC1:GDPComplexR-HSA-445010 (Reactome)
RAC1:GTPComplexR-HSA-442641 (Reactome)
RAC2 ProteinP15153 (Uniprot-TrEMBL)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOA/B/C:GTPComplexR-HSA-419161 (Reactome)
RHOB ProteinP62745 (Uniprot-TrEMBL)
RHOC ProteinP08134 (Uniprot-TrEMBL)
RHOG ProteinP84095 (Uniprot-TrEMBL)
RND1 ProteinQ92730 (Uniprot-TrEMBL)
ROCK1 ProteinQ13464 (Uniprot-TrEMBL)
ROCK1,ROCK2ComplexR-HSA-419057 (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.
ROCK2 ProteinO75116 (Uniprot-TrEMBL)
RRAS ProteinP10301 (Uniprot-TrEMBL)
RhoA (Mg cofactor):GDPComplexR-HSA-194489 (Reactome)
RhoA (Mg cofactor):GTPComplexR-HSA-194545 (Reactome)
RhoA,B,C:GDPComplexR-HSA-419164 (Reactome)
Rnd1-GTPComplexR-HSA-421104 (Reactome)
SEMA3A ProteinQ14563 (Uniprot-TrEMBL)
SEMA3A:PLXND1ComplexR-HSA-209639 (Reactome)
SEMA3E ProteinO15041 (Uniprot-TrEMBL)
SEMA3EProteinO15041 (Uniprot-TrEMBL)
SEMA4A ProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4A:PLXND1ComplexR-HSA-416694 (Reactome)
SEMA4AProteinQ9H3S1 (Uniprot-TrEMBL)
SEMA4D ProteinQ92854 (Uniprot-TrEMBL)
SEMA4D dimerComplexR-HSA-373690 (Reactome)
SEMA4D:CD72ComplexR-HSA-373697 (Reactome)
SEMA4D:PTPRCComplexR-HSA-373689 (Reactome)
SEMA4D:pPlexin-B1:ErbB2 complexComplexR-HSA-373695 (Reactome)
SEMA4DProteinQ92854 (Uniprot-TrEMBL)
SEMA5A ProteinQ13591 (Uniprot-TrEMBL)
SEMA5A:PLXNB3ComplexR-HSA-416696 (Reactome)
SEMA5AProteinQ13591 (Uniprot-TrEMBL)
SEMA6A ProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6A:PLXNA2,PLXNA4ComplexR-HSA-416728 (Reactome)
SEMA6AProteinQ9H2E6 (Uniprot-TrEMBL)
SEMA6D ProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA6D:PLXNA1:TREM2:DAP12ComplexR-HSA-416720 (Reactome)
SEMA6DProteinQ8NFY4 (Uniprot-TrEMBL)
SEMA7A ProteinO75326 (Uniprot-TrEMBL)
SEMA7A:Integrin alpha1beta1ComplexR-HSA-434927 (Reactome)
SEMA7A:PLXNC1ComplexR-HSA-434928 (Reactome)
SEMA7AProteinO75326 (Uniprot-TrEMBL)
Sema3A dimerComplexR-HSA-399861 (Reactome)
Sema3A:NP-1:Plexin-A:Fes:CRMPComplexR-HSA-399860 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:FesComplexR-HSA-399859 (Reactome)
Sema3A:Nrp-1:Plexin A:FynComplexR-HSA-399858 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sComplexR-HSA-399867 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sComplexR-HSA-399870 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5ComplexR-HSA-399868 (Reactome)
Sema3A:Nrp-1:PlexinA:FynComplexR-HSA-399869 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAKComplexR-HSA-399876 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAKComplexR-HSA-399874 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1ComplexR-HSA-399877 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPComplexR-HSA-399872 (Reactome)
Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEFComplexR-HSA-416580 (Reactome)
Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1ComplexR-HSA-416601 (Reactome)
Sema4D:pPlexin-B1:ErbB2:Rac1:Rnd1ComplexR-HSA-419626 (Reactome)
Sema4D:pPlexin-B1:Met:RAC1-GTPComplexR-HSA-400679 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1ComplexR-HSA-416587 (Reactome)
Sema4D:pPlexin-B1:MetComplexR-HSA-419621 (Reactome)
Smooth

muscle/non-muscle

myosin II		ComplexR-HSA-419194 (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-LIMKComplexR-HSA-419709 (Reactome)
p-S,T508-LIMK1 ProteinP53667 (Uniprot-TrEMBL)
p-S141,T402-PAK2 ProteinQ13177 (Uniprot-TrEMBL)
p-S144,T423-PAK1 ProteinQ13153 (Uniprot-TrEMBL)
p-S154,T436-PAK3 ProteinO75914 (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-MRLC-smooth muscle/non-muscle myosin IIComplexR-HSA-419195 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including smooth muscle contraction, cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10, MYH14 (NMHC-IIA, B and C) or MYH11, two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYL12B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 (commonly referred in the literature as Thr-18 and Ser-19) increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective (Ikebe and Hartshorne 1985, Ikebe et al. 1988). 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- or diphosphorylating MRLC (Amano et al., 1996, Ueda et al., 2002, Watanabe et al. 2007).
p-T19,S20-MYL12B ProteinO14950 (Uniprot-TrEMBL)
p-T19,S20-MYL9 ProteinP24844 (Uniprot-TrEMBL)
p-T505-LIMK2 ProteinP53671 (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-PLXNA2 ProteinO75051 (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-1ComplexR-HSA-399878 (Reactome)
pLIMK dimer:HSP-90ComplexR-HSA-419632 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ADPArrowR-HSA-373750 (Reactome)
ADPArrowR-HSA-399934 (Reactome)
ADPArrowR-HSA-399939 (Reactome)
ADPArrowR-HSA-399944 (Reactome)
ADPArrowR-HSA-399946 (Reactome)
ADPArrowR-HSA-399947 (Reactome)
ADPArrowR-HSA-399950 (Reactome)
ADPArrowR-HSA-399951 (Reactome)
ADPArrowR-HSA-399952 (Reactome)
ADPArrowR-HSA-419087 (Reactome)
ADPArrowR-HSA-419197 (Reactome)
ADPArrowR-HSA-419644 (Reactome)
ADPArrowR-HSA-419646 (Reactome)
ARHGAP35R-HSA-416562 (Reactome)
ATPR-HSA-373750 (Reactome)
ATPR-HSA-399934 (Reactome)
ATPR-HSA-399939 (Reactome)
ATPR-HSA-399944 (Reactome)
ATPR-HSA-399946 (Reactome)
ATPR-HSA-399947 (Reactome)
ATPR-HSA-399950 (Reactome)
ATPR-HSA-399951 (Reactome)
ATPR-HSA-399952 (Reactome)
ATPR-HSA-419087 (Reactome)
ATPR-HSA-419197 (Reactome)
ATPR-HSA-419644 (Reactome)
ATPR-HSA-419646 (Reactome)
Activated ROCK:RhoA/B/C:GTPArrowR-HSA-419049 (Reactome)
Activated ROCK:RhoA/B/C:GTPmim-catalysisR-HSA-419087 (Reactome)
Activated ROCK:RhoA/B/C:GTPmim-catalysisR-HSA-419197 (Reactome)
Active LIMK1ArrowR-HSA-419644 (Reactome)
Active LIMK1R-HSA-399950 (Reactome)
Active LIMK1mim-catalysisR-HSA-399950 (Reactome)
CD72R-HSA-373748 (Reactome)
CFL1R-HSA-399950 (Reactome)
CRMP's tetramersR-HSA-399944 (Reactome)
CRMP's tetramersR-HSA-399947 (Reactome)
Cdk5:p35R-HSA-399946 (Reactome)
FARP2:PIP5KIgammaArrowR-HSA-399936 (Reactome)
FARP2ArrowR-HSA-399933 (Reactome)
FARP2R-HSA-399936 (Reactome)
FARP2R-HSA-399942 (Reactome)
FARP2mim-catalysisR-HSA-399938 (Reactome)
FESR-HSA-399934 (Reactome)
GDPArrowR-HSA-399938 (Reactome)
GDPArrowR-HSA-416588 (Reactome)
GSK3Bmim-catalysisR-HSA-399951 (Reactome)
GTPR-HSA-399938 (Reactome)
GTPR-HSA-416588 (Reactome)
HSP90AA1,HSP90AB1ArrowR-HSA-419644 (Reactome)
HSP90AA1,HSP90AB1R-HSA-419645 (Reactome)
Integrin alpha1beta1R-HSA-434990 (Reactome)
LARG and PDZ-RhoGEFR-HSA-416594 (Reactome)
LIM KinasesR-HSA-419087 (Reactome)
LIMK1R-HSA-399952 (Reactome)
NRP1:PlexinA1-4:FARP2:FYNArrowR-HSA-399942 (Reactome)
NRP1:PlexinA1-4:FARP2:FYNR-HSA-399933 (Reactome)
NRP1:PlexinA1-4:FYNR-HSA-399931 (Reactome)
NRP1R-HSA-399942 (Reactome)
PAK1,2,3 dimerR-HSA-399930 (Reactome)
PAK1,2,3ArrowR-HSA-399930 (Reactome)
PIP5K1gamma:Talin-1R-HSA-399936 (Reactome)
PLXNA1:TREM2:DAP12R-HSA-416725 (Reactome)
PLXNA2,PLXNA4R-HSA-416723 (Reactome)
PLXNB3R-HSA-416698 (Reactome)
PLXNC1R-HSA-434989 (Reactome)
PLXND1R-HSA-416683 (Reactome)
PLXND1R-HSA-416690 (Reactome)
PTPRCR-HSA-373746 (Reactome)
PiArrowR-HSA-399935 (Reactome)
PiArrowR-HSA-416546 (Reactome)
PiArrowR-HSA-416559 (Reactome)
Plexin-A1-4:FYNR-HSA-399942 (Reactome)
Plexin-B1:ErbB2R-HSA-373750 (Reactome)
Plexin-B1:ErbB2mim-catalysisR-HSA-373750 (Reactome)
Plexin-B1:MetR-HSA-419646 (Reactome)
Plexin-B1:Metmim-catalysisR-HSA-419646 (Reactome)
R-HSA-373746 (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.
R-HSA-373748 (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.

R-HSA-373750 (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.
R-HSA-399928 (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.
R-HSA-399930 (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.
R-HSA-399931 (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.
R-HSA-399933 (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.
R-HSA-399934 (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.
R-HSA-399935 (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.
R-HSA-399936 (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.
R-HSA-399938 (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.
R-HSA-399939 (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.
R-HSA-399941 (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.
R-HSA-399942 (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.
R-HSA-399944 (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.
R-HSA-399946 (Reactome) 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. CDK5:p35 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.
R-HSA-399947 (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.
R-HSA-399950 (Reactome) The EPHB2-FAK pathway partially promotes dendritic spine stability through LIMK-mediated cofilin (CFL1) phosphorylation (Shi et al. 2009). CFL1 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 CFL1 on the conserved serine 3 residue located near the actin-binding site. After phosphorylation, CFL1 is inactive, loses its affinity for actin and dissociates from G-actin monomers. Once freed, ADP-actin monomers can exchange ADP with cytoplasmic ATP, ready for reincorporation at the barbed end of a growing filament (Gungabissoon & Bamburg 2003).
R-HSA-399951 (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.
R-HSA-399952 (Reactome) LIM kinases are serine protein kinases with a unique combination of two N-terminal LIM motifs, a central PDZ domain, and a C-terminal protein kinase domain. LIMK1 is one of the downstream targets of PAK1 and is activated through phosphorylation by PAK1 on T508 within its activation loop (Edwards et al. 1999, Aizawa et al. 2001). 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. Phosphorylated cofilin is inactive, resulting in stabilization of the actin cytoskeleton.
R-HSA-400677 (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.
R-HSA-400682 (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.
R-HSA-416546 (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.

R-HSA-416559 (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.
R-HSA-416562 (Reactome) Plexin-B1 can mediate inhibition of RhoA via the Sema4D-dependent recruitment of p190RhoGAP into the semaphorin receptor complex.
R-HSA-416588 (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.
R-HSA-416594 (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.
R-HSA-416683 (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.
R-HSA-416690 (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.
R-HSA-416698 (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.
R-HSA-416723 (Reactome) Sema6A binds plexinA2 and plexinA4 to establish lamina-restricted axon projection in the hippocampus.
R-HSA-416725 (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.
R-HSA-419049 (Reactome) 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 and allowing catalytic activity (Araki et al. 2001). Proteolytic cleavage at the C-terminus by caspase-3 and granzyme B also activates ROCK1 and ROCK2, causing plasma membrane blebbing during apoptosis (Coleman et al. 2001, Sebbagh et al. 2005). Multiple targets of ROCK contribute to the stabilization of actin filaments and the generation of actin-myosin contractile force.
R-HSA-419087 (Reactome) LIM kinases are serine protein kinases with a unique combination of two N-terminal LIM motifs, a central PDZ domain, and a C-terminal protein kinase domain. ROCK1 and ROCK2 phosphorylate and activate LIM kinases LIMK1 and LIMK2 at Thr508 and Thr505, respectively (Ohashi et al. 2000, Sumi et al. 2001). These threonine residues lay within the activation loop of the kinase domain. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, resulting in stabilization of the actin cytoskeleton (Pandey et al. 2006).
R-HSA-419197 (Reactome) Nonmuscle myosin II (NMM2) is an actin-based motor protein that plays a crucial role in a variety of cellular processes, including smooth muscle contraction, cell migration, polarity formation, and cytokinesis. NMM2 consists of two myosin heavy chains encoded by MYH9, MYH10, MYH14 (NMHC-IIA, B and C) or MYH11, two copies of MYL6 essential light chain protein, and two regulatory light chains (MRLCs), MYL9 and MYL12B. Myosin II activity is stimulated by phosphorylation of MRLC. Diphosphorylation at Thr-19 and Ser-20 (commonly referred in the literature as Thr-18 and Ser-19) increases both actin-activated Mg2+ ATPase activity and the stability of myosin II filaments; monophosphorylation at Ser-20 is less effective (Ikebe and Hartshorne 1985, Ikebe et al. 1988). 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- or diphosphorylating MRLC (Amano et al., 1996, Ueda et al., 2002, Watanabe et al. 2007).
R-HSA-419644 (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.
R-HSA-419645 (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.
R-HSA-419646 (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.
R-HSA-434989 (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.
R-HSA-434990 (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.
R-Ras-GDPArrowR-HSA-399935 (Reactome)
R-Ras-GDPArrowR-HSA-416546 (Reactome)
R-Ras-GTPR-HSA-399935 (Reactome)
R-Ras-GTPR-HSA-416546 (Reactome)
RAC1:GDPR-HSA-399938 (Reactome)
RAC1:GTPArrowR-HSA-399938 (Reactome)
RAC1:GTPR-HSA-399941 (Reactome)
RAC1:GTPR-HSA-400682 (Reactome)
RHOA/B/C:GTPArrowR-HSA-416588 (Reactome)
RHOA/B/C:GTPR-HSA-419049 (Reactome)
ROCK1,ROCK2R-HSA-419049 (Reactome)
RhoA (Mg cofactor):GDPArrowR-HSA-416559 (Reactome)
RhoA (Mg cofactor):GTPR-HSA-416559 (Reactome)
RhoA,B,C:GDPR-HSA-416588 (Reactome)
Rnd1-GTPR-HSA-399928 (Reactome)
Rnd1-GTPR-HSA-400677 (Reactome)
SEMA3A:PLXND1ArrowR-HSA-416683 (Reactome)
SEMA3ER-HSA-416683 (Reactome)
SEMA4A:PLXND1ArrowR-HSA-416690 (Reactome)
SEMA4AR-HSA-416690 (Reactome)
SEMA4D dimerR-HSA-373750 (Reactome)
SEMA4D dimerR-HSA-419646 (Reactome)
SEMA4D:CD72ArrowR-HSA-373748 (Reactome)
SEMA4D:PTPRCArrowR-HSA-373746 (Reactome)
SEMA4D:pPlexin-B1:ErbB2 complexArrowR-HSA-373750 (Reactome)
SEMA4DR-HSA-373746 (Reactome)
SEMA4DR-HSA-373748 (Reactome)
SEMA5A:PLXNB3ArrowR-HSA-416698 (Reactome)
SEMA5AR-HSA-416698 (Reactome)
SEMA6A:PLXNA2,PLXNA4ArrowR-HSA-416723 (Reactome)
SEMA6AR-HSA-416723 (Reactome)
SEMA6D:PLXNA1:TREM2:DAP12ArrowR-HSA-416725 (Reactome)
SEMA6DR-HSA-416725 (Reactome)
SEMA7A:Integrin alpha1beta1ArrowR-HSA-434990 (Reactome)
SEMA7A:PLXNC1ArrowR-HSA-434989 (Reactome)
SEMA7AR-HSA-434989 (Reactome)
SEMA7AR-HSA-434990 (Reactome)
Sema3A dimerR-HSA-399931 (Reactome)
Sema3A dimerR-HSA-399933 (Reactome)
Sema3A:NP-1:Plexin-A:Fes:CRMPArrowR-HSA-399947 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:FesArrowR-HSA-399934 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:FesR-HSA-399941 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:FesR-HSA-399947 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:Fesmim-catalysisR-HSA-399934 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:Fesmim-catalysisR-HSA-399947 (Reactome)
Sema3A:Nrp-1:Plexin A:FynArrowR-HSA-399933 (Reactome)
Sema3A:Nrp-1:Plexin A:FynR-HSA-399934 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sArrowR-HSA-399944 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sArrowR-HSA-399951 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sR-HSA-399951 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5ArrowR-HSA-399946 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5R-HSA-399944 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5mim-catalysisR-HSA-399944 (Reactome)
Sema3A:Nrp-1:PlexinA:FynArrowR-HSA-399931 (Reactome)
Sema3A:Nrp-1:PlexinA:FynR-HSA-399946 (Reactome)
Sema3A:Nrp-1:PlexinA:Fynmim-catalysisR-HSA-399946 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAKArrowR-HSA-399930 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAKR-HSA-399939 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAKmim-catalysisR-HSA-399939 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAKArrowR-HSA-399939 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAKmim-catalysisR-HSA-399952 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1ArrowR-HSA-399928 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1mim-catalysisR-HSA-399935 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPArrowR-HSA-399941 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPR-HSA-399928 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPR-HSA-399930 (Reactome)
Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEFArrowR-HSA-416594 (Reactome)
Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEFmim-catalysisR-HSA-416588 (Reactome)
Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1ArrowR-HSA-416562 (Reactome)
Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1mim-catalysisR-HSA-416559 (Reactome)
Sema4D:pPlexin-B1:ErbB2:Rac1:Rnd1R-HSA-416594 (Reactome)
Sema4D:pPlexin-B1:Met:RAC1-GTPArrowR-HSA-400682 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1ArrowR-HSA-400677 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1R-HSA-416562 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1mim-catalysisR-HSA-416546 (Reactome)
Sema4D:pPlexin-B1:MetArrowR-HSA-419646 (Reactome)
Sema4D:pPlexin-B1:MetR-HSA-400677 (Reactome)
Sema4D:pPlexin-B1:MetR-HSA-400682 (Reactome)
Smooth

muscle/non-muscle

myosin II		R-HSA-419197 (Reactome)
TLN1ArrowR-HSA-399936 (Reactome)
p-LIMKArrowR-HSA-419087 (Reactome)
p-T19,S20-MRLC-smooth muscle/non-muscle myosin IIArrowR-HSA-419197 (Reactome)
p-T508-LIMK1ArrowR-HSA-399952 (Reactome)
p-T508-LIMK1R-HSA-419645 (Reactome)
pCofilin: Active LIMK-1ArrowR-HSA-399950 (Reactome)
pLIMK dimer:HSP-90ArrowR-HSA-419645 (Reactome)
pLIMK dimer:HSP-90R-HSA-419644 (Reactome)
pLIMK dimer:HSP-90mim-catalysisR-HSA-419644 (Reactome)
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