Semaphorin interactions (Homo sapiens)

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1. Oinuma I, Katoh H, Harada A, Negishi M.; ''Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells.''; PubMed Europe PMC Scholia
2. Raper JA.; ''Semaphorins and their receptors in vertebrates and invertebrates.''; PubMed Europe PMC Scholia
3. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T, Matsumoto M, Yoshida K, Yakura H, Pan C, Parnes JR, Kikutani H.; ''Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling.''; PubMed Europe PMC Scholia
4. Dickson BJ.; ''Molecular mechanisms of axon guidance.''; PubMed Europe PMC Scholia
5. Pasterkamp RJ, Verhaagen J.; ''Semaphorins in axon regeneration: developmental guidance molecules gone wrong?''; PubMed Europe PMC Scholia
6. Sebbagh M, Hamelin J, Bertoglio J, Solary E, Bréard J.; ''Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner.''; PubMed Europe PMC Scholia
7. Takegahara N, Takamatsu H, Toyofuku T, Tsujimura T, Okuno T, Yukawa K, Mizui M, Yamamoto M, Prasad DV, Suzuki K, Ishii M, Terai K, Moriya M, Nakatsuji Y, Sakoda S, Sato S, Akira S, Takeda K, Inui M, Takai T, Ikawa M, Okabe M, Kumanogoh A, Kikutani H.; ''Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.''; PubMed Europe PMC Scholia
8. Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K.; ''GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity.''; PubMed Europe PMC Scholia
9. Gatti A, Huang Z, Tuazon PT, Traugh JA.; ''Multisite autophosphorylation of p21-activated protein kinase gamma-PAK as a function of activation.''; PubMed Europe PMC Scholia
10. Toyofuku T, Yoshida J, Sugimoto T, Zhang H, Kumanogoh A, Hori M, Kikutani H.; ''FARP2 triggers signals for Sema3A-mediated axonal repulsion.''; PubMed Europe PMC Scholia
11. Leung T, Chen XQ, Manser E, Lim L.; ''The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton.''; PubMed Europe PMC Scholia
12. Tanna AP, Johnson M.; ''Rho Kinase Inhibitors as a Novel Treatment for Glaucoma and Ocular Hypertension.''; PubMed Europe PMC Scholia
13. Coleman ML, Sahai EA, Yeo M, Bosch M, Dewar A, Olson MF.; ''Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I.''; PubMed Europe PMC Scholia
14. Billard C, Delaire S, Raffoux E, Bensussan A, Boumsell L.; ''Switch in the protein tyrosine phosphatase associated with human CD100 semaphorin at terminal B-cell differentiation stage.''; PubMed Europe PMC Scholia
15. Swiercz JM, Worzfeld T, Offermanns S.; ''ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.''; PubMed Europe PMC Scholia
16. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K.; ''Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase).''; PubMed Europe PMC Scholia
17. Uchida Y, Ohshima T, Sasaki Y, Suzuki H, Yanai S, Yamashita N, Nakamura F, Takei K, Ihara Y, Mikoshiba K, Kolattukudy P, Honnorat J, Goshima Y.; ''Semaphorin3A signalling is mediated via sequential Cdk5 and GSK3beta phosphorylation of CRMP2: implication of common phosphorylating mechanism underlying axon guidance and Alzheimer's disease.''; PubMed Europe PMC Scholia
18. Aizawa H, Wakatsuki S, Ishii A, Moriyama K, Sasaki Y, Ohashi K, Sekine-Aizawa Y, Sehara-Fujisawa A, Mizuno K, Goshima Y, Yahara I.; ''Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse.''; PubMed Europe PMC Scholia
19. Edwards DC, Sanders LC, Bokoch GM, Gill GN.; ''Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics.''; PubMed Europe PMC Scholia
20. Gu C, Yoshida Y, Livet J, Reimert DV, Mann F, Merte J, Henderson CE, Jessell TM, Kolodkin AL, Ginty DD.; ''Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins.''; PubMed Europe PMC Scholia
21. Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H.; ''Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses.''; PubMed Europe PMC Scholia
22. Pasterkamp RJ, Kolodkin AL.; ''Semaphorin junction: making tracks toward neural connectivity.''; PubMed Europe PMC Scholia
23. Herold C, Elhabazi A, Bismuth G, Bensussan A, Boumsell L.; ''CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion.''; PubMed Europe PMC Scholia
24. Sumi T, Matsumoto K, Nakamura T.; ''Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase.''; PubMed Europe PMC Scholia
25. Nakamura F, Kalb RG, Strittmatter SM.; ''Molecular basis of semaphorin-mediated axon guidance.''; PubMed Europe PMC Scholia
26. Garnock-Jones KP.; ''Ripasudil: first global approval.''; PubMed Europe PMC Scholia
27. Li R, Soosairajah J, Harari D, Citri A, Price J, Ng HL, Morton CJ, Parker MW, Yarden Y, Bernard O.; ''Hsp90 increases LIM kinase activity by promoting its homo-dimerization.''; PubMed Europe PMC Scholia
28. Toyofuku T, Yabuki M, Kamei J, Kamei M, Makino N, Kumanogoh A, Hori M.; ''Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1.''; PubMed Europe PMC Scholia
29. Ikebe M, Koretz J, Hartshorne DJ.; ''Effects of phosphorylation of light chain residues threonine 18 and serine 19 on the properties and conformation of smooth muscle myosin.''; PubMed Europe PMC Scholia
30. Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA.; ''Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions.''; PubMed Europe PMC Scholia
31. Aurandt J, Vikis HG, Gutkind JS, Ahn N, Guan KL.; ''The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG.''; PubMed Europe PMC Scholia
32. Swiercz JM, Kuner R, Offermanns S.; ''Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2.''; PubMed Europe PMC Scholia
33. Tamagnone L, Artigiani S, Chen H, He Z, Ming GI, Song H, Chedotal A, Winberg ML, Goodman CS, Poo M, Tessier-Lavigne M, Comoglio PM.; ''Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.''; PubMed Europe PMC Scholia
34. Artigiani S, Conrotto P, Fazzari P, Gilestro GF, Barberis D, Giordano S, Comoglio PM, Tamagnone L.; ''Plexin-B3 is a functional receptor for semaphorin 5A.''; PubMed Europe PMC Scholia
35. Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S.; ''The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase.''; PubMed Europe PMC Scholia
36. Bernard O.; ''Lim kinases, regulators of actin dynamics.''; PubMed Europe PMC Scholia
37. Bernard O, Ganiatsas S, Kannourakis G, Dringen R.; ''Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons.''; PubMed Europe PMC Scholia
38. Barberis D, Casazza A, Sordella R, Corso S, Artigiani S, Settleman J, Comoglio PM, Tamagnone L.; ''p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling.''; PubMed Europe PMC Scholia
39. Vikis HG, Li W, He Z, Guan KL.; ''The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner.''; PubMed Europe PMC Scholia
40. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K.; ''Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop.''; PubMed Europe PMC Scholia
41. Araki S, Ito M, Kureishi Y, Feng J, Machida H, Isaka N, Amano M, Kaibuchi K, Hartshorne DJ, Nakano T.; ''Arachidonic acid-induced Ca2+ sensitization of smooth muscle contraction through activation of Rho-kinase.''; PubMed Europe PMC Scholia
42. Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L, Comoglio PM.; ''The semaphorin 4D receptor controls invasive growth by coupling with Met.''; PubMed Europe PMC Scholia
43. Halloran MC, Wolman MA.; ''Repulsion or adhesion: receptors make the call.''; PubMed Europe PMC Scholia
44. Oinuma I, Katoh H, Negishi M.; ''Semaphorin 4D/Plexin-B1-mediated R-Ras GAP activity inhibits cell migration by regulating beta(1) integrin activity.''; PubMed Europe PMC Scholia
45. Ahmed A, Eickholt BJ.; ''Intracellular kinases in semaphorin signaling.''; PubMed Europe PMC Scholia
46. Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S.; ''Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors.''; PubMed Europe PMC Scholia
47. Zhou Y, Gunput RA, Pasterkamp RJ.; ''Semaphorin signaling: progress made and promises ahead.''; PubMed Europe PMC Scholia
48. Watanabe T, Hosoya H, Yonemura S.; ''Regulation of myosin II dynamics by phosphorylation and dephosphorylation of its light chain in epithelial cells.''; PubMed Europe PMC Scholia
49. Sasaki Y, Cheng C, Uchida Y, Nakajima O, Ohshima T, Yagi T, Taniguchi M, Nakayama T, Kishida R, Kudo Y, Ohno S, Nakamura F, Goshima Y.; ''Fyn and Cdk5 mediate semaphorin-3A signaling, which is involved in regulation of dendrite orientation in cerebral cortex.''; PubMed Europe PMC Scholia
50. Chong C, Tan L, Lim L, Manser E.; ''The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity.''; PubMed Europe PMC Scholia
51. Sturdivant JM, Royalty SM, Lin CW, Moore LA, Yingling JD, Laethem CL, Sherman B, Heintzelman GR, Kopczynski CC, deLong MA.; ''Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma.''; PubMed Europe PMC Scholia
52. Ueda K, Murata-Hori M, Tatsuka M, Hosoya H.; ''Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain in nonmuscle cells.''; PubMed Europe PMC Scholia
53. Mitsui N, Inatome R, Takahashi S, Goshima Y, Yamamura H, Yanagi S.; ''Involvement of Fes/Fps tyrosine kinase in semaphorin3A signaling.''; PubMed Europe PMC Scholia
54. Koncina E, Roth L, Gonthier B, Bagnard D.; ''Role of semaphorins during axon growth and guidance.''; PubMed Europe PMC Scholia
55. Ito Y, Oinuma I, Katoh H, Kaibuchi K, Negishi M.; ''Sema4D/plexin-B1 activates GSK-3beta through R-Ras GAP activity, inducing growth cone collapse.''; PubMed Europe PMC Scholia
56. Pandey D, Pandey D, Goyal P, Bamburg JR, Siess W.; ''Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets.''; PubMed Europe PMC Scholia
57. Ikebe M, Hartshorne DJ.; ''Phosphorylation of smooth muscle myosin at two distinct sites by myosin light chain kinase.''; PubMed Europe PMC Scholia
58. Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM.; ''Structural bases for CRMP function in plexin-dependent semaphorin3A signaling.''; PubMed Europe PMC Scholia
59. Schmidt EF, Strittmatter SM.; ''The CRMP family of proteins and their role in Sema3A signaling.''; PubMed Europe PMC Scholia
60. Vikis HG, Li W, Guan KL.; ''The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding.''; PubMed Europe PMC Scholia
61. Whitford KL, Ghosh A.; ''Plexin signaling via off-track and rho family GTPases.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:16761 (ChEBI)
ARHGAP35 [cytosol]	Protein	Q9NRY4 (Uniprot-TrEMBL)
ARHGAP35	Protein	Q9NRY4 (Uniprot-TrEMBL)
ARHGEF11 [cytosol]	Protein	O15085 (Uniprot-TrEMBL)
ARHGEF12 [cytosol]	Protein	Q9NZN5 (Uniprot-TrEMBL)
ATP	Metabolite	CHEBI:15422 (ChEBI)
Activated ROCK:RhoA/B/C:GTP	Complex	REACT_19928 (Reactome)
Active LIMK1	Complex	REACT_19790 (Reactome)
CD72 [plasma membrane]	Protein	P21854 (Uniprot-TrEMBL)
CD72	Protein	P21854 (Uniprot-TrEMBL)
CDK5 [cytosol]	Protein	Q00535 (Uniprot-TrEMBL)
CDK5R1(1-307) [cytosol]	Protein	Q15078 (Uniprot-TrEMBL)
CFL1	Protein	P23528 (Uniprot-TrEMBL)
CRMP's tetramers	Complex	REACT_19835 (Reactome)
CRMP1 [cytosol]	Protein	Q14194 (Uniprot-TrEMBL)
Cdk5:p35	Complex	REACT_19863 (Reactome)
DPYSL2 [cytosol]	Protein	Q16555 (Uniprot-TrEMBL)
DPYSL3 [cytosol]	Protein	Q14195 (Uniprot-TrEMBL)
DPYSL4 [cytosol]	Protein	O14531 (Uniprot-TrEMBL)
DPYSL5 [cytosol]	Protein	Q9BPU6 (Uniprot-TrEMBL)
ERBB2 [plasma membrane]	Protein	P04626 (Uniprot-TrEMBL)
FARP2 [cytosol]	Protein	O94887 (Uniprot-TrEMBL)
FARP2:PIP5KIgamma	Complex	REACT_19748 (Reactome)
FARP2	Protein	O94887 (Uniprot-TrEMBL)
FES [cytosol]	Protein	P07332 (Uniprot-TrEMBL)
FES	Protein	P07332 (Uniprot-TrEMBL)
FYN(2-537) [cytosol]	Protein	P06241 (Uniprot-TrEMBL)
GDP [cytosol]	Metabolite	CHEBI:17552 (ChEBI)
GDP [plasma membrane]	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GSK3B	Protein	P49841 (Uniprot-TrEMBL)
GTP [cytosol]	Metabolite	CHEBI:15996 (ChEBI)
GTP [plasma membrane]	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
HSP-90	Protein	REACT_19960 (Reactome)
HSP90AA1 [cytosol]	Protein	P07900 (Uniprot-TrEMBL)
HSP90AB1 [cytosol]	Protein	P08238 (Uniprot-TrEMBL)
ITGA1 [plasma membrane]	Protein	P56199 (Uniprot-TrEMBL)
ITGB1 [plasma membrane]	Protein	P05556 (Uniprot-TrEMBL)
Integrin alpha1beta1	Complex	REACT_14015 (Reactome)
LARG and PDZ-RhoGEF	Protein	REACT_20012 (Reactome)
LIM Kinases, phosphorylated	Protein	REACT_19576 (Reactome)
LIM Kinases	Protein	REACT_20207 (Reactome)
LIMK1	Protein	P53667 (Uniprot-TrEMBL)
MET [plasma membrane]	Protein	P08581 (Uniprot-TrEMBL)
MYH10 [cytosol]	Protein	P35580 (Uniprot-TrEMBL)
MYH11 [cytosol]	Protein	P35749 (Uniprot-TrEMBL)
MYH14 [cytosol]	Protein	Q7Z406 (Uniprot-TrEMBL)
MYH9 [cytosol]	Protein	P35579 (Uniprot-TrEMBL)
MYL12B(2-172) [cytosol]	Protein	O14950 (Uniprot-TrEMBL)
MYL6 [cytosol]	Protein	P60660 (Uniprot-TrEMBL)
MYL9 [cytosol]	Protein	P24844 (Uniprot-TrEMBL)
Mg2+ [plasma membrane]	Metabolite	CHEBI:18420 (ChEBI)
NRP1 [plasma membrane]	Protein	O14786 (Uniprot-TrEMBL)
NRP1:PlexinA1-4:FARP2:FYN	Complex	REACT_20390 (Reactome)
NRP1:PlexinA1-4:FYN	Complex	REACT_20319 (Reactome)
NRP1	Protein	O14786 (Uniprot-TrEMBL)
PAK homodimer	Complex	REACT_19479 (Reactome)
PAK1 [cytosol]	Protein	Q13153 (Uniprot-TrEMBL)
PAK2(1-524) [cytosol]	Protein	Q13177 (Uniprot-TrEMBL)
PAK	Protein	REACT_19640 (Reactome)
PIP5K1C [cytosol]	Protein	O60331 (Uniprot-TrEMBL)
PIP5K1gamma:Talin-1	Complex	REACT_19891 (Reactome)
PLXNA1 [plasma membrane]	Protein	Q9UIW2 (Uniprot-TrEMBL)
PLXNA1:TREM2:DAP12	Complex	REACT_20126 (Reactome)
PLXNA2(50-1909) [plasma membrane]	Protein	O75051 (Uniprot-TrEMBL)
PLXNA2,PLXNA4	Protein	REACT_20091 (Reactome)
PLXNA3 [plasma membrane]	Protein	P51805 (Uniprot-TrEMBL)
PLXNA4 [plasma membrane]	Protein	Q9HCM2 (Uniprot-TrEMBL)
PLXNB1 [plasma membrane]	Protein	O43157 (Uniprot-TrEMBL)
PLXNB3 [plasma membrane]	Protein	Q9ULL4 (Uniprot-TrEMBL)
PLXNB3	Protein	Q9ULL4 (Uniprot-TrEMBL)
PLXNC1 [plasma membrane]	Protein	O60486 (Uniprot-TrEMBL)
PLXNC1	Protein	O60486 (Uniprot-TrEMBL)
PLXND1 [plasma membrane]	Protein	Q9Y4D7 (Uniprot-TrEMBL)
PLXND1	Protein	Q9Y4D7 (Uniprot-TrEMBL)
PTPRC [plasma membrane]	Protein	P08575 (Uniprot-TrEMBL)
PTPRC	Protein	P08575 (Uniprot-TrEMBL)
Phospho-activated smooth muscle/non-muscle myosin 2	Complex	REACT_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.
Pi	Metabolite	CHEBI:18367 (ChEBI)
Plexin-A1-4:FYN	Complex	REACT_19507 (Reactome)
Plexin-B1:ErbB2	Complex	REACT_19954 (Reactome)
Plexin-B1:Met	Complex	REACT_19866 (Reactome)
R-Ras-GDP	Complex	REACT_20329 (Reactome)
R-Ras-GTP	Complex	REACT_20411 (Reactome)
RAC1 [cytosol]	Protein	P63000 (Uniprot-TrEMBL)
RAC1-GDP	Complex	REACT_22018 (Reactome)
RAC1-GTP	Complex	REACT_21594 (Reactome)
RHOA [plasma membrane]	Protein	P61586 (Uniprot-TrEMBL)
RHOB [plasma membrane]	Protein	P62745 (Uniprot-TrEMBL)
RHOC [plasma membrane]	Protein	P08134 (Uniprot-TrEMBL)
RND1 [cytosol]	Protein	Q92730 (Uniprot-TrEMBL)
ROCK1(1-1354) [cytosol]	Protein	Q13464 (Uniprot-TrEMBL)
ROCK2 [cytosol]	Protein	O75116 (Uniprot-TrEMBL)
ROCK	Protein	REACT_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 [plasma membrane]	Protein	P10301 (Uniprot-TrEMBL)
RhoA (Mg cofactor):GDP	Complex	REACT_13852 (Reactome)
RhoA (Mg cofactor):GTP	Complex	REACT_14306 (Reactome)
RhoA,B,C:GDP	Complex	REACT_20118 (Reactome)
RhoA/B/C:GTP	Complex	REACT_19589 (Reactome)
Rnd1-GTP	Complex	REACT_20300 (Reactome)
SEMA3A [extracellular region]	Protein	Q14563 (Uniprot-TrEMBL)
SEMA3A:PLXND1	Complex	REACT_20367 (Reactome)
SEMA3E [extracellular region]	Protein	O15041 (Uniprot-TrEMBL)
SEMA3E	Protein	O15041 (Uniprot-TrEMBL)
SEMA4A [plasma membrane]	Protein	Q9H3S1 (Uniprot-TrEMBL)
SEMA4A:PLXND1	Complex	REACT_19803 (Reactome)
SEMA4A	Protein	Q9H3S1 (Uniprot-TrEMBL)
SEMA4D [plasma membrane]	Protein	Q92854 (Uniprot-TrEMBL)
SEMA4D dimer	Complex	REACT_19817 (Reactome)
SEMA4D:CD72	Complex	REACT_20194 (Reactome)
SEMA4D:PTPRC	Complex	REACT_19862 (Reactome)
SEMA4D:pPlexin-B1:ErbB2 complex	Complex	REACT_20256 (Reactome)
SEMA4D	Protein	Q92854 (Uniprot-TrEMBL)
SEMA5A [plasma membrane]	Protein	Q13591 (Uniprot-TrEMBL)
SEMA5A:PLXNB3	Complex	REACT_19434 (Reactome)
SEMA5A	Protein	Q13591 (Uniprot-TrEMBL)
SEMA6A [plasma membrane]	Protein	Q9H2E6 (Uniprot-TrEMBL)
SEMA6A:PLXNA2,PLXNA4	Complex	REACT_19923 (Reactome)
SEMA6A	Protein	Q9H2E6 (Uniprot-TrEMBL)
SEMA6D [plasma membrane]	Protein	Q8NFY4 (Uniprot-TrEMBL)
SEMA6D:PLXNA1:TREM2:DAP12	Complex	REACT_19554 (Reactome)
SEMA6D	Protein	Q8NFY4 (Uniprot-TrEMBL)
SEMA7A [plasma membrane]	Protein	O75326 (Uniprot-TrEMBL)
SEMA7A:Integrin alpha1beta1	Complex	REACT_20443 (Reactome)
SEMA7A:PLXNC1	Complex	REACT_20419 (Reactome)
SEMA7A	Protein	O75326 (Uniprot-TrEMBL)
Sema3A dimer	Complex	REACT_19939 (Reactome)
Sema3A:NP-1:Plexin-A:Fes:CRMP	Complex	REACT_20015 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:Fes	Complex	REACT_19958 (Reactome)
Sema3A:Nrp-1:Plexin A:Fyn	Complex	REACT_19816 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP's	Complex	REACT_19706 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP's	Complex	REACT_20425 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5	Complex	REACT_20429 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn	Complex	REACT_20413 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK	Complex	REACT_20083 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAK	Complex	REACT_19495 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1	Complex	REACT_19802 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP	Complex	REACT_20187 (Reactome)
Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEF	Complex	REACT_20349 (Reactome)
Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1	Complex	REACT_19579 (Reactome)
Sema4D:pPlexin-B1:ErbB2:Rac1:Rnd1	Complex	REACT_19890 (Reactome)
Sema4D:pPlexin-B1:Met:RAC1-GTP	Complex	REACT_20028 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1	Complex	REACT_19721 (Reactome)
Sema4D:pPlexin-B1:Met	Complex	REACT_19905 (Reactome)
Smooth muscle/non-muscle myosin II	Complex	REACT_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 [cytosol]	Protein	Q9Y490 (Uniprot-TrEMBL)
TLN1	Protein	Q9Y490 (Uniprot-TrEMBL)
TREM2 [plasma membrane]	Protein	Q9NZC2 (Uniprot-TrEMBL)
TYROBP [plasma membrane]	Protein	O43914 (Uniprot-TrEMBL)
p-S,T508-LIMK1 [cytosol]	Protein	P53667 (Uniprot-TrEMBL)
p-S141,T402-PAK2(1-524) [cytosol]	Protein	Q13177 (Uniprot-TrEMBL)
p-S144,T423-PAK1 [cytosol]	Protein	Q13153 (Uniprot-TrEMBL)
p-S3-CFL1 [cytosol]	Protein	P23528 (Uniprot-TrEMBL)
p-S522-CRMP1 [cytosol]	Protein	Q14194 (Uniprot-TrEMBL)
p-S522-DPYSL2 [cytosol]	Protein	Q16555 (Uniprot-TrEMBL)
p-S522-DPYSL3 [cytosol]	Protein	Q14195 (Uniprot-TrEMBL)
p-S534-DPYSL5 [cytosol]	Protein	Q9BPU6 (Uniprot-TrEMBL)
p-S544-DPYSL4 [cytosol]	Protein	O14531 (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-MYL12B(2-172) [cytosol]	Protein	O14950 (Uniprot-TrEMBL)
p-T19,S20-MYL9 [cytosol]	Protein	P24844 (Uniprot-TrEMBL)
p-T508-LIMK1 [cytosol]	Protein	P53667 (Uniprot-TrEMBL)
p-T508-LIMK1	Protein	P53667 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-CRMP1 [cytosol]	Protein	Q14194 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL2 [cytosol]	Protein	Q16555 (Uniprot-TrEMBL)
p-T509,T514,S518,S522-DPYSL3 [cytosol]	Protein	Q14195 (Uniprot-TrEMBL)
p-Y-CRMP1 [cytosol]	Protein	Q14194 (Uniprot-TrEMBL)
p-Y-DPYSL2 [cytosol]	Protein	Q16555 (Uniprot-TrEMBL)
p-Y-DPYSL3 [cytosol]	Protein	Q14195 (Uniprot-TrEMBL)
p-Y-DPYSL4 [cytosol]	Protein	O14531 (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 [cytosol]	Protein	Q9BPU6 (Uniprot-TrEMBL)
p-Y-PLXNA1 [plasma membrane]	Protein	Q9UIW2 (Uniprot-TrEMBL)
p-Y-PLXNA2(50-1909) [plasma membrane]	Protein	O75051 (Uniprot-TrEMBL)
p-Y-PLXNA3 [plasma membrane]	Protein	P51805 (Uniprot-TrEMBL)
p-Y-PLXNA4 [plasma membrane]	Protein	Q9HCM2 (Uniprot-TrEMBL)
p-Y-PLXNB1 [plasma membrane]	Protein	O43157 (Uniprot-TrEMBL)
p-Y15-CDK5 [cytosol]	Protein	Q00535 (Uniprot-TrEMBL)
pCofilin: Active LIMK-1	Complex	REACT_20103 (Reactome)
pLIMK dimer:HSP-90	Complex	REACT_19543 (Reactome)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	ADP	Arrow	REACT_19161 (Reactome)
	ADP	Arrow	REACT_19168 (Reactome)
	ADP	Arrow	REACT_19191 (Reactome)
	ADP	Arrow	REACT_19197 (Reactome)
	ADP	Arrow	REACT_19221 (Reactome)
	ADP	Arrow	REACT_19276 (Reactome)
	ADP	Arrow	REACT_19282 (Reactome)
	ADP	Arrow	REACT_19285 (Reactome)
	ADP	Arrow	REACT_19321 (Reactome)
	ADP	Arrow	REACT_19381 (Reactome)
	ADP	Arrow	REACT_19393 (Reactome)
	ADP	Arrow	REACT_19398 (Reactome)
	ADP	Arrow	REACT_19420 (Reactome)
ARHGAP35			REACT_19356 (Reactome)
ATP			REACT_19161 (Reactome)
ATP			REACT_19168 (Reactome)
ATP			REACT_19191 (Reactome)
ATP			REACT_19197 (Reactome)
ATP			REACT_19221 (Reactome)
ATP			REACT_19276 (Reactome)
ATP			REACT_19282 (Reactome)
ATP			REACT_19285 (Reactome)
ATP			REACT_19321 (Reactome)
ATP			REACT_19381 (Reactome)
ATP			REACT_19393 (Reactome)
ATP			REACT_19398 (Reactome)
ATP			REACT_19420 (Reactome)
	Activated ROCK:RhoA/B/C:GTP	Arrow	REACT_19389 (Reactome)
Activated ROCK:RhoA/B/C:GTP		mim-catalysis	REACT_19191 (Reactome)
Activated ROCK:RhoA/B/C:GTP		mim-catalysis	REACT_19282 (Reactome)
	Active LIMK1	Arrow	REACT_19168 (Reactome)
Active LIMK1			REACT_19276 (Reactome)
Active LIMK1		mim-catalysis	REACT_19276 (Reactome)
CD72			REACT_19336 (Reactome)
CFL1			REACT_19276 (Reactome)
CRMP's tetramers			REACT_19161 (Reactome)
CRMP's tetramers			REACT_19285 (Reactome)
Cdk5:p35			REACT_19393 (Reactome)
	FARP2:PIP5KIgamma	Arrow	REACT_19403 (Reactome)
	FARP2	Arrow	REACT_19173 (Reactome)
FARP2			REACT_19128 (Reactome)
FARP2			REACT_19403 (Reactome)
FARP2		mim-catalysis	REACT_19363 (Reactome)
FES			REACT_19420 (Reactome)
	GDP	Arrow	REACT_19137 (Reactome)
	GDP	Arrow	REACT_19363 (Reactome)
GSK3B		mim-catalysis	REACT_19321 (Reactome)
GTP			REACT_19137 (Reactome)
GTP			REACT_19363 (Reactome)
	HSP-90	Arrow	REACT_19168 (Reactome)
HSP-90			REACT_19307 (Reactome)
Integrin alpha1beta1			REACT_19139 (Reactome)
LARG and PDZ-RhoGEF			REACT_19153 (Reactome)
	LIM Kinases, phosphorylated	Arrow	REACT_19282 (Reactome)
LIM Kinases			REACT_19282 (Reactome)
LIMK1			REACT_19221 (Reactome)
	NRP1:PlexinA1-4:FARP2:FYN	Arrow	REACT_19128 (Reactome)
NRP1:PlexinA1-4:FARP2:FYN			REACT_19173 (Reactome)
NRP1:PlexinA1-4:FYN			REACT_19368 (Reactome)
NRP1			REACT_19128 (Reactome)
PAK homodimer			REACT_19269 (Reactome)
	PAK	Arrow	REACT_19269 (Reactome)
PIP5K1gamma:Talin-1			REACT_19403 (Reactome)
PLXNA1:TREM2:DAP12			REACT_19177 (Reactome)
PLXNA2,PLXNA4			REACT_19345 (Reactome)
PLXNB3			REACT_19322 (Reactome)
PLXNC1			REACT_19190 (Reactome)
PLXND1			REACT_19273 (Reactome)
PLXND1			REACT_19408 (Reactome)
PTPRC			REACT_19295 (Reactome)
	Phospho-activated smooth muscle/non-muscle myosin 2	Arrow	REACT_19191 (Reactome)
	Pi	Arrow	REACT_19117 (Reactome)
	Pi	Arrow	REACT_19120 (Reactome)
	Pi	Arrow	REACT_19242 (Reactome)
Plexin-A1-4:FYN			REACT_19128 (Reactome)
Plexin-B1:ErbB2			REACT_19381 (Reactome)
Plexin-B1:ErbB2		mim-catalysis	REACT_19381 (Reactome)
Plexin-B1:Met			REACT_19398 (Reactome)
Plexin-B1:Met		mim-catalysis	REACT_19398 (Reactome)
	R-Ras-GDP	Arrow	REACT_19117 (Reactome)
	R-Ras-GDP	Arrow	REACT_19120 (Reactome)
R-Ras-GTP			REACT_19117 (Reactome)
R-Ras-GTP			REACT_19120 (Reactome)
RAC1-GDP			REACT_19363 (Reactome)
	RAC1-GTP	Arrow	REACT_19363 (Reactome)
RAC1-GTP			REACT_19160 (Reactome)
RAC1-GTP			REACT_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.
ROCK			REACT_19389 (Reactome)
	RhoA (Mg cofactor):GDP	Arrow	REACT_19242 (Reactome)
RhoA (Mg cofactor):GTP			REACT_19242 (Reactome)
RhoA,B,C:GDP			REACT_19137 (Reactome)
	RhoA/B/C:GTP	Arrow	REACT_19137 (Reactome)
RhoA/B/C:GTP			REACT_19389 (Reactome)
Rnd1-GTP			REACT_19337 (Reactome)
Rnd1-GTP			REACT_19382 (Reactome)
	SEMA3A:PLXND1	Arrow	REACT_19273 (Reactome)
SEMA3E			REACT_19273 (Reactome)
	SEMA4A:PLXND1	Arrow	REACT_19408 (Reactome)
SEMA4A			REACT_19408 (Reactome)
SEMA4D dimer			REACT_19381 (Reactome)
SEMA4D dimer			REACT_19398 (Reactome)
	SEMA4D:CD72	Arrow	REACT_19336 (Reactome)
	SEMA4D:PTPRC	Arrow	REACT_19295 (Reactome)
	SEMA4D:pPlexin-B1:ErbB2 complex	Arrow	REACT_19381 (Reactome)
SEMA4D			REACT_19295 (Reactome)
SEMA4D			REACT_19336 (Reactome)
	SEMA5A:PLXNB3	Arrow	REACT_19322 (Reactome)
SEMA5A			REACT_19322 (Reactome)
	SEMA6A:PLXNA2,PLXNA4	Arrow	REACT_19345 (Reactome)
SEMA6A			REACT_19345 (Reactome)
	SEMA6D:PLXNA1:TREM2:DAP12	Arrow	REACT_19177 (Reactome)
SEMA6D			REACT_19177 (Reactome)
	SEMA7A:Integrin alpha1beta1	Arrow	REACT_19139 (Reactome)
	SEMA7A:PLXNC1	Arrow	REACT_19190 (Reactome)
SEMA7A			REACT_19139 (Reactome)
SEMA7A			REACT_19190 (Reactome)
Sema3A dimer			REACT_19173 (Reactome)
Sema3A dimer			REACT_19368 (Reactome)
	Sema3A:NP-1:Plexin-A:Fes:CRMP	Arrow	REACT_19161 (Reactome)
	Sema3A:NRP-1:pPlexin-A:Fyn:Fes	Arrow	REACT_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-catalysis	REACT_19161 (Reactome)
Sema3A:NRP-1:pPlexin-A:Fyn:Fes		mim-catalysis	REACT_19420 (Reactome)
	Sema3A:Nrp-1:Plexin A:Fyn	Arrow	REACT_19173 (Reactome)
Sema3A:Nrp-1:Plexin A:Fyn			REACT_19420 (Reactome)
	Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP's	Arrow	REACT_19285 (Reactome)
	Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP's	Arrow	REACT_19321 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP's			REACT_19321 (Reactome)
	Sema3A:Nrp-1:PlexinA:Fyn:pCdk5	Arrow	REACT_19393 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5			REACT_19285 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn:pCdk5		mim-catalysis	REACT_19285 (Reactome)
	Sema3A:Nrp-1:PlexinA:Fyn	Arrow	REACT_19368 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn			REACT_19393 (Reactome)
Sema3A:Nrp-1:PlexinA:Fyn		mim-catalysis	REACT_19393 (Reactome)
	Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK	Arrow	REACT_19269 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK			REACT_19197 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:PAK		mim-catalysis	REACT_19197 (Reactome)
	Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAK	Arrow	REACT_19197 (Reactome)
Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAK		mim-catalysis	REACT_19221 (Reactome)
	Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1	Arrow	REACT_19337 (Reactome)
Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1		mim-catalysis	REACT_19117 (Reactome)
	Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP	Arrow	REACT_19160 (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)
	Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEF	Arrow	REACT_19153 (Reactome)
Sema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEF		mim-catalysis	REACT_19137 (Reactome)
	Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1	Arrow	REACT_19356 (Reactome)
Sema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1		mim-catalysis	REACT_19242 (Reactome)
Sema4D:pPlexin-B1:ErbB2:Rac1:Rnd1			REACT_19153 (Reactome)
	Sema4D:pPlexin-B1:Met:RAC1-GTP	Arrow	REACT_19354 (Reactome)
	Sema4D:pPlexin-B1:Met:Rnd1	Arrow	REACT_19382 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1			REACT_19356 (Reactome)
Sema4D:pPlexin-B1:Met:Rnd1		mim-catalysis	REACT_19120 (Reactome)
	Sema4D:pPlexin-B1:Met	Arrow	REACT_19398 (Reactome)
Sema4D:pPlexin-B1:Met			REACT_19354 (Reactome)
Sema4D:pPlexin-B1:Met			REACT_19382 (Reactome)
Smooth muscle/non-muscle myosin II			REACT_19191 (Reactome)
	TLN1	Arrow	REACT_19403 (Reactome)
	p-T508-LIMK1	Arrow	REACT_19221 (Reactome)
p-T508-LIMK1			REACT_19307 (Reactome)
	pCofilin: Active LIMK-1	Arrow	REACT_19276 (Reactome)
	pLIMK dimer:HSP-90	Arrow	REACT_19307 (Reactome)
pLIMK dimer:HSP-90			REACT_19168 (Reactome)
pLIMK dimer:HSP-90		mim-catalysis	REACT_19168 (Reactome)