Semaphorin interactions (Homo sapiens)

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1-517, 1815, 164933-3542, 431130, 317-101930-322533, 38, 3926, 2747, 4812, 134621-246, 145040, 41446, 791920, 2128, 297, 9, 1033, 36, 3745cytosolextracellular regioncytosolOrthophosphateSema5A:Plexin-B3Sema4D:pPlexin-B1:Met:RAC1-GTPSema3A:Nrp-1:PlexinA:FynATPADPSema4D:pPlexin-B1:Met:Rnd1FARP2:PIP5KIgammaATPLARG and PDZ-RhoGEFPlexin D1 precursorSema3A dimerSema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sIntegrin alpha1beta1GTPSEMA4D:pPlexin-B1:ErbB2 complexSema4A:Plexin-D1pLIMK dimer:HSP-90SEMA4D:CD45 complexPhospho-activated smooth muscle/non-muscle myosin 2Sema4D:pPlexin-B1:MetRhoA,B,C:GDPSEMA4D dimerSema6A:Plexin-A (2and 4)ATPATPLIM Kinases, phosphorylatedPlexin-A (2 and 4)ROCKSema7A:Integrin alpha1beta1Active LIMK1SEMA7AADPActivated ROCK:RhoA/B/C:GTPRAC1-GTPATPSema3A:Nrp-1:PlexinA:Fyn:pCdk5pLIMK-1 (T508)RhoA (Mg cofactor):GTPATPADPSemaphorin 4A precursorGRLF1/p190-A variant 1Semaphorin-6ALeukocyte common antigen precursorSemaphorin 4DSema4D:pPlexin-B1:ErbB2:Rac1:Rnd1LIM KinasesRAC1-GTPNrp-1 complexed with PlexinA:FARP2:FynPlexin-B1:ErbB2ADPPAKNrp-1 complexed with PlexinA:FynSema3A:Nrp-1:PlexinA:Rac1-GTP:PAKNeuropilin-1ATPADPATPTalin-1OrthophosphatePlexin-A1-Trem2-DAP12Sema3A:NRP-1:pPlexin-A:Fyn:FesATPATPADPCD72Cofilin-1Sema3A:Nrp-1:PlexinA:Fyn:Cdk5:pCRMP'sGDPR-Ras-GDPSema4D:Plexin-B1:Rac-Rnd1:LARG/PDZ-RhoGEFSemaphorin-6DCRMP's tetramersSemaphorin 3E precursorLIM domain kinase 1 (LIMK-1)Sema3A:Nrp-1:PlexinA:Rac1-GTP:pPAKPlexin-A:FynPlexin D1 precursorRhoA (Mg cofactor):GDPATPGDPADPHSP-90Sema3E bound to Plexin D1 receptorADPR-Ras-GTPADPpCofilin: Active LIMK-1ATPPIP5K1gamma:Talin-1Plexin-B3ADPRnd1-GTPSema3A:Nrp-1:Plexin A:FynADPR-Ras-GDPADPPlexin-C1GTPPlexin-A1:Sema6D:Trem2:DAP12RhoA/B/C:GTPFARP2Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTP:Rnd1Sema3A:Nrp-1:pPlexinA:Fyn:Fes:Rac-1-GTPSema4D:Plexin-B1:p190RhoGAP:Rac:Rnd1R-Ras-GTPPlexin-B1:MetSEMA4D:CD72 complexFESSema3A:NP-1:Plexin-A:Fes:CRMPCdk5:p35RAC1-GDPPAK homodimerGSK3B_1ATPSema7A:Plexin-C1Smooth muscle/non-muscle myosin IIRnd1-GTPADPSEMA5AOrthophosphate


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.

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Quality Tags

Ontology Terms

 

Bibliography

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  15. Swiercz JM, Worzfeld T, Offermanns S.; ''ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.''; PubMed Europe PMC Scholia
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  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
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  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
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  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
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  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
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  36. Bernard O.; ''Lim kinases, regulators of actin dynamics.''; PubMed Europe PMC Scholia
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  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
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  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

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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
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Activated ROCK:

RhoA/B/C:GTP

ComplexREACT_19928 (Reactome)
Active LIMK1 ComplexREACT_19790 (Reactome)
CD72 ProteinP21854 (UniProt)
CRMP's tetramers ComplexREACT_19835 (Reactome)
Cdk5:p35 ComplexREACT_19863 (Reactome)
Cofilin-1 ProteinP23528 (UniProt)
FARP2 ProteinO94887 (UniProt)
FARP2:PIP5KIgamma ComplexREACT_19748 (Reactome)
FES ProteinP07332 (UniProt)
GDP Metabolite17552 (ChEBI)
GRLF1/p190-A

variant 1

ProteinQ9NRY4 (UniProt)
GSK3B_1 ProteinP49841-1 (UniProt)
GTP Metabolite15996 (ChEBI)
HSP-90 ProteinREACT_19960 (Reactome)
Integrin alpha1beta1 ComplexREACT_14015 (Reactome)
LARG and PDZ-

RhoGEF

ProteinREACT_20012 (Reactome)
LIM Kinases ProteinREACT_20207 (Reactome)
LIM Kinases,

phosphorylated

ProteinREACT_19576 (Reactome)
LIM domain kinase 1

(LIMK-1)

ProteinP53667 (UniProt)
Leukocyte common

antigen precursor

ProteinP08575 (UniProt)
Neuropilin-1 ProteinO14786-1 (UniProt)
Nrp-1 complexed

with PlexinA:FARP2: Fyn

ComplexREACT_20390 (Reactome)
Nrp-1 complexed

with PlexinA:Fyn

ComplexREACT_20319 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAK ProteinREACT_19640 (Reactome)
PAK homodimer ComplexREACT_19479 (Reactome)
PIP5K1gamma:

Talin-1

ComplexREACT_19891 (Reactome)
Phospho-activated

smooth muscle/non- muscle myosin 2

ComplexREACT_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.
Plexin D1 precursor ProteinQ9Y4D7 (UniProt)
Plexin-A (2 and 4) ProteinREACT_20091 (Reactome)
Plexin-A1-Trem2-

DAP12

ComplexREACT_20126 (Reactome)
Plexin-A1:Sema6D:

Trem2:DAP12

ComplexREACT_19554 (Reactome)
Plexin-A:Fyn ComplexREACT_19507 (Reactome)
Plexin-B1:ErbB2 ComplexREACT_19954 (Reactome)
Plexin-B1:Met ComplexREACT_19866 (Reactome)
Plexin-B3 ProteinQ9ULL4 (UniProt)
Plexin-C1 ProteinO60486 (UniProt)
R-Ras-GDP ComplexREACT_20329 (Reactome)
R-Ras-GTP ComplexREACT_20411 (Reactome)
RAC1-GDP ComplexREACT_22018 (Reactome)
RAC1-GTP ComplexREACT_21594 (Reactome)
ROCK ProteinREACT_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.
RhoA (Mg cofactor):

GDP

ComplexREACT_13852 (Reactome)
RhoA (Mg cofactor):

GTP

ComplexREACT_14306 (Reactome)
RhoA,B,C:GDP ComplexREACT_20118 (Reactome)
RhoA/B/C:GTP ComplexREACT_19589 (Reactome)
Rnd1-GTP ComplexREACT_20300 (Reactome)
SEMA4D dimer ComplexREACT_19817 (Reactome)
SEMA4D:CD45

complex

ComplexREACT_19862 (Reactome)
SEMA4D:CD72

complex

ComplexREACT_20194 (Reactome)
SEMA4D:pPlexin-B1:

ErbB2 complex

ComplexREACT_20256 (Reactome)
SEMA5A ProteinQ13591 (UniProt)
SEMA7A ProteinO75326 (UniProt)
Sema3A dimer ComplexREACT_19939 (Reactome)
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

ComplexREACT_20413 (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: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

ComplexREACT_20187 (Reactome)
Sema3A:Nrp-1:

pPlexinA:Fyn:Fes: Rac-1-GTP:Rnd1

ComplexREACT_19802 (Reactome)
Sema3E bound to

Plexin D1 receptor

ComplexREACT_20367 (Reactome)
Sema4A:Plexin-D1 ComplexREACT_19803 (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

ComplexREACT_19905 (Reactome)
Sema4D:pPlexin-B1:

Met:RAC1-GTP

ComplexREACT_20028 (Reactome)
Sema4D:pPlexin-B1:

Met:Rnd1

ComplexREACT_19721 (Reactome)
Sema5A:Plexin-B3 ComplexREACT_19434 (Reactome)
Sema6A:Plexin-A

(2and 4)

ComplexREACT_19923 (Reactome)
Sema7A:Integrin

alpha1beta1

ComplexREACT_20443 (Reactome)
Sema7A:Plexin-C1 ComplexREACT_20419 (Reactome)
Semaphorin 3E

precursor

ProteinO15041 (UniProt)
Semaphorin 4A

precursor

ProteinQ9H3S1 (UniProt)
Semaphorin 4D ProteinQ92854 (UniProt)
Semaphorin-6A ProteinQ9H2E6 (UniProt)
Semaphorin-6D ProteinQ8NFY4 (UniProt)
Smooth muscle/non-

muscle myosin II

ComplexREACT_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.
Talin-1 ProteinQ9Y490 (UniProt)
pCofilin: Active

LIMK-1

ComplexREACT_20103 (Reactome)
pLIMK dimer:HSP-90 ComplexREACT_19543 (Reactome)
pLIMK-1 (T508) ProteinP53667 (UniProt)

Annotated Interactions

No annotated interactions

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