Rap1 signaling pathway - Homo sapiens (human)
Rap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an active GTP-bound conformation. A variety of extracellular signals control this cycle through the regulation of several unique guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Rap1 plays a dominant role in the control of cell-cell and cell-matrix interactions by regulating the function of integrins and other adhesion molecules in various cell types. Rap1 also regulates MAP kinase (MAPK) activity in a manner highly dependent on the context of cell types.
Environmental Information Processing; Signal transduction
Pathway map Ortholog table
D10190 Tivozanib hydrochloride (USAN)
D10392 Lifitegrast sodium (USAN)
D10465 Golvatinib tartrate (USAN)
D12369 Etrumadenant (USAN/INN)
Homo sapiens (human) [GN:
5906 RAP1A; RAP1A, member of RAS oncogene family [KO: K04353]
5908 RAP1B; RAP1B, member of RAS oncogene family [KO: K07836]
9771 RAPGEF5; Rap guanine nucleotide exchange factor 5 [KO: K08019]
9732 DOCK4; dedicator of cytokinesis 4 [KO: K17697]
2902 GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO: K05208]
2903 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO: K05209]
2904 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO: K05210]
2149 F2R; coagulation factor II thrombin receptor [KO: K03914]
9002 F2RL3; F2R like thrombin or trypsin receptor 3 [KO: K04236]
1902 LPAR1; lysophosphatidic acid receptor 1 [KO: K04289]
9170 LPAR2; lysophosphatidic acid receptor 2 [KO: K04291]
23566 LPAR3; lysophosphatidic acid receptor 3 [KO: K04294]
2846 LPAR4; lysophosphatidic acid receptor 4 [KO: K04275]
57121 LPAR5; lysophosphatidic acid receptor 5 [KO: K08390]
135 ADORA2A; adenosine A2a receptor [KO: K04266]
136 ADORA2B; adenosine A2b receptor [KO: K04267]
10411 RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO: K08014]
11069 RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO: K04351]
25780 RASGRP3; RAS guanyl releasing protein 3 [KO: K12362]
10235 RASGRP2; RAS guanyl releasing protein 2 [KO: K12361]
8822 FGF17; fibroblast growth factor 17 [KO: K04358]
2255 FGF10; fibroblast growth factor 10 [KO: K04358]
8823 FGF16; fibroblast growth factor 16 [KO: K04358]
8817 FGF18; fibroblast growth factor 18 [KO: K04358]
9965 FGF19; fibroblast growth factor 19 [KO: K22603]
8074 FGF23; fibroblast growth factor 23 [KO: K22428]
3479 IGF1; insulin like growth factor 1 [KO: K05459]
5154 PDGFA; platelet derived growth factor subunit A [KO: K04359]
5155 PDGFB; platelet derived growth factor subunit B [KO: K17386]
56034 PDGFC; platelet derived growth factor C [KO: K05450]
80310 PDGFD; platelet derived growth factor D [KO: K05450]
1435 CSF1; colony stimulating factor 1 [KO: K05453]
7422 VEGFA; vascular endothelial growth factor A [KO: K05448]
7423 VEGFB; vascular endothelial growth factor B [KO: K16858]
7424 VEGFC; vascular endothelial growth factor C [KO: K05449]
2277 VEGFD; vascular endothelial growth factor D [KO: K05449]
4804 NGFR; nerve growth factor receptor [KO: K02583]
1398 CRK; CRK proto-oncogene, adaptor protein [KO: K04438]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO: K04438]
2889 RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO: K06277]
9564 BCAR1; BCAR1 scaffold protein, Cas family member [KO: K05726]
9223 MAGI1; membrane associated guanylate kinase, WW and PDZ domain containing 1 [KO: K05631]
9863 MAGI2; membrane associated guanylate kinase, WW and PDZ domain containing 2 [KO: K05629]
260425 MAGI3; membrane associated guanylate kinase, WW and PDZ domain containing 3 [KO: K06112]
9693 RAPGEF2; Rap guanine nucleotide exchange factor 2 [KO: K08018]
51735 RAPGEF6; Rap guanine nucleotide exchange factor 6 [KO: K08020]
27040 LAT; linker for activation of T cells [KO: K07362]
3937 LCP2; lymphocyte cytosolic protein 2 [KO: K07361]
8631 SKAP1; src kinase associated phosphoprotein 1 [KO: K17699]
2770 GNAI1; G protein subunit alpha i1 [KO: K04630]
2773 GNAI3; G protein subunit alpha i3 [KO: K04630]
2771 GNAI2; G protein subunit alpha i2 [KO: K04630]
2775 GNAO1; G protein subunit alpha o1 [KO: K04534]
5909 RAP1GAP; RAP1 GTPase activating protein [KO: K17700]
26037 SIPA1L1; signal induced proliferation associated 1 like 1 [KO: K17701]
6494 SIPA1; signal-induced proliferation-associated 1 [KO: K08013]
57568 SIPA1L2; signal induced proliferation associated 1 like 2 [KO: K17702]
23094 SIPA1L3; signal induced proliferation associated 1 like 3 [KO: K17703]
5900 RALGDS; ral guanine nucleotide dissociation stimulator [KO: K08732]
54518 APBB1IP; amyloid beta precursor protein binding family B member 1 interacting protein [KO: K17704]
3674 ITGA2B; integrin subunit alpha 2b [KO: K06476]
7408 VASP; vasodilator stimulated phosphoprotein [KO: K06274]
64411 ARAP3; ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3 [KO: K12490]
387 RHOA; ras homolog family member A [KO: K04513]
9855 FARP2; FERM, ARH/RhoGEF and pleckstrin domain protein 2 [KO: K06082]
998 CDC42; cell division cycle 42 [KO: K04393]
10451 VAV3; vav guanine nucleotide exchange factor 3 [KO: K05730]
7409 VAV1; vav guanine nucleotide exchange factor 1 [KO: K05730]
7410 VAV2; vav guanine nucleotide exchange factor 2 [KO: K05730]
7074 TIAM1; TIAM Rac1 associated GEF 1 [KO: K05731]
56288 PARD3; par-3 family cell polarity regulator [KO: K04237]
50855 PARD6A; par-6 family cell polarity regulator alpha [KO: K06093]
84552 PARD6G; par-6 family cell polarity regulator gamma [KO: K06093]
84612 PARD6B; par-6 family cell polarity regulator beta [KO: K06093]
4301 AFDN; afadin, adherens junction formation factor [KO: K05702]
889 KRIT1; KRIT1 ankyrin repeat containing [KO: K17705]
10636 RGS14; regulator of G protein signaling 14 [KO: K17706]
83593 RASSF5; Ras association domain family member 5 [KO: K08015]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO: K00922] [EC: 184.108.40.206]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 220.127.116.11]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 18.104.22.168]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO: K02649]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO: K02649]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO: K02649]
3265 HRAS; HRas proto-oncogene, GTPase [KO: K02833]
3845 KRAS; KRAS proto-oncogene, GTPase [KO: K07827]
4893 NRAS; NRAS proto-oncogene, GTPase [KO: K07828]
Kooistra MR, Dube N, Bos JL
Rap1: a key regulator in cell-cell junction formation.
Bos JL, de Rooij J, Reedquist KA
Rap1 signalling: adhering to new models.
Minato N, Kometani K, Hattori M
Regulation of immune responses and hematopoiesis by the Rap1 signal.
Linking Rap to cell adhesion.
Cellular functions of the Rap1 GTP-binding protein: a pattern emerges.
Zwartkruis FJ, Bos JL
Ras and Rap1: two highly related small GTPases with distinct function.
Hattori M, Minato N
Rap1 GTPase: functions, regulation, and malignancy.
Pannekoek WJ, Kooistra MR, Zwartkruis FJ, Bos JL
Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors.
Boettner B, Van Aelst L
Control of cell adhesion dynamics by Rap1 signaling.
Xia Z, Storm DR.
The role of calmodulin as a signal integrator for synaptic plasticity.
Mor A, Dustin ML, Philips MR
Small GTPases and LFA-1 reciprocally modulate adhesion and signaling.
Burbach BJ, Medeiros RB, Mueller KL, Shimizu Y
T-cell receptor signaling to integrins.
Does Rap1 deserve a bad Rap?
Banihashemi B, Albert PR
Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements.
Banno A, Ginsberg MH
Doebele RC, Schulze-Hoepfner FT, Hong J, Chlenski A, Zeitlin BD, Goel K, Gomes S, Liu Y, Abe MK, Nor JE, Lingen MW, Rosner MR
A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis.
Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F
Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications.
hsa04660 T cell receptor signaling pathway
hsa04810 Regulation of actin cytoskeleton