Entry
Name
Rap1 signaling pathway - Homo sapiens (human)
Description
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.
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
Ortholog table
Drug
D10190 Tivozanib hydrochloride (USAN)
D10392 Lifitegrast sodium (USAN)
D10465 Golvatinib tartrate (USAN)
D12369 Etrumadenant (USAN/INN)
D12635 Sozinibercept (USAN/INN)
D12733 Dordaviprone (USAN/INN)
D12734 Dordaviprone hydrochloride (JAN/USAN)
D12809 Bafisontamab (USAN/INN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
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:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
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 ]
Compound
Reference
Authors
Kooistra MR, Dube N, Bos JL
Title
Rap1: a key regulator in cell-cell junction formation.
Journal
Reference
Authors
Bos JL, de Rooij J, Reedquist KA
Title
Rap1 signalling: adhering to new models.
Journal
Reference
Authors
Minato N, Kometani K, Hattori M
Title
Regulation of immune responses and hematopoiesis by the Rap1 signal.
Journal
Reference
Authors
Bos JL
Title
Linking Rap to cell adhesion.
Journal
Reference
Authors
Caron E
Title
Cellular functions of the Rap1 GTP-binding protein: a pattern emerges.
Journal
Reference
Authors
Zwartkruis FJ, Bos JL
Title
Ras and Rap1: two highly related small GTPases with distinct function.
Journal
Reference
Authors
Hattori M, Minato N
Title
Rap1 GTPase: functions, regulation, and malignancy.
Journal
Reference
Authors
Pannekoek WJ, Kooistra MR, Zwartkruis FJ, Bos JL
Title
Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors.
Journal
Reference
Authors
Boettner B, Van Aelst L
Title
Control of cell adhesion dynamics by Rap1 signaling.
Journal
Reference
Authors
Xia Z, Storm DR.
Title
The role of calmodulin as a signal integrator for synaptic plasticity.
Journal
Reference
Authors
Mor A, Dustin ML, Philips MR
Title
Small GTPases and LFA-1 reciprocally modulate adhesion and signaling.
Journal
Reference
Authors
Burbach BJ, Medeiros RB, Mueller KL, Shimizu Y
Title
T-cell receptor signaling to integrins.
Journal
Reference
Authors
Stork PJ
Title
Does Rap1 deserve a bad Rap?
Journal
Reference
Authors
Banihashemi B, Albert PR
Title
Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements.
Journal
Reference
Authors
Banno A, Ginsberg MH
Title
Integrin activation.
Journal
Reference
Authors
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
Title
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.
Journal
Reference
Authors
Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F
Title
Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications.
Journal
Related pathway
hsa04660 T cell receptor signaling pathway
hsa04810 Regulation of actin cytoskeleton
KO pathway