RAP2B_HUMAN
ID RAP2B_HUMAN Reviewed; 183 AA.
AC P61225; P17964; Q96EG5; Q9CXG0;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Ras-related protein Rap-2b;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P10114};
DE Flags: Precursor;
GN Name=RAP2B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Platelet;
RX PubMed=2115998; DOI=10.1093/nar/18.14.4281;
RA Farrell F.X., Ohmstede C.A., Reep B.R., Lapetina E.G.;
RT "cDNA sequence of a new ras-related gene (rap2b) isolated from human
RT platelets with sequence homology to rap2.";
RL Nucleic Acids Res. 18:4281-4281(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Platelet;
RX PubMed=2118648; DOI=10.1073/pnas.87.17.6527;
RA Ohmstede C.A., Farrell F.X., Reep B.R., Clemetson K.J., Lapetina E.G.;
RT "RAP2B: a RAS-related GTP-binding protein from platelets.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:6527-6531(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP ISOPRENYLATION AT CYS-180, AND METHYLATION AT CYS-180.
RX PubMed=8424780; DOI=10.1042/bj2890349;
RA Farrell F.X., Yamamoto K., Lapetina E.G.;
RT "Prenyl group identification of rap2 proteins: a ras superfamily member
RT other than ras that is farnesylated.";
RL Biochem. J. 289:349-355(1993).
RN [6]
RP FUNCTION.
RX PubMed=11877431; DOI=10.1074/jbc.m112024200;
RA Evellin S., Nolte J., Tysack K., vom Dorp F., Thiel M., Weernink P.A.O.,
RA Jakobs K.H., Webb E.J., Lomasney J.W., Schmidt M.;
RT "Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine
RT receptor mediated by cyclic AMP and the GTPase Rap2B.";
RL J. Biol. Chem. 277:16805-16813(2002).
RN [7]
RP INTERACTION WITH PLCE1.
RX PubMed=12444546; DOI=10.1038/sj.onc.1206003;
RA Song C., Satoh T., Edamatsu H., Wu D., Tadano M., Gao X., Kataoka T.;
RT "Differential roles of Ras and Rap1 in growth factor-dependent activation
RT of phospholipase C epsilon.";
RL Oncogene 21:8105-8113(2002).
RN [8]
RP FUNCTION.
RX PubMed=15143162; DOI=10.1128/mcb.24.11.4664-4676.2004;
RA Stope M.B., Vom Dorp F., Szatkowski D., Boehm A., Keiper M., Nolte J.,
RA Oude Weernink P.A., Rosskopf D., Evellin S., Jakobs K.H., Schmidt M.;
RT "Rap2B-dependent stimulation of phospholipase C-epsilon by epidermal growth
RT factor receptor mediated by c-Src phosphorylation of RasGRP3.";
RL Mol. Cell. Biol. 24:4664-4676(2004).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16540189; DOI=10.1016/j.bbamcr.2006.02.001;
RA Greco F., Ciana A., Pietra D., Balduini C., Minetti G., Torti M.;
RT "Rap2, but not Rap1 GTPase is expressed in human red blood cells and is
RT involved in vesiculation.";
RL Biochim. Biophys. Acta 1763:330-335(2006).
RN [10]
RP INTERACTION WITH SGSM1; SGSM2 AND SGSM3.
RX PubMed=17509819; DOI=10.1016/j.ygeno.2007.03.013;
RA Yang H., Sasaki T., Minoshima S., Shimizu N.;
RT "Identification of three novel proteins (SGSM1, 2, 3) which modulate small
RT G protein (RAP and RAB)-mediated signaling pathway.";
RL Genomics 90:249-260(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Small GTP-binding protein which cycles between a GDP-bound
CC inactive and a GTP-bound active form. Involved in EGFR and CHRM3
CC signaling pathways through stimulation of PLCE1. May play a role in
CC cytoskeletal rearrangements and regulate cell spreading through
CC activation of the effector TNIK. May regulate membrane vesiculation in
CC red blood cells. {ECO:0000269|PubMed:11877431,
CC ECO:0000269|PubMed:15143162, ECO:0000269|PubMed:16540189}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P10114};
CC -!- SUBUNIT: Interacts with PLCE1. Interacts with SGSM1, SGSM2 and SGSM3.
CC The GTP-bound form of RAP2B interacts with RUNDC3A (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P61225; Q13554: CAMK2B; NbExp=3; IntAct=EBI-750871, EBI-1058722;
CC P61225; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-750871, EBI-11523526;
CC P61225; P52306-5: RAP1GDS1; NbExp=3; IntAct=EBI-750871, EBI-12832744;
CC P61225; Q8WWW0: RASSF5; NbExp=3; IntAct=EBI-750871, EBI-367390;
CC P61225; Q59EK9: RUNDC3A; NbExp=4; IntAct=EBI-750871, EBI-747225;
CC P61225; Q59EK9-3: RUNDC3A; NbExp=3; IntAct=EBI-750871, EBI-11957366;
CC -!- SUBCELLULAR LOCATION: Recycling endosome membrane
CC {ECO:0000269|PubMed:16540189}; Lipid-anchor
CC {ECO:0000269|PubMed:16540189}; Cytoplasmic side
CC {ECO:0000269|PubMed:16540189}. Note=Associated with red blood cells-
CC released vesicles.
CC -!- TISSUE SPECIFICITY: Expressed in red blood cells (at protein level).
CC {ECO:0000269|PubMed:16540189}.
CC -!- DOMAIN: The effector domain mediates the interaction with RUNDC3A.
CC {ECO:0000250}.
CC -!- PTM: Palmitoylated. Unlike RAP2A and RAP2C, palmitoylation of RAP2B is
CC not required for association with recycling endosome membranes and
CC activation of TNIK. {ECO:0000250|UniProtKB:P61226}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RAP2BID275.html";
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DR EMBL; X52987; CAA37178.1; -; mRNA.
DR EMBL; AF493915; AAM12629.1; -; mRNA.
DR EMBL; BC012362; AAH12362.1; -; mRNA.
DR CCDS; CCDS3170.1; -.
DR PIR; A33121; TVHUR2.
DR RefSeq; NP_002877.2; NM_002886.3.
DR PDB; 1N4P; X-ray; 2.65 A; M/N=180-183.
DR PDB; 1N4Q; X-ray; 2.40 A; M/N/O/P/Q/R=180-183.
DR PDB; 1N4R; X-ray; 2.80 A; M/N/O/P/Q/R=180-183.
DR PDBsum; 1N4P; -.
DR PDBsum; 1N4Q; -.
DR PDBsum; 1N4R; -.
DR AlphaFoldDB; P61225; -.
DR SMR; P61225; -.
DR BioGRID; 111847; 33.
DR IntAct; P61225; 9.
DR STRING; 9606.ENSP00000319096; -.
DR iPTMnet; P61225; -.
DR MetOSite; P61225; -.
DR PhosphoSitePlus; P61225; -.
DR SwissPalm; P61225; -.
DR BioMuta; RAP2B; -.
DR DMDM; 47117762; -.
DR EPD; P61225; -.
DR jPOST; P61225; -.
DR MassIVE; P61225; -.
DR MaxQB; P61225; -.
DR PaxDb; P61225; -.
DR PeptideAtlas; P61225; -.
DR PRIDE; P61225; -.
DR ProteomicsDB; 57278; -.
DR Antibodypedia; 33622; 273 antibodies from 28 providers.
DR DNASU; 5912; -.
DR Ensembl; ENST00000323534.5; ENSP00000319096.2; ENSG00000181467.5.
DR GeneID; 5912; -.
DR KEGG; hsa:5912; -.
DR MANE-Select; ENST00000323534.5; ENSP00000319096.2; NM_002886.4; NP_002877.2.
DR UCSC; uc003ezr.5; human.
DR CTD; 5912; -.
DR DisGeNET; 5912; -.
DR GeneCards; RAP2B; -.
DR HGNC; HGNC:9862; RAP2B.
DR HPA; ENSG00000181467; Low tissue specificity.
DR MIM; 179541; gene.
DR neXtProt; NX_P61225; -.
DR OpenTargets; ENSG00000181467; -.
DR PharmGKB; PA34223; -.
DR VEuPathDB; HostDB:ENSG00000181467; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000160283; -.
DR HOGENOM; CLU_041217_9_8_1; -.
DR InParanoid; P61225; -.
DR OMA; IEDCFRT; -.
DR OrthoDB; 1353024at2759; -.
DR PhylomeDB; P61225; -.
DR TreeFam; TF313014; -.
DR PathwayCommons; P61225; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P61225; -.
DR BioGRID-ORCS; 5912; 18 hits in 1078 CRISPR screens.
DR ChiTaRS; RAP2B; human.
DR GeneWiki; RAP2B; -.
DR GenomeRNAi; 5912; -.
DR Pharos; P61225; Tbio.
DR PRO; PR:P61225; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P61225; protein.
DR Bgee; ENSG00000181467; Expressed in esophagus squamous epithelium and 200 other tissues.
DR Genevisible; P61225; HS.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0044291; C:cell-cell contact zone; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IMP:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IBA:GO_Central.
DR GO; GO:0030168; P:platelet activation; IDA:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IDA:UniProtKB.
DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0032486; P:Rap protein signal transduction; ISS:UniProtKB.
DR GO; GO:0061097; P:regulation of protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd04176; Rap2; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041840; Rap2.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR020849; Small_GTPase_Ras-type.
DR PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endosome; GTP-binding; Hydrolase; Lipoprotein; Membrane;
KW Methylation; Nucleotide-binding; Palmitate; Prenylation;
KW Reference proteome.
FT CHAIN 1..180
FT /note="Ras-related protein Rap-2b"
FT /id="PRO_0000030215"
FT PROPEP 181..183
FT /note="Removed in mature form"
FT /evidence="ECO:0000305|PubMed:8424780"
FT /id="PRO_0000030216"
FT MOTIF 32..40
FT /note="Effector region"
FT /evidence="ECO:0000305"
FT BINDING 10..17
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 57..61
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 180
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305|PubMed:8424780"
FT LIPID 176
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61226"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P61226"
FT LIPID 180
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000269|PubMed:8424780"
FT CONFLICT 170
FT /note="P -> S (in Ref. 1; CAA37178 and 2; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 183 AA; 20504 MW; A1139C2D5E7F5865 CRC64;
MREYKVVVLG SGGVGKSALT VQFVTGSFIE KYDPTIEDFY RKEIEVDSSP SVLEILDTAG
TEQFASMRDL YIKNGQGFIL VYSLVNQQSF QDIKPMRDQI IRVKRYERVP MILVGNKVDL
EGEREVSYGE GKALAEEWSC PFMETSAKNK ASVDELFAEI VRQMNYAAQP NGDEGCCSAC
VIL
