Palmitoylation summaryValidated by 2 independant techniques or by a targeted study.
High confidence hit in 4 palmitoyl-proteome studies.
9/15human palmitoyl-proteome articles3orthologues in palmitoyl-proteomes0targeted study0orthologue in targeted studies0sitePredicted2cysteines in main isoform
Protein general information
UniProt names and subcellular location Protein identifiers Protein names Subcellular locations Ras-related protein Rap-2a
Source Identifiers UniProt gene names RAP2A IPI ID IPI00019346 Refseq protein ID NP_066361.1 Ensembl protein ENSP00000245304 Ensembl gene ENSG00000125249 UniProt AC P10114 UniProt ID RAP2A_HUMAN UniProt secondary AC B2RCJ1, Q5JSC1, Q5JSC2 Protein length Isoform 1 (main): 183 aa Known functions (from UniProt) Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading. Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B. Interacts (GTP-bound form) with RUNDC3A. Interacts with RGS14; the interaction is GTP-dependent (By similarity). Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound form preferentially) with TNIK (via the CNH domain); the interaction is direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts with MINK1. Interacts (GTP-bound form preferentially) with MAP4K4. Interacts with cytoskeletal actin. May also localize to the Golgi (PubMed:7962206) and the gelatinase-containing granules of neutrophils (PubMed:8391995). Colocalizes with RASGEF1B to midbody at telophase (PubMed:23894443). The effector domain mediates the interaction with RUNDC3A. Ubiquitinated; undergoes 'Lys-63' monoubiquitination and diubiquitination by NEDD4. Multiple lysine residues are probably modified. Ubiquitination requires TNIK, prevents interaction with effectors and inactivates RAP2A. Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK (By similarity). Belongs to the small GTPase superfamily. Ras family.
Cysteine summary and predictions
Pos in alignment 140 176 177 180 Topology U U U U Disulfide no no no no SS prediction C C C C SS UniProt NA NA NA NA Isoform 1
Topology U Undefined E Extracellular/Lumenal T Transmembrane C Cytosolic/Nuclear Prediction scores From top to bottom: Cysteine position, CSS-Palm 4.0 score, PalmPred score
Color code for cysteine position: Predicted (high confidence prediction with CSS-Palm or/and PalmPred) / Predicted but not validated (in terms of disulfide bond and cellular location) / Not predicted
Color code for CSS-Palm 4.0: High confidence, Medium confidence, Low confidence, Not predicted.
Color code for PalmPred: High confidence (score > 0.4), Medium confidence (0.1 > score > 0.4), Low confidence (score < 0.1), Not predicted.
Feature type Isoform 1 phosphorylation 11, 66 ubiquitination 5, 31
UniProt AC UniProt ID Orthology source Organism Gene names Description Isoforms # palmitome articles # targeted studies # of distinct techniques # of known sites Predicted Q80ZJ1 RAP2A_MOUSE OMA, Ensembl, InParanoid Mouse Rap2a Ras-related protein Rap-2a 2 5/8 0 3 0 Yes Q8BU31 RAP2C_MOUSE OrthoDB Mouse Rap2c Ras-related protein Rap-2c 1 6/8 0 3 0 Yes Q2MGM2 Q2MGM2_DROME MetaPhors Fruit fly Rap2l, CG3204, Dmel_CG3204 Ras-associated protein 2-like, isoform B 1 0/0 0 0 0 No Q9C820 RAG3D_ARATH MetaPhors Arabidopsis thaliana RABG3D, RAB72, At1g52280, F19K6.10 Ras-related protein RABG3d (AtRABG3d) (Ras-related protein Rab72) (AtRab72) 1 0/1 0 0 0 Yes Q38922 RAB1B_ARATH MetaPhors Arabidopsis thaliana RABB1B, GB2, RAB2C, At4g35860, F4B14.130 Ras-related protein RABB1b (AtRABB1b) (Ras-related protein GB2) (AtGB2) (Ras-related protein Rab2C) (AtRab2C) 3 0/1 0 0 0 Yes Q948K6 RABG1_ARATH MetaPhors Arabidopsis thaliana RABG1, RAB78, At5g39620, MIJ24.90 Ras-related protein RABG1 (AtRABG1) (Ras-related protein Rab78) (AtRab78) 1 1/1 0 1 0 Yes O23561 RAB1A_ARATH MetaPhors Arabidopsis thaliana RABB1A, RAB2B, At4g17160, dl4615c, FCAALL.364 Ras-related protein RABB1a (AtRABB1a) (Ras-related protein Rab2B) (AtRab2B) 1 0/1 0 0 0 Yes O49841 RAC2A_ARATH MetaPhors Arabidopsis thaliana RABC2A, RAB18B, At5g03530, F12E4.310 Ras-related protein RABC2a (AtRABC2a) (Ras-related protein Rab18B) (AtRab18B) 1 0/1 0 0 0 Yes B8JIV0 B8JIV0_DANRE MetaPhors Zebrafish rap2ab Uncharacterized protein 1 0/0 0 0 0 Yes Q78P65 Q78P65_RAT MetaPhors Rat Rap2a, rCG_36947 RCG36947 (Rap2A-like protein) 1 0/1 0 0 0 No D3ZK56 D3ZK56_RAT OrthoDB Rat Rap2c, rCG_53223 Protein Rap2c (RCG53223) 1 0/1 0 0 0 Yes J9P6K0 J9P6K0_CANLF OrthoDB, OMA, Ensembl Dog RAP2A Uncharacterized protein 1 0/0 0 0 0 Yes E1BNQ3 E1BNQ3_BOVIN OrthoDB, OMA, Ensembl Cow RAP2A Uncharacterized protein 1 0/0 0 0 0 Yes E7F144 E7F144_DANRE OrthoDB, OMA Zebrafish CABZ01067868.1, LOC100332969 Uncharacterized protein 1 0/0 0 0 0 Yes P04388 RAS2_DROME OrthoDB Fruit fly Ras64B, ras2, CG1167 Ras-like protein 2 1 0/0 0 0 0 Yes P08642 RASH_CHICK OrthoDB Chicken HRAS, HRAS1 GTPase HRas (H-Ras-1) (Transforming protein p21) (c-H-ras) (p21ras) [Cleaved into: GTPase HRas, N-terminally processed] 1 0/0 0 0 0 Yes Q2MJK3 RASN_PIG OrthoDB Pig NRAS GTPase NRas (Transforming protein N-Ras) 1 0/0 0 0 0 No P08646 RAS1_DROME OrthoDB Fruit fly Ras85D, Ras1, CG9375 Ras-like protein 1 (Dras1) (Dmras85D) 1 0/0 0 0 0 Yes O96692 O96692_DROME Ensembl, InParanoid Fruit fly Rap2l, CG3204, Dmel_CG3204 RE63021p (Ras-associated protein 2-like, isoform A) (Ras-related protein 2-like protein) 1 0/0 0 0 0 Yes
Biological process Cellular component Molecular function GO:2480272 Establishment of protein localization
GO:6000292 Establishment of epithelial cell apical/basal polarity
GO:6000277 Cellular response to drug
GO:2480266 Cellular protein localization
GO:2220553 Small gtpase mediated signal transduction
GO:2480232 Actin cytoskeleton reorganization
GO:6000272 Microvillus assembly
GO:6000287 Protein localization to plasma membrane
GO:2480285 Regulation of dendrite morphogenesis
GO:2480221 Negative regulation of cell migration
GO:3472766 Gtp catabolic process
GO:2480274 Regulation of jnk cascade
GO:2480264 Rap protein signal transduction
GO:6000270 Positive regulation of protein phosphorylation
GO:2480239 Positive regulation of protein autophosphorylation
GO:6000271 Plasma membrane
GO:6000281 Extracellular vesicular exosome
GO:2480307 Recycling endosome membrane
GO:2480301 Recycling endosome
GO:2480216 Protein binding
GO:2220534 Gtp binding
GO:2220525 Gtpase activity
Palmitoylation hits and sites
Hit ID Study # Reference Hit list Isoform # Sites (ID, position, characterisation techniques) SPalmH:17703 Study 8 List Isoform 1 None SPalmH:18057 Study 9 List Isoform 1 None SPalmH:19778 Study 11 List - None SPalmH:20966 Study 10 List - None SPalmH:1113 Study 4 HC - None SPalmH:1710 Study 1 HC - None SPalmH:2273 Study 2 List - None SPalmH:15829 Study 3 HC - None SPalmH:16898 Study 5 List - None SPalmH:12518 Study 6 List Isoform 1 None SPalmH:17464 Study 7 HC - None
Study # Reference Organism Cell type Subcellular location Technique(s) Palmitome study? Study 1 Yang W et al., 2010 Homo sapiens DU145 Total membrane ABE (Acyl-Biotin Exchange) Yes Study 2 Dowal L et al., 2011 Homo sapiens Platelet Total membrane ABE (Acyl-Biotin Exchange) Yes Study 3 Ivaldi C et al., 2012 Homo sapiens B-cell Total membrane ABE (Acyl-Biotin Exchange) Yes Study 4 Martin BR et al., 2009 Homo sapiens Jurkat Total membrane Labeling of substrate with 17-ODYA (17-octadecynoic acid) Yes Study 5 Wei X et al., 2014 Homo sapiens HUVEC Total cell lysate ABE (Acyl-Biotin Exchange) Yes Study 6 Morrison E et al., 2015 Homo sapiens Primary CD4 + T cells Total cell lysate In gel SILAC labelling with H2(18)O and H2(16)O, ABE (Acyl-Biotin Exchange) Yes Study 7 Yang W et al., 2010 Homo sapiens DU145 Non-lipid raft ABE (Acyl-Biotin Exchange) Yes Study 8 Peng T et al., 2015 Homo sapiens HEK293 Total cell lysate Labeling of substrate with alk16 Yes Study 9 Peng T et al., 2015 Homo sapiens HEK293 Total cell lysate Labeling of substrate with photo cleavable x-alk16 Yes Study 10 Pinner AL et al., 2016 Homo sapiens Brain Total cell lysate ABE (Acyl-Biotin Exchange) Yes Study 11 Hernandez JL et al., 2016 Homo sapiens MCF7 Total cell lysate Labeling of substrate with alk16 Yes