RPGP2_HUMAN
ID RPGP2_HUMAN Reviewed; 730 AA.
AC Q684P5; B2RTY5; Q684P4; Q6AI00; Q6ZVF0; Q9UPW2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Rap1 GTPase-activating protein 2;
DE Short=Rap1GAP2;
DE AltName: Full=GTPase-activating Rap/Ran-GAP domain-like protein 4;
GN Name=RAP1GAP2; Synonyms=GARNL4, KIAA1039, RAP1GA2;
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] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION AT
RP SER-7, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-7
RP AND ASN-357.
RX PubMed=15632203; DOI=10.1182/blood-2004-09-3605;
RA Schultess J., Danielewski O., Smolenski A.P.;
RT "Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human
RT platelets.";
RL Blood 105:3185-3192(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Cervix;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 287-730.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND THR-49, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45; THR-49 AND SER-544, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-558 AND SER-564, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: GTPase activator for the nuclear Ras-related regulatory
CC protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-
CC bound state. {ECO:0000269|PubMed:15632203}.
CC -!- INTERACTION:
CC Q684P5; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-3452992, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15632203}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:15632203}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Rap1GAP2b;
CC IsoId=Q684P5-1; Sequence=Displayed;
CC Name=2; Synonyms=Rap1GAP2a;
CC IsoId=Q684P5-2; Sequence=VSP_029889;
CC Name=3; Synonyms=Rap1GAP2c;
CC IsoId=Q684P5-3; Sequence=VSP_029888;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in platelets
CC with isoform 2 being the predominant form. Expressed in lymphocytes,
CC heart, testis and pancreas. {ECO:0000269|PubMed:15632203}.
CC -!- PTM: In vitro phosphorylated by cGMP-dependent protein kinase 1 (cGKI)
CC at Ser-7; the phosphorylation probably does not regulate GAP activity.
CC {ECO:0000269|PubMed:15632203}.
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DR EMBL; AJ628446; CAF31652.1; -; mRNA.
DR EMBL; AJ628447; CAF31653.1; -; mRNA.
DR EMBL; AK124640; BAC85912.1; -; mRNA.
DR EMBL; CR627427; CAH10514.1; -; mRNA.
DR EMBL; BC140870; AAI40871.1; -; mRNA.
DR EMBL; BC140871; AAI40872.1; -; mRNA.
DR EMBL; AB028962; BAA82991.1; -; mRNA.
DR CCDS; CCDS45573.1; -. [Q684P5-1]
DR CCDS; CCDS45574.1; -. [Q684P5-2]
DR CCDS; CCDS82035.1; -. [Q684P5-3]
DR RefSeq; NP_001093868.1; NM_001100398.1. [Q684P5-2]
DR RefSeq; NP_001316987.1; NM_001330058.1. [Q684P5-3]
DR RefSeq; NP_055900.4; NM_015085.4. [Q684P5-1]
DR RefSeq; XP_011522043.1; XM_011523741.2. [Q684P5-3]
DR RefSeq; XP_016879859.1; XM_017024370.1.
DR AlphaFoldDB; Q684P5; -.
DR SMR; Q684P5; -.
DR BioGRID; 116732; 8.
DR IntAct; Q684P5; 4.
DR STRING; 9606.ENSP00000254695; -.
DR iPTMnet; Q684P5; -.
DR PhosphoSitePlus; Q684P5; -.
DR BioMuta; RAP1GAP2; -.
DR DMDM; 162416269; -.
DR EPD; Q684P5; -.
DR jPOST; Q684P5; -.
DR MassIVE; Q684P5; -.
DR MaxQB; Q684P5; -.
DR PaxDb; Q684P5; -.
DR PeptideAtlas; Q684P5; -.
DR PRIDE; Q684P5; -.
DR ProteomicsDB; 65988; -. [Q684P5-1]
DR ProteomicsDB; 65989; -. [Q684P5-2]
DR ProteomicsDB; 65990; -. [Q684P5-3]
DR Antibodypedia; 5443; 35 antibodies from 15 providers.
DR DNASU; 23108; -.
DR Ensembl; ENST00000254695.13; ENSP00000254695.8; ENSG00000132359.15. [Q684P5-1]
DR Ensembl; ENST00000366401.8; ENSP00000389824.2; ENSG00000132359.15. [Q684P5-2]
DR Ensembl; ENST00000540393.6; ENSP00000439688.2; ENSG00000132359.15. [Q684P5-3]
DR Ensembl; ENST00000542807.1; ENSP00000444890.1; ENSG00000132359.15. [Q684P5-1]
DR GeneID; 23108; -.
DR KEGG; hsa:23108; -.
DR MANE-Select; ENST00000254695.13; ENSP00000254695.8; NM_015085.5; NP_055900.4.
DR UCSC; uc010ckd.4; human. [Q684P5-1]
DR CTD; 23108; -.
DR DisGeNET; 23108; -.
DR GeneCards; RAP1GAP2; -.
DR HGNC; HGNC:29176; RAP1GAP2.
DR HPA; ENSG00000132359; Tissue enhanced (bone marrow, pancreas).
DR MIM; 618714; gene.
DR neXtProt; NX_Q684P5; -.
DR OpenTargets; ENSG00000132359; -.
DR PharmGKB; PA165432528; -.
DR VEuPathDB; HostDB:ENSG00000132359; -.
DR eggNOG; KOG3686; Eukaryota.
DR GeneTree; ENSGT00940000160935; -.
DR HOGENOM; CLU_010739_2_2_1; -.
DR InParanoid; Q684P5; -.
DR OMA; ICPNKEP; -.
DR PhylomeDB; Q684P5; -.
DR TreeFam; TF318626; -.
DR PathwayCommons; Q684P5; -.
DR Reactome; R-HSA-392517; Rap1 signalling.
DR SignaLink; Q684P5; -.
DR BioGRID-ORCS; 23108; 5 hits in 1066 CRISPR screens.
DR ChiTaRS; RAP1GAP2; human.
DR GeneWiki; RAP1GAP2; -.
DR GenomeRNAi; 23108; -.
DR Pharos; Q684P5; Tbio.
DR PRO; PR:Q684P5; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q684P5; protein.
DR Bgee; ENSG00000132359; Expressed in Brodmann (1909) area 23 and 169 other tissues.
DR ExpressionAtlas; Q684P5; baseline and differential.
DR Genevisible; Q684P5; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IGI:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; EXP:Reactome.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; TAS:Reactome.
DR GO; GO:0008361; P:regulation of cell size; IMP:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 3.40.50.11210; -; 1.
DR InterPro; IPR035974; Rap/Ran-GAP_sf.
DR InterPro; IPR000331; Rap/Ran_GAP_dom.
DR Pfam; PF02145; Rap_GAP; 1.
DR SUPFAM; SSF111347; SSF111347; 1.
DR PROSITE; PS50085; RAPGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; GTPase activation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..730
FT /note="Rap1 GTPase-activating protein 2"
FT /id="PRO_0000312716"
FT DOMAIN 248..464
FT /note="Rap-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00165"
FT REGION 32..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 552..730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 579..616
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 632..649
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 659..689
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 7
FT /note="Phosphoserine; by PKG/PRKG1; in vitro"
FT /evidence="ECO:0000269|PubMed:15632203"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 49
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SVL6"
FT MOD_RES 544
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 558
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 612
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SVL6"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SVL6"
FT VAR_SEQ 1..19
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_029888"
FT VAR_SEQ 68..82
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15632203"
FT /id="VSP_029889"
FT VARIANT 202
FT /note="L -> M (in dbSNP:rs17762452)"
FT /id="VAR_037553"
FT MUTAGEN 7
FT /note="S->A: Abolishes phosphorylation by PKG/PRKG1."
FT /evidence="ECO:0000269|PubMed:15632203"
FT MUTAGEN 357
FT /note="N->A: Abolishes GAP activity."
FT /evidence="ECO:0000269|PubMed:15632203"
FT CONFLICT 285
FT /note="P -> L (in Ref. 2; BAC85912)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="K -> N (in Ref. 1; CAF31652/CAF31653)"
FT /evidence="ECO:0000305"
FT CONFLICT 726
FT /note="S -> P (in Ref. 3; CAH10514)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 730 AA; 80056 MW; 8E7584ADC2DA0B08 CRC64;
MFGRKRSVSF GGFGWIDKTM LASLKVKKQE LANSSDATLP DRPLSPPLTA PPTMKSSEFF
EMLEKMQGIK LEEQKPGPQK NKDDYIPYPS IDEVVEKGGP YPQVILPQFG GYWIEDPENV
GTPTSLGSSI CEEEEEDNLS PNTFGYKLEC KGEARAYRRH FLGKDHLNFY CTGSSLGNLI
LSVKCEEAEG IEYLRVILRS KLKTVHERIP LAGLSKLPSV PQIAKAFCDD AVGLRFNPVL
YPKASQMIVS YDEHEVNNTF KFGVIYQKAR QTLEEELFGN NEESPAFKEF LDLLGDTITL
QDFKGFRGGL DVTHGQTGVE SVYTTFRDRE IMFHVSTKLP FTDGDAQQLQ RKRHIGNDIV
AIIFQEENTP FVPDMIASNF LHAYIVVQVE TPGTETPSYK VSVTAREDVP TFGPPLPSPP
VFQKGPEFRE FLLTKLTNAE NACCKSDKFA KLEDRTRAAL LDNLHDELHA HTQAMLGLGP
EEDKFENGGH GGFLESFKRA IRVRSHSMET MVGGQKKSHS GGIPGSLSGG ISHNSMEVTK
TTFSPPVVAA TVKNQSRSPI KRRSGLFPRL HTGSEGQGDS RARCDSTSST PKTPDGGHSS
QEIKSETSSN PSSPEICPNK EKPFMKLKEN GRAISRSSSS TSSVSSTAGE GEAMEEGDSG
GSQPSTTSPF KQEVFVYSPS PSSESPSLGA AATPIIMSRS PTDAKSRNSP RSNLKFRFDK
LSHASSGAGH
