RASA2_HUMAN
ID RASA2_HUMAN Reviewed; 850 AA.
AC Q15283; A8K7K1; G3V0F9; O00695; Q15284; Q92594; Q99577; Q9UEQ2;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ras GTPase-activating protein 2;
DE AltName: Full=GTPase-activating protein 1m;
DE Short=GAP1m;
GN Name=RASA2; Synonyms=GAP1M, RASGAP;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=8917095; DOI=10.1016/0378-1119(96)00144-8;
RA Kobayashi M., Masui T., Kusuda J., Kameoka Y., Hashimoto K., Iwashita S.;
RT "Human rasGTPase-activating protein (human counterpart of GAP1m): sequence
RT of the cDNA, primary structure of the protein, production and chromosomal
RT localization.";
RL Gene 175:173-177(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=8812506; DOI=10.1006/geno.1996.0412;
RA Li S., Satoh H., Watanabe T., Nakamura S., Hattori S.;
RT "cDNA cloning and chromosomal mapping of a novel human GAP (GAP1M), a
RT GTPase-activating protein of Ras.";
RL Genomics 35:625-627(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Blood;
RX PubMed=9382842; DOI=10.1016/s0960-9822(06)00423-4;
RA Lockyer P.J., Bottomley J.R., Reynolds J.S., McNulty T.J.,
RA Venkateswarlu K., Potter B.V.L., Dempsey C.E., Cullen P.J.;
RT "Distinct subcellular localisations of the putative inositol 1,3,4,5-
RT tetrakisphosphate receptors GAP1(IP4BP) and GAP1m result from the
RT GAP1(IP4BP) PH domain directing plasma membrane targeting.";
RL Curr. Biol. 7:1007-1010(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds
CC inositol tetrakisphosphate (IP4).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, perinuclear region.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15283-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15283-2; Sequence=VSP_046545;
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D78155; BAA11230.1; -; mRNA.
DR EMBL; D78156; BAA11231.1; -; Genomic_DNA.
DR EMBL; D82880; BAA11621.1; -; mRNA.
DR EMBL; D82881; BAA11622.1; -; Genomic_DNA.
DR EMBL; AF115573; AAD09821.1; -; mRNA.
DR EMBL; AC010184; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78999.1; -; Genomic_DNA.
DR EMBL; AK292016; BAF84705.1; -; mRNA.
DR CCDS; CCDS3117.1; -. [Q15283-2]
DR PIR; JC5047; JC5047.
DR RefSeq; NP_001290174.1; NM_001303245.1. [Q15283-1]
DR RefSeq; NP_001290175.1; NM_001303246.1.
DR RefSeq; NP_006497.2; NM_006506.3. [Q15283-2]
DR AlphaFoldDB; Q15283; -.
DR SMR; Q15283; -.
DR BioGRID; 111857; 26.
DR STRING; 9606.ENSP00000286364; -.
DR iPTMnet; Q15283; -.
DR PhosphoSitePlus; Q15283; -.
DR BioMuta; RASA2; -.
DR DMDM; 519668674; -.
DR EPD; Q15283; -.
DR jPOST; Q15283; -.
DR MassIVE; Q15283; -.
DR MaxQB; Q15283; -.
DR PaxDb; Q15283; -.
DR PeptideAtlas; Q15283; -.
DR PRIDE; Q15283; -.
DR ProteomicsDB; 32185; -.
DR ProteomicsDB; 60511; -. [Q15283-1]
DR Antibodypedia; 18019; 54 antibodies from 19 providers.
DR DNASU; 5922; -.
DR Ensembl; ENST00000286364.9; ENSP00000286364.3; ENSG00000155903.14. [Q15283-2]
DR GeneID; 5922; -.
DR KEGG; hsa:5922; -.
DR MANE-Select; ENST00000286364.9; ENSP00000286364.3; NM_006506.5; NP_006497.2. [Q15283-2]
DR UCSC; uc003etz.2; human. [Q15283-1]
DR CTD; 5922; -.
DR DisGeNET; 5922; -.
DR GeneCards; RASA2; -.
DR GeneReviews; RASA2; -.
DR HGNC; HGNC:9872; RASA2.
DR HPA; ENSG00000155903; Low tissue specificity.
DR MalaCards; RASA2; -.
DR MIM; 601589; gene.
DR neXtProt; NX_Q15283; -.
DR OpenTargets; ENSG00000155903; -.
DR Orphanet; 648; Noonan syndrome.
DR PharmGKB; PA34233; -.
DR VEuPathDB; HostDB:ENSG00000155903; -.
DR eggNOG; KOG2059; Eukaryota.
DR GeneTree; ENSGT00940000158201; -.
DR HOGENOM; CLU_008096_1_1_1; -.
DR InParanoid; Q15283; -.
DR OrthoDB; 145372at2759; -.
DR PhylomeDB; Q15283; -.
DR TreeFam; TF105302; -.
DR PathwayCommons; Q15283; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR SignaLink; Q15283; -.
DR BioGRID-ORCS; 5922; 37 hits in 1080 CRISPR screens.
DR ChiTaRS; RASA2; human.
DR GenomeRNAi; 5922; -.
DR Pharos; Q15283; Tdark.
DR PRO; PR:Q15283; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q15283; protein.
DR Bgee; ENSG00000155903; Expressed in epithelium of nasopharynx and 186 other tissues.
DR ExpressionAtlas; Q15283; baseline and differential.
DR Genevisible; Q15283; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IEA:InterPro.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd13370; PH_GAP1m_mammal-like; 1.
DR Gene3D; 1.10.506.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR037773; RASA2_PH.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR001562; Znf_Btk_motif.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR Pfam; PF00779; BTK; 1.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00616; RasGAP; 2.
DR PRINTS; PR00402; TECBTKDOMAIN.
DR SMART; SM00107; BTK; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
DR PROSITE; PS51113; ZF_BTK; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; GTPase activation;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..850
FT /note="Ras GTPase-activating protein 2"
FT /id="PRO_0000056638"
FT DOMAIN 20..138
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 149..289
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 356..550
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT DOMAIN 604..706
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 708..744
FT /note="Btk-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 825..850
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 716
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 727
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 728
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 738
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P58069"
FT VAR_SEQ 646
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8812506,
FT ECO:0000303|PubMed:9382842"
FT /id="VSP_046545"
FT CONFLICT 216
FT /note="T -> A (in Ref. 1; BAA11230)"
FT /evidence="ECO:0000305"
FT CONFLICT 225
FT /note="F -> S (in Ref. 4; BAF84705)"
FT /evidence="ECO:0000305"
FT CONFLICT 645
FT /note="G -> EFIER (in Ref. 2; BAA11621)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 850 AA; 96614 MW; 1F357940CA106E5E CRC64;
MAAAAPAAAA ASSEAPAASA TAEPEAGDQD SREVRVLQSL RGKICEAKNL LPYLGPHKMR
DCFCTINLDQ EEVYRTQVVE KSLSPFFSEE FYFEIPRTFQ YLSFYVYDKN VLQRDLRIGK
VAIKKEDLCN HSGKETWFSL QPVDSNSEVQ GKVHLELKLN ELITENGTVC QQLVVHIKAC
HGLPLINGQS CDPYATVSLV GPSRNDQKKT KVKKKTSNPQ FNEIFYFEVT RSSSYTRKSQ
FQVEEEDIEK LEIRIDLWNN GNLVQDVFLG EIKVPVNVLR TDSSHQAWYL LQPRDNGNKS
SKTDDLGSLR LNICYTEDYV LPSEYYGPLK TLLLKSPDVQ PISASAAYIL SEICRDKNDA
VLPLVRLLLH HDKLVPFATA VAELDLKDTQ DANTIFRGNS LATRCLDEMM KIVGGHYLKV
TLKPILDEIC DSSKSCEIDP IKLKEGDNVE NNKENLRYYV DKLFNTIVKS SMSCPTVMCD
IFYSLRQMAT QRFPNDPHVQ YSAVSSFVFL RFFAVAVVSP HTFHLRPHHP DAQTIRTLTL
ISKTIQTLGS WGSLSKSKSS FKETFMCEFF KMFQEEGYII AVKKFLDEIS STETKESSGT
SEPVHLKEGE MYKRAQGRTR IGKKNFKKRW FCLTSRELTY HKQPGSKDAI YTIPVKNILA
VEKLEESSFN KKNMFQVIHT EKPLYVQANN CVEANEWIDV LCRVSRCNQN RLSFYHPSVY
LNGNWLCCQE TGENTLGCKP CTAGVPADIQ IDIDEDRETE RIYSLFTLSL LKLQKMEEAC
GTIAVYQGPQ KEPDDYSNFV IEDSVTTFKT IQQIKSIIEK LDEPHEKYRK KRSSSAKYGS
KENPIVGKAS
