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 24-JAN-2024, entry version 190. 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; 9606-ENSP00000286364; -. DR PeptideAtlas; Q15283; -. DR ProteomicsDB; 32185; -. DR ProteomicsDB; 60511; -. [Q15283-1] DR Pumba; Q15283; -. DR Antibodypedia; 18019; 69 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 AGR; HGNC:9872; -. 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; 24454at2759; -. 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; 46 hits in 1160 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 188 other cell types or tissues. DR ExpressionAtlas; Q15283; baseline and differential. 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:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd08401; C2A_RasA2_RasA3; 1. DR CDD; cd04010; C2B_RasA3; 1. DR CDD; cd13370; PH_GAP1m_mammal-like; 1. DR CDD; cd05394; RasGAP_RASA2; 1. DR Gene3D; 2.60.40.150; C2 domain; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. 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:SF21; RAS GTPASE-ACTIVATING PROTEIN 2; 1. DR PANTHER; PTHR10194; RAS GTPASE-ACTIVATING PROTEINS; 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; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 1. 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. DR Genevisible; Q15283; HS. 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 //