RASA3_HUMAN
ID RASA3_HUMAN Reviewed; 834 AA.
AC Q14644; A6NL15; F8W6X8; Q8IUY2;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Ras GTPase-activating protein 3;
DE AltName: Full=GAP1(IP4BP);
DE AltName: Full=Ins P4-binding protein;
GN Name=RASA3;
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] (ISOFORM 1).
RC TISSUE=Peripheral blood;
RX PubMed=7637787; DOI=10.1038/376527a0;
RA Cullen P.J., Hsuan J.J., Truong O., Letcher A.J., Jackson T.J.,
RA Dawson A.P., Irvine R.F.;
RT "Identification of a specific Ins(1,3,4,5)P4-binding protein as a member of
RT the GAP1 family.";
RL Nature 376:527-530(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Testis;
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 MUTAGENESIS.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-809, AND IDENTIFICATION BY
RP 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-809, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
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).
RN [11]
RP ACETYLATION AT ALA-2, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=25489052; DOI=10.1093/hmg/ddu611;
RA Myklebust L.M., Van Damme P., Stoeve S.I., Doerfel M.J., Abboud A.,
RA Kalvik T.V., Grauffel C., Jonckheere V., Wu Y., Swensen J., Kaasa H.,
RA Liszczak G., Marmorstein R., Reuter N., Lyon G.J., Gevaert K., Arnesen T.;
RT "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-
RT acetylation defects.";
RL Hum. Mol. Genet. 24:1956-1976(2015).
CC -!- FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Binds
CC inositol tetrakisphosphate (IP4) with high affinity. Might be a
CC specific IP4 receptor.
CC -!- SUBCELLULAR LOCATION: Cell membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14644-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14644-2; Sequence=VSP_056141;
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DR EMBL; X89399; CAA61580.1; -; mRNA.
DR EMBL; AK289746; BAF82435.1; -; mRNA.
DR EMBL; AK294913; BAH11922.1; -; mRNA.
DR EMBL; AL161774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX537329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038456; AAH38456.1; -; mRNA.
DR EMBL; BC047242; AAH47242.1; -; mRNA.
DR CCDS; CCDS32016.1; -. [Q14644-1]
DR RefSeq; NP_001307750.1; NM_001320821.1.
DR RefSeq; NP_001307751.1; NM_001320822.1. [Q14644-2]
DR RefSeq; NP_031394.2; NM_007368.3. [Q14644-1]
DR RefSeq; XP_011533143.1; XM_011534841.2. [Q14644-2]
DR RefSeq; XP_011533144.1; XM_011534842.2. [Q14644-2]
DR AlphaFoldDB; Q14644; -.
DR SMR; Q14644; -.
DR BioGRID; 116497; 26.
DR IntAct; Q14644; 2.
DR STRING; 9606.ENSP00000335029; -.
DR iPTMnet; Q14644; -.
DR PhosphoSitePlus; Q14644; -.
DR BioMuta; RASA3; -.
DR DMDM; 206729910; -.
DR EPD; Q14644; -.
DR jPOST; Q14644; -.
DR MassIVE; Q14644; -.
DR MaxQB; Q14644; -.
DR PaxDb; Q14644; -.
DR PeptideAtlas; Q14644; -.
DR PRIDE; Q14644; -.
DR ProteomicsDB; 29852; -.
DR ProteomicsDB; 60089; -. [Q14644-1]
DR Antibodypedia; 26027; 294 antibodies from 32 providers.
DR DNASU; 22821; -.
DR Ensembl; ENST00000334062.8; ENSP00000335029.7; ENSG00000185989.11. [Q14644-1]
DR Ensembl; ENST00000630618.2; ENSP00000486064.1; ENSG00000280477.2. [Q14644-1]
DR GeneID; 22821; -.
DR KEGG; hsa:22821; -.
DR MANE-Select; ENST00000334062.8; ENSP00000335029.7; NM_007368.4; NP_031394.2.
DR UCSC; uc001vui.4; human. [Q14644-1]
DR CTD; 22821; -.
DR DisGeNET; 22821; -.
DR GeneCards; RASA3; -.
DR HGNC; HGNC:20331; RASA3.
DR HPA; ENSG00000185989; Low tissue specificity.
DR MIM; 605182; gene.
DR neXtProt; NX_Q14644; -.
DR OpenTargets; ENSG00000185989; -.
DR PharmGKB; PA134905447; -.
DR VEuPathDB; HostDB:ENSG00000185989; -.
DR eggNOG; KOG2059; Eukaryota.
DR GeneTree; ENSGT00940000157953; -.
DR HOGENOM; CLU_008096_1_1_1; -.
DR InParanoid; Q14644; -.
DR OMA; FDHSLNN; -.
DR OrthoDB; 145372at2759; -.
DR PhylomeDB; Q14644; -.
DR TreeFam; TF105302; -.
DR PathwayCommons; Q14644; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR SignaLink; Q14644; -.
DR BioGRID-ORCS; 22821; 24 hits in 1083 CRISPR screens.
DR ChiTaRS; RASA3; human.
DR GeneWiki; RASA3; -.
DR GenomeRNAi; 22821; -.
DR Pharos; Q14644; Tbio.
DR PRO; PR:Q14644; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q14644; protein.
DR Bgee; ENSG00000185989; Expressed in granulocyte and 96 other tissues.
DR Genevisible; Q14644; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031235; C:intrinsic component of the cytoplasmic side of the plasma membrane; IDA:BHF-UCL.
DR GO; GO:0015278; F:calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0005096; F:GTPase activator activity; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; cd13371; PH_GAP1_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; IPR037774; RASA3_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; Cell membrane; GTPase activation;
KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25489052"
FT CHAIN 2..834
FT /note="Ras GTPase-activating protein 3"
FT /id="PRO_0000056642"
FT DOMAIN 1..112
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 123..263
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 330..524
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT DOMAIN 576..677
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 679..715
FT /note="Btk-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 687
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 698
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 699
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 709
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:0000269|PubMed:25489052"
FT MOD_RES 66
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q60790"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60790"
FT MOD_RES 110
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 809
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 833
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60790"
FT VAR_SEQ 1..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056141"
FT MUTAGEN 599
FT /note="K->Q: No binding to IP4 and loss of plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:9382842"
FT MUTAGEN 600
FT /note="K->Q: No binding to IP4 and loss of plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:9382842"
FT MUTAGEN 601
FT /note="R->Q: No binding to IP4 and loss of plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:9382842"
FT CONFLICT 785..786
FT /note="AG -> RW (in Ref. 1; CAA61580)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 834 AA; 95699 MW; 97C3467C957DA8A1 CRC64;
MAVEDEGLRV FQSVKIKIGE AKNLPSYPGP SKMRDCYCTV NLDQEEVFRT KIVEKSLCPF
YGEDFYCEIP RSFRHLSFYI FDRDVFRRDS IIGKVAIQKE DLQKYHNRDT WFQLQHVDAD
SEVQGKVHLE LRLSEVITDT GVVCHKLATR IVECQGLPIV NGQCDPYATV TLAGPFRSEA
KKTKVKRKTN NPQFDEVFYF EVTRPCSYSK KSHFDFEEED VDKLEIRVDL WNASNLKFGD
EFLGELRIPL KVLRQSSSYE AWYFLQPRDN GSKSLKPDDL GSLRLNVVYT EDHVFSSDYY
SPLRDLLLKS ADVEPVSASA AHILGEVCRE KQEAAVPLVR LFLHYGRVVP FISAIASAEV
KRTQDPNTIF RGNSLASKCI DETMKLAGMH YLHVTLKPAI EEICQSHKPC EIDPVKLKDG
ENLENNMENL RQYVDRVFHA ITESGVSCPT VMCDIFFSLR EAAAKRFQDD PDVRYTAVSS
FIFLRFFAPA ILSPNLFQLT PHHTDPQTSR TLTLISKTVQ TLGSLSKSKS ASFKESYMAT
FYEFFNEQKY ADAVKNFLDL ISSSGRRDPK SVEQPIVLKE GFMIKRAQGR KRFGMKNFKK
RWFRLTNHEF TYHKSKGDQP LYSIPIENIL AVEKLEEESF KMKNMFQVIQ PERALYIQAN
NCVEAKDWID ILTKVSQCNQ KRLTVYHPSA YLSGHWLCCR APSDSAPGCS PCTGGLPANI
QLDIDGDRET ERIYSLFNLY MSKLEKMQEA CGSKSVYDGP EQEEYSTFVI DDPQETYKTL
KQVIAGVGAL EQEHAQYKRD KFKKTKYGSQ EHPIGDKSFQ NYIRQQSETS THSI
