SIPA1_HUMAN
ID SIPA1_HUMAN Reviewed; 1042 AA.
AC Q96FS4; O14518; O60484; O60618; Q2YD83;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Signal-induced proliferation-associated protein 1;
DE Short=Sipa-1;
DE AltName: Full=GTPase-activating protein Spa-1;
DE AltName: Full=p130 SPA-1;
GN Name=SIPA1; Synonyms=SPA1;
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], FUNCTION, SUBCELLULAR LOCATION, AND VARIANT
RP PHE-182.
RC TISSUE=Peripheral blood lymphocyte;
RX PubMed=9346962; DOI=10.1074/jbc.272.44.28081;
RA Kurachi H., Wada Y., Tsukamoto N., Maeda M., Kubota H., Hattori M.,
RA Iwai K., Minato N.;
RT "Human SPA-1 product selectively expressed in lymphoid tissues is a
RT specific GTPase-activating protein for Rap1 and Rap2.";
RL J. Biol. Chem. 272:28081-28088(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=9651531; DOI=10.1016/s0378-1119(98)00212-1;
RA Ebrahimi S., Wang E., Udar N., Arnold E., Burbee D., Small K.,
RA Sawicki M.P.;
RT "Genomic organization and cloning of the human homologue of murine Sipa-
RT 1.";
RL Gene 214:215-221(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Pancreas;
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 [4]
RP IDENTIFICATION BY 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-64; SER-67 AND SER-839, 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-817 AND SER-839, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-67; SER-304; SER-314;
RP SER-817; SER-839 AND SER-912, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-182, AND IDENTIFICATION BY
RP 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 proteins Rap1 and Rap2 in vitro, converting them to the putatively
CC inactive GDP-bound state (PubMed:9346962). Affects cell cycle
CC progression (By similarity). {ECO:0000250|UniProtKB:P46062,
CC ECO:0000269|PubMed:9346962}.
CC -!- SUBUNIT: Interacts with RRP1B; the interaction leads to inhibition of
CC SIPA1 GTPase activity. {ECO:0000250|UniProtKB:P46062}.
CC -!- INTERACTION:
CC Q96FS4; P38936: CDKN1A; NbExp=2; IntAct=EBI-1054981, EBI-375077;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9346962}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:9346962}. Endomembrane system;
CC Peripheral membrane protein {ECO:0000269|PubMed:9346962}. Note=Mostly
CC localized in the perinuclear membraneous region.
CC {ECO:0000269|PubMed:9346962}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal as well as in adult tissues.
CC Expressed abundantly in the lymphoid tissues such as thymus, spleen and
CC peripheral blood lymphocytes and also shows a significant expression in
CC the spinal cord.
CC -!- INDUCTION: Repressed by 12-O-tetradecanoylphorbol-13-acetate (TPA) in
CC promyelocytic HL-60 cells.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SIPA1ID46282ch11q13.html";
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DR EMBL; AB005666; BAA22197.1; -; mRNA.
DR EMBL; AF052238; AAC32559.1; -; Genomic_DNA.
DR EMBL; AF052233; AAC32559.1; JOINED; Genomic_DNA.
DR EMBL; AF052234; AAC32559.1; JOINED; Genomic_DNA.
DR EMBL; AF052235; AAC32559.1; JOINED; Genomic_DNA.
DR EMBL; AF052236; AAC32559.1; JOINED; Genomic_DNA.
DR EMBL; AF052237; AAC32559.1; JOINED; Genomic_DNA.
DR EMBL; AF029789; AAC32547.1; -; mRNA.
DR EMBL; BC010492; AAH10492.1; -; mRNA.
DR EMBL; BC110353; AAI10354.1; -; mRNA.
DR CCDS; CCDS8108.1; -.
DR RefSeq; NP_006738.3; NM_006747.3.
DR RefSeq; NP_694985.29; NM_153253.29.
DR RefSeq; XP_005274246.1; XM_005274189.2.
DR RefSeq; XP_011543516.1; XM_011545214.1.
DR AlphaFoldDB; Q96FS4; -.
DR SMR; Q96FS4; -.
DR BioGRID; 112385; 38.
DR IntAct; Q96FS4; 26.
DR MINT; Q96FS4; -.
DR STRING; 9606.ENSP00000377771; -.
DR GlyGen; Q96FS4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96FS4; -.
DR PhosphoSitePlus; Q96FS4; -.
DR BioMuta; SIPA1; -.
DR DMDM; 20455286; -.
DR EPD; Q96FS4; -.
DR jPOST; Q96FS4; -.
DR MassIVE; Q96FS4; -.
DR MaxQB; Q96FS4; -.
DR PaxDb; Q96FS4; -.
DR PeptideAtlas; Q96FS4; -.
DR PRIDE; Q96FS4; -.
DR ProteomicsDB; 76551; -.
DR Antibodypedia; 29889; 330 antibodies from 32 providers.
DR DNASU; 6494; -.
DR Ensembl; ENST00000394224.3; ENSP00000377771.3; ENSG00000213445.10.
DR Ensembl; ENST00000534313.6; ENSP00000436269.1; ENSG00000213445.10.
DR GeneID; 6494; -.
DR KEGG; hsa:6494; -.
DR MANE-Select; ENST00000534313.6; ENSP00000436269.1; NM_006747.4; NP_006738.3.
DR UCSC; uc001ofb.3; human.
DR CTD; 6494; -.
DR DisGeNET; 6494; -.
DR GeneCards; SIPA1; -.
DR HGNC; HGNC:10885; SIPA1.
DR HPA; ENSG00000213445; Tissue enhanced (lymphoid).
DR MIM; 602180; gene.
DR neXtProt; NX_Q96FS4; -.
DR OpenTargets; ENSG00000213445; -.
DR PharmGKB; PA35785; -.
DR VEuPathDB; HostDB:ENSG00000213445; -.
DR eggNOG; KOG3686; Eukaryota.
DR GeneTree; ENSGT00940000160644; -.
DR InParanoid; Q96FS4; -.
DR OMA; PYDNIGG; -.
DR OrthoDB; 28453at2759; -.
DR PhylomeDB; Q96FS4; -.
DR TreeFam; TF318626; -.
DR PathwayCommons; Q96FS4; -.
DR Reactome; R-HSA-392517; Rap1 signalling.
DR SignaLink; Q96FS4; -.
DR BioGRID-ORCS; 6494; 40 hits in 1082 CRISPR screens.
DR ChiTaRS; SIPA1; human.
DR GeneWiki; SIPA1; -.
DR GenomeRNAi; 6494; -.
DR Pharos; Q96FS4; Tbio.
DR PRO; PR:Q96FS4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96FS4; protein.
DR Bgee; ENSG00000213445; Expressed in granulocyte and 113 other tissues.
DR ExpressionAtlas; Q96FS4; baseline and differential.
DR Genevisible; Q96FS4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0030133; C:transport vesicle; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; EXP:Reactome.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
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:0042631; P:cellular response to water deprivation; IEA:Ensembl.
DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; NAS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; NAS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.40.50.11210; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR035974; Rap/Ran-GAP_sf.
DR InterPro; IPR000331; Rap/Ran_GAP_dom.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF02145; Rap_GAP; 1.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF111347; SSF111347; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50085; RAPGAP; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; GTPase activation; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..1042
FT /note="Signal-induced proliferation-associated protein 1"
FT /id="PRO_0000056744"
FT DOMAIN 321..539
FT /note="Rap-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00165"
FT DOMAIN 687..763
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 830..903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 946..980
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 972..1034
FT /evidence="ECO:0000255"
FT COMPBIAS 135..152
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 831..886
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 961..980
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 64
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 912
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 80
FT /note="R -> Q (in dbSNP:rs35045265)"
FT /id="VAR_049148"
FT VARIANT 106
FT /note="A -> S (in dbSNP:rs3741379)"
FT /id="VAR_049149"
FT VARIANT 174
FT /note="E -> D (in dbSNP:rs34912782)"
FT /id="VAR_049150"
FT VARIANT 182
FT /note="S -> F (in dbSNP:rs3741378)"
FT /evidence="ECO:0000269|PubMed:9346962"
FT /id="VAR_049151"
FT CONFLICT 30
FT /note="Q -> H (in Ref. 2; AAC32559/AAC32547)"
FT /evidence="ECO:0000305"
FT CONFLICT 53..56
FT /note="SGSD -> RAAN (in Ref. 2; AAC32559/AAC32547)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="L -> Q (in Ref. 2; AAC32559/AAC32547)"
FT /evidence="ECO:0000305"
FT CONFLICT 468
FT /note="T -> R (in Ref. 2; AAC32559)"
FT /evidence="ECO:0000305"
FT CONFLICT 658
FT /note="T -> P (in Ref. 2; AAC32547)"
FT /evidence="ECO:0000305"
FT CONFLICT 721..724
FT /note="GLRP -> AAA (in Ref. 2; AAC32559/AAC32547)"
FT /evidence="ECO:0000305"
FT CONFLICT 781..782
FT /note="EP -> DA (in Ref. 2; AAC32559)"
FT /evidence="ECO:0000305"
FT CONFLICT 796
FT /note="Q -> H (in Ref. 1; BAA22197)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="S -> C (in Ref. 1; BAA22197)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1042 AA; 112149 MW; FB52C7231EA3B6B9 CRC64;
MPMWAGGVGS PRRGMAPAST DDLFARKLRQ PARPPLTPHT FEPRPVRGPL LRSGSDAGEA
RPPTPASPRA RAHSHEEASR PAATSTRLFT DPLALLGLPA EEPEPAFPPV LEPRWFAHYD
VQSLLFDWAP RSQGMGSHSE ASSGTLASAE DQAASSDLLH GAPGFVCELG GEGELGLGGP
ASPPVPPALP NAAVSILEEP QNRTSAYSLE HADLGAGYYR KYFYGKEHQN FFGMDESLGP
VAVSLRREEK EGSGGGTLHS YRVIVRTTQL RTLRGTISED ALPPGPPRGL SPRKLLEHVA
PQLSPSCLRL GSASPKVPRT LLTLDEQVLS FQRKVGILYC RAGQGSEEEM YNNQEAGPAF
MQFLTLLGDV VRLKGFESYR AQLDTKTDST GTHSLYTTYQ DHEIMFHVST MLPYTPNNQQ
QLLRKRHIGN DIVTIVFQEP GSKPFCPTTI RSHFQHVFLV VRAHTPCTPH TTYRVAVSRT
QDTPAFGPAL PAGGGPFAAN ADFRAFLLAK ALNGEQAAGH ARQFHAMATR TRQQYLQDLA
TNEVTTTSLD SASRFGLPSL GGRRRAAPRG PGAELQAAGS LVWGVRAAPG ARVAAGAQAS
GPEGIEVPCL LGISAEALVL VAPRDGRVVF NCACRDVLAW TFSEQQLDLY HGRGEAITLR
FDGSPGQAVG EVVARLQLVS RGCETRELAL PRDGQGRLGF EVDAEGFVTH VERFTFAETA
GLRPGARLLR VCGQTLPSLR PEAAAQLLRS APKVCVTVLP PDESGRPRRS FSELYTLSLQ
EPSRRGAPDP VQDEVQGVTL LPTTKQLLHL CLQDGGSPPG PGDLAEERTE FLHSQNSLSP
RSSLSDEAPV LPNTTPDLLL ATTAKPSVPS ADSETPLTQD RPGSPSGSED KGNPAPELRA
SFLPRTLSLR NSISRIMSEA GSGTLEDEWQ AISEIASTCN TILESLSREG QPIPESGDPK
GTPKSDAEPE PGNLSEKVSH LESMLRKLQE DLQKEKADRA ALEEEVRSLR HNNRRLQAES
ESAATRLLLA SKQLGSPTAD LA
