SGSM3_HUMAN
ID SGSM3_HUMAN Reviewed; 749 AA.
AC Q96HU1; B0QY79; Q7Z709; Q9NT69;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Small G protein signaling modulator 3;
DE AltName: Full=Merlin-associated protein;
DE AltName: Full=RUN and TBC1 domain-containing protein 3;
DE AltName: Full=Rab-GTPase-activating protein-like protein;
DE Short=RabGAPLP;
GN Name=SGSM3 {ECO:0000312|HGNC:HGNC:25228};
GN Synonyms=MAP {ECO:0000303|PubMed:15541357},
GN RABGAPLP {ECO:0000312|EMBL:BAE02561.1},
GN RUTBC3 {ECO:0000312|EMBL:AAH08078.1};
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] {ECO:0000305, ECO:0000312|EMBL:AAQ81879.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INTERACTION WITH NF2.
RX PubMed=15541357; DOI=10.1016/j.bbrc.2004.10.095;
RA Lee I.K., Kim K.-S., Kim H., Lee J.Y., Ryu C.H., Chun H.J., Lee K.-U.,
RA Lim Y., Kim Y.H., Huh P.-W., Lee K.-H., Han S.-I., Jun T.-Y., Rha H.K.;
RT "MAP, a protein interacting with a tumor suppressor, merlin, through the
RT run domain.";
RL Biochem. Biophys. Res. Commun. 325:774-783(2004).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAE02561.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH PDCD6IP, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Fetus {ECO:0000269|PubMed:15849434};
RX PubMed=15849434; DOI=10.1271/bbb.69.861;
RA Ichioka F., Horii M., Katoh K., Terasawa Y., Shibata H., Maki M.;
RT "Identification of Rab GTPase-activating protein-like protein (RabGAPLP) as
RT a novel Alix/AIP1-interacting protein.";
RL Biosci. Biotechnol. Biochem. 69:861-865(2005).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAF63513.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RAB3A; RAB4A;
RP RAB5A; RAB8A; RAB11A; RAP1A; RAP1B; RAP2A AND RAP2B, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain {ECO:0000269|PubMed:17509819};
RX PubMed=17509819; DOI=10.1016/j.ygeno.2007.03.013;
RA Yang H., Sasaki T., Minoshima S., Shimizu N.;
RT "Identification of three novel proteins (SGSM1, 2, 3) which modulate small
RT G protein (RAP and RAB)-mediated signaling pathway.";
RL Genomics 90:249-260(2007).
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAG30327.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6] {ECO:0000305, ECO:0000312|EMBL:EAW60379.1}
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] {ECO:0000305, ECO:0000312|EMBL:AAH08078.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Rhabdomyosarcoma {ECO:0000312|EMBL:AAH08078.1};
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 615-749.
RC TISSUE=Amygdala;
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 [9]
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).
CC -!- FUNCTION: May play a cooperative role in NF2-mediated growth
CC suppression of cells. {ECO:0000269|PubMed:15541357}.
CC -!- SUBUNIT: Interacts with GJA1. Interaction with GJA1 induces its
CC degradation (By similarity). Interacts via its RUN domain with the C-
CC terminal region of NF2. Interacts with RAB3A, RAB4A, RAB5A, RAB8A,
CC RAB11A, RAP1A, RAP1B, RAP2A, RAP2B and PDCD6IP. No interaction with
CC RAB27A. {ECO:0000250|UniProtKB:Q8VCZ6, ECO:0000269|PubMed:15541357,
CC ECO:0000269|PubMed:15849434, ECO:0000269|PubMed:17509819}.
CC -!- INTERACTION:
CC Q96HU1; P31513: FMO3; NbExp=3; IntAct=EBI-7362971, EBI-12361463;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15849434}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:15461802, ECO:0000269|PubMed:15489334,
CC ECO:0000269|PubMed:15541357, ECO:0000269|PubMed:15849434,
CC ECO:0000269|PubMed:17509819};
CC IsoId=Q96HU1-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:10591208};
CC IsoId=Q96HU1-2; Sequence=VSP_052561;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17509819}.
CC -!- SIMILARITY: Belongs to the small G protein signaling modulator family.
CC {ECO:0000305}.
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DR EMBL; AY308849; AAQ81879.1; -; mRNA.
DR EMBL; AB196956; BAE02561.1; -; mRNA.
DR EMBL; AB275763; BAF63513.1; -; mRNA.
DR EMBL; CR456441; CAG30327.1; -; mRNA.
DR EMBL; AL022238; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60378.1; -; Genomic_DNA.
DR EMBL; CH471095; EAW60379.1; -; Genomic_DNA.
DR EMBL; BC008078; AAH08078.1; -; mRNA.
DR EMBL; AL137499; CAB70773.1; -; mRNA.
DR CCDS; CCDS14002.1; -. [Q96HU1-1]
DR PIR; T46252; T46252.
DR RefSeq; NP_001288778.1; NM_001301849.1.
DR RefSeq; NP_056520.2; NM_015705.5. [Q96HU1-1]
DR AlphaFoldDB; Q96HU1; -.
DR SMR; Q96HU1; -.
DR BioGRID; 118164; 23.
DR IntAct; Q96HU1; 6.
DR MINT; Q96HU1; -.
DR STRING; 9606.ENSP00000248929; -.
DR TCDB; 8.A.87.1.5; the tbc1 domain (tbc1) family.
DR iPTMnet; Q96HU1; -.
DR PhosphoSitePlus; Q96HU1; -.
DR BioMuta; SGSM3; -.
DR DMDM; 74760858; -.
DR EPD; Q96HU1; -.
DR jPOST; Q96HU1; -.
DR MassIVE; Q96HU1; -.
DR MaxQB; Q96HU1; -.
DR PaxDb; Q96HU1; -.
DR PeptideAtlas; Q96HU1; -.
DR PRIDE; Q96HU1; -.
DR ProteomicsDB; 76785; -. [Q96HU1-1]
DR ProteomicsDB; 76786; -. [Q96HU1-2]
DR Antibodypedia; 45865; 126 antibodies from 30 providers.
DR DNASU; 27352; -.
DR Ensembl; ENST00000248929.14; ENSP00000248929.8; ENSG00000100359.21. [Q96HU1-1]
DR GeneID; 27352; -.
DR KEGG; hsa:27352; -.
DR MANE-Select; ENST00000248929.14; ENSP00000248929.8; NM_015705.6; NP_056520.2.
DR UCSC; uc003ayu.2; human. [Q96HU1-1]
DR CTD; 27352; -.
DR DisGeNET; 27352; -.
DR GeneCards; SGSM3; -.
DR HGNC; HGNC:25228; SGSM3.
DR HPA; ENSG00000100359; Low tissue specificity.
DR MIM; 610440; gene.
DR neXtProt; NX_Q96HU1; -.
DR OpenTargets; ENSG00000100359; -.
DR PharmGKB; PA162403194; -.
DR VEuPathDB; HostDB:ENSG00000100359; -.
DR eggNOG; KOG2222; Eukaryota.
DR GeneTree; ENSGT00940000157282; -.
DR HOGENOM; CLU_020721_0_0_1; -.
DR InParanoid; Q96HU1; -.
DR OMA; NSPGWVQ; -.
DR PhylomeDB; Q96HU1; -.
DR TreeFam; TF317336; -.
DR PathwayCommons; Q96HU1; -.
DR SignaLink; Q96HU1; -.
DR BioGRID-ORCS; 27352; 11 hits in 1074 CRISPR screens.
DR ChiTaRS; SGSM3; human.
DR GenomeRNAi; 27352; -.
DR Pharos; Q96HU1; Tbio.
DR PRO; PR:Q96HU1; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q96HU1; protein.
DR Bgee; ENSG00000100359; Expressed in body of pancreas and 97 other tissues.
DR ExpressionAtlas; Q96HU1; baseline and differential.
DR Genevisible; Q96HU1; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005921; C:gap junction; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0048227; P:plasma membrane to endosome transport; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR GO; GO:0032486; P:Rap protein signal transduction; IEP:UniProtKB.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; IEP:UniProtKB.
DR CDD; cd11813; SH3_SGSM3; 1.
DR Gene3D; 1.20.58.900; -; 1.
DR InterPro; IPR000195; Rab-GTPase-TBC_dom.
DR InterPro; IPR035969; Rab-GTPase_TBC_sf.
DR InterPro; IPR004012; Run_dom.
DR InterPro; IPR037213; Run_dom_sf.
DR InterPro; IPR035833; SGSM3_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR Pfam; PF02759; RUN; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00593; RUN; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50002; SH3; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Coiled coil; Cytoplasm; Growth arrest;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..749
FT /note="Small G protein signaling modulator 3"
FT /id="PRO_0000307810"
FT DOMAIN 114..305
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT DOMAIN 480..539
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 555..718
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT COILED 415..439
FT /evidence="ECO:0000255"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCZ6"
FT VAR_SEQ 456
FT /note="V -> VVSRQLPGLLPNTALTPPTPLVGLCSLWQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10591208"
FT /id="VSP_052561"
FT VARIANT 20
FT /note="W -> R (in dbSNP:rs9611338)"
FT /id="VAR_051345"
FT VARIANT 279
FT /note="H -> Q (in dbSNP:rs34243479)"
FT /id="VAR_051346"
SQ SEQUENCE 749 AA; 85354 MW; 3DA4F7961EF79056 CRC64;
MSGSHTPACG PFSALTPSIW PQEILAKYTQ KEESAEQPEF YYDEFGFRVY KEEGDEPGSS
LLANSPLMED APQRLRWQAH LEFTHNHDVG DLTWDKIAVS LPRSEKLRSL VLAGIPHGMR
PQLWMRLSGA LQKKRNSELS YREIVKNSSN DETIAAKQIE KDLLRTMPSN ACFASMGSIG
VPRLRRVLRA LAWLYPEIGY CQGTGMVAAC LLLFLEEEDA FWMMSAIIED LLPASYFSTT
LLGVQTDQRV LRHLIVQYLP RLDKLLQEHD IELSLITLHW FLTAFASVVD IKLLLRIWDL
FFYEGSRVLF QLTLGMLHLK EEELIQSENS ASIFNTLSDI PSQMEDAELL LGVAMRLAGS
LTDVAVETQR RKHLAYLIAD QGQLLGAGTL TNLSQVVRRR TQRRKSTITA LLFGEDDLEA
LKAKNIKQTE LVADLREAIL RVARHFQCTD PKNCSVELTP DYSMESHQRD HENYVACSRS
HRRRAKALLD FERHDDDELG FRKNDIITIV SQKDEHCWVG ELNGLRGWFP AKFVEVLDER
SKEYSIAGDD SVTEGVTDLV RGTLCPALKA LFEHGLKKPS LLGGACHPWL FIEEAAGREV
ERDFASVYSR LVLCKTFRLD EDGKVLTPEE LLYRAVQSVN VTHDAVHAQM DVKLRSLICV
GLNEQVLHLW LEVLCSSLPT VEKWYQPWSF LRSPGWVQIK CELRVLCCFA FSLSQDWELP
AKREAQQPLK EGVRDMLVKH HLFSWDVDG
