SGSM2_HUMAN
ID SGSM2_HUMAN Reviewed; 1006 AA.
AC O43147; A5LGW2; B4DH69; Q49AC2; Q6ZUY2; Q8IXU4;
DT 17-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 4.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Small G protein signaling modulator 2;
DE AltName: Full=RUN and TBC1 domain-containing protein 1;
GN Name=SGSM2; Synonyms=KIAA0397, RUTBC1;
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 2), VARIANTS MET-63; LYS-238; SER-244;
RP ARG-329; GLN-374 AND VAL-968, INTERACTION WITH RAB4A; RAB11A; RAP1A; RAP1B;
RP RAP2A AND RAP2B, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS MET-63;
RP LYS-238; SER-244; ARG-329; GLN-374 AND VAL-968.
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 [7]
RP FUNCTION, INTERACTION WITH RAB9A, MUTAGENESIS OF ARG-803, AND DOMAIN
RP RAB-GAP TBC.
RX PubMed=21808068; DOI=10.1074/jbc.m111.261115;
RA Nottingham R.M., Ganley I.G., Barr F.A., Lambright D.G., Pfeffer S.R.;
RT "RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32
RT and Rab33B proteins.";
RL J. Biol. Chem. 286:33213-33222(2011).
RN [8]
RP FUNCTION, INTERACTION WITH RAB9A, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ARG-803, AND DOMAIN RAB-GAP TBC.
RX PubMed=26620560; DOI=10.1074/jbc.m115.684043;
RA Marubashi S., Shimada H., Fukuda M., Ohbayashi N.;
RT "RUTBC1 functions as a GTPase-activating protein for Rab32/38 and regulates
RT melanogenic enzyme trafficking in melanocytes.";
RL J. Biol. Chem. 291:1427-1440(2016).
CC -!- FUNCTION: Possesses GTPase activator activity towards RAB32, RAB33B and
CC RAB38 (PubMed:26620560, PubMed:21808068). Regulates the trafficking of
CC melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in
CC melanocytes by inactivating RAB32 and RAB38. Inhibits RAB32 and RAB38
CC activation both directly by promoting their GTPase activity and
CC indirectly by disrupting the RAB9A-HPS4 interaction which is required
CC for RAB32/38 activation (PubMed:26620560).
CC {ECO:0000269|PubMed:21808068, ECO:0000269|PubMed:26620560}.
CC -!- SUBUNIT: Interacts with RAB4A, RAB11A, RAP1A, RAP1B, RAP2A and RAP2B.
CC No interaction with RAB27A (PubMed:17509819). Interacts with RAB9A
CC (PubMed:26620560, PubMed:21808068). {ECO:0000269|PubMed:17509819,
CC ECO:0000269|PubMed:21808068, ECO:0000269|PubMed:26620560}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:26620560}.
CC Melanosome {ECO:0000269|PubMed:26620560}. Note=Melanosomal localization
CC is mediated by RAB9A. {ECO:0000269|PubMed:26620560}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O43147-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43147-2; Sequence=VSP_024596;
CC Name=3;
CC IsoId=O43147-3; Sequence=VSP_024594, VSP_024595, VSP_024597,
CC VSP_024598;
CC Name=5;
CC IsoId=O43147-5; Sequence=VSP_035964;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17509819}.
CC -!- DOMAIN: The Rab-GAP TBC domain possesses GTPase activator activity.
CC {ECO:0000269|PubMed:21808068, ECO:0000269|PubMed:26620560}.
CC -!- SIMILARITY: Belongs to the RUTBC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23693.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB275762; BAF63512.1; -; mRNA.
DR EMBL; AB007857; BAA23693.3; ALT_INIT; mRNA.
DR EMBL; AK125203; BAC86084.1; -; mRNA.
DR EMBL; AK294955; BAG58030.1; -; mRNA.
DR EMBL; AC006435; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450226; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039204; AAH39204.1; -; mRNA.
DR EMBL; BC040590; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS32526.1; -. [O43147-2]
DR CCDS; CCDS45570.1; -. [O43147-1]
DR CCDS; CCDS86557.1; -. [O43147-5]
DR RefSeq; NP_001091979.1; NM_001098509.1. [O43147-1]
DR RefSeq; NP_001333629.1; NM_001346700.1. [O43147-5]
DR RefSeq; NP_055668.2; NM_014853.2. [O43147-2]
DR AlphaFoldDB; O43147; -.
DR SMR; O43147; -.
DR BioGRID; 115234; 26.
DR IntAct; O43147; 16.
DR STRING; 9606.ENSP00000268989; -.
DR iPTMnet; O43147; -.
DR PhosphoSitePlus; O43147; -.
DR BioMuta; SGSM2; -.
DR EPD; O43147; -.
DR jPOST; O43147; -.
DR MassIVE; O43147; -.
DR MaxQB; O43147; -.
DR PaxDb; O43147; -.
DR PeptideAtlas; O43147; -.
DR PRIDE; O43147; -.
DR ProteomicsDB; 48761; -. [O43147-1]
DR ProteomicsDB; 48762; -. [O43147-2]
DR ProteomicsDB; 48764; -. [O43147-5]
DR Antibodypedia; 10736; 82 antibodies from 22 providers.
DR DNASU; 9905; -.
DR Ensembl; ENST00000268989.8; ENSP00000268989.3; ENSG00000141258.13. [O43147-2]
DR Ensembl; ENST00000426855.6; ENSP00000415107.2; ENSG00000141258.13. [O43147-1]
DR Ensembl; ENST00000574563.5; ENSP00000459126.1; ENSG00000141258.13. [O43147-5]
DR GeneID; 9905; -.
DR KEGG; hsa:9905; -.
DR MANE-Select; ENST00000268989.8; ENSP00000268989.3; NM_014853.3; NP_055668.2. [O43147-2]
DR UCSC; uc002fum.5; human. [O43147-1]
DR CTD; 9905; -.
DR DisGeNET; 9905; -.
DR GeneCards; SGSM2; -.
DR HGNC; HGNC:29026; SGSM2.
DR HPA; ENSG00000141258; Low tissue specificity.
DR MIM; 611418; gene.
DR neXtProt; NX_O43147; -.
DR OpenTargets; ENSG00000141258; -.
DR PharmGKB; PA162403141; -.
DR VEuPathDB; HostDB:ENSG00000141258; -.
DR eggNOG; KOG1648; Eukaryota.
DR GeneTree; ENSGT00940000159315; -.
DR HOGENOM; CLU_006235_0_0_1; -.
DR InParanoid; O43147; -.
DR OMA; CHRSHCH; -.
DR OrthoDB; 171826at2759; -.
DR PhylomeDB; O43147; -.
DR TreeFam; TF318216; -.
DR PathwayCommons; O43147; -.
DR SignaLink; O43147; -.
DR BioGRID-ORCS; 9905; 43 hits in 1081 CRISPR screens.
DR ChiTaRS; SGSM2; human.
DR GeneWiki; SGSM2; -.
DR GenomeRNAi; 9905; -.
DR Pharos; O43147; Tbio.
DR PRO; PR:O43147; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O43147; protein.
DR Bgee; ENSG00000141258; Expressed in pancreatic ductal cell and 202 other tissues.
DR ExpressionAtlas; O43147; baseline and differential.
DR Genevisible; O43147; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0090630; P:activation of GTPase activity; IBA:GO_Central.
DR GO; GO:0034499; P:late endosome to Golgi transport; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR CDD; cd15784; PH_RUTBC; 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; IPR037745; SGSM1/2.
DR InterPro; IPR021935; SGSM1/2_RBD.
DR Pfam; PF12068; PH_RBD; 1.
DR Pfam; PF00566; RabGAP-TBC; 1.
DR Pfam; PF02759; RUN; 1.
DR SMART; SM00593; RUN; 1.
DR SMART; SM00164; TBC; 1.
DR SUPFAM; SSF140741; SSF140741; 1.
DR SUPFAM; SSF47923; SSF47923; 2.
DR PROSITE; PS50826; RUN; 1.
DR PROSITE; PS50086; TBC_RABGAP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; GTPase activation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1006
FT /note="Small G protein signaling modulator 2"
FT /id="PRO_0000284662"
FT DOMAIN 34..191
FT /note="RUN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00178"
FT DOMAIN 566..939
FT /note="Rab-GAP TBC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT REGION 96..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 657..768
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..727
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80U12"
FT VAR_SEQ 1..412
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024594"
FT VAR_SEQ 413..430
FT /note="ATDYVFRIIYPGHRHEHN -> MLSMICSRNLTAPNPMKD (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024595"
FT VAR_SEQ 430
FT /note="N -> ITINYHHLAASRAASVDDDEEEEDKLHAMLSMICSRNLTAPNPMKD
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17509819"
FT /id="VSP_024596"
FT VAR_SEQ 552..569
FT /note="NYKELELLRQVYYGGIEH -> VPTLGFQGHRSRGWGGQE (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024597"
FT VAR_SEQ 570..1006
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_024598"
FT VAR_SEQ 978..1006
FT /note="ERAEHHDAQEILRIARDLVHKVQMLIENK -> GTSLKTTCKK (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_035964"
FT VARIANT 63
FT /note="L -> M (in dbSNP:rs17853891)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031795"
FT VARIANT 238
FT /note="R -> K (in dbSNP:rs745400)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031796"
FT VARIANT 244
FT /note="R -> S (in dbSNP:rs17853888)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031797"
FT VARIANT 329
FT /note="H -> R (in dbSNP:rs17857178)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031798"
FT VARIANT 374
FT /note="R -> Q (in dbSNP:rs2248821)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031799"
FT VARIANT 968
FT /note="D -> V (in dbSNP:rs17857180)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17509819"
FT /id="VAR_031800"
FT MUTAGEN 803
FT /note="R->A: Loss of GTPase activator activity towards
FT RAB32, RAB33B and RAB38."
FT /evidence="ECO:0000269|PubMed:21808068,
FT ECO:0000269|PubMed:26620560"
FT CONFLICT 159
FT /note="E -> G (in Ref. 4; BAG58030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1006 AA; 113285 MW; 352F6F6D6017B570 CRC64;
MGSAEDAVKE KLLWNVKKEV KQIMEEAVTR KFVHEDSSHI IALCGAVEAC LLHQLRRRAA
GFLRSDKMAA LFTKVGKTCP VAGEICHKVQ ELQQQAEGRK PSGVSQEALR RQGSASGKAP
ALSPQALKHV WVRTALIEKV LDKVVQYLAE NCSKYYEKEA LLADPVFGPI LASLLVGPCA
LEYTKLKTAD HYWTDPSADE LVQRHRIRGP PTRQDSPAKR PALGIRKRHS SGSASEDRLA
ACARECVESL HQNSRTRLLY GKNHVLVQPK EDMEAVPGYL SLHQSAESLT LKWTPNQLMN
GTLGDSELEK SVYWDYALVV PFSQVVCIHC HQQKSGGTLV LVSQDGIQRP PLHFPQGGHL
LSFLSCLENG LLPRGQLEPP LWTQQGKGKV FPKLRKRSSI RSVDMEEMGT GRATDYVFRI
IYPGHRHEHN AGDMIEMQGF GPSLPAWHLE PLCSQGSSCL SCSSSSSPHA TPSHCSCIPD
RLPLRLLCES MKRQIVSRAF YGWLAHCRHL STVRTHLSAL VHHSVIPPDR PPGASAGLTK
DVWSKYQKDK KNYKELELLR QVYYGGIEHE IRKDVWPFLL GHYKFGMSKK EMEQVDAVVA
ARYQQVLAEW KACEVVVRQR EREAHPATRT KFSSGSSIDS HVQRLIHRDS TISNDVFISV
DDLEPPEPQD PEDSRPKPEQ EAGPGTPGTA VVEQQHSVEF DSPDSGLPSS RNYSVASGIQ
SSLDEGQSVG FEEEDGGGEE GSSGPGPAAH TLREPQDPSQ EKPQAGELEA GEELAAVCAA
AYTIELLDTV ALNLHRIDKD VQRCDRNYWY FTPPNLERLR DVMCSYVWEH LDVGYVQGMC
DLLAPLLVTL DNDQLAYSCF SHLMKRMSQN FPNGGAMDTH FANMRSLIQI LDSELFELMH
QNGDYTHFYF CYRWFLLDFK RELLYEDVFA VWEVIWAARH ISSEHFVLFI ALALVEAYRE
IIRDNNMDFT DIIKFFNERA EHHDAQEILR IARDLVHKVQ MLIENK
