GPSM2_HUMAN
ID GPSM2_HUMAN Reviewed; 684 AA.
AC P81274; Q5T1N8; Q6IBL7; Q8N0Z5;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=G-protein-signaling modulator 2;
DE AltName: Full=Mosaic protein LGN {ECO:0000303|PubMed:8973305};
GN Name=GPSM2; Synonyms=LGN;
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], AND INTERACTION WITH GNAI2.
RC TISSUE=B-cell;
RX PubMed=8973305; DOI=10.1016/s0378-1119(96)00456-8;
RA Mochizuki N., Cho G., Wen B., Insel P.A.;
RT "Identification and cDNA cloning of a novel human mosaic protein, LGN,
RT based on interaction with G alpha i2.";
RL Gene 181:39-43(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Katagiri T., Fukukawa C., Nakamura Y.;
RT "Involvement of C0671 overexpression in breast cancer cell growth.";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-684.
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-684.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION, INTERACTION WITH NUMA1, AND SUBCELLULAR LOCATION.
RX PubMed=11781568; DOI=10.1038/ncb1201-1069;
RA Du Q., Stukenberg P.T., Macara I.G.;
RT "A mammalian partner of inscuteable binds NuMA and regulates mitotic
RT spindle organization.";
RL Nat. Cell Biol. 3:1069-1075(2001).
RN [9]
RP FUNCTION, INTERACTION WITH LLGL2, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=15632202; DOI=10.1074/jbc.c400440200;
RA Yasumi M., Sakisaka T., Hoshino T., Kimura T., Sakamoto Y., Yamanaka T.,
RA Ohno S., Takai Y.;
RT "Direct binding of Lgl2 to LGN during mitosis and its requirement for
RT normal cell division.";
RL J. Biol. Chem. 280:6761-6765(2005).
RN [10]
RP INTERACTION WITH INSC, AND IDENTIFICATION IN A COMPLEX WITH INSC AND F2RL2.
RX PubMed=16458856; DOI=10.1016/j.bbrc.2006.01.050;
RA Izaki T., Kamakura S., Kohjima M., Sumimoto H.;
RT "Two forms of human Inscuteable-related protein that links Par3 to the Pins
RT homologues LGN and AGS3.";
RL Biochem. Biophys. Res. Commun. 341:1001-1006(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483; THR-486 AND SER-541, 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 [12]
RP INVOLVEMENT IN CMCS.
RX PubMed=20602914; DOI=10.1016/j.ajhg.2010.05.010;
RA Walsh T., Shahin H., Elkan-Miller T., Lee M.K., Thornton A.M., Roeb W.,
RA Abu Rayyan A., Loulus S., Avraham K.B., King M.C., Kanaan M.;
RT "Whole exome sequencing and homozygosity mapping identify mutation in the
RT cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss
RT DFNB82.";
RL Am. J. Hum. Genet. 87:90-94(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408 AND SER-565, 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 [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-228 AND ARG-243.
RX PubMed=21816348; DOI=10.1016/j.molcel.2011.07.011;
RA Zhu J., Wen W., Zheng Z., Shang Y., Wei Z., Xiao Z., Pan Z., Du Q.,
RA Wang W., Zhang M.;
RT "LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in
RT asymmetric cell division for the Par3/mInsc/LGN and Galphai/LGN/NuMA
RT pathways.";
RL Mol. Cell 43:418-431(2011).
RN [15]
RP INVOLVEMENT IN CMCS.
RX PubMed=22578326; DOI=10.1016/j.ajhg.2012.04.008;
RA Doherty D., Chudley A.E., Coghlan G., Ishak G.E., Innes A.M., Lemire E.G.,
RA Rogers R.C., Mhanni A.A., Phelps I.G., Jones S.J., Zhan S.H., Fejes A.P.,
RA Shahin H., Kanaan M., Akay H., Tekin M., Triggs-Raine B., Zelinski T.;
RT "GPSM2 mutations cause the brain malformations and hearing loss in Chudley-
RT McCullough syndrome.";
RL Am. J. Hum. Genet. 90:1088-1093(2012).
RN [16]
RP FUNCTION, INTERACTION WITH NUMA1, AND SUBCELLULAR LOCATION.
RX PubMed=22327364; DOI=10.1038/ncb2440;
RA Kiyomitsu T., Cheeseman I.M.;
RT "Chromosome- and spindle-pole-derived signals generate an intrinsic code
RT for spindle position and orientation.";
RL Nat. Cell Biol. 14:311-317(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-565, 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 [18]
RP IDENTIFICATION IN A SPINDLE ORIENTATION COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=26766442; DOI=10.1016/j.devcel.2015.12.016;
RA Chiu C.W., Monat C., Robitaille M., Lacomme M., Daulat A.M., Macleod G.,
RA McNeill H., Cayouette M., Angers S.;
RT "SAPCD2 controls spindle orientation and asymmetric divisions by negatively
RT regulating the Galphai-LGN-NuMA ternary complex.";
RL Dev. Cell 36:50-62(2016).
RN [19]
RP INTERACTION WITH NUMA1.
RX PubMed=27462074; DOI=10.1074/jbc.m116.724831;
RA Chu X., Chen X., Wan Q., Zheng Z., Du Q.;
RT "Nuclear mitotic apparatus (NuMA) interacts with and regulates astrin at
RT the mitotic spindle.";
RL J. Biol. Chem. 291:20055-20067(2016).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 20-421 IN COMPLEX WITH INSC,
RP INTERACTION WITH INSC; NUMA1; FRMPD1 AND FRMPD4, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ARG-228 AND ASN-290.
RX PubMed=22074847; DOI=10.1073/pnas.1110951108;
RA Yuzawa S., Kamakura S., Iwakiri Y., Hayase J., Sumimoto H.;
RT "Structural basis for interaction between the conserved cell polarity
RT proteins Inscuteable and Leu-Gly-Asn repeat-enriched protein (LGN).";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19210-19215(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 20-421 IN COMPLEX WITH FRMPD4,
RP AND INTERACTION WITH FRMPD4.
RX PubMed=25664792; DOI=10.1107/s2053230x14028143;
RA Takayanagi H., Yuzawa S., Sumimoto H.;
RT "Structural basis for the recognition of the scaffold protein Frmpd4/Preso1
RT by the TPR domain of the adaptor protein LGN.";
RL Acta Crystallogr. F 71:175-183(2015).
CC -!- FUNCTION: Plays an important role in mitotic spindle pole organization
CC via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202,
CC PubMed:21816348). Required for cortical dynein-dynactin complex
CC recruitment during metaphase (PubMed:22327364). Plays a role in
CC metaphase spindle orientation (PubMed:22327364). Also plays an
CC important role in asymmetric cell divisions (PubMed:21816348). Has
CC guanine nucleotide dissociation inhibitor (GDI) activity towards G(i)
CC alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their
CC activity (By similarity). {ECO:0000250|UniProtKB:Q8VDU0,
CC ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202,
CC ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364}.
CC -!- SUBUNIT: Interacts with the dynein-dynactin complex; this interaction
CC is inhibited in a PLK1-dependent manner (PubMed:22327364). Part of a
CC spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1
CC (PubMed:26766442). Interacts with LLGL2 (PubMed:15632202). Interacts
CC (via TPR repeat region) with INSC/inscuteable (PubMed:16458856,
CC PubMed:22074847). Interacts (via TPR repeat region) with NUMA1 (via C-
CC terminus); this interaction is direct, inhibited in a PLK1-dependent
CC manner, prevents the binding of NUMA1 with SPAG5 and promotes spindle
CC pole organization (PubMed:11781568, PubMed:22327364, PubMed:27462074).
CC INSC and NUMA1 compete for the same binding site, but INSC has higher
CC affinity and can displace NUMA1 (in vitro) (PubMed:22074847). Interacts
CC with GNAI2 (PubMed:8973305). Interacts (via GoLoco domains) with the
CC GDP-bound form of GNAI1 and GNAI3; has much lower affinity for the GTP-
CC bound form. Interaction with GDP-bound GNAI3 strongly enhances the
CC affinity for NUMA1 (By similarity). Interacts (via TPR repeat region)
CC with FRMPD1 (PubMed:22074847). INSC and FRMPD1 compete for the same
CC binding site, but INSC has higher affinity and can displace FRMPD1 (in
CC vitro) (By similarity). Interacts (via TPR repeat region) with FRMPD4
CC (PubMed:22074847, PubMed:25664792). Identified in a complex with INSC
CC and F2RL2/Par3 (PubMed:16458856). Interacts with TASOR (By similarity).
CC {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568,
CC ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:16458856,
CC ECO:0000269|PubMed:22074847, ECO:0000269|PubMed:22327364,
CC ECO:0000269|PubMed:25664792, ECO:0000269|PubMed:26766442,
CC ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:8973305}.
CC -!- INTERACTION:
CC P81274; Q8TER5-2: ARHGEF40; NbExp=3; IntAct=EBI-618655, EBI-10275150;
CC P81274; Q99501: GAS2L1; NbExp=3; IntAct=EBI-618655, EBI-10981762;
CC P81274; P63096: GNAI1; NbExp=3; IntAct=EBI-618655, EBI-618639;
CC P81274; P08754: GNAI3; NbExp=3; IntAct=EBI-618655, EBI-357563;
CC P81274; P81274: GPSM2; NbExp=7; IntAct=EBI-618655, EBI-618655;
CC P81274; Q1MX18: INSC; NbExp=3; IntAct=EBI-618655, EBI-12081118;
CC P81274; Q6NSJ5: LRRC8E; NbExp=3; IntAct=EBI-618655, EBI-8647013;
CC P81274; Q14980: NUMA1; NbExp=6; IntAct=EBI-618655, EBI-521611;
CC P81274; Q9P202: WHRN; NbExp=3; IntAct=EBI-618655, EBI-310886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11781568,
CC ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:22074847}. Cytoplasm,
CC cell cortex {ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348,
CC ECO:0000269|PubMed:22074847, ECO:0000269|PubMed:22327364}. Cytoplasm,
CC cytoskeleton, spindle pole {ECO:0000269|PubMed:11781568,
CC ECO:0000269|PubMed:21816348}. Lateral cell membrane
CC {ECO:0000269|PubMed:26766442}. Note=Localizes in the cytoplasm during
CC interphase and at cell cortex during metaphase (PubMed:11781568,
CC PubMed:15632202, PubMed:22074847). Colocalizes with NUMA1 to mitotic
CC spindle poles (PubMed:11781568, PubMed:21816348). Localized at the
CC central and lateral cell cortex regions in a RanGTP-dependent manner
CC (PubMed:22327364). In horizontally retinal progenitor dividing cells,
CC localized to the lateral cortical region. In vertically retinal
CC progenitor dividing cells, localized at the polar cortical region (By
CC similarity). {ECO:0000250|UniProtKB:Q8VDU0,
CC ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202,
CC ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22074847,
CC ECO:0000269|PubMed:22327364}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- DISEASE: Chudley-McCullough syndrome (CMCS) [MIM:604213]: An autosomal
CC recessive neurologic disorder characterized by early-onset
CC sensorineural deafness and specific brain anomalies on MRI, including
CC hypoplasia of the corpus callosum, enlarged cysterna magna with mild
CC focal cerebellar dysplasia, and nodular heterotopia. Some patients have
CC hydrocephalus. Psychomotor development is normal.
CC {ECO:0000269|PubMed:20602914, ECO:0000269|PubMed:22578326}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Dysfunction of LGN is associated with the phenotype of
CC multiple micronuclei due to chromosomal mis-segregation and defect in
CC cell division through mis-localization of mitotic spindle regulator
CC protein NUMA1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GPSM family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
CC {ECO:0000305}.
CC -!- CAUTION: Mutations in GPSM2 have been identified in people with
CC profound congenital non-syndromic deafness designated as DFNB82
CC (PubMed:20602914). Subsequent brain imaging of these individuals has
CC revealed frontal polymicrogyria, abnormal corpus callosum, and gray
CC matter heterotopia, consistent with a diagnosis of Chudley-McCullough
CC syndrome (PubMed:22578326). {ECO:0000305|PubMed:20602914,
CC ECO:0000305|PubMed:22578326}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB40385.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH27732.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U54999; AAB40385.1; ALT_INIT; mRNA.
DR EMBL; AB445462; BAH84760.1; -; mRNA.
DR EMBL; AL449266; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56340.1; -; Genomic_DNA.
DR EMBL; BC027732; AAH27732.1; ALT_INIT; mRNA.
DR EMBL; AY136740; AAN01266.1; -; mRNA.
DR EMBL; CR456786; CAG33067.1; -; mRNA.
DR CCDS; CCDS792.2; -.
DR PIR; JC5334; G02540.
DR RefSeq; NP_001307967.1; NM_001321038.1.
DR RefSeq; NP_001307968.1; NM_001321039.1.
DR RefSeq; NP_037428.3; NM_013296.4.
DR RefSeq; XP_011539603.1; XM_011541301.2.
DR RefSeq; XP_011539604.1; XM_011541302.2.
DR RefSeq; XP_016856586.1; XM_017001097.1.
DR RefSeq; XP_016856587.1; XM_017001098.1.
DR PDB; 3SF4; X-ray; 2.60 A; A/B/C=20-421.
DR PDB; 4WND; X-ray; 1.50 A; A=20-421.
DR PDB; 4WNE; X-ray; 2.00 A; A=20-421.
DR PDB; 4WNF; X-ray; 2.90 A; A=20-421.
DR PDB; 4WNG; X-ray; 2.11 A; A=20-421.
DR PDB; 5A6C; X-ray; 2.90 A; A/B=22-357.
DR PDB; 6HC2; X-ray; 4.31 A; A/C/E/G/I/K/M/O/Q/S/U/W=14-374.
DR PDBsum; 3SF4; -.
DR PDBsum; 4WND; -.
DR PDBsum; 4WNE; -.
DR PDBsum; 4WNF; -.
DR PDBsum; 4WNG; -.
DR PDBsum; 5A6C; -.
DR PDBsum; 6HC2; -.
DR AlphaFoldDB; P81274; -.
DR SMR; P81274; -.
DR BioGRID; 118949; 24.
DR CORUM; P81274; -.
DR DIP; DIP-399N; -.
DR IntAct; P81274; 21.
DR MINT; P81274; -.
DR STRING; 9606.ENSP00000385510; -.
DR iPTMnet; P81274; -.
DR PhosphoSitePlus; P81274; -.
DR BioMuta; GPSM2; -.
DR DMDM; 294862507; -.
DR EPD; P81274; -.
DR jPOST; P81274; -.
DR MassIVE; P81274; -.
DR MaxQB; P81274; -.
DR PaxDb; P81274; -.
DR PeptideAtlas; P81274; -.
DR PRIDE; P81274; -.
DR ProteomicsDB; 57693; -.
DR Antibodypedia; 1983; 205 antibodies from 34 providers.
DR DNASU; 29899; -.
DR Ensembl; ENST00000264126.9; ENSP00000264126.3; ENSG00000121957.15.
DR Ensembl; ENST00000406462.6; ENSP00000385510.1; ENSG00000121957.15.
DR Ensembl; ENST00000446797.2; ENSP00000392138.2; ENSG00000121957.15.
DR Ensembl; ENST00000642355.1; ENSP00000496104.1; ENSG00000121957.15.
DR Ensembl; ENST00000645164.2; ENSP00000496756.2; ENSG00000121957.15.
DR Ensembl; ENST00000676184.1; ENSP00000502178.1; ENSG00000121957.15.
DR GeneID; 29899; -.
DR KEGG; hsa:29899; -.
DR MANE-Select; ENST00000264126.9; ENSP00000264126.3; NM_013296.5; NP_037428.3.
DR UCSC; uc010ovc.3; human.
DR CTD; 29899; -.
DR DisGeNET; 29899; -.
DR GeneCards; GPSM2; -.
DR HGNC; HGNC:29501; GPSM2.
DR HPA; ENSG00000121957; Tissue enhanced (brain, tongue).
DR MalaCards; GPSM2; -.
DR MIM; 604213; phenotype.
DR MIM; 609245; gene.
DR neXtProt; NX_P81274; -.
DR OpenTargets; ENSG00000121957; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 314597; Chudley-McCullough syndrome.
DR PharmGKB; PA134993615; -.
DR VEuPathDB; HostDB:ENSG00000121957; -.
DR eggNOG; KOG1130; Eukaryota.
DR GeneTree; ENSGT00940000161257; -.
DR HOGENOM; CLU_012445_1_0_1; -.
DR InParanoid; P81274; -.
DR OMA; PEDRSFH; -.
DR OrthoDB; 733786at2759; -.
DR PhylomeDB; P81274; -.
DR TreeFam; TF328344; -.
DR PathwayCommons; P81274; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P81274; -.
DR SIGNOR; P81274; -.
DR BioGRID-ORCS; 29899; 14 hits in 1086 CRISPR screens.
DR ChiTaRS; GPSM2; human.
DR GeneWiki; GPSM2; -.
DR GenomeRNAi; 29899; -.
DR Pharos; P81274; Tbio.
DR PRO; PR:P81274; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P81274; protein.
DR Bgee; ENSG00000121957; Expressed in tibia and 196 other tissues.
DR ExpressionAtlas; P81274; baseline and differential.
DR Genevisible; P81274; HS.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0099738; C:cell cortex region; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0097575; C:lateral cell cortex; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0070840; F:dynein complex binding; IDA:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IBA:GO_Central.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0051661; P:maintenance of centrosome location; IMP:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB.
DR GO; GO:1904778; P:positive regulation of protein localization to cell cortex; IMP:UniProtKB.
DR GO; GO:1905832; P:positive regulation of spindle assembly; IMP:UniProtKB.
DR GO; GO:0031291; P:Ran protein signal transduction; IMP:UniProtKB.
DR GO; GO:0060236; P:regulation of mitotic spindle organization; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 3.
DR IDEAL; IID00313; -.
DR InterPro; IPR003109; GoLoco_motif.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF02188; GoLoco; 4.
DR Pfam; PF13176; TPR_7; 2.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00390; GoLoco; 4.
DR SMART; SM00028; TPR; 7.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50877; GOLOCO; 4.
DR PROSITE; PS50005; TPR; 6.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cell division; Cell membrane; Cytoplasm;
KW Cytoskeleton; Deafness; Membrane; Mitosis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; TPR repeat; Transport.
FT CHAIN 1..684
FT /note="G-protein-signaling modulator 2"
FT /id="PRO_0000106358"
FT REPEAT 24..57
FT /note="TPR 1"
FT REPEAT 62..95
FT /note="TPR 2"
FT REPEAT 102..135
FT /note="TPR 3"
FT REPEAT 142..184
FT /note="TPR 4"
FT REPEAT 202..235
FT /note="TPR 5"
FT REPEAT 242..275
FT /note="TPR 6"
FT REPEAT 282..315
FT /note="TPR 7"
FT REPEAT 322..355
FT /note="TPR 8"
FT DOMAIN 489..511
FT /note="GoLoco 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 544..566
FT /note="GoLoco 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 594..616
FT /note="GoLoco 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 628..650
FT /note="GoLoco 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT REGION 22..357
FT /note="Important for interaction with NUMA1; INSC and
FT FRMPD1"
FT /evidence="ECO:0000250|UniProtKB:Q8VDU0"
FT BINDING 608
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q8VDU0"
FT BINDING 613
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q8VDU0"
FT BINDING 642
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q8VDU0"
FT BINDING 647
FT /ligand="GDP"
FT /ligand_id="ChEBI:CHEBI:58189"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q8VDU0"
FT MOD_RES 132
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000255"
FT MOD_RES 352
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000255"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 486
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 501
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255"
FT MOD_RES 541
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 607
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000255"
FT MUTAGEN 228
FT /note="R->A: Abolishes location at mitotic spindle poles;
FT when associated with A-243."
FT /evidence="ECO:0000269|PubMed:21816348"
FT MUTAGEN 228
FT /note="R->E: Strongly reduces interaction with INSC.
FT Abolishes interaction with INSC; when associated with R-
FT 290."
FT /evidence="ECO:0000269|PubMed:22074847"
FT MUTAGEN 243
FT /note="R->A: Abolishes location at mitotic spindle poles;
FT when associated with A-228."
FT /evidence="ECO:0000269|PubMed:21816348"
FT MUTAGEN 290
FT /note="N->R: Abolishes interaction with INSC; when
FT associated with E-228."
FT /evidence="ECO:0000269|PubMed:22074847"
FT CONFLICT 400
FT /note="R -> L (in Ref. 1; AAB40385)"
FT /evidence="ECO:0000305"
FT HELIX 24..36
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 40..53
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 58..74
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 78..94
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 98..115
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 118..134
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 138..158
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:4WNF"
FT HELIX 172..194
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 198..215
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 218..234
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 238..254
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 258..272
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 278..294
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 298..314
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 318..334
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 338..354
FT /evidence="ECO:0007829|PDB:4WND"
FT HELIX 358..376
FT /evidence="ECO:0007829|PDB:3SF4"
SQ SEQUENCE 684 AA; 76662 MW; D007A4765F57CB90 CRC64;
MEENLISMRE DHSFHVRYRM EASCLELALE GERLCKSGDC RAGVSFFEAA VQVGTEDLKT
LSAIYSQLGN AYFYLHDYAK ALEYHHHDLT LARTIGDQLG EAKASGNLGN TLKVLGNFDE
AIVCCQRHLD ISRELNDKVG EARALYNLGN VYHAKGKSFG CPGPQDVGEF PEEVRDALQA
AVDFYEENLS LVTALGDRAA QGRAFGNLGN THYLLGNFRD AVIAHEQRLL IAKEFGDKAA
ERRAYSNLGN AYIFLGEFET ASEYYKKTLL LARQLKDRAV EAQSCYSLGN TYTLLQDYEK
AIDYHLKHLA IAQELNDRIG EGRACWSLGN AYTALGNHDQ AMHFAEKHLE ISREVGDKSG
ELTARLNLSD LQMVLGLSYS TNNSIMSENT EIDSSLNGVR PKLGRRHSME NMELMKLTPE
KVQNWNSEIL AKQKPLIAKP SAKLLFVNRL KGKKYKTNSS TKVLQDASNS IDHRIPNSQR
KISADTIGDE GFFDLLSRFQ SNRMDDQRCC LQEKNCHTAS TTTSSTPPKM MLKTSSVPVV
SPNTDEFLDL LASSQSRRLD DQRASFSNLP GLRLTQNSQS VLSHLMTNDN KEADEDFFDI
LVKCQGSRLD DQRCAPPPAT TKGPTVPDED FFSLILRSQG KRMDEQRVLL QRDQNRDTDF
GLKDFLQNNA LLEFKNSGKK SADH
