GPS2_HUMAN
ID GPS2_HUMAN Reviewed; 327 AA.
AC Q13227; B4DXA1; Q6FHM8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=G protein pathway suppressor 2 {ECO:0000303|PubMed:19917673, ECO:0000303|PubMed:8943324};
DE Short=GPS-2 {ECO:0000303|PubMed:19917673};
GN Name=GPS2 {ECO:0000312|HGNC:HGNC:4550};
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), TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=8943324; DOI=10.1128/mcb.16.12.6698;
RA Spain B.H., Bowdish K.S., Pacal A., Flueckiger Staub S., Koo D.,
RA Chang K.-Y.R., Xie W., Colicelli J.;
RT "Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress
RT G-protein- and mitogen-activated protein kinase-mediated signal
RT transduction in yeast and mammalian cells.";
RL Mol. Cell. Biol. 16:6698-6706(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
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 IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE N-COR
RP COMPLEX WITH NCOR1; NCOR2; TBL1X; TBL1R AND HDAC3.
RX PubMed=11931768; DOI=10.1016/s1097-2765(02)00468-9;
RA Zhang J., Kalkum M., Chait B.T., Roeder R.G.;
RT "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK
RT pathway through the integral subunit GPS2.";
RL Mol. Cell 9:611-623(2002).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE N-COR COMPLEX.
RX PubMed=19858209; DOI=10.1074/jbc.m109.062109;
RA Cheng X., Kao H.Y.;
RT "G protein pathway suppressor 2 (GPS2) is a transcriptional corepressor
RT important for estrogen receptor alpha-mediated transcriptional
RT regulation.";
RL J. Biol. Chem. 284:36395-36404(2009).
RN [10]
RP FUNCTION, AND INTERACTION WITH NR1H3.
RX PubMed=19481530; DOI=10.1016/j.molcel.2009.05.006;
RA Jakobsson T., Venteclef N., Toresson G., Damdimopoulos A.E., Ehrlund A.,
RA Lou X., Sanyal S., Steffensen K.R., Gustafsson J.A., Treuter E.;
RT "GPS2 is required for cholesterol efflux by triggering histone
RT demethylation, LXR recruitment, and coregulator assembly at the ABCG1
RT locus.";
RL Mol. Cell 34:510-518(2009).
RN [11]
RP METHYLATION AT ARG-323, AND MUTAGENESIS OF SER-319; GLN-320; ASN-321;
RP PRO-322; PHE-324; TYR-325 AND LYS-327.
RX PubMed=19917673; DOI=10.1096/fj.09-136283;
RA Jarmalavicius S., Trefzer U., Walden P.;
RT "Differential arginine methylation of the G-protein pathway suppressor GPS-
RT 2 recognized by tumor-specific T cells in melanoma.";
RL FASEB J. 24:937-946(2010).
RN [12]
RP FUNCTION, INTERACTION WITH NR5A2 AND NR1H2, AND MUTAGENESIS OF
RP 61-SER--LEU-94; 69-ILE-LEU-70; 76-LEU--LEU-79 AND 86-LEU--LEU-90.
RX PubMed=20159957; DOI=10.1101/gad.545110;
RA Venteclef N., Jakobsson T., Ehrlund A., Damdimopoulos A., Mikkonen L.,
RA Ellis E., Nilsson L.M., Parini P., Jaenne O.A., Gustafsson J.A.,
RA Steffensen K.R., Treuter E.;
RT "GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions
RT of LRH-1 and LXRbeta in the hepatic acute phase response.";
RL Genes Dev. 24:381-395(2010).
RN [13]
RP INTERACTION WITH ANKRD26.
RX PubMed=22666460; DOI=10.1371/journal.pone.0038130;
RA Liu X.F., Bera T.K., Kahue C., Escobar T., Fei Z., Raciti G.A., Pastan I.;
RT "ANKRD26 and its interacting partners TRIO, GPS2, HMMR and DIPA regulate
RT adipogenesis in 3T3-L1 cells.";
RL PLoS ONE 7:E38130-E38130(2012).
RN [14]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH HCV NS5A (MICROBIAL
RP INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=24223774; DOI=10.1371/journal.pone.0078195;
RA Xu G., Xin X., Zheng C.;
RT "GPS2 is required for the association of NS5A with VAP-A and hepatitis C
RT virus replication.";
RL PLoS ONE 8:E78195-E78195(2013).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TBL1X, SUMOYLATION AT
RP LYS-45 AND LYS-71, AND MUTAGENESIS OF LYS-45 AND LYS-71.
RX PubMed=24943844; DOI=10.1091/mbc.e13-12-0733;
RA Bi H., Li S., Wang M., Jia Z., Chang A.K., Pang P., Wu H.;
RT "SUMOylation of GPS2 protein regulates its transcription-suppressing
RT function.";
RL Mol. Biol. Cell 25:2499-2508(2014).
RN [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-312 AND ARG-323, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [17]
RP INDUCTION.
RX PubMed=27270589; DOI=10.1038/nm.4114;
RA Fan R., Toubal A., Goni S., Drareni K., Huang Z., Alzaid F., Ballaire R.,
RA Ancel P., Liang N., Damdimopoulos A., Hainault I., Soprani A.,
RA Aron-Wisnewsky J., Foufelle F., Lawrence T., Gautier J.F., Venteclef N.,
RA Treuter E.;
RT "Loss of the co-repressor GPS2 sensitizes macrophage activation upon
RT metabolic stress induced by obesity and type 2 diabetes.";
RL Nat. Med. 22:780-791(2016).
RN [18]
RP FUNCTION, AND INDUCTION.
RX PubMed=27460081; DOI=10.1007/s13277-016-5220-x;
RA Huang X.D., Xiao F.J., Wang S.X., Yin R.H., Lu C.R., Li Q.F., Liu N.,
RA Zhang Y., Wang L.S., Li P.Y.;
RT "G protein pathway suppressor 2 (GPS2) acts as a tumor suppressor in
RT liposarcoma.";
RL Tumor Biol. 37:13333-13343(2016).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29499132; DOI=10.1016/j.molcel.2018.01.037;
RA Cardamone M.D., Tanasa B., Cederquist C.T., Huang J., Mahdaviani K., Li W.,
RA Rosenfeld M.G., Liesa M., Perissi V.;
RT "Mitochondrial retrograde signaling in mammals is mediated by the
RT transcriptional cofactor GPS2 via direct mitochondria-to-nucleus
RT translocation.";
RL Mol. Cell 69:757-772(2018).
RN [20] {ECO:0007744|PDB:2L5G}
RP STRUCTURE BY NMR OF 53-90, IDENTIFICATION IN THE N-COR COMPLEX, INTERACTION
RP WITH TBL1X, AND MUTAGENESIS OF 19-HIS--ILE-22.
RX PubMed=21240272; DOI=10.1038/nsmb.1983;
RA Oberoi J., Fairall L., Watson P.J., Yang J.C., Czimmerer Z., Kampmann T.,
RA Goult B.T., Greenwood J.A., Gooch J.T., Kallenberger B.C., Nagy L.,
RA Neuhaus D., Schwabe J.W.;
RT "Structural basis for the assembly of the SMRT/NCoR core transcriptional
RT repression machinery.";
RL Nat. Struct. Mol. Biol. 18:177-184(2011).
CC -!- FUNCTION: Key regulator of inflammation, lipid metabolism and
CC mitochondrion homeostasis that acts by inhibiting the activity of the
CC ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-
CC linked ubiquitination (By similarity). In the nucleus, can both acts as
CC a corepressor and coactivator of transcription, depending on the
CC context (PubMed:24943844). Acts as a transcription coactivator in
CC adipocytes by promoting the recruitment of PPARG to promoters: acts by
CC inhibiting the activity of the ubiquitin-conjugating enzyme
CC UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone
CC H3 'Lys-9' (H3K9) demethylation (By similarity). Promotes cholesterol
CC efflux by acting as a transcription coactivator (PubMed:19481530). Acts
CC as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby
CC restricting the activation of Toll-like receptors (TLRs) and B-cell
CC antigen receptors (BCRs) signaling pathways (By similarity). Acts as a
CC key mediator of mitochondrial stress response: in response to
CC mitochondrial depolarization, relocates from the mitochondria to the
CC nucleus following desumoylation and specifically promotes expression of
CC nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes
CC transcription of nuclear-encoded mitochondrial genes by inhibiting
CC UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of
CC the N-Cor repressor complex by repressing active PPARG
CC (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in
CC macrophages and is required for insulin sensitivity by acting as a
CC corepressor (By similarity). Plays an anti-inflammatory role during the
CC hepatic acute phase response by interacting with sumoylated NR1H2 and
CC NR5A2 proteins, thereby preventing N-Cor corepressor complex
CC dissociation (PubMed:20159957). In the cytosol, also plays a non-
CC transcriptional role by regulating insulin signaling and pro-
CC inflammatory pathways (By similarity). In the cytoplasm, acts as a
CC negative regulator of inflammation by inhibiting the pro-inflammatory
CC TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (By
CC similarity). In the cytoplasm of adipocytes, restricts the activation
CC of insulin signaling via inhibition of UBE2N/Ubc13-mediated
CC ubiquitination of AKT (By similarity). Able to suppress G-protein- and
CC mitogen-activated protein kinase-mediated signal transduction
CC (PubMed:8943324). Acts as a tumor-suppressor in liposarcoma
CC (PubMed:27460081). {ECO:0000250|UniProtKB:Q921N8,
CC ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:19858209,
CC ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:24943844,
CC ECO:0000269|PubMed:27460081, ECO:0000269|PubMed:29499132,
CC ECO:0000269|PubMed:8943324}.
CC -!- FUNCTION: (Microbial infection) Required for efficient replication of
CC hepatitis C virus (HCV) by promoting the interaction between VAPA and
CC HCV virus protein NS5A. {ECO:0000269|PubMed:24223774}.
CC -!- SUBUNIT: Component of the N-Cor repressor complex, at least composed of
CC NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:11931768,
CC PubMed:19858209, PubMed:21240272). Interacts (when sumoylated at Lys-
CC 71) with TBL1X; leading to protect GPS2 from degradation by the
CC proteasome (PubMed:24943844, PubMed:21240272). Interacts with UBE2N;
CC leading to inhibit UBE2N/Ubc13 activity (By similarity). Interacts with
CC TRAF1 (By similarity). Interacts with TRAF2 (By similarity). Interacts
CC with TRAF6 (By similarity). Interacts with PPARG (when in the liganded
CC conformation) (By similarity). Interacts with (sumoylated) NR1H2;
CC interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase
CC protein promoters prevents N-Cor corepressor complex dissociation
CC (PubMed:20159957). Interacts with (sumoylated) NR5A2; interaction with
CC sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters
CC prevents N-Cor corepressor complex dissociation (PubMed:20159957).
CC Interacts with NR1H3 (PubMed:19481530). Interacts with RFX4 (By
CC similarity). Interacts with ANKRD26 (PubMed:22666460).
CC {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:11931768,
CC ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:19858209,
CC ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:21240272,
CC ECO:0000269|PubMed:22666460, ECO:0000305|PubMed:24943844}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via coiled coil domain) with
CC hepatitis C virus (HCV) NS5A. {ECO:0000269|PubMed:24223774}.
CC -!- INTERACTION:
CC Q13227; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-713355, EBI-357530;
CC Q13227; P18848: ATF4; NbExp=13; IntAct=EBI-713355, EBI-492498;
CC Q13227; Q9Y2D1: ATF5; NbExp=3; IntAct=EBI-713355, EBI-492509;
CC Q13227; O95429: BAG4; NbExp=3; IntAct=EBI-713355, EBI-2949658;
CC Q13227; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-713355, EBI-11976299;
CC Q13227; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-713355, EBI-3867333;
CC Q13227; Q15038: DAZAP2; NbExp=3; IntAct=EBI-713355, EBI-724310;
CC Q13227; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-713355, EBI-12193763;
CC Q13227; Q5TD97: FHL5; NbExp=3; IntAct=EBI-713355, EBI-750641;
CC Q13227; Q13547: HDAC1; NbExp=2; IntAct=EBI-713355, EBI-301834;
CC Q13227; O15379: HDAC3; NbExp=6; IntAct=EBI-713355, EBI-607682;
CC Q13227; P31943: HNRNPH1; NbExp=3; IntAct=EBI-713355, EBI-351590;
CC Q13227; P49639: HOXA1; NbExp=3; IntAct=EBI-713355, EBI-740785;
CC Q13227; Q5TA45: INTS11; NbExp=3; IntAct=EBI-713355, EBI-748258;
CC Q13227; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-713355, EBI-3044087;
CC Q13227; Q15323: KRT31; NbExp=7; IntAct=EBI-713355, EBI-948001;
CC Q13227; O76011: KRT34; NbExp=3; IntAct=EBI-713355, EBI-1047093;
CC Q13227; O76013-2: KRT36; NbExp=3; IntAct=EBI-713355, EBI-11958506;
CC Q13227; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-713355, EBI-1052037;
CC Q13227; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-713355, EBI-11953846;
CC Q13227; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-713355, EBI-9996449;
CC Q13227; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-713355, EBI-3957694;
CC Q13227; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-713355, EBI-12111050;
CC Q13227; Q3LI66: KRTAP6-2; NbExp=5; IntAct=EBI-713355, EBI-11962084;
CC Q13227; P57077: MAP3K7CL; NbExp=2; IntAct=EBI-713355, EBI-748831;
CC Q13227; A0A024RBS3: NCOR2; NbExp=4; IntAct=EBI-713355, EBI-15904969;
CC Q13227; Q9UHB4: NDOR1; NbExp=5; IntAct=EBI-713355, EBI-10249760;
CC Q13227; O43482: OIP5; NbExp=5; IntAct=EBI-713355, EBI-536879;
CC Q13227; Q16633: POU2AF1; NbExp=3; IntAct=EBI-713355, EBI-943588;
CC Q13227; Q15311: RALBP1; NbExp=11; IntAct=EBI-713355, EBI-749285;
CC Q13227; Q93062: RBPMS; NbExp=3; IntAct=EBI-713355, EBI-740322;
CC Q13227; Q86VW0: SESTD1; NbExp=7; IntAct=EBI-713355, EBI-6117072;
CC Q13227; Q53HV7-2: SMUG1; NbExp=3; IntAct=EBI-713355, EBI-12275818;
CC Q13227; O60907-2: TBL1X; NbExp=6; IntAct=EBI-713355, EBI-15904933;
CC Q13227; Q9UBB9: TFIP11; NbExp=6; IntAct=EBI-713355, EBI-1105213;
CC Q13227; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-713355, EBI-11952721;
CC Q13227; Q15654: TRIP6; NbExp=3; IntAct=EBI-713355, EBI-742327;
CC Q13227; Q8WUN7: UBTD2; NbExp=3; IntAct=EBI-713355, EBI-12867288;
CC Q13227; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-713355, EBI-2559305;
CC Q13227; P12504: vif; Xeno; NbExp=2; IntAct=EBI-713355, EBI-779991;
CC Q13227; PRO_0000037551 [Q9WMX2]; Xeno; NbExp=2; IntAct=EBI-713355, EBI-6863748;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19858209,
CC ECO:0000269|PubMed:24943844, ECO:0000269|PubMed:29499132}.
CC Mitochondrion {ECO:0000269|PubMed:29499132}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:24223774, ECO:0000269|PubMed:24943844,
CC ECO:0000269|PubMed:29499132}. Note=Sumoylation regulates the
CC subcellular location (PubMed:24943844). Relocates from the mitochondria
CC to the nucleus following desumoylation, leading to mediate
CC mitochondrial stress response (By similarity).
CC {ECO:0000250|UniProtKB:Q921N8, ECO:0000269|PubMed:24943844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13227-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13227-2; Sequence=VSP_057012;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8943324}.
CC -!- INDUCTION: Down-regulated in liposarcoma (PubMed:27460081). Down-
CC regulated in macrophages of patients with adipose tissue inflammation
CC and type-2 diabetes (PubMed:27270589). {ECO:0000269|PubMed:27270589,
CC ECO:0000269|PubMed:27460081}.
CC -!- PTM: Sumoylation regulates its subcellular location (PubMed:24943844).
CC Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the
CC cytoplasm and the nucleus (PubMed:24943844). Sumoylation at Lys-71 is
CC required for interaction with TBL1X (By similarity). Sumoylated at Lys-
CC 45 and Lys-71 in mitochondrion (By similarity). Desumoylation by SENP1
CC leads to relocation from the mitochondria to the nucleus (By
CC similarity). {ECO:0000250|UniProtKB:Q921N8,
CC ECO:0000269|PubMed:24943844}.
CC -!- PTM: Ubiquitinated at the C-terminus by SIAH2; leading to its
CC degradation by the proteasome. Interaction with TBL1X and methylation
CC at Arg-323 protect GPS2 against ubiquitination and degradation.
CC {ECO:0000250|UniProtKB:Q921N8}.
CC -!- PTM: Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323
CC protects from degradation by the proteasome.
CC {ECO:0000250|UniProtKB:Q921N8}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB75677.2; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; U28963; AAB60432.1; -; mRNA.
DR EMBL; BT006998; AAP35644.1; -; mRNA.
DR EMBL; AK301877; BAG63313.1; -; mRNA.
DR EMBL; CR541723; CAG46524.1; -; mRNA.
DR EMBL; CR541750; CAG46550.1; -; mRNA.
DR EMBL; AL122080; CAB59255.1; -; mRNA.
DR EMBL; AL157493; CAB75677.2; ALT_SEQ; mRNA.
DR EMBL; AC026954; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013652; AAH13652.1; -; mRNA.
DR EMBL; BC103901; AAI03902.1; -; mRNA.
DR EMBL; BC103903; AAI03904.1; -; mRNA.
DR EMBL; BC107738; AAI07739.1; -; mRNA.
DR CCDS; CCDS11100.1; -. [Q13227-1]
DR PIR; T34562; T34562.
DR RefSeq; NP_004480.1; NM_004489.4. [Q13227-1]
DR PDB; 2L5G; NMR; -; A=53-90.
DR PDBsum; 2L5G; -.
DR AlphaFoldDB; Q13227; -.
DR BMRB; Q13227; -.
DR SMR; Q13227; -.
DR BioGRID; 109132; 131.
DR CORUM; Q13227; -.
DR DIP; DIP-34427N; -.
DR IntAct; Q13227; 121.
DR MINT; Q13227; -.
DR STRING; 9606.ENSP00000370104; -.
DR GlyGen; Q13227; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13227; -.
DR PhosphoSitePlus; Q13227; -.
DR BioMuta; GPS2; -.
DR DMDM; 6226623; -.
DR EPD; Q13227; -.
DR jPOST; Q13227; -.
DR MassIVE; Q13227; -.
DR MaxQB; Q13227; -.
DR PaxDb; Q13227; -.
DR PeptideAtlas; Q13227; -.
DR PRIDE; Q13227; -.
DR ProteomicsDB; 5420; -.
DR ProteomicsDB; 59233; -. [Q13227-1]
DR Antibodypedia; 11906; 222 antibodies from 26 providers.
DR DNASU; 2874; -.
DR Ensembl; ENST00000380728.7; ENSP00000370104.2; ENSG00000132522.16. [Q13227-1]
DR Ensembl; ENST00000389167.9; ENSP00000379841.4; ENSG00000132522.16. [Q13227-1]
DR Ensembl; ENST00000672046.1; ENSP00000500677.1; ENSG00000288325.1. [Q13227-1]
DR Ensembl; ENST00000673265.1; ENSP00000500255.1; ENSG00000288325.1. [Q13227-1]
DR GeneID; 2874; -.
DR KEGG; hsa:2874; -.
DR MANE-Select; ENST00000380728.7; ENSP00000370104.2; NM_004489.5; NP_004480.1.
DR UCSC; uc002gfx.2; human. [Q13227-1]
DR CTD; 2874; -.
DR DisGeNET; 2874; -.
DR GeneCards; GPS2; -.
DR HGNC; HGNC:4550; GPS2.
DR HPA; ENSG00000132522; Low tissue specificity.
DR MIM; 601935; gene.
DR neXtProt; NX_Q13227; -.
DR OpenTargets; ENSG00000132522; -.
DR PharmGKB; PA28945; -.
DR VEuPathDB; HostDB:ENSG00000132522; -.
DR eggNOG; ENOG502RFJB; Eukaryota.
DR GeneTree; ENSGT00390000004049; -.
DR InParanoid; Q13227; -.
DR OMA; QIEHANQ; -.
DR OrthoDB; 1206280at2759; -.
DR PhylomeDB; Q13227; -.
DR TreeFam; TF329067; -.
DR PathwayCommons; Q13227; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-9022537; Loss of MECP2 binding ability to the NCoR/SMRT complex.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR SignaLink; Q13227; -.
DR BioGRID-ORCS; 2874; 37 hits in 1088 CRISPR screens.
DR ChiTaRS; GPS2; human.
DR GeneWiki; GPS2_(gene); -.
DR GenomeRNAi; 2874; -.
DR Pharos; Q13227; Tbio.
DR PRO; PR:Q13227; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q13227; protein.
DR Bgee; ENSG00000132522; Expressed in left testis and 94 other tissues.
DR ExpressionAtlas; Q13227; baseline and differential.
DR Genevisible; Q13227; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR GO; GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc.
DR GO; GO:0050859; P:negative regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:1900045; P:negative regulation of protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:UniProtKB.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045598; P:regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0098780; P:response to mitochondrial depolarisation; ISS:UniProtKB.
DR IDEAL; IID00320; -.
DR InterPro; IPR026094; GPS2.
DR PANTHER; PTHR22654; PTHR22654; 1.
DR Pfam; PF15991; G_path_suppress; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Coiled coil; Cytoplasm;
KW Host-virus interaction; Isopeptide bond; Methylation; Mitochondrion;
KW Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..327
FT /note="G protein pathway suppressor 2"
FT /id="PRO_0000087565"
FT REGION 26..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..94
FT /note="interaction with SUMO"
FT /evidence="ECO:0000269|PubMed:20159957"
FT REGION 177..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 14..109
FT /evidence="ECO:0000255"
FT COMPBIAS 253..273
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 312
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 323
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:19917673,
FT ECO:0007744|PubMed:24129315"
FT MOD_RES 323
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000269|PubMed:19917673"
FT CROSSLNK 45
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000269|PubMed:24943844"
FT CROSSLNK 71
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000269|PubMed:24943844"
FT VAR_SEQ 301..327
FT /note="SGFAATSQPGPRLPFIQHSQNPRFYHK -> TAP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057012"
FT VARIANT 306
FT /note="T -> A (in dbSNP:rs2292065)"
FT /id="VAR_021972"
FT MUTAGEN 19..22
FT /note="HRHI->AEHA: Abolishes interaction with TBL1X."
FT /evidence="ECO:0000269|PubMed:21240272"
FT MUTAGEN 45
FT /note="K->R: Abolishes sumoylation; when associated with R-
FT 71."
FT /evidence="ECO:0000269|PubMed:24943844"
FT MUTAGEN 61..94
FT /note="Missing: Abolishes interaction with sumoylated NR1H2
FT and NR5A2 proteins."
FT /evidence="ECO:0000269|PubMed:20159957"
FT MUTAGEN 69..70
FT /note="IL->AA: Weakly affects interaction with sumoylated
FT NR1H2 and NR5A2 proteins."
FT /evidence="ECO:0000269|PubMed:20159957"
FT MUTAGEN 71
FT /note="K->R: Abolishes sumoylation; when associated with R-
FT 45."
FT /evidence="ECO:0000269|PubMed:24943844"
FT MUTAGEN 76..79
FT /note="LLAL->RRAR: Weakly affects interaction with
FT sumoylated NR1H2 and NR5A2 proteins."
FT /evidence="ECO:0000269|PubMed:20159957"
FT MUTAGEN 86..90
FT /note="LFLQL->RFRQR: Weakly affects interaction with
FT sumoylated NR1H2 and NR5A2 proteins."
FT /evidence="ECO:0000269|PubMed:20159957"
FT MUTAGEN 319
FT /note="S->A: Does not affect methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 320
FT /note="Q->A: Does not affect methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 321
FT /note="N->A: Strongly decreases methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 322
FT /note="P->A: Strongly decreases methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 324
FT /note="F->A: Abolishes methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 325
FT /note="Y->A: Abolishes methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT MUTAGEN 327
FT /note="K->A: Decreases methylation."
FT /evidence="ECO:0000269|PubMed:19917673"
FT HELIX 57..89
FT /evidence="ECO:0007829|PDB:2L5G"
SQ SEQUENCE 327 AA; 36689 MW; AE65DA578C978C9B CRC64;
MPALLERPKL SNAMARALHR HIMMERERKR QEEEEVDKMM EQKMKEEQER RKKKEMEERM
SLEETKEQIL KLEEKLLALQ EEKHQLFLQL KKVLHEEEKR RRKEQSDLTT LTSAAYQQSL
TVHTGTHLLS MQGSPGGHNR PGTLMAADRA KQMFGPQVLT TRHYVGSAAA FAGTPEHGQF
QGSPGGAYGT AQPPPHYGPT QPAYSPSQQL RAPSAFPAVQ YLSQPQPQPY AVHGHFQPTQ
TGFLQPGGAL SLQKQMEHAN QQTGFSDSSS LRPMHPQALH PAPGLLASPQ LPVQMQPAGK
SGFAATSQPG PRLPFIQHSQ NPRFYHK
