SOCS7_MOUSE
ID SOCS7_MOUSE Reviewed; 579 AA.
AC Q8VHQ2; B1AQY1; Q3UH08;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Suppressor of cytokine signaling 7;
DE Short=SOCS-7;
GN Name=Socs7; Synonyms=Cish7, Nap4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Hilton D.J., Viney E.M., Alexander W.S., Willson T.A., Nicola N.A.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP INTERACTION WITH IRS4 AND PIK3R1, AND TISSUE SPECIFICITY.
RX PubMed=12052866; DOI=10.1128/mcb.22.13.4567-4578.2002;
RA Krebs D.L., Uren R.T., Metcalf D., Rakar S., Zhang J.-G., Starr R.,
RA De Souza D.P., Hanzinikolas K., Eyles J., Connolly L.M., Simpson R.J.,
RA Nicola N.A., Nicholson S.E., Baca M., Hilton D.J., Alexander W.S.;
RT "SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6
RT gene exhibit mild growth retardation.";
RL Mol. Cell. Biol. 22:4567-4578(2002).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=15242778; DOI=10.1016/j.yexcr.2004.04.002;
RA Martens N., Wery M., Wang P., Braet F., Gertler A., Hooghe R.,
RA Vandenhaute J., Hooghe-Peters E.L.;
RT "The suppressor of cytokine signaling (SOCS)-7 interacts with the actin
RT cytoskeleton through vinexin.";
RL Exp. Cell Res. 298:239-248(2004).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15494444; DOI=10.1073/pnas.0406870101;
RA Krebs D.L., Metcalf D., Merson T.D., Voss A.K., Thomas T., Zhang J.-G.,
RA Rakar S., O'bryan M.K., Willson T.A., Viney E.M., Mielke L.A., Nicola N.A.,
RA Hilton D.J., Alexander W.S.;
RT "Development of hydrocephalus in mice lacking SOCS7.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15446-15451(2004).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16127460; DOI=10.1172/jci23853;
RA Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D.,
RA Rothman P.B.;
RT "Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of
RT Langerhans.";
RL J. Clin. Invest. 115:2462-2471(2005).
CC -!- FUNCTION: Regulates signaling cascades probably through protein
CC ubiquitination and/or sequestration. Functions in insulin signaling and
CC glucose homeostasis through IRS1 ubiquitination and subsequent
CC proteasomal degradation. Inhibits also prolactin, growth hormone and
CC leptin signaling by preventing STAT3 and STAT5 activation, sequestering
CC them in the cytoplasm and reducing their binding to DNA. May be a
CC substrate recognition component of a SCF-like E3 ubiquitin-protein
CC ligase complex which mediates the ubiquitination and subsequent
CC proteasomal degradation of target proteins (By similarity).
CC {ECO:0000250, ECO:0000269|PubMed:15494444,
CC ECO:0000269|PubMed:16127460}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with phosphorylated IRS4 and PIK3R1. Interacts, via
CC the third proline-rich region, with the second SH3 domain of the
CC adapter protein NCK1. Also interacts with GRB2, INSR, IRS1, PLCG1,
CC SORBS3/vinexin and phosphorylated STAT3 and STAT5 (By similarity).
CC Interacts with SEPT6 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15242778}. Cell
CC membrane {ECO:0000269|PubMed:15242778}; Peripheral membrane protein
CC {ECO:0000269|PubMed:15242778}; Cytoplasmic side
CC {ECO:0000269|PubMed:15242778}. Nucleus {ECO:0000269|PubMed:15242778}.
CC Note=Mostly cytoplasmic, but shuttles between the cytoplasm and the
CC nucleus. Rapidly relocalizes to the nucleus after UV irradiation.
CC Cytoplasmic location depends upon SEPT7 presence (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in brain
CC and testis where it is expressed by spermatocytes and early spermatids.
CC Also significantly expressed in spleen, skeletal muscle and kidney.
CC {ECO:0000269|PubMed:12052866, ECO:0000269|PubMed:15494444,
CC ECO:0000269|PubMed:16127460}.
CC -!- DEVELOPMENTAL STAGE: Ubiquitously expressed at low level in 12.5 dpc
CC and 15.5 dpc embryos. More significantly expressed in the nervous
CC system at 12.5 dpc and the cortical plate at 15.5 dpc. Expressed in the
CC brain postnatally in particular in the hippocampal formation and the
CC medial habenular nuclei at P7. Low-level expression in other brain
CC areas was present at P7 and was reduced to very low levels at P14 and
CC P21. The hippocampal granule cell layer and the cerebellar granular
CC layer maintained moderate expression levels at P7, P14, and P21.
CC {ECO:0000269|PubMed:15494444}.
CC -!- DOMAIN: The SOCS box domain is required for IRS1 ubiquitination and
CC subsequent proteasomal degradation. {ECO:0000250}.
CC -!- DOMAIN: The SOCS box domain mediates the interaction with the Elongin
CC BC complex, an adapter module in different E3 ubiquitin ligase
CC complexes. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are smaller and half of them develop fatal
CC hydrocephalus between 3 to 15 weeks of age. They display subtle
CC alterations in glucose homeostasis with an enhanced response to insulin
CC which causes hypoglycemia. Pancreatic islets become progressively
CC larger. {ECO:0000269|PubMed:15494444}.
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DR EMBL; AF424814; AAL60516.1; -; mRNA.
DR EMBL; AK147580; BAE28006.1; -; mRNA.
DR EMBL; AK147650; BAE28049.1; -; mRNA.
DR EMBL; AL596088; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_619598.1; NM_138657.3.
DR AlphaFoldDB; Q8VHQ2; -.
DR SMR; Q8VHQ2; -.
DR BioGRID; 228649; 6.
DR IntAct; Q8VHQ2; 1.
DR MINT; Q8VHQ2; -.
DR STRING; 10090.ENSMUSP00000040896; -.
DR iPTMnet; Q8VHQ2; -.
DR PhosphoSitePlus; Q8VHQ2; -.
DR PaxDb; Q8VHQ2; -.
DR PeptideAtlas; Q8VHQ2; -.
DR PRIDE; Q8VHQ2; -.
DR ProteomicsDB; 261317; -.
DR Antibodypedia; 72315; 225 antibodies from 31 providers.
DR DNASU; 192157; -.
DR Ensembl; ENSMUST00000045540; ENSMUSP00000040896; ENSMUSG00000038485.
DR GeneID; 192157; -.
DR KEGG; mmu:192157; -.
DR UCSC; uc007lea.1; mouse.
DR CTD; 30837; -.
DR MGI; MGI:2651588; Socs7.
DR VEuPathDB; HostDB:ENSMUSG00000038485; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000156314; -.
DR HOGENOM; CLU_022661_0_0_1; -.
DR InParanoid; Q8VHQ2; -.
DR OMA; QVQCPLY; -.
DR OrthoDB; 924518at2759; -.
DR PhylomeDB; Q8VHQ2; -.
DR TreeFam; TF321368; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 192157; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Socs7; mouse.
DR PRO; PR:Q8VHQ2; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8VHQ2; protein.
DR Bgee; ENSMUSG00000038485; Expressed in seminiferous tubule of testis and 221 other tissues.
DR ExpressionAtlas; Q8VHQ2; baseline and differential.
DR Genevisible; Q8VHQ2; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046935; F:1-phosphatidylinositol-3-kinase regulator activity; IBA:GO_Central.
DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IMP:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IDA:MGI.
DR GO; GO:0021942; P:radial glia guided migration of Purkinje cell; IMP:MGI.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR CDD; cd10388; SH2_SOCS7; 1.
DR CDD; cd03741; SOCS_SOCS7; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR028423; SOCS7.
DR InterPro; IPR035866; SOCS7_SH2.
DR InterPro; IPR037346; SOCS7_SOCS.
DR InterPro; IPR001496; SOCS_box.
DR InterPro; IPR036036; SOCS_box-like_dom_sf.
DR PANTHER; PTHR10155:SF5; PTHR10155:SF5; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF07525; SOCS_box; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00253; SOCS; 1.
DR SMART; SM00969; SOCS_box; 1.
DR SUPFAM; SSF158235; SSF158235; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50225; SOCS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Growth regulation; Membrane; Nucleus;
KW Reference proteome; SH2 domain; Signal transduction inhibitor;
KW Ubl conjugation pathway.
FT CHAIN 1..579
FT /note="Suppressor of cytokine signaling 7"
FT /id="PRO_0000181254"
FT DOMAIN 398..507
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 502..552
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..492
FT /note="Mediates interaction with SORBS3"
FT /evidence="ECO:0000250"
FT REGION 295..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 155..169
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..199
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 579 AA; 62784 MW; FAB66BF2A0BE685A CRC64;
MVFRNVGRPP EEEDAEAARE PGPSELLCPR HRCALDPKAL PPGLALERTW GPVAGLEAQL
AALGLGQPAG PGIKTAGGGC CPCPCPPQPP PPQPPPPAAA PQAGEDPTET SDALLVLEGL
ESEAESLETN SCSEEELSSP GRGGGGVGGR LLLQPPGPEL PPVPFPLQDL VPPGRLSRGE
QQQQQPPPPP PPPGPLRPLA GPSRKGSFKI RLSRLFRTKS CNGGSGGGDG TGKRPSGDLA
ASAASLTDMG GSAVRELDTG RKPRLTRTQS AFSPVSFSPL FTGETVSLVD VDISQRGLTS
PHPPTPPPPP RRSLSLLDDI SGTLPTSVLV APMGSSLQSF PLPPPPPPHA PDAFPRIAPI
RASESLHSQP PQHLQCPLYR PDSSSFAASL RELEKCGWYW GPMNWEDAEM KLKGKPDGSF
LVRDSSDPRY ILSLSFRSQG ITHHTRMEHY RGTFSLWCHP KFEDRCQSVV EFIKRAIMHS
KNGKFLYFLR SRVPGLPPTP VQLLYPVSRF SNVKSLQHLC RFRIRQLVRI DHIPDLPLPK
PLISYIRKFY YYDPQEEVYL SLKEAQLISK QKQEVEPST
