SOCS7_HUMAN
ID SOCS7_HUMAN Reviewed; 581 AA.
AC O14512; A2VCU2; Q0IJ63;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Suppressor of cytokine signaling 7;
DE Short=SOCS-7;
DE AltName: Full=Nck, Ash and phospholipase C gamma-binding protein;
DE AltName: Full=Nck-associated protein 4;
DE Short=NAP-4;
GN Name=SOCS7; Synonyms=NAP4, SOCS6;
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), TISSUE SPECIFICITY, AND INTERACTION
RP WITH NCK1; GRB2 AND PLCG1.
RC TISSUE=Brain;
RX PubMed=9344857; DOI=10.1006/bbrc.1997.7492;
RA Matuoka K., Miki H., Takahashi K., Takenawa T.;
RT "A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2
RT domain and nuclear signaling motifs.";
RL Biochem. Biophys. Res. Commun. 239:488-492(1997).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 147-581.
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 [4]
RP INDUCTION.
RX PubMed=10969179; DOI=10.1016/s0165-5728(00)00300-3;
RA Dogusan Z., Hooghe-Peters E.L., Berus D., Velkeniers B., Hooghe R.;
RT "Expression of SOCS genes in normal and leukemic human leukocytes
RT stimulated by prolactin, growth hormone and cytokines.";
RL J. Neuroimmunol. 109:34-39(2000).
RN [5]
RP INTERACTION WITH SORBS3, AND 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, AND INTERACTION WITH STAT3 AND STAT5.
RX PubMed=15677474; DOI=10.1074/jbc.m411596200;
RA Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.;
RT "Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and
RT leptin signaling by interacting with STAT5 or STAT3 and attenuating their
RT nuclear translocation.";
RL J. Biol. Chem. 280:13817-13823(2005).
RN [7]
RP FUNCTION, INTERACTION WITH INSR AND IRS1, AND MUTAGENESIS OF
RP 425-ARG--SER-427.
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).
RN [8]
RP INTERACTION WITH SEPT6, AND SUBCELLULAR LOCATION.
RX PubMed=17803907; DOI=10.1016/j.cell.2007.06.053;
RA Kremer B.E., Adang L.A., Macara I.G.;
RT "Septins regulate actin organization and cell-cycle arrest through nuclear
RT accumulation of NCK mediated by SOCS7.";
RL Cell 130:837-850(2007).
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:15677474,
CC ECO:0000269|PubMed:16127460}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with phosphorylated IRS4 and PIK3R1 (By similarity).
CC Interacts, via the third proline-rich region, with the second SH3
CC domain of the adapter protein NCK1. Also interacts with GRB2, INSR,
CC IRS1, PLCG1, SORBS3/vinexin, and phosphorylated STAT3 and STAT5.
CC Interacts with SEPT6. {ECO:0000250, ECO:0000269|PubMed:15242778,
CC ECO:0000269|PubMed:15677474, ECO:0000269|PubMed:16127460,
CC ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:9344857}.
CC -!- INTERACTION:
CC O14512; Q8IZP0: ABI1; NbExp=2; IntAct=EBI-1539606, EBI-375446;
CC O14512; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1539606, EBI-3867333;
CC O14512; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-1539606, EBI-371922;
CC O14512; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-1539606, EBI-7960826;
CC O14512; P62993: GRB2; NbExp=3; IntAct=EBI-1539606, EBI-401755;
CC O14512; Q9UJY1: HSPB8; NbExp=3; IntAct=EBI-1539606, EBI-739074;
CC O14512; Q96PV6: LENG8; NbExp=3; IntAct=EBI-1539606, EBI-739546;
CC O14512; Q99750: MDFI; NbExp=3; IntAct=EBI-1539606, EBI-724076;
CC O14512; Q8IVT2: MISP; NbExp=3; IntAct=EBI-1539606, EBI-2555085;
CC O14512; O43639: NCK2; NbExp=3; IntAct=EBI-1539606, EBI-713635;
CC O14512; Q6X4W1-2: NSMF; NbExp=3; IntAct=EBI-1539606, EBI-12028784;
CC O14512; O94875-10: SORBS2; NbExp=3; IntAct=EBI-1539606, EBI-12037893;
CC O14512; O60504: SORBS3; NbExp=3; IntAct=EBI-1539606, EBI-741237;
CC O14512; Q63HR2: TNS2; NbExp=3; IntAct=EBI-1539606, EBI-949753;
CC O14512; P07947: YES1; NbExp=3; IntAct=EBI-1539606, EBI-515331;
CC O14512-1; Q14141: SEPTIN6; NbExp=2; IntAct=EBI-1539617, EBI-745901;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side. Nucleus. Note=Mostly cytoplasmic, but
CC shuttles between the cytoplasm and the nucleus. Rapidly relocalizes to
CC the nucleus after UV irradiation. Cytoplasmic location depends upon
CC SEPT7 presence.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14512-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14512-2; Sequence=VSP_021645;
CC -!- TISSUE SPECIFICITY: Expressed in brain and leukocytes. Also in fetal
CC lung fibroblasts and fetal brain. {ECO:0000269|PubMed:9344857}.
CC -!- INDUCTION: By IL6/interleukin-6, prolactin and growth hormone.
CC {ECO:0000269|PubMed:10969179}.
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 (By similarity). It is required for IRS1 ubiquitination and
CC subsequent proteasomal degradation. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI28608.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={ECO:0000305};
CC Sequence=BAA22432.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB005216; BAA22432.1; ALT_SEQ; mRNA.
DR EMBL; AC115992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC128607; AAI28608.1; ALT_SEQ; mRNA.
DR PIR; PC4427; PC4427.
DR RefSeq; NP_055413.1; NM_014598.3.
DR AlphaFoldDB; O14512; -.
DR SMR; O14512; -.
DR BioGRID; 119053; 51.
DR IntAct; O14512; 17.
DR MINT; O14512; -.
DR STRING; 9606.ENSP00000482229; -.
DR iPTMnet; O14512; -.
DR PhosphoSitePlus; O14512; -.
DR BioMuta; SOCS7; -.
DR jPOST; O14512; -.
DR MassIVE; O14512; -.
DR PaxDb; O14512; -.
DR PeptideAtlas; O14512; -.
DR PRIDE; O14512; -.
DR ProteomicsDB; 48055; -. [O14512-1]
DR ProteomicsDB; 48056; -. [O14512-2]
DR Antibodypedia; 72315; 225 antibodies from 31 providers.
DR DNASU; 30837; -.
DR Ensembl; ENST00000615473.2; ENSP00000480736.1; ENSG00000274229.2. [O14512-1]
DR Ensembl; ENST00000665913.1; ENSP00000499750.1; ENSG00000274211.6. [O14512-1]
DR GeneID; 30837; -.
DR KEGG; hsa:30837; -.
DR UCSC; uc002hqa.4; human. [O14512-1]
DR CTD; 30837; -.
DR DisGeNET; 30837; -.
DR GeneCards; SOCS7; -.
DR HGNC; HGNC:29846; SOCS7.
DR HPA; ENSG00000274211; Tissue enhanced (testis).
DR MIM; 608788; gene.
DR neXtProt; NX_O14512; -.
DR OpenTargets; ENSG00000274211; -.
DR PharmGKB; PA164742488; -.
DR VEuPathDB; HostDB:ENSG00000274211; -.
DR eggNOG; KOG4566; Eukaryota.
DR GeneTree; ENSGT00940000156314; -.
DR InParanoid; O14512; -.
DR OrthoDB; 924518at2759; -.
DR PhylomeDB; O14512; -.
DR TreeFam; TF321368; -.
DR PathwayCommons; O14512; -.
DR SignaLink; O14512; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 30837; 12 hits in 1111 CRISPR screens.
DR ChiTaRS; SOCS7; human.
DR GeneWiki; SOCS7; -.
DR GenomeRNAi; 30837; -.
DR Pharos; O14512; Tbio.
DR PRO; PR:O14512; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O14512; protein.
DR Bgee; ENSG00000274211; Expressed in right testis and 109 other tissues.
DR ExpressionAtlas; O14512; baseline and differential.
DR Genevisible; O14512; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0017124; F:SH3 domain binding; NAS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
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; IEA:UniProtKB-UniPathway.
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 Alternative splicing; Cell membrane; Cytoplasm; Growth regulation;
KW Membrane; Nucleus; Reference proteome; SH2 domain;
KW Signal transduction inhibitor; Ubl conjugation pathway.
FT CHAIN 1..581
FT /note="Suppressor of cytokine signaling 7"
FT /id="PRO_0000181253"
FT DOMAIN 400..509
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 504..554
FT /note="SOCS box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00194"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 123..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..494
FT /note="Mediates interaction with SORBS3"
FT /evidence="ECO:0000269|PubMed:15242778"
FT REGION 297..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..201
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..250
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9344857"
FT /id="VSP_021645"
FT MUTAGEN 425..427
FT /note="RDS->KDC: Loss of IRS1 ubiquitination and
FT degradation."
FT /evidence="ECO:0000269|PubMed:16127460"
FT CONFLICT 357
FT /note="P -> S (in Ref. 3; AAI28608)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 581 AA; 62969 MW; 3F326532262AF6AA CRC64;
MVFRNVGRPP EEEDVEAAPE PGPSELLCPR HRCALDPKAL PPGLALERTW GPAAGLEAQL
AALGLGQPAG PGVKTVGGGC CPCPCPPQPP PPQPQPPAAA PQAGEDPTET SDALLVLEGL
ESEAESLETN SCSEEELSSP GRGGGGGGRL LLQPPGPELP PVPFPLQDLV PLGRLSRGEQ
QQQQQQQPPP PPPPPGPLRP LAGPSRKGSF KIRLSRLFRT KSCNGGSGGG DGTGKRPSGE
LAASAASLTD MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL
TSPHPPTPPP PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP HAPDAFPRIA
PIRAAESLHS QPPQHLQCPL YRPDSSSFAA SLRELEKCGW YWGPMNWEDA EMKLKGKPDG
SFLVRDSSDP RYILSLSFRS QGITHHTRME HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM
HSKNGKFLYF LRSRVPGLPP TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL
PKPLISYIRK FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T
