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O14512

- SOCS7_HUMAN

UniProt

O14512 - SOCS7_HUMAN

Protein

Suppressor of cytokine signaling 7

Gene

SOCS7

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 127 (01 Oct 2014)
      Sequence version 2 (28 Nov 2006)
      Previous versions | rss
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    Functioni

    Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins By similarity.By similarity

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. SH3 domain binding Source: UniProtKB

    GO - Biological processi

    1. fat cell differentiation Source: Ensembl
    2. insulin receptor signaling pathway Source: Ensembl
    3. intracellular signal transduction Source: InterPro
    4. negative regulation of signal transduction Source: UniProtKB-KW
    5. protein ubiquitination Source: UniProtKB-UniPathway
    6. regulation of growth Source: UniProtKB-KW

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Growth regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    SignaLinkiO14512.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Suppressor of cytokine signaling 7
    Short name:
    SOCS-7
    Alternative name(s):
    Nck, Ash and phospholipase C gamma-binding protein
    Nck-associated protein 4
    Short name:
    NAP-4
    Gene namesi
    Name:SOCS7
    Synonyms:NAP4, SOCS6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:29846. SOCS7.

    Subcellular locationi

    Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus
    Note: Mostly cytoplasmic, but shuttles between the cytoplasm and the nucleus. Rapidly relocalizes to the nucleus after UV irradiation. Cytoplasmic location depends upon SEPT7 presence.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. intracellular membrane-bounded organelle Source: HPA
    3. nucleolus Source: HPA
    4. nucleus Source: HPA
    5. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi425 – 4273RDS → KDC: Loss of IRS1 ubiquitination and degradation. 1 Publication

    Organism-specific databases

    PharmGKBiPA164742488.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 581581Suppressor of cytokine signaling 7PRO_0000181253Add
    BLAST

    Proteomic databases

    PaxDbiO14512.
    PRIDEiO14512.

    PTM databases

    PhosphoSiteiO14512.

    Expressioni

    Tissue specificityi

    Expressed in brain and leukocytes. Also in fetal lung fibroblasts and fetal brain.1 Publication

    Inductioni

    By IL6/interleukin-6, prolactin and growth hormone.1 Publication

    Gene expression databases

    ArrayExpressiO14512.
    BgeeiO14512.
    CleanExiHS_SOCS6.
    HS_SOCS7.
    GenevestigatoriO14512.

    Organism-specific databases

    HPAiHPA003484.
    HPA004475.

    Interactioni

    Subunit structurei

    Interacts with phosphorylated IRS4 and PIK3R1 By similarity. Interacts, via the third proline-rich region, with the second SH3 domain of the adapter protein NCK1. Also interacts with GRB2, INSR, IRS1, PLCG1, SORBS3/vinexin, and phosphorylated STAT3 and STAT5. Interacts with SEPT6.By similarity5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ABI1Q8IZP02EBI-1539606,EBI-375446
    SEPT6Q141412EBI-1539617,EBI-745901

    Protein-protein interaction databases

    BioGridi119053. 6 interactions.
    IntActiO14512. 2 interactions.
    MINTiMINT-1202522.
    STRINGi9606.ENSP00000330659.

    Structurei

    3D structure databases

    ProteinModelPortaliO14512.
    SMRiO14512. Positions 385-553.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini400 – 509110SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini504 – 55451SOCS boxPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni124 – 494371Mediates interaction with SORBS3Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi82 – 9716Poly-ProAdd
    BLAST
    Compositional biasi141 – 1488Poly-Gly
    Compositional biasi180 – 1878Poly-Gln
    Compositional biasi188 – 19710Poly-Pro
    Compositional biasi303 – 31210Poly-Pro
    Compositional biasi343 – 3508Poly-Pro

    Domaini

    The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes By similarity. It is required for IRS1 ubiquitination and subsequent proteasomal degradation.By similarity

    Sequence similaritiesi

    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SOCS box domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG318341.
    HOGENOMiHOG000035093.
    HOVERGENiHBG079201.
    InParanoidiO14512.
    KOiK04699.
    OMAiKTVGGGC.
    PhylomeDBiO14512.
    TreeFamiTF321368.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR028413. SOCS.
    IPR028423. SOCS7.
    IPR001496. SOCS_C.
    [Graphical view]
    PANTHERiPTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF30. PTHR10385:SF30. 1 hit.
    PfamiPF00017. SH2. 1 hit.
    PF07525. SOCS_box. 1 hit.
    [Graphical view]
    SMARTiSM00252. SH2. 1 hit.
    SM00253. SOCS. 1 hit.
    SM00969. SOCS_box. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    PS50225. SOCS. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O14512-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MVFRNVGRPP EEEDVEAAPE PGPSELLCPR HRCALDPKAL PPGLALERTW    50
    GPAAGLEAQL AALGLGQPAG PGVKTVGGGC CPCPCPPQPP PPQPQPPAAA 100
    PQAGEDPTET SDALLVLEGL ESEAESLETN SCSEEELSSP GRGGGGGGRL 150
    LLQPPGPELP PVPFPLQDLV PLGRLSRGEQ QQQQQQQPPP PPPPPGPLRP 200
    LAGPSRKGSF KIRLSRLFRT KSCNGGSGGG DGTGKRPSGE LAASAASLTD 250
    MGGSAGRELD AGRKPKLTRT QSAFSPVSFS PLFTGETVSL VDVDISQRGL 300
    TSPHPPTPPP PPRRSLSLLD DISGTLPTSV LVAPMGSSLQ SFPLPPPPPP 350
    HAPDAFPRIA PIRAAESLHS QPPQHLQCPL YRPDSSSFAA SLRELEKCGW 400
    YWGPMNWEDA EMKLKGKPDG SFLVRDSSDP RYILSLSFRS QGITHHTRME 450
    HYRGTFSLWC HPKFEDRCQS VVEFIKRAIM HSKNGKFLYF LRSRVPGLPP 500
    TPVQLLYPVS RFSNVKSLQH LCRFRIRQLV RIDHIPDLPL PKPLISYIRK 550
    FYYYDPQEEV YLSLKEAQLI SKQKQEVEPS T 581
    Length:581
    Mass (Da):62,969
    Last modified:November 28, 2006 - v2
    Checksum:i3F326532262AF6AA
    GO
    Isoform 2 (identifier: O14512-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-250: Missing.

    Show »
    Length:331
    Mass (Da):37,461
    Checksum:iC0D465C715B14D11
    GO

    Sequence cautioni

    The sequence AAI28608.1 differs from that shown. Reason: Contaminating sequence. The N-terminus may be contaminated with vector sequence.
    The sequence BAA22432.1 differs from that shown. Reason: Erroneous termination at position 582. Translated as stop.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti357 – 3571P → S in AAI28608. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 250250Missing in isoform 2. 1 PublicationVSP_021645Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005216 mRNA. Translation: BAA22432.1. Sequence problems.
    AC115992 Genomic DNA. No translation available.
    AC124789 Genomic DNA. No translation available.
    BC128607 mRNA. Translation: AAI28608.1. Sequence problems.
    CCDSiCCDS32637.1. [O14512-1]
    PIRiPC4427.
    RefSeqiNP_055413.1. NM_014598.3. [O14512-1]
    UniGeneiHs.514132.

    Genome annotation databases

    GeneIDi30837.
    KEGGihsa:30837.
    UCSCiuc002hqa.3. human. [O14512-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005216 mRNA. Translation: BAA22432.1 . Sequence problems.
    AC115992 Genomic DNA. No translation available.
    AC124789 Genomic DNA. No translation available.
    BC128607 mRNA. Translation: AAI28608.1 . Sequence problems.
    CCDSi CCDS32637.1. [O14512-1 ]
    PIRi PC4427.
    RefSeqi NP_055413.1. NM_014598.3. [O14512-1 ]
    UniGenei Hs.514132.

    3D structure databases

    ProteinModelPortali O14512.
    SMRi O14512. Positions 385-553.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119053. 6 interactions.
    IntActi O14512. 2 interactions.
    MINTi MINT-1202522.
    STRINGi 9606.ENSP00000330659.

    PTM databases

    PhosphoSitei O14512.

    Proteomic databases

    PaxDbi O14512.
    PRIDEi O14512.

    Protocols and materials databases

    DNASUi 30837.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 30837.
    KEGGi hsa:30837.
    UCSCi uc002hqa.3. human. [O14512-1 ]

    Organism-specific databases

    CTDi 30837.
    GeneCardsi GC17P036508.
    HGNCi HGNC:29846. SOCS7.
    HPAi HPA003484.
    HPA004475.
    MIMi 608788. gene.
    neXtProti NX_O14512.
    PharmGKBi PA164742488.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG318341.
    HOGENOMi HOG000035093.
    HOVERGENi HBG079201.
    InParanoidi O14512.
    KOi K04699.
    OMAi KTVGGGC.
    PhylomeDBi O14512.
    TreeFami TF321368.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    SignaLinki O14512.

    Miscellaneous databases

    GeneWikii SOCS7.
    GenomeRNAii 30837.
    NextBioi 52958.
    PROi O14512.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14512.
    Bgeei O14512.
    CleanExi HS_SOCS6.
    HS_SOCS7.
    Genevestigatori O14512.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR028413. SOCS.
    IPR028423. SOCS7.
    IPR001496. SOCS_C.
    [Graphical view ]
    PANTHERi PTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF30. PTHR10385:SF30. 1 hit.
    Pfami PF00017. SH2. 1 hit.
    PF07525. SOCS_box. 1 hit.
    [Graphical view ]
    SMARTi SM00252. SH2. 1 hit.
    SM00253. SOCS. 1 hit.
    SM00969. SOCS_box. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    PS50225. SOCS. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel ligand for an SH3 domain of the adaptor protein Nck bears an SH2 domain and nuclear signaling motifs."
      Matuoka K., Miki H., Takahashi K., Takenawa T.
      Biochem. Biophys. Res. Commun. 239:488-492(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH NCK1; GRB2 AND PLCG1.
      Tissue: Brain.
    2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 147-581.
    4. "Expression of SOCS genes in normal and leukemic human leukocytes stimulated by prolactin, growth hormone and cytokines."
      Dogusan Z., Hooghe-Peters E.L., Berus D., Velkeniers B., Hooghe R.
      J. Neuroimmunol. 109:34-39(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    5. "The suppressor of cytokine signaling (SOCS)-7 interacts with the actin cytoskeleton through vinexin."
      Martens N., Wery M., Wang P., Braet F., Gertler A., Hooghe R., Vandenhaute J., Hooghe-Peters E.L.
      Exp. Cell Res. 298:239-248(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SORBS3, SUBCELLULAR LOCATION.
    6. "Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation."
      Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.
      J. Biol. Chem. 280:13817-13823(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STAT3 AND STAT5.
    7. "Deletion of SOCS7 leads to enhanced insulin action and enlarged islets of Langerhans."
      Banks A.S., Li J., McKeag L., Hribal M.L., Kashiwada M., Accili D., Rothman P.B.
      J. Clin. Invest. 115:2462-2471(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH INSR AND IRS1, MUTAGENESIS OF 425-ARG--SER-427.
    8. "Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7."
      Kremer B.E., Adang L.A., Macara I.G.
      Cell 130:837-850(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SEPT6, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiSOCS7_HUMAN
    AccessioniPrimary (citable) accession number: O14512
    Secondary accession number(s): A2VCU2, Q0IJ63
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: November 28, 2006
    Last modified: October 1, 2014
    This is version 127 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3