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O15524

- SOCS1_HUMAN

UniProt

O15524 - SOCS1_HUMAN

Protein

Suppressor of cytokine signaling 1

Gene

SOCS1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS1 is involved in negative regulation of cytokines that signal through the JAK/STAT3 pathway. Through binding to JAKs, inhibits their kinase activity. In vitro, also suppresses Tec protein-tyrosine activity. Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival By similarity. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2. SOCS1 appears to be a negative regulator in IGF1R signaling pathway.By similarity2 Publications

    Pathwayi

    GO - Molecular functioni

    1. insulin-like growth factor receptor binding Source: UniProtKB
    2. kinase inhibitor activity Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. protein kinase binding Source: UniProtKB
    5. protein kinase inhibitor activity Source: ProtInc

    GO - Biological processi

    1. cellular response to amino acid stimulus Source: Ensembl
    2. cytokine-mediated signaling pathway Source: UniProtKB
    3. fat cell differentiation Source: Ensembl
    4. interferon-gamma-mediated signaling pathway Source: Reactome
    5. JAK-STAT cascade Source: ProtInc
    6. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
    7. negative regulation of insulin receptor signaling pathway Source: UniProtKB
    8. negative regulation of JAK-STAT cascade Source: UniProtKB
    9. negative regulation of protein kinase activity Source: GOC
    10. negative regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
    11. protein ubiquitination Source: UniProtKB-UniPathway
    12. regulation of growth Source: UniProtKB-KW
    13. regulation of interferon-gamma-mediated signaling pathway Source: Reactome
    14. regulation of protein phosphorylation Source: UniProtKB
    15. regulation of type I interferon-mediated signaling pathway Source: Reactome
    16. type I interferon signaling pathway Source: Reactome

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Growth regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_111133. Growth hormone receptor signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_24980. Regulation of IFNG signaling.
    REACT_25078. Interferon gamma signaling.
    REACT_25216. Regulation of IFNA signaling.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinkiO15524.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Suppressor of cytokine signaling 1
    Short name:
    SOCS-1
    Alternative name(s):
    JAK-binding protein
    Short name:
    JAB
    STAT-induced STAT inhibitor 1
    Short name:
    SSI-1
    Tec-interacting protein 3
    Short name:
    TIP-3
    Gene namesi
    Name:SOCS1
    Synonyms:SSI1, TIP3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:19383. SOCS1.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasmic vesicle 1 Publication
    Note: Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
    3. cytosol Source: Reactome
    4. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasmic vesicle, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134863068.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 211211Suppressor of cytokine signaling 1PRO_0000181235Add
    BLAST

    Proteomic databases

    PaxDbiO15524.
    PRIDEiO15524.

    Expressioni

    Tissue specificityi

    Expressed in all tissues with high expression in spleen, small intestine and peripheral blood leukocytes.

    Inductioni

    By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families.

    Gene expression databases

    ArrayExpressiO15524.
    BgeeiO15524.
    CleanExiHS_SOCS1.
    GenevestigatoriO15524.

    Organism-specific databases

    HPAiCAB010355.

    Interactioni

    Subunit structurei

    Interacts with multiple activated signaling proteins of the tyrosine kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2 and VAV. Binding to JAKs is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK JH1 domain. Binds the SH3 domain of GRB2 via diproline determinants in the N-terminus, and the N-terminal regulatory domain of VAV By similarity. Interacts with the Elongin BC complex (TCEB1 and TCEB2). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains Elongin BC, CUL5, RBX1 and SOCS1 By similarity. Interacts (via SH2 domain and SOCS box) with TRIM8 By similarity. Interacts with AXL, CUL2 and FGFR3. Interacts with INSR By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    COMMD1Q8N6683EBI-968198,EBI-1550112
    ERBB2P046262EBI-968198,EBI-641062
    RELAQ042062EBI-968198,EBI-73886
    TCEB1Q153692EBI-968198,EBI-301231

    Protein-protein interaction databases

    BioGridi114203. 52 interactions.
    DIPiDIP-29662N.
    IntActiO15524. 10 interactions.
    MINTiMINT-196452.
    STRINGi9606.ENSP00000329418.

    Structurei

    3D structure databases

    ProteinModelPortaliO15524.
    SMRiO15524. Positions 55-211.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini79 – 17496SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini161 – 21050SOCS boxPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni55 – 6612Kinase inhibitory region (KIR)Add
    BLAST
    Regioni67 – 7812Extended SH2 subdomain (ESS)Add
    BLAST
    Regioni173 – 18210Interaction with Elongin BC complexBy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi26 – 327Poly-Ser

    Domaini

    The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.
    The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box By similarity.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

    eggNOGiNOG298538.
    HOGENOMiHOG000236320.
    HOVERGENiHBG002457.
    InParanoidiO15524.
    KOiK04694.
    OMAiKANHARR.
    OrthoDBiEOG7TMZSZ.
    PhylomeDBiO15524.
    TreeFamiTF321368.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR028413. SOCS.
    IPR028411. SOCS1.
    IPR001496. SOCS_C.
    [Graphical view]
    PANTHERiPTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF5. PTHR10385:SF5. 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]

    Sequencei

    Sequence statusi: Complete.

    O15524-1 [UniParc]FASTAAdd to Basket

    « Hide

    MVAHNQVAAD NAVSTAAEPR RRPEPSSSSS SSPAAPARPR PCPAVPAPAP    50
    GDTHFRTFRS HADYRRITRA SALLDACGFY WGPLSVHGAH ERLRAEPVGT 100
    FLVRDSRQRN CFFALSVKMA SGPTSIRVHF QAGRFHLDGS RESFDCLFEL 150
    LEHYVAAPRR MLGAPLRQRR VRPLQELCRQ RIVATVGREN LARIPLNPVL 200
    RDYLSSFPFQ I 211
    Length:211
    Mass (Da):23,551
    Last modified:January 1, 1998 - v1
    Checksum:i7CC983533F78B127
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti9 – 91A → G in CAB92528. 1 PublicationCurated
    Sequence conflicti15 – 162TA → CP in BAA21537. (PubMed:9202126)Curated
    Sequence conflicti35 – 351A → G in CAB92528. 1 PublicationCurated
    Sequence conflicti178 – 1781C → F in CAB92528. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti210 – 2101Q → H.
    Corresponds to variant rs11549428 [ dbSNP | Ensembl ].
    VAR_061808

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005043 mRNA. Translation: BAA22431.1.
    AB000734 mRNA. Translation: BAA23521.1.
    U88326 mRNA. Translation: AAB62401.1.
    AF132440 Genomic DNA. Translation: AAD27709.1.
    Z46940 Genomic DNA. Translation: CAB92528.1.
    AB000676 mRNA. Translation: BAA21537.1.
    CCDSiCCDS10546.1.
    RefSeqiNP_003736.1. NM_003745.1.
    UniGeneiHs.50640.

    Genome annotation databases

    EnsembliENST00000332029; ENSP00000329418; ENSG00000185338.
    GeneIDi8651.
    KEGGihsa:8651.
    UCSCiuc002dar.1. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB005043 mRNA. Translation: BAA22431.1 .
    AB000734 mRNA. Translation: BAA23521.1 .
    U88326 mRNA. Translation: AAB62401.1 .
    AF132440 Genomic DNA. Translation: AAD27709.1 .
    Z46940 Genomic DNA. Translation: CAB92528.1 .
    AB000676 mRNA. Translation: BAA21537.1 .
    CCDSi CCDS10546.1.
    RefSeqi NP_003736.1. NM_003745.1.
    UniGenei Hs.50640.

    3D structure databases

    ProteinModelPortali O15524.
    SMRi O15524. Positions 55-211.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114203. 52 interactions.
    DIPi DIP-29662N.
    IntActi O15524. 10 interactions.
    MINTi MINT-196452.
    STRINGi 9606.ENSP00000329418.

    Proteomic databases

    PaxDbi O15524.
    PRIDEi O15524.

    Protocols and materials databases

    DNASUi 8651.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000332029 ; ENSP00000329418 ; ENSG00000185338 .
    GeneIDi 8651.
    KEGGi hsa:8651.
    UCSCi uc002dar.1. human.

    Organism-specific databases

    CTDi 8651.
    GeneCardsi GC16M011255.
    HGNCi HGNC:19383. SOCS1.
    HPAi CAB010355.
    MIMi 603597. gene.
    neXtProti NX_O15524.
    PharmGKBi PA134863068.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG298538.
    HOGENOMi HOG000236320.
    HOVERGENi HBG002457.
    InParanoidi O15524.
    KOi K04694.
    OMAi KANHARR.
    OrthoDBi EOG7TMZSZ.
    PhylomeDBi O15524.
    TreeFami TF321368.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_111133. Growth hormone receptor signaling.
    REACT_111225. Regulation of KIT signaling.
    REACT_24980. Regulation of IFNG signaling.
    REACT_25078. Interferon gamma signaling.
    REACT_25216. Regulation of IFNA signaling.
    REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
    SignaLinki O15524.

    Miscellaneous databases

    GeneWikii Suppressor_of_cytokine_signaling_1.
    GenomeRNAii 8651.
    NextBioi 32445.
    PROi O15524.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O15524.
    Bgeei O15524.
    CleanExi HS_SOCS1.
    Genevestigatori O15524.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR028413. SOCS.
    IPR028411. SOCS1.
    IPR001496. SOCS_C.
    [Graphical view ]
    PANTHERi PTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF5. PTHR10385:SF5. 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. "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3."
      Minamoto S., Ikegame K., Ueno K., Narazaki M., Naka T., Yamamoto H., Matsumoto T., Saito H., Hosoe S., Kishimoto T.
      Biochem. Biophys. Res. Commun. 237:79-83(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: T-cell lymphoma.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Myeloid leukemia cell.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively."
      Yandava C.N., Pillari A., Drazen J.M.
      Genomics 61:108-111(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. Schlueter G.
      Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-211.
      Tissue: B-cell.
    7. "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor."
      Dey B.R., Spence S.L., Nissley P., Furlanetto R.W.
      J. Biol. Chem. 273:24095-24101(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IGF1R.
    8. Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, INTERACTION WITH CUL2.
    9. "Socs-1 inhibits TEL-JAK2-mediated transformation of hematopoietic cells through inhibition of JAK2 kinase activity and induction of proteasome-mediated degradation."
      Frantsve J., Schwaller J., Sternberg D.W., Kutok J., Gilliland D.G.
      Mol. Cell. Biol. 21:3547-3557(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.
    10. "SOCS proteins: negative regulators of cytokine signaling."
      Krebs D.L., Hilton D.J.
      Stem Cells 19:378-387(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    11. "Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin."
      Hafizi S., Alindri F., Karlsson R., Dahlbaeck B.
      Biochem. Biophys. Res. Commun. 299:793-800(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXL.
    12. "Cytokine signaling in the brain: putting a SOCS in it?"
      Wang J., Campbell I.L.
      J. Neurosci. Res. 67:423-427(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    13. "Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling."
      Ben-Zvi T., Yayon A., Gertler A., Monsonego-Ornan E.
      J. Cell Sci. 119:380-387(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FGFR3, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiSOCS1_HUMAN
    AccessioniPrimary (citable) accession number: O15524
    Secondary accession number(s): O15097, Q9NSA7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 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 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3