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O14544

- SOCS6_HUMAN

UniProt

O14544 - SOCS6_HUMAN

Protein

Suppressor of cytokine signaling 6

Gene

SOCS6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 2 (23 Sep 2008)
      Previous versions | rss
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    Functioni

    SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins By similarity. Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor.By similarity1 Publication

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. defense response Source: ProtInc
    2. JAK-STAT cascade Source: ProtInc
    3. negative regulation of signal transduction Source: UniProtKB-KW
    4. negative regulation of T cell activation Source: Ensembl
    5. proteasomal protein catabolic process Source: MGI
    6. protein ubiquitination Source: UniProtKB-UniPathway
    7. regulation of growth Source: UniProtKB-KW

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Growth regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_111225. Regulation of KIT signaling.
    SignaLinkiO14544.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Suppressor of cytokine signaling 6
    Short name:
    SOCS-6
    Alternative name(s):
    Cytokine-inducible SH2 protein 4
    Short name:
    CIS-4
    Suppressor of cytokine signaling 4
    Short name:
    SOCS-4
    Gene namesi
    Name:SOCS6
    Synonyms:CIS4, SOCS4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 18

    Organism-specific databases

    HGNCiHGNC:16833. SOCS6.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: ProtInc
    2. immunological synapse Source: MGI

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134917653.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 535535Suppressor of cytokine signaling 6PRO_0000181251Add
    BLAST

    Proteomic databases

    MaxQBiO14544.
    PaxDbiO14544.
    PRIDEiO14544.

    PTM databases

    PhosphoSiteiO14544.

    Expressioni

    Gene expression databases

    ArrayExpressiO14544.
    BgeeiO14544.
    CleanExiHS_SOCS4.
    HS_SOCS6.
    GenevestigatoriO14544.

    Organism-specific databases

    HPAiCAB010189.
    HPA035477.

    Interactioni

    Subunit structurei

    Interacts with RBCK1. Interacts with phosphorylated IRS4 By similarity. Interacts with PIM3 By similarity. Interacts with KIT (phosphorylated).By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARP102754EBI-3929549,EBI-608057
    GAB1Q134809EBI-3929549,EBI-517684
    KITP1072112EBI-3929549,EBI-1379503
    METP085814EBI-3929549,EBI-1039152

    Protein-protein interaction databases

    BioGridi114719. 22 interactions.
    IntActiO14544. 12 interactions.
    MINTiMINT-4821450.
    STRINGi9606.ENSP00000306939.

    Structurei

    Secondary structure

    1
    535
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi372 – 38211
    Helixi391 – 3977
    Turni398 – 4003
    Beta strandi406 – 4105
    Beta strandi417 – 4248
    Beta strandi427 – 43610
    Beta strandi439 – 4424
    Beta strandi451 – 4533
    Helixi454 – 46714
    Beta strandi471 – 4744

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2VIFX-ray1.45A361-499[»]
    ProteinModelPortaliO14544.
    SMRiO14544. Positions 367-535.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO14544.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini384 – 491108SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini486 – 53550SOCS boxPROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi105 – 1084Poly-Ser

    Domaini

    The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.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.
    HOGENOMiHOG000027792.
    HOVERGENiHBG057479.
    InParanoidiO14544.
    KOiK10322.
    OMAiTTGVMLQ.
    OrthoDBiEOG7SXW3G.
    PhylomeDBiO14544.
    TreeFamiTF321368.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR028413. SOCS.
    IPR028421. SOCS6.
    IPR001496. SOCS_C.
    [Graphical view]
    PANTHERiPTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF25. PTHR10385:SF25. 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.

    O14544-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKKISLKTLR KSFNLNKSKE ETDFMVVQQP SLASDFGKDD SLFGSCYGKD    50
    MASCDINGED EKGGKNRSKS ESLMGTLKRR LSAKQKSKGK AGTPSGSSAD 100
    EDTFSSSSAP IVFKDVRAQR PIRSTSLRSH HYSPAPWPLR PTNSEETCIK 150
    MEVRVKALVH SSSPSPALNG VRKDFHDLQS ETTCQEQANS LKSSASHNGD 200
    LHLHLDEHVP VVIGLMPQDY IQYTVPLDEG MYPLEGSRSY CLDSSSPMEV 250
    SAVPPQVGGR AFPEDESQVD QDLVVAPEIF VDQSVNGLLI GTTGVMLQSP 300
    RAGHDDVPPL SPLLPPMQNN QIQRNFSGLT GTEAHVAESM RCHLNFDPNS 350
    APGVARVYDS VQSSGPMVVT SLTEELKKLA KQGWYWGPIT RWEAEGKLAN 400
    VPDGSFLVRD SSDDRYLLSL SFRSHGKTLH TRIEHSNGRF SFYEQPDVEG 450
    HTSIVDLIEH SIRDSENGAF CYSRSRLPGS ATYPVRLTNP VSRFMQVRSL 500
    QYLCRFVIRQ YTRIDLIQKL PLPNKMKDYL QEKHY 535
    Length:535
    Mass (Da):59,528
    Last modified:September 23, 2008 - v2
    Checksum:iAE513312A999B763
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti74 – 741M → I in BAA22538. (PubMed:9344848)Curated
    Sequence conflicti161 – 1611S → T in BAA22538. (PubMed:9344848)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB006968 mRNA. Translation: BAA22538.1.
    CH471117 Genomic DNA. Translation: EAW66522.1.
    BC020082 mRNA. Translation: AAH20082.1.
    CCDSiCCDS11998.1.
    PIRiJC5762.
    RefSeqiNP_004223.2. NM_004232.3.
    XP_005266840.1. XM_005266783.1.
    XP_006722640.1. XM_006722577.1.
    UniGeneiHs.44439.

    Genome annotation databases

    EnsembliENST00000397942; ENSP00000381034; ENSG00000170677.
    ENST00000582322; ENSP00000463395; ENSG00000170677.
    GeneIDi9306.
    KEGGihsa:9306.
    UCSCiuc002lkr.1. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB006968 mRNA. Translation: BAA22538.1 .
    CH471117 Genomic DNA. Translation: EAW66522.1 .
    BC020082 mRNA. Translation: AAH20082.1 .
    CCDSi CCDS11998.1.
    PIRi JC5762.
    RefSeqi NP_004223.2. NM_004232.3.
    XP_005266840.1. XM_005266783.1.
    XP_006722640.1. XM_006722577.1.
    UniGenei Hs.44439.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2VIF X-ray 1.45 A 361-499 [» ]
    ProteinModelPortali O14544.
    SMRi O14544. Positions 367-535.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114719. 22 interactions.
    IntActi O14544. 12 interactions.
    MINTi MINT-4821450.
    STRINGi 9606.ENSP00000306939.

    PTM databases

    PhosphoSitei O14544.

    Proteomic databases

    MaxQBi O14544.
    PaxDbi O14544.
    PRIDEi O14544.

    Protocols and materials databases

    DNASUi 9306.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000397942 ; ENSP00000381034 ; ENSG00000170677 .
    ENST00000582322 ; ENSP00000463395 ; ENSG00000170677 .
    GeneIDi 9306.
    KEGGi hsa:9306.
    UCSCi uc002lkr.1. human.

    Organism-specific databases

    CTDi 9306.
    GeneCardsi GC18P067956.
    HGNCi HGNC:16833. SOCS6.
    HPAi CAB010189.
    HPA035477.
    MIMi 605118. gene.
    neXtProti NX_O14544.
    PharmGKBi PA134917653.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG318341.
    HOGENOMi HOG000027792.
    HOVERGENi HBG057479.
    InParanoidi O14544.
    KOi K10322.
    OMAi TTGVMLQ.
    OrthoDBi EOG7SXW3G.
    PhylomeDBi O14544.
    TreeFami TF321368.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_111225. Regulation of KIT signaling.
    SignaLinki O14544.

    Miscellaneous databases

    EvolutionaryTracei O14544.
    GeneWikii SOCS6.
    GenomeRNAii 9306.
    NextBioi 34859.
    PROi O14544.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14544.
    Bgeei O14544.
    CleanExi HS_SOCS4.
    HS_SOCS6.
    Genevestigatori O14544.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR028413. SOCS.
    IPR028421. SOCS6.
    IPR001496. SOCS_C.
    [Graphical view ]
    PANTHERi PTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF25. PTHR10385:SF25. 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. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. 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].
      Tissue: Skin.
    4. "Signal transduction via the stem cell factor receptor/c-Kit."
      Ronnstrand L.
      Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING AND KIT DEGRADATION.
    5. "Structural basis for c-KIT inhibition by the suppressor of cytokine signaling 6 (SOCS6) ubiquitin ligase."
      Zadjali F., Pike A.C., Vesterlund M., Sun J., Wu C., Li S.S., Ronnstrand L., Knapp S., Bullock A.N., Flores-Morales A.
      J. Biol. Chem. 286:480-490(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 361-499 IN COMPLEX WITH KIT, FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASE FOR KIT.

    Entry informationi

    Entry nameiSOCS6_HUMAN
    AccessioniPrimary (citable) accession number: O14544
    Secondary accession number(s): Q8WUM3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: September 23, 2008
    Last modified: October 1, 2014
    This is version 125 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 18
      Human chromosome 18: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3