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O75159

- SOCS5_HUMAN

UniProt

O75159 - SOCS5_HUMAN

Protein

Suppressor of cytokine signaling 5

Gene

SOCS5

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 1 (01 Nov 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. 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. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T-helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes differentiation into the Th2 phenotype. Can also partially inhibit IL6 and LIF signaling.1 Publication

    Pathwayi

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. receptor tyrosine kinase binding Source: UniProtKB

    GO - Biological processi

    1. cell growth Source: UniProtKB
    2. cytokine-mediated signaling pathway Source: UniProtKB
    3. epidermal growth factor receptor signaling pathway Source: Ensembl
    4. JAK-STAT cascade Source: InterPro
    5. negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
    6. negative regulation of signal transduction Source: UniProtKB
    7. negative regulation of T-helper 2 cell differentiation Source: UniProtKB
    8. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    9. positive regulation of T-helper 1 cell differentiation Source: UniProtKB
    10. protein ubiquitination Source: UniProtKB-UniPathway
    11. regulation of growth Source: UniProtKB-KW

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Growth regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    SignaLinkiO75159.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Suppressor of cytokine signaling 5
    Short name:
    SOCS-5
    Alternative name(s):
    Cytokine-inducible SH2 protein 6
    Short name:
    CIS-6
    Cytokine-inducible SH2-containing protein 5
    Gene namesi
    Name:SOCS5
    Synonyms:CIS6, CISH5, CISH6, KIAA0671
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:16852. SOCS5.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi406 – 4061R → K: Abrogates the ability to induce EGFR degradation. 1 Publication
    Mutagenesisi484 – 4841L → P: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with F-488. 1 Publication
    Mutagenesisi488 – 4881C → F: Abrogates the interaction with TCEB1 and TCEB2 and the ability to suppress EGFR signaling; when associated with P-484. 1 Publication

    Organism-specific databases

    PharmGKBiPA134884627.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 536536Suppressor of cytokine signaling 5PRO_0000181249Add
    BLAST

    Post-translational modificationi

    Phosphorylated. Phosphorylation is induced by EGF.1 Publication

    Proteomic databases

    MaxQBiO75159.
    PaxDbiO75159.
    PRIDEiO75159.

    PTM databases

    PhosphoSiteiO75159.

    Expressioni

    Inductioni

    Up-regulated by EGF (at protein level).1 Publication

    Gene expression databases

    ArrayExpressiO75159.
    BgeeiO75159.
    CleanExiHS_SOCS5.
    GenevestigatoriO75159.

    Organism-specific databases

    HPAiCAB025510.
    HPA020884.

    Interactioni

    Subunit structurei

    Interacts with IL4R; inhibits IL4 signaling By similarity. Interacts with EGFR. Interacts with TCEB1 AND TCEB2; mediates EGFR ubiquitination and degradation.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    METP085812EBI-970130,EBI-1039152

    Protein-protein interaction databases

    BioGridi115013. 7 interactions.
    IntActiO75159. 6 interactions.
    MINTiMINT-2835826.
    STRINGi9606.ENSP00000305133.

    Structurei

    3D structure databases

    ProteinModelPortaliO75159.
    SMRiO75159. Positions 369-524.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini381 – 47696SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini471 – 52050SOCS boxPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 5050Required for interaction with IL4RBy similarityAdd
    BLAST

    Domaini

    The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

    Sequence similaritiesi

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

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG258974.
    HOGENOMiHOG000027791.
    HOVERGENiHBG054138.
    InParanoidiO75159.
    KOiK04698.
    OMAiQVSGDSH.
    OrthoDBiEOG7XH6QR.
    PhylomeDBiO75159.
    TreeFamiTF321368.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR028413. SOCS.
    IPR022252. SOCS4/SOCS5_dom.
    IPR028420. SOCS5.
    IPR001496. SOCS_C.
    [Graphical view]
    PANTHERiPTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF28. PTHR10385:SF28. 1 hit.
    PfamiPF00017. SH2. 1 hit.
    PF12610. SOCS. 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.

    O75159-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDKVGKMWNN FKYRCQNLFG HEGGSRSENV DMNSNRCLSV KEKNISIGDS    50
    TPQQQSSPLR ENIALQLGLS PSKNSSRRNQ NCATEIPQIV EISIEKDNDS 100
    CVTPGTRLAR RDSYSRHAPW GGKKKHSCST KTQSSLDADK KFGRTRSGLQ 150
    RRERRYGVSS VHDMDSVSSR TVGSRSLRQR LQDTVGLCFP MRTYSKQSKP 200
    LFSNKRKIHL SELMLEKCPF PAGSDLAQKW HLIKQHTAPV SPHSTFFDTF 250
    DPSLVSTEDE EDRLRERRRL SIEEGVDPPP NAQIHTFEAT AQVNPLYKLG 300
    PKLAPGMTEI SGDSSAIPQA NCDSEEDTTT LCLQSRRQKQ RQISGDSHTH 350
    VSRQGAWKVH TQIDYIHCLV PDLLQITGNP CYWGVMDRYE AEALLEGKPE 400
    GTFLLRDSAQ EDYLFSVSFR RYNRSLHARI EQWNHNFSFD AHDPCVFHSS 450
    TVTGLLEHYK DPSSCMFFEP LLTISLNRTF PFSLQYICRA VICRCTTYDG 500
    IDGLPLPSML QDFLKEYHYK QKVRVRWLER EPVKAK 536
    Length:536
    Mass (Da):61,246
    Last modified:November 1, 1998 - v1
    Checksum:i0629CDCF2A97E9D8
    GO

    Sequence cautioni

    The sequence BAA31646.2 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti478 – 4781R → M in AAH32862. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF073958 mRNA. Translation: AAD40484.1.
    AB014571 mRNA. Translation: BAA31646.2. Different initiation.
    AL136896 mRNA. Translation: CAB66830.1.
    AK290194 mRNA. Translation: BAF82883.1.
    AC020604 Genomic DNA. Translation: AAY24289.1.
    CH471053 Genomic DNA. Translation: EAX00236.1.
    CH471053 Genomic DNA. Translation: EAX00237.1.
    BC032862 mRNA. Translation: AAH32862.1.
    CCDSiCCDS1830.1.
    PIRiT46499.
    RefSeqiNP_054730.1. NM_014011.4.
    NP_659198.1. NM_144949.2.
    UniGeneiHs.468426.

    Genome annotation databases

    EnsembliENST00000306503; ENSP00000305133; ENSG00000171150.
    ENST00000394861; ENSP00000378330; ENSG00000171150.
    GeneIDi9655.
    KEGGihsa:9655.
    UCSCiuc002rvf.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF073958 mRNA. Translation: AAD40484.1 .
    AB014571 mRNA. Translation: BAA31646.2 . Different initiation.
    AL136896 mRNA. Translation: CAB66830.1 .
    AK290194 mRNA. Translation: BAF82883.1 .
    AC020604 Genomic DNA. Translation: AAY24289.1 .
    CH471053 Genomic DNA. Translation: EAX00236.1 .
    CH471053 Genomic DNA. Translation: EAX00237.1 .
    BC032862 mRNA. Translation: AAH32862.1 .
    CCDSi CCDS1830.1.
    PIRi T46499.
    RefSeqi NP_054730.1. NM_014011.4.
    NP_659198.1. NM_144949.2.
    UniGenei Hs.468426.

    3D structure databases

    ProteinModelPortali O75159.
    SMRi O75159. Positions 369-524.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115013. 7 interactions.
    IntActi O75159. 6 interactions.
    MINTi MINT-2835826.
    STRINGi 9606.ENSP00000305133.

    PTM databases

    PhosphoSitei O75159.

    Proteomic databases

    MaxQBi O75159.
    PaxDbi O75159.
    PRIDEi O75159.

    Protocols and materials databases

    DNASUi 9655.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000306503 ; ENSP00000305133 ; ENSG00000171150 .
    ENST00000394861 ; ENSP00000378330 ; ENSG00000171150 .
    GeneIDi 9655.
    KEGGi hsa:9655.
    UCSCi uc002rvf.3. human.

    Organism-specific databases

    CTDi 9655.
    GeneCardsi GC02P046926.
    HGNCi HGNC:16852. SOCS5.
    HPAi CAB025510.
    HPA020884.
    MIMi 607094. gene.
    neXtProti NX_O75159.
    PharmGKBi PA134884627.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG258974.
    HOGENOMi HOG000027791.
    HOVERGENi HBG054138.
    InParanoidi O75159.
    KOi K04698.
    OMAi QVSGDSH.
    OrthoDBi EOG7XH6QR.
    PhylomeDBi O75159.
    TreeFami TF321368.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    SignaLinki O75159.

    Miscellaneous databases

    GeneWikii SOCS5.
    GenomeRNAii 9655.
    NextBioi 36245.
    PROi O75159.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O75159.
    Bgeei O75159.
    CleanExi HS_SOCS5.
    Genevestigatori O75159.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR028413. SOCS.
    IPR022252. SOCS4/SOCS5_dom.
    IPR028420. SOCS5.
    IPR001496. SOCS_C.
    [Graphical view ]
    PANTHERi PTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF28. PTHR10385:SF28. 1 hit.
    Pfami PF00017. SH2. 1 hit.
    PF12610. SOCS. 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 expression of CIS6, chromosomal assignment to 3p22 and 2p21 by in situ hybridization."
      Magrangeas F., Apiou F., Denis S., Weidle U., Jacques Y., Minvielle S.
      Cytogenet. Cell Genet. 88:78-81(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Placenta.
    2. "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
      Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Thalamus.
    5. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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: Brain.
    8. "Suppressors of cytokine signaling 4 and 5 regulate epidermal growth factor receptor signaling."
      Kario E., Marmor M.D., Adamsky K., Citri A., Amit I., Amariglio N., Rechavi G., Yarden Y.
      J. Biol. Chem. 280:7038-7048(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN EGFR DEGRADATION, INDUCTION BY EGF, PHOSPHORYLATION, MUTAGENESIS OF ARG-406; LEU-484 AND CYS-488, INTERACTION WITH EGFR; TCEB1 AND TCEB2.

    Entry informationi

    Entry nameiSOCS5_HUMAN
    AccessioniPrimary (citable) accession number: O75159
    Secondary accession number(s): Q53SD4, Q8IYZ4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 127 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 2
      Human chromosome 2: 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