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O14508

- SOCS2_HUMAN

UniProt

O14508 - SOCS2_HUMAN

Protein

Suppressor of cytokine signaling 2

Gene

SOCS2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (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. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable 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.

    Pathwayi

    GO - Molecular functioni

    1. growth hormone receptor binding Source: UniProtKB
    2. insulin-like growth factor receptor binding Source: UniProtKB
    3. JAK pathway signal transduction adaptor activity Source: ProtInc
    4. protein binding Source: IntAct
    5. SH3/SH2 adaptor activity Source: ProtInc

    GO - Biological processi

    1. aging Source: Ensembl
    2. cellular response to hormone stimulus Source: BHF-UCL
    3. growth hormone receptor signaling pathway Source: BHF-UCL
    4. JAK-STAT cascade Source: ProtInc
    5. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
    6. negative regulation of apoptotic process Source: ProtInc
    7. negative regulation of JAK-STAT cascade Source: InterPro
    8. positive regulation of signal transduction Source: GOC
    9. protein ubiquitination Source: UniProtKB-UniPathway
    10. regulation of cell growth Source: UniProtKB
    11. regulation of signal transduction Source: UniProtKB
    12. response to estradiol Source: BHF-UCL

    Keywords - Molecular functioni

    Signal transduction inhibitor

    Keywords - Biological processi

    Growth regulation, Ubl conjugation pathway

    Enzyme and pathway databases

    ReactomeiREACT_111133. Growth hormone receptor signaling.
    SignaLinkiO14508.
    UniPathwayiUPA00143.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Suppressor of cytokine signaling 2
    Short name:
    SOCS-2
    Alternative name(s):
    Cytokine-inducible SH2 protein 2
    Short name:
    CIS-2
    STAT-induced STAT inhibitor 2
    Short name:
    SSI-2
    Gene namesi
    Name:SOCS2
    Synonyms:CIS2, SSI2, STATI2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:19382. SOCS2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA128394542.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 198198Suppressor of cytokine signaling 2PRO_0000181238Add
    BLAST

    Proteomic databases

    MaxQBiO14508.
    PaxDbiO14508.
    PRIDEiO14508.

    Expressioni

    Tissue specificityi

    High expression in heart, placenta, lung, kidney and prostate.

    Inductioni

    By a subset of cytokines, including EPO/erythropoietin and CSF2/GM-CSF.

    Gene expression databases

    ArrayExpressiO14508.
    BgeeiO14508.
    CleanExiHS_SOCS2.
    GenevestigatoriO14508.

    Organism-specific databases

    HPAiCAB010356.

    Interactioni

    Subunit structurei

    Interacts with IGF1 receptor, prolactin receptor and growth hormone (GH) receptor. Associates with the Elongin BC complex.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EPORP192353EBI-617737,EBI-617321
    KITP107214EBI-617737,EBI-1379503
    TCEB1Q153692EBI-617737,EBI-301231

    Protein-protein interaction databases

    BioGridi114362. 22 interactions.
    DIPiDIP-29569N.
    IntActiO14508. 10 interactions.
    MINTiMINT-1459522.
    STRINGi9606.ENSP00000339428.

    Structurei

    Secondary structure

    1
    198
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi33 – 4513
    Helixi55 – 628
    Beta strandi70 – 745
    Beta strandi76 – 794
    Beta strandi81 – 888
    Beta strandi91 – 10010
    Beta strandi103 – 1064
    Turni108 – 1125
    Helixi113 – 1153
    Beta strandi119 – 1213
    Helixi122 – 13211
    Helixi163 – 17412
    Helixi178 – 1803
    Beta strandi181 – 1833
    Helixi185 – 1928

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2C9WX-ray1.90A32-198[»]
    4JGHX-ray3.00A32-198[»]
    ProteinModelPortaliO14508.
    SMRiO14508. Positions 28-198.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO14508.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini48 – 156109SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini151 – 19747SOCS boxPROSITE-ProRule annotationAdd
    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

    eggNOGiNOG320153.
    HOGENOMiHOG000236320.
    HOVERGENiHBG002457.
    InParanoidiO14508.
    KOiK04695.
    OMAiWELPLPT.
    OrthoDBiEOG71RXKX.
    PhylomeDBiO14508.
    TreeFamiTF321368.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR028413. SOCS.
    IPR028410. SOCS2.
    IPR001496. SOCS_C.
    [Graphical view]
    PANTHERiPTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF27. PTHR10385:SF27. 1 hit.
    PfamiPF00017. SH2. 1 hit.
    PF07525. SOCS_box. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    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.

    O14508-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTLRCLEPSG NGGEGTRSQW GTAGSAEEPS PQAARLAKAL RELGQTGWYW    50
    GSMTVNEAKE KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ 100
    DGKFRLDSII CVKSKLKQFD SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL 150
    YLTKPLYTSA PSLQHLCRLT INKCTGAIWG LPLPTRLKDY LEEYKFQV 198
    Length:198
    Mass (Da):22,172
    Last modified:January 1, 1998 - v1
    Checksum:iDAFC4AD97F8182BF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti2 – 21T → N in AAC98896. 1 PublicationCurated
    Sequence conflicti5 – 51C → R in BAA22536. (PubMed:9344848)Curated
    Sequence conflicti31 – 399PQAARLAKA → RRRRVWRR in AAC98896. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti52 – 521S → N.
    Corresponds to variant rs3741676 [ dbSNP | Ensembl ].
    VAR_052032

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB004903 mRNA. Translation: BAA22429.1.
    AB006966 mRNA. Translation: BAA22536.1.
    AF020590 mRNA. Translation: AAC98896.1.
    AF037989 mRNA. Translation: AAC34745.1.
    AK290546 mRNA. Translation: BAF83235.1.
    AK313165 mRNA. Translation: BAG35983.1.
    CH471054 Genomic DNA. Translation: EAW97492.1.
    BC010399 mRNA. Translation: AAH10399.1.
    AF132441 Genomic DNA. Translation: AAD27710.1.
    CCDSiCCDS9047.1.
    PIRiJC5626.
    JC5760.
    RefSeqiNP_001257396.1. NM_001270467.1.
    NP_001257397.1. NM_001270468.1.
    NP_001257398.1. NM_001270469.1.
    NP_001257399.1. NM_001270470.1.
    NP_001257400.1. NM_001270471.1.
    NP_003868.1. NM_003877.4.
    UniGeneiHs.485572.
    Hs.594327.
    Hs.736572.
    Hs.737206.

    Genome annotation databases

    EnsembliENST00000340600; ENSP00000339428; ENSG00000120833.
    ENST00000536696; ENSP00000442898; ENSG00000120833.
    ENST00000549122; ENSP00000447161; ENSG00000120833.
    ENST00000549206; ENSP00000448815; ENSG00000120833.
    ENST00000551556; ENSP00000449227; ENSG00000120833.
    GeneIDi8835.
    KEGGihsa:8835.
    UCSCiuc001tcw.2. 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
    AB004903 mRNA. Translation: BAA22429.1 .
    AB006966 mRNA. Translation: BAA22536.1 .
    AF020590 mRNA. Translation: AAC98896.1 .
    AF037989 mRNA. Translation: AAC34745.1 .
    AK290546 mRNA. Translation: BAF83235.1 .
    AK313165 mRNA. Translation: BAG35983.1 .
    CH471054 Genomic DNA. Translation: EAW97492.1 .
    BC010399 mRNA. Translation: AAH10399.1 .
    AF132441 Genomic DNA. Translation: AAD27710.1 .
    CCDSi CCDS9047.1.
    PIRi JC5626.
    JC5760.
    RefSeqi NP_001257396.1. NM_001270467.1.
    NP_001257397.1. NM_001270468.1.
    NP_001257398.1. NM_001270469.1.
    NP_001257399.1. NM_001270470.1.
    NP_001257400.1. NM_001270471.1.
    NP_003868.1. NM_003877.4.
    UniGenei Hs.485572.
    Hs.594327.
    Hs.736572.
    Hs.737206.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2C9W X-ray 1.90 A 32-198 [» ]
    4JGH X-ray 3.00 A 32-198 [» ]
    ProteinModelPortali O14508.
    SMRi O14508. Positions 28-198.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114362. 22 interactions.
    DIPi DIP-29569N.
    IntActi O14508. 10 interactions.
    MINTi MINT-1459522.
    STRINGi 9606.ENSP00000339428.

    Proteomic databases

    MaxQBi O14508.
    PaxDbi O14508.
    PRIDEi O14508.

    Protocols and materials databases

    DNASUi 8835.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000340600 ; ENSP00000339428 ; ENSG00000120833 .
    ENST00000536696 ; ENSP00000442898 ; ENSG00000120833 .
    ENST00000549122 ; ENSP00000447161 ; ENSG00000120833 .
    ENST00000549206 ; ENSP00000448815 ; ENSG00000120833 .
    ENST00000551556 ; ENSP00000449227 ; ENSG00000120833 .
    GeneIDi 8835.
    KEGGi hsa:8835.
    UCSCi uc001tcw.2. human.

    Organism-specific databases

    CTDi 8835.
    GeneCardsi GC12P093963.
    HGNCi HGNC:19382. SOCS2.
    HPAi CAB010356.
    MIMi 605117. gene.
    neXtProti NX_O14508.
    PharmGKBi PA128394542.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG320153.
    HOGENOMi HOG000236320.
    HOVERGENi HBG002457.
    InParanoidi O14508.
    KOi K04695.
    OMAi WELPLPT.
    OrthoDBi EOG71RXKX.
    PhylomeDBi O14508.
    TreeFami TF321368.

    Enzyme and pathway databases

    UniPathwayi UPA00143 .
    Reactomei REACT_111133. Growth hormone receptor signaling.
    SignaLinki O14508.

    Miscellaneous databases

    ChiTaRSi SOCS2. human.
    EvolutionaryTracei O14508.
    GeneWikii SOCS2.
    GenomeRNAii 8835.
    NextBioi 33160.
    PROi O14508.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14508.
    Bgeei O14508.
    CleanExi HS_SOCS2.
    Genevestigatori O14508.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR028413. SOCS.
    IPR028410. SOCS2.
    IPR001496. SOCS_C.
    [Graphical view ]
    PANTHERi PTHR10385. PTHR10385. 1 hit.
    PTHR10385:SF27. PTHR10385:SF27. 1 hit.
    Pfami PF00017. SH2. 1 hit.
    PF07525. SOCS_box. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    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].
    3. "Cloning of a novel human gene coding human suppressor of cytokine signaling-2 (HsSOCS-2)."
      Tu Q., Yu L., Zhang Q.
      Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "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: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Fetal brain.
    5. "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: Brain and Lung.
    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. "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] OF 173-198.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Crystal structure of the SOCS2-elongin C-elongin B complex defines a prototypical SOCS box ubiquitin ligase."
      Bullock A.N., Debreczeni J.E., Edwards A.M., Sundstrom M., Knapp S.
      Proc. Natl. Acad. Sci. U.S.A. 103:7637-7642(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH THE ELONGIN BC COMPLEX.

    Entry informationi

    Entry nameiSOCS2_HUMAN
    AccessioniPrimary (citable) accession number: O14508
    Secondary accession number(s): A8K3D1
    , O14542, O95102, Q9UKS5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2002
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 132 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3