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O15524

- SOCS1_HUMAN

UniProt

O15524 - SOCS1_HUMAN

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Protein
Suppressor of cytokine signaling 1
Gene
SOCS1, SSI1, TIP3
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.2 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. JAK-STAT cascade Source: ProtInc
  2. JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  3. cellular response to amino acid stimulus Source: Ensembl
  4. cytokine-mediated signaling pathway Source: UniProtKB
  5. fat cell differentiation Source: Ensembl
  6. interferon-gamma-mediated signaling pathway Source: Reactome
  7. negative regulation of JAK-STAT cascade Source: UniProtKB
  8. negative regulation of insulin receptor signaling pathway 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
Complete GO annotation...

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

GO - Cellular componenti

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

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 1
PRO_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.4 Publications

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini79 – 17496SH2
Add
BLAST
Domaini161 – 21050SOCS box
Add
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 complex By 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.

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SOCS box domain.

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

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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

Natural variant

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

Sequence conflict

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

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: September 3, 2014
This is version 121 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

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