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O15524 (SOCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SOCS1
Synonyms:SSI1, TIP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length211 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.7 Ref.8 Ref.11 Ref.13

Subcellular location

Nucleus. Cytoplasmic vesicle. Note: Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3. Ref.13

Tissue specificity

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

Induction

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

Domain

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 similarities

Contains 1 SH2 domain.

Contains 1 SOCS box domain.

Ontologies

Keywords
   Biological processGrowth regulation
Ubl conjugation pathway
   Cellular componentCytoplasmic vesicle
Nucleus
   Coding sequence diversityPolymorphism
   DomainSH2 domain
   Molecular functionSignal transduction inhibitor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJAK-STAT cascade

Traceable author statement Ref.6. Source: ProtInc

JAK-STAT cascade involved in growth hormone signaling pathway

Traceable author statement. Source: Reactome

cellular response to amino acid stimulus

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

negative regulation of JAK-STAT cascade

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase activity

Traceable author statement Ref.3. Source: GOC

negative regulation of tyrosine phosphorylation of Stat3 protein

Inferred from sequence or structural similarity. Source: UniProtKB

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of growth

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of type I interferon-mediated signaling pathway

Traceable author statement. Source: Reactome

type I interferon signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Traceable author statement Ref.6. Source: ProtInc

cytoplasmic membrane-bounded vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioninsulin-like growth factor receptor binding

Inferred from physical interaction Ref.7. Source: UniProtKB

kinase inhibitor activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 17183367. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.7. Source: UniProtKB

protein kinase inhibitor activity

Traceable author statement Ref.3. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 211211Suppressor of cytokine signaling 1
PRO_0000181235

Regions

Domain79 – 17496SH2
Domain161 – 21050SOCS box
Region55 – 6612Kinase inhibitory region (KIR)
Region67 – 7812Extended SH2 subdomain (ESS)
Region173 – 18210Interaction with Elongin BC complex By similarity
Compositional bias26 – 327Poly-Ser

Natural variations

Natural variant2101Q → H.
Corresponds to variant rs11549428 [ dbSNP | Ensembl ].
VAR_061808

Experimental info

Sequence conflict91A → G in CAB92528. Ref.5
Sequence conflict15 – 162TA → CP in BAA21537. Ref.6
Sequence conflict351A → G in CAB92528. Ref.5
Sequence conflict1781C → F in CAB92528. Ref.5

Sequences

Sequence LengthMass (Da)Tools
O15524 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 7CC983533F78B127

FASTA21123,551
        10         20         30         40         50         60 
MVAHNQVAAD NAVSTAAEPR RRPEPSSSSS SSPAAPARPR PCPAVPAPAP GDTHFRTFRS 

        70         80         90        100        110        120 
HADYRRITRA SALLDACGFY WGPLSVHGAH ERLRAEPVGT FLVRDSRQRN CFFALSVKMA 

       130        140        150        160        170        180 
SGPTSIRVHF QAGRFHLDGS RESFDCLFEL LEHYVAAPRR MLGAPLRQRR VRPLQELCRQ 

       190        200        210 
RIVATVGREN LARIPLNPVL RDYLSSFPFQ I 

« Hide

References

[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]"SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase."
Ohya K., Kajigaya S., Yamashita Y., Miyazato A., Hatake K., Miura Y., Ikeda U., Shimada K., Ozawa K., Mano H.
J. Biol. Chem. 272:27178-27182(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Myeloid leukemia cell.
[3]"A family of cytokine-inducible inhibitors of signaling."
Starr R., Willson T.A., Viney E.M., Murray L.J.L., Rayner J.R., Jenkins B.J., Gonda T.J., Alexander W.S., Metcalf D., Nicola N.A., Hilton D.J.
Nature 387:917-921(1997) [PubMed] [Europe PMC] [Abstract]
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]"A new protein containing an SH2 domain that inhibits JAK kinases."
Endo T.A., Masuhara M., Yokouchi M., Suzuki R., Sakamoto H., Mitsui K., Matsumoto A., Tanimura S., Ohtsubo M., Misawa H., Miyazaki T., Leonor N., Taniguchi T., Fujita T., Kanakura Y., Komiya S., Yoshimura A.
Nature 387:921-924(1997) [PubMed] [Europe PMC] [Abstract]
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]"The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2."
Kamizono S., Hanada T., Yasukawa H., Minoguchi S., Kato R., Minoguchi M., Hattori K., Hatakeyama S., Yada M., Morita S., Kitamura T., Kato H., Nakayama K.I., Yoshimura A.
J. Biol. Chem. 276:12530-12538(2001) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10546.1.
RefSeqNP_003736.1. NM_003745.1.
UniGeneHs.50640.

3D structure databases

ProteinModelPortalO15524.
SMRO15524. Positions 55-211.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114203. 52 interactions.
DIPDIP-29662N.
IntActO15524. 10 interactions.
MINTMINT-196452.
STRING9606.ENSP00000329418.

Proteomic databases

PaxDbO15524.
PRIDEO15524.

Protocols and materials databases

DNASU8651.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332029; ENSP00000329418; ENSG00000185338.
GeneID8651.
KEGGhsa:8651.
UCSCuc002dar.1. human.

Organism-specific databases

CTD8651.
GeneCardsGC16M011255.
HGNCHGNC:19383. SOCS1.
HPACAB010355.
MIM603597. gene.
neXtProtNX_O15524.
PharmGKBPA134863068.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG298538.
HOGENOMHOG000236320.
HOVERGENHBG002457.
InParanoidO15524.
KOK04694.
OMAKANHARR.
OrthoDBEOG7TMZSZ.
PhylomeDBO15524.
TreeFamTF321368.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6900. Immune System.
SignaLinkO15524.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressO15524.
BgeeO15524.
CleanExHS_SOCS1.
GenevestigatorO15524.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
IPR028413. SOCS.
IPR028411. SOCS1.
IPR001496. SOCS_C.
[Graphical view]
PANTHERPTHR10385. PTHR10385. 1 hit.
PTHR10385:SF5. PTHR10385:SF5. 1 hit.
PfamPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
SMARTSM00252. SH2. 1 hit.
SM00253. SOCS. 1 hit.
SM00969. SOCS_box. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSuppressor_of_cytokine_signaling_1.
GenomeRNAi8651.
NextBio32445.
PROO15524.
SOURCESearch...

Entry information

Entry nameSOCS1_HUMAN
AccessionPrimary (citable) accession number: O15524
Secondary accession number(s): O15097, Q9NSA7
Entry history
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM