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Protein

Suppressor of cytokine signaling 1

Gene

SOCS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.By similarity2 Publications

Pathway:iprotein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • insulin-like growth factor receptor binding Source: UniProtKB
  • kinase inhibitor activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein kinase inhibitor activity Source: ProtInc

GO - Biological processi

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_25162. Interferon alpha/beta signaling.
REACT_25216. Regulation of IFNA signaling.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
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 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:19383. SOCS1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytoplasmic membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134863068.

Polymorphism and mutation databases

BioMutaiSOCS1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 211211Suppressor of cytokine signaling 1PRO_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

BgeeiO15524.
CleanExiHS_SOCS1.
ExpressionAtlasiO15524. baseline and differential.
GenevisibleiO15524. HS.

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).By similarity

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. 51 interactions.
DIPiDIP-29662N.
IntActiO15524. 13 interactions.
MINTiMINT-196452.
STRINGi9606.ENSP00000329418.

Structurei

3D structure databases

ProteinModelPortaliO15524.
SMRiO15524. Positions 55-211.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini79 – 17496SH2PROSITE-ProRule annotationAdd
BLAST
Domaini161 – 21050SOCS boxPROSITE-ProRule annotationAdd
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 complexBy 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).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

eggNOGiNOG298538.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO15524.
KOiK04694.
OMAiETFDCLF.
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

« Hide

        10         20         30         40         50
MVAHNQVAAD NAVSTAAEPR RRPEPSSSSS SSPAAPARPR PCPAVPAPAP
60 70 80 90 100
GDTHFRTFRS HADYRRITRA SALLDACGFY WGPLSVHGAH ERLRAEPVGT
110 120 130 140 150
FLVRDSRQRN CFFALSVKMA SGPTSIRVHF QAGRFHLDGS RESFDCLFEL
160 170 180 190 200
LEHYVAAPRR MLGAPLRQRR VRPLQELCRQ RIVATVGREN LARIPLNPVL
210
RDYLSSFPFQ I
Length:211
Mass (Da):23,551
Last modified:January 1, 1998 - v1
Checksum:i7CC983533F78B127
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti9 – 91A → G in CAB92528 (Ref. 5) Curated
Sequence conflicti15 – 162TA → CP in BAA21537 (PubMed:9202126).Curated
Sequence conflicti35 – 351A → G in CAB92528 (Ref. 5) Curated
Sequence conflicti178 – 1781C → F in CAB92528 (Ref. 5) Curated

Natural variant

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO15524.
SMRiO15524. Positions 55-211.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114203. 51 interactions.
DIPiDIP-29662N.
IntActiO15524. 13 interactions.
MINTiMINT-196452.
STRINGi9606.ENSP00000329418.

Polymorphism and mutation databases

BioMutaiSOCS1.

Proteomic databases

PaxDbiO15524.
PRIDEiO15524.

Protocols and materials databases

DNASUi8651.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332029; ENSP00000329418; ENSG00000185338.
GeneIDi8651.
KEGGihsa:8651.
UCSCiuc002dar.1. human.

Organism-specific databases

CTDi8651.
GeneCardsiGC16M011255.
HGNCiHGNC:19383. SOCS1.
HPAiCAB010355.
MIMi603597. gene.
neXtProtiNX_O15524.
PharmGKBiPA134863068.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG298538.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO15524.
KOiK04694.
OMAiETFDCLF.
OrthoDBiEOG7TMZSZ.
PhylomeDBiO15524.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiREACT_111133. Growth hormone receptor signaling.
REACT_111225. Regulation of KIT signaling.
REACT_24980. Regulation of IFNG signaling.
REACT_25078. Interferon gamma signaling.
REACT_25162. Interferon alpha/beta signaling.
REACT_25216. Regulation of IFNA signaling.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_75842. Antigen processing: Ubiquitination & Proteasome degradation.
SignaLinkiO15524.

Miscellaneous databases

GeneWikiiSuppressor_of_cytokine_signaling_1.
GenomeRNAii8651.
NextBioi32445.
PROiO15524.
SOURCEiSearch...

Gene expression databases

BgeeiO15524.
CleanExiHS_SOCS1.
ExpressionAtlasiO15524. baseline and differential.
GenevisibleiO15524. HS.

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]
ProtoNetiSearch...

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: July 22, 2015
This is version 129 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.