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Protein

Suppressor of cytokine signaling 1

Gene

SOCS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Pathwayi: protein 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

  • 1-phosphatidylinositol-3-kinase regulator activity Source: GO_Central
  • 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

Keywordsi

Molecular functionSignal transduction inhibitor
Biological processGrowth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1266695 Interleukin-7 signaling
R-HSA-1433559 Regulation of KIT signaling
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-877300 Interferon gamma signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912694 Regulation of IFNA signaling
R-HSA-982772 Growth hormone receptor signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiO15524
SIGNORiO15524
UniPathwayi
UPA00143

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
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000185338.4
HGNCiHGNC:19383 SOCS1
MIMi603597 gene
neXtProtiNX_O15524

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi8651
OpenTargetsiENSG00000185338
PharmGKBiPA134863068

Polymorphism and mutation databases

BioMutaiSOCS1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812351 – 211Suppressor of cytokine signaling 1Add BLAST211

Proteomic databases

PaxDbiO15524
PeptideAtlasiO15524
PRIDEiO15524
ProteomicsDBi48724

PTM databases

iPTMnetiO15524
PhosphoSitePlusiO15524

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

BgeeiENSG00000185338 Expressed in 170 organ(s), highest expression level in right lobe of liver
CleanExiHS_SOCS1
ExpressionAtlasiO15524 baseline and differential
GenevisibleiO15524 HS

Organism-specific databases

HPAiCAB010355
HPA074108

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 (ELOB and ELOC). 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). Interacts with TRIM8 (PubMed:12163497).By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114203, 62 interactors
DIPiDIP-29662N
IntActiO15524, 15 interactors
MINTiO15524
STRINGi9606.ENSP00000329418

Structurei

3D structure databases

ProteinModelPortaliO15524
SMRiO15524
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini79 – 174SH2PROSITE-ProRule annotationAdd BLAST96
Domaini161 – 210SOCS boxPROSITE-ProRule annotationAdd BLAST50

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni55 – 66Kinase inhibitory region (KIR)Add BLAST12
Regioni67 – 78Extended SH2 subdomain (ESS)Add BLAST12
Regioni173 – 182Interaction with Elongin BC complexBy similarity10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi26 – 32Poly-Ser7

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-x3-C-x3-[AILV] and is part of the SOCS box (By similarity).By similarity

Sequence similaritiesi

Belongs to the SOCS1 family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG4566 Eukaryota
ENOG4111V4J LUCA
GeneTreeiENSGT00760000119136
HOGENOMiHOG000236320
HOVERGENiHBG002457
InParanoidiO15524
KOiK04694
OMAiCGFYWGP
OrthoDBiEOG091G0TJW
PhylomeDBiO15524
TreeFamiTF321368

Family and domain databases

CDDicd10382 SH2_SOCS1, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR028411 SOCS1
IPR035861 SOCS1_SH2
IPR001496 SOCS_box
IPR036036 SOCS_box-like_dom_sf
PANTHERiPTHR44621 PTHR44621, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF07525 SOCS_box, 1 hit
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00253 SOCS, 1 hit
SM00969 SOCS_box, 1 hit
SUPFAMiSSF158235 SSF158235, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50225 SOCS, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti9A → G in CAB92528 (Ref. 5) Curated1
Sequence conflicti15 – 16TA → CP in BAA21537 (PubMed:9202126).Curated2
Sequence conflicti35A → G in CAB92528 (Ref. 5) Curated1
Sequence conflicti178C → F in CAB92528 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061808210Q → H. Corresponds to variant dbSNP:rs11549428EnsemblClinVar.1

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
ENST00000644787; ENSP00000496577; ENSG00000185338
GeneIDi8651
KEGGihsa:8651

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114203, 62 interactors
DIPiDIP-29662N
IntActiO15524, 15 interactors
MINTiO15524
STRINGi9606.ENSP00000329418

PTM databases

iPTMnetiO15524
PhosphoSitePlusiO15524

Polymorphism and mutation databases

BioMutaiSOCS1

Proteomic databases

PaxDbiO15524
PeptideAtlasiO15524
PRIDEiO15524
ProteomicsDBi48724

Protocols and materials databases

DNASUi8651
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332029; ENSP00000329418; ENSG00000185338
ENST00000644787; ENSP00000496577; ENSG00000185338
GeneIDi8651
KEGGihsa:8651

Organism-specific databases

CTDi8651
DisGeNETi8651
EuPathDBiHostDB:ENSG00000185338.4
GeneCardsiSOCS1
HGNCiHGNC:19383 SOCS1
HPAiCAB010355
HPA074108
MIMi603597 gene
neXtProtiNX_O15524
OpenTargetsiENSG00000185338
PharmGKBiPA134863068
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4566 Eukaryota
ENOG4111V4J LUCA
GeneTreeiENSGT00760000119136
HOGENOMiHOG000236320
HOVERGENiHBG002457
InParanoidiO15524
KOiK04694
OMAiCGFYWGP
OrthoDBiEOG091G0TJW
PhylomeDBiO15524
TreeFamiTF321368

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-1266695 Interleukin-7 signaling
R-HSA-1433559 Regulation of KIT signaling
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-877300 Interferon gamma signaling
R-HSA-877312 Regulation of IFNG signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-912694 Regulation of IFNA signaling
R-HSA-982772 Growth hormone receptor signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiO15524
SIGNORiO15524

Miscellaneous databases

GeneWikiiSuppressor_of_cytokine_signaling_1
GenomeRNAii8651
PROiPR:O15524
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185338 Expressed in 170 organ(s), highest expression level in right lobe of liver
CleanExiHS_SOCS1
ExpressionAtlasiO15524 baseline and differential
GenevisibleiO15524 HS

Family and domain databases

CDDicd10382 SH2_SOCS1, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR028411 SOCS1
IPR035861 SOCS1_SH2
IPR001496 SOCS_box
IPR036036 SOCS_box-like_dom_sf
PANTHERiPTHR44621 PTHR44621, 1 hit
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PF07525 SOCS_box, 1 hit
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00253 SOCS, 1 hit
SM00969 SOCS_box, 1 hit
SUPFAMiSSF158235 SSF158235, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit
PS50225 SOCS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSOCS1_HUMAN
AccessioniPrimary (citable) accession number: O15524
Secondary accession number(s): O15097, Q9NSA7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 161 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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