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Protein

Suppressor of cytokine signaling 1

Gene

Socs1

Organism
Mus musculus (Mouse)
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 (By similarity). Appears to be a major regulator of signaling by interleukin 6 (IL6) and leukemia inhibitory factor (LIF). Regulates interferon-gamma mediated sensory neuron survival. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Seems to recognize JAK2 (By similarity). SOCS1 appears to be a negative regulator in IGF1R signaling pathway (By similarity).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

GO - Biological processi

  • cellular response to amino acid stimulus Source: MGI
  • cellular response to cytokine stimulus Source: MGI
  • cellular response to organic cyclic compound Source: MGI
  • cytokine-mediated signaling pathway Source: MGI
  • fat cell differentiation Source: MGI
  • JAK-STAT cascade Source: MGI
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • negative regulation of insulin receptor signaling pathway Source: MGI
  • negative regulation of JAK-STAT cascade Source: MGI
  • negative regulation of protein kinase activity Source: GO_Central
  • negative regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
  • negative regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of activation of JAK2 kinase activity Source: MGI
  • regulation of cytokine secretion Source: MGI
  • regulation of growth Source: UniProtKB-KW
  • regulation of interferon-gamma-mediated signaling pathway Source: InterPro
  • regulation of JAK-STAT cascade Source: MGI
  • regulation of protein phosphorylation Source: MGI
  • regulation of type I interferon-mediated signaling pathway Source: Reactome
  • regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1433559. Regulation of KIT signaling.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-912694. Regulation of IFNA signaling.
R-MMU-982772. Growth hormone receptor signaling.
SABIO-RKO35716.
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
Gene namesi
Name:Socs1
Synonyms:Cish1, Ssi1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1354910. Socs1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasmic vesicle By similarity

  • Note: Detected in perinuclear cytoplasmic vesicles upon interaction with FGFR3.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice exhibit lymphocyte deficiency and degeneration of the liver parenchyma. Animals die within 3 weeks of age.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi51P → A: No effect on LIF signal transduction suppression. 1
Mutagenesisi52G → A: No effect on LIF signal transduction suppression. 1
Mutagenesisi53D → A or R: No effect on LIF signal transduction suppression. 1
Mutagenesisi54T → A: No effect on LIF signal transduction suppression. 1
Mutagenesisi55H → A or D: No effect on JAK signal transduction suppression. 1 Publication1
Mutagenesisi56F → A, S or D: Loss of JAK signal transduction suppression. 1 Publication1
Mutagenesisi56F → E or S: Reduced binding to JH1. 1 Publication1
Mutagenesisi56F → L: No effect on JAK signal transduction inhibition nor on binding to JH1. 1 Publication1
Mutagenesisi57R → A or E: No effect on JAK signal transduction suppression. 1 Publication1
Mutagenesisi58T → A: No effect on JAK signal transduction suppression. 1 Publication1
Mutagenesisi59F → A or E: Loss of JAK signal transduction suppression. Reduced binding to JH1. 2 Publications1
Mutagenesisi59F → D: Loss of JAK signal transduction suppression. Destabilization of SOCS1. 2 Publications1
Mutagenesisi59F → L: No effect on JAK signal transduction suppression nor on binding to JH1. 2 Publications1
Mutagenesisi60R → A: No effect on LIF signal transduction suppression. 1 Publication1
Mutagenesisi61S → E: No effect on JAK signal transduction suppression. 1 Publication1
Mutagenesisi62H → E: No effect on JAK signal transduction suppression. 1 Publication1
Mutagenesisi64D → R: Loss of JAK signal transduction suppression. Reduced binding to JH1. 1 Publication1
Mutagenesisi65Y → A: Some loss of JAK signal transduction signaling. Reduced binding to JH1. 1 Publication1
Mutagenesisi68I → E: Loss of binding to JH1/Y-1007 of JAK2 and loss of signal transduction suppression. 1
Mutagenesisi70R → E: No effect on LIF signal transduction suppression. 1
Mutagenesisi75L → E: Loss of binding to JH1/Y-1007 of JAK2 and loss of signal transduction suppression. 1
Mutagenesisi105R → K: Loss of LIF signal transduction suppression. Loss of binding to KIT. No effect on binding to VAV. 1 Publication1
Mutagenesisi105R → Q: Loss of IL-6 signal transduction suppression. No effect on binding to TYK2. 1 Publication1
Mutagenesisi175L → P: Abolishes interaction with elongin BC complex; when associated with F-179. 1 Publication1
Mutagenesisi179C → F: Abolishes interaction with elongin BC complex; when associated with P-175. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812361 – 212Suppressor of cytokine signaling 1Add BLAST212

Proteomic databases

EPDiO35716.
PaxDbiO35716.
PRIDEiO35716.

PTM databases

iPTMnetiO35716.

Expressioni

Tissue specificityi

High expression in thymus. Lower expression in lung and spleen. Expressed in both Th1 and Th2 cells.1 Publication

Developmental stagei

In the developing brain, expressed at low levels from E10 stages to young adulthood (P25) with peak levels from E14 to P8. In the cortex, expression first observed at E14 uniformly in all cells. Also expressed in the innermost layers of the developing retina. Levels of expression remain unchanged from P8 until adulthood. In the peripheral nervous system, high levels found in virtually all neurons of the dorsal root ganglion.

Inductioni

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

Gene expression databases

BgeeiENSMUSG00000038037.
CleanExiMM_SOCS1.
GenevisibleiO35716. MM.

Interactioni

Subunit structurei

Interacts with multiple activated 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 domain 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. 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. Interacts (via SH2 domain and SOCS box) with TRIM8. Interacts with CUL2. Interacts with AXL and FGFR3 (By similarity). Interacts with INSR.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198719. 32 interactors.
IntActiO35716. 6 interactors.
MINTiMINT-84865.
STRINGi10090.ENSMUSP00000038121.

Structurei

3D structure databases

ProteinModelPortaliO35716.
SMRiO35716.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 175SH2PROSITE-ProRule annotationAdd BLAST96
Domaini162 – 211SOCS boxPROSITE-ProRule annotationAdd BLAST50

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni56 – 67Kinase inhibitory region (KIR)Add BLAST12
Regioni68 – 79Extended SH2 subdomain (ESS)Add BLAST12
Regioni174 – 183Interaction with Elongin BC complex10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi26 – 33Poly-Ser8

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.

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SOCS box domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO35716.
KOiK04694.
OMAiETFDCLF.
OrthoDBiEOG091G0TJW.
PhylomeDBiO35716.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028411. SOCS1.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF72. PTHR24369:SF72. 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]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35716-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVARNQVAAD NAISPAAEPR RRSEPSSSSS SSSPAAPVRP RPCPAVPAPA
60 70 80 90 100
PGDTHFRTFR SHSDYRRITR TSALLDACGF YWGPLSVHGA HERLRAEPVG
110 120 130 140 150
TFLVRDSRQR NCFFALSVKM ASGPTSIRVH FQAGRFHLDG SRETFDCLFE
160 170 180 190 200
LLEHYVAAPR RMLGAPLRQR RVRPLQELCR QRIVAAVGRE NLARIPLNPV
210
LRDYLSSFPF QI
Length:212
Mass (Da):23,715
Last modified:January 1, 1998 - v1
Checksum:i4621E05DC3D44C69
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti141S → N in BAA21538 (PubMed:9202126).Curated1
Sequence conflicti141S → N in BAA21539 (PubMed:9202127).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88325 mRNA. Translation: AAB62400.1.
AB000677 mRNA. Translation: BAA21538.1.
AB000710 mRNA. Translation: BAA21539.1.
AF120490 mRNA. Translation: AAD24777.1.
AF180302 mRNA. Translation: AAD53324.1.
AK028632 mRNA. Translation: BAC26040.1.
AK154706 mRNA. Translation: BAE32775.1.
BC132366 mRNA. Translation: AAI32367.1.
BC132368 mRNA. Translation: AAI32369.1.
CCDSiCCDS27952.1.
RefSeqiNP_001258532.1. NM_001271603.1.
NP_034026.1. NM_009896.2.
UniGeneiMm.130.

Genome annotation databases

EnsembliENSMUST00000038099; ENSMUSP00000038121; ENSMUSG00000038037.
GeneIDi12703.
KEGGimmu:12703.
UCSCiuc007yed.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88325 mRNA. Translation: AAB62400.1.
AB000677 mRNA. Translation: BAA21538.1.
AB000710 mRNA. Translation: BAA21539.1.
AF120490 mRNA. Translation: AAD24777.1.
AF180302 mRNA. Translation: AAD53324.1.
AK028632 mRNA. Translation: BAC26040.1.
AK154706 mRNA. Translation: BAE32775.1.
BC132366 mRNA. Translation: AAI32367.1.
BC132368 mRNA. Translation: AAI32369.1.
CCDSiCCDS27952.1.
RefSeqiNP_001258532.1. NM_001271603.1.
NP_034026.1. NM_009896.2.
UniGeneiMm.130.

3D structure databases

ProteinModelPortaliO35716.
SMRiO35716.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198719. 32 interactors.
IntActiO35716. 6 interactors.
MINTiMINT-84865.
STRINGi10090.ENSMUSP00000038121.

PTM databases

iPTMnetiO35716.

Proteomic databases

EPDiO35716.
PaxDbiO35716.
PRIDEiO35716.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000038099; ENSMUSP00000038121; ENSMUSG00000038037.
GeneIDi12703.
KEGGimmu:12703.
UCSCiuc007yed.1. mouse.

Organism-specific databases

CTDi8651.
MGIiMGI:1354910. Socs1.

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO35716.
KOiK04694.
OMAiETFDCLF.
OrthoDBiEOG091G0TJW.
PhylomeDBiO35716.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-1433559. Regulation of KIT signaling.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-912694. Regulation of IFNA signaling.
R-MMU-982772. Growth hormone receptor signaling.
SABIO-RKO35716.

Miscellaneous databases

PROiO35716.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038037.
CleanExiMM_SOCS1.
GenevisibleiO35716. MM.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028411. SOCS1.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF72. PTHR24369:SF72. 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]
SUPFAMiSSF158235. SSF158235. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50001. SH2. 1 hit.
PS50225. SOCS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSOCS1_MOUSE
AccessioniPrimary (citable) accession number: O35716
Secondary accession number(s): A2RT46, O35960, Q3U3L0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.