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Protein

Suppressor of cytokine signaling 1

Gene

Socs1

Organism
Mus musculus (Mouse)
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 (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 similarity3 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
  • negative regulation of CD8-positive, alpha-beta T cell differentiation Source: UniProtKB
  • 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 STAT protein Source: MGI
  • positive regulation of CD4-positive, alpha-beta T cell differentiation Source: UniProtKB
  • positive regulation of regulatory T cell differentiation Source: MGI
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of activation of Janus 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 tyrosine phosphorylation of STAT protein Source: MGI

Keywordsi

Molecular functionSignal transduction inhibitor
Biological processGrowth regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-6785807 Interleukin-4 and 13 signaling
R-MMU-877300 Interferon gamma signaling
R-MMU-877312 Regulation of IFNG signaling
R-MMU-909733 Interferon alpha/beta signaling
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1354910 Socs1

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

Disruption phenotypei

Mice exhibit lymphocyte deficiency and degeneration of the liver parenchyma. Animals die within 3 weeks of age. Mutants show a much higher frequency of CD8 single positive thymocytes (PubMed:24880459).2 Publications

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
PhosphoSitePlusiO35716

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 (ELOB and ELOC). 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. Interacts with TRIM8 (By similarity).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198719, 31 interactors
IntActiO35716, 6 interactors
MINTiO35716
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-x3-C-x3-[AILV] and is part of the SOCS box.

Sequence similaritiesi

Belongs to the SOCS1 family.Curated

Keywords - Domaini

SH2 domain

Phylogenomic databases

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

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

Similar proteinsi

Entry informationi

Entry nameiSOCS1_MOUSE
AccessioniPrimary (citable) accession number: O35716
Secondary accession number(s): A2RT46, O35960, Q3U3L0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: May 23, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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