Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Suppressor of cytokine signaling 3

Gene

Socs3

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. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Regulates IL-6 signaling in vivo. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Seems to recognize IL6ST.By similarity5 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

  • branching involved in labyrinthine layer morphogenesis Source: MGI
  • cytokine-mediated signaling pathway Source: GO_Central
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • negative regulation of apoptotic process Source: InterPro
  • negative regulation of inflammatory response Source: MGI
  • 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 signal transduction Source: MGI
  • negative regulation of tyrosine phosphorylation of Stat1 protein Source: MGI
  • negative regulation of tyrosine phosphorylation of Stat3 protein Source: MGI
  • placenta blood vessel development Source: MGI
  • positive regulation of cell differentiation Source: MGI
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of cell differentiation Source: MGI
  • regulation of growth Source: UniProtKB-KW
  • regulation of protein phosphorylation Source: MGI
  • spongiotrophoblast differentiation Source: MGI
  • trophoblast giant cell differentiation 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-1059683. Interleukin-6 signaling.
R-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-8849474. PTK6 Activates STAT3.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-982772. Growth hormone receptor signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of cytokine signaling 3
Short name:
SOCS-3
Alternative name(s):
Cytokine-inducible SH2 protein 3
Short name:
CIS-3
Protein EF-10
Gene namesi
Name:Socs3
Synonyms:Cis3, Cish3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1201791. Socs3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22L → A: No effect on LIF-induced signal transduction suppression. 1 Publication1
Mutagenesisi22L → D: Abolishes binding to JAK2. No effect on binding to EPOR. 1 Publication1
Mutagenesisi25F → A: Loss of LIF/EPO-induced signal transduction suppression. Abolishes binding to JAK2 and to EPOR. 1 Publication1
Mutagenesisi30E → R: No effect on LIF-induced signal transduction suppression. 1
Mutagenesisi45G → A: Abolishes binding to EPOR. No effect on binding to JAK2. 1 Publication1
Mutagenesisi71R → K: Little effect on LIF-induced signal transduction suppression. Loss of EPO-induced signal transduction suppression. Abolishes binding to JAK2 and EPOR. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812441 – 225Suppressor of cytokine signaling 3Add BLAST225

Post-translational modificationi

Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO35718.
PRIDEiO35718.

PTM databases

iPTMnetiO35718.
PhosphoSitePlusiO35718.

Expressioni

Tissue specificityi

Low expression in lung, spleen and thymus. Expressed in Th2 but not TH1 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, first expressed uniformly in all cells at E14. Not expressed in the retina. Highly expressed in fetal liver progenitors at E12.5.

Inductioni

By a subset of cytokines including EPO, leptin, LIF, IL-2, IL-3, IL-4, IGF1, growth hormone and prolactin.1 Publication

Gene expression databases

BgeeiENSMUSG00000053113.
CleanExiMM_SOCS3.
GenevisibleiO35718. MM.

Interactioni

Subunit structurei

Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK2 JH1 domain (By similarity). Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors (PubMed:10882725). Interaction with CSNK1E stabilizes SOCS3 protein (By similarity). Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, elongin BC complex and SOCS3 (By similarity). Interacts with CUL5, RNF7, TCEB1 and TCEB2 (By similarity). Interacts with FGFR3 (By similarity). Interacts with INSR (PubMed:10821852). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (PubMed:15213237). Interacts with NOD2 (via CARD domain); the interaction promotes NOD2 degradation (PubMed:23019338).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Il6stQ005603EBI-2659360,EBI-3862992

Protein-protein interaction databases

BioGridi198718. 13 interactors.
DIPiDIP-29137N.
IntActiO35718. 9 interactors.
MINTiMINT-2569503.
STRINGi10090.ENSMUSP00000059129.

Structurei

Secondary structure

1225
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 43Combined sources12
Beta strandi45 – 48Combined sources4
Helixi53 – 61Combined sources9
Beta strandi67 – 72Combined sources6
Beta strandi79 – 86Combined sources8
Beta strandi89 – 96Combined sources8
Helixi98 – 100Combined sources3
Beta strandi102 – 104Combined sources3
Beta strandi117 – 119Combined sources3
Helixi120 – 126Combined sources7
Beta strandi137 – 139Combined sources3
Beta strandi165 – 167Combined sources3
Beta strandi174 – 176Combined sources3
Helixi189 – 199Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BBUNMR-A22-185[»]
2HMHX-ray2.00A15-185[»]
2JZ3NMR-A186-225[»]
4GL9X-ray3.90E/F/G/H22-128[»]
E/F/G/H179-185[»]
DisProtiDP00446.
ProteinModelPortaliO35718.
SMRiO35718.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO35718.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 142SH2PROSITE-ProRule annotationAdd BLAST97
Domaini177 – 224SOCS boxPROSITE-ProRule annotationAdd BLAST48

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni22 – 33Kinase inhibitory region (KIR)Add BLAST12
Regioni34 – 45Extended SH2 subdomain (ESS)Add BLAST12

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.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

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG105645.
InParanoidiO35718.
KOiK04696.
OMAiKRTYYIY.
OrthoDBiEOG091G0NEU.
PhylomeDBiO35718.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
InterProiIPR000980. SH2.
IPR028414. SOCS3.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF78. PTHR24369:SF78. 2 hits.
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.

O35718-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA
60 70 80 90 100
VTGGEANLLL SAEPAGTFLI RDSSDQRHFF TLSVKTQSGT KNLRIQCEGG
110 120 130 140 150
SFSLQSDPRS TQPVPRFDCV LKLVHHYMPP PGTPSFSLPP TEPSSEVPEQ
160 170 180 190 200
PPAQALPGST PKRAYYIYSG GEKIPLVLSR PLSSNVATLQ HLCRKTVNGH
210 220
LDSYEKVTQL PGPIREFLDQ YDAPL
Length:225
Mass (Da):24,776
Last modified:January 1, 1998 - v1
Checksum:iCD3859561D4CCDED
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88328 mRNA. Translation: AAB62403.1.
AF314501 Genomic DNA. Translation: AAK60601.1.
AK047165 mRNA. Translation: BAC32977.1.
AK139241 mRNA. Translation: BAE23929.1.
AK152468 mRNA. Translation: BAE31244.1.
AK152514 mRNA. Translation: BAE31277.1.
AK157708 mRNA. Translation: BAE34161.1.
AK159395 mRNA. Translation: BAE35049.1.
AK170406 mRNA. Translation: BAE41773.1.
AK172399 mRNA. Translation: BAE42985.1.
BC052031 mRNA. Translation: AAH52031.1.
AF117732 Genomic DNA. Translation: AAD18024.1.
U72673 mRNA. Translation: AAB51035.1. Sequence problems.
CCDSiCCDS25697.1.
RefSeqiNP_031733.1. NM_007707.3.
XP_011247009.1. XM_011248707.2.
UniGeneiMm.3468.

Genome annotation databases

EnsembliENSMUST00000054002; ENSMUSP00000059129; ENSMUSG00000053113.
GeneIDi12702.
KEGGimmu:12702.
UCSCiuc007moi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88328 mRNA. Translation: AAB62403.1.
AF314501 Genomic DNA. Translation: AAK60601.1.
AK047165 mRNA. Translation: BAC32977.1.
AK139241 mRNA. Translation: BAE23929.1.
AK152468 mRNA. Translation: BAE31244.1.
AK152514 mRNA. Translation: BAE31277.1.
AK157708 mRNA. Translation: BAE34161.1.
AK159395 mRNA. Translation: BAE35049.1.
AK170406 mRNA. Translation: BAE41773.1.
AK172399 mRNA. Translation: BAE42985.1.
BC052031 mRNA. Translation: AAH52031.1.
AF117732 Genomic DNA. Translation: AAD18024.1.
U72673 mRNA. Translation: AAB51035.1. Sequence problems.
CCDSiCCDS25697.1.
RefSeqiNP_031733.1. NM_007707.3.
XP_011247009.1. XM_011248707.2.
UniGeneiMm.3468.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BBUNMR-A22-185[»]
2HMHX-ray2.00A15-185[»]
2JZ3NMR-A186-225[»]
4GL9X-ray3.90E/F/G/H22-128[»]
E/F/G/H179-185[»]
DisProtiDP00446.
ProteinModelPortaliO35718.
SMRiO35718.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198718. 13 interactors.
DIPiDIP-29137N.
IntActiO35718. 9 interactors.
MINTiMINT-2569503.
STRINGi10090.ENSMUSP00000059129.

PTM databases

iPTMnetiO35718.
PhosphoSitePlusiO35718.

Proteomic databases

PaxDbiO35718.
PRIDEiO35718.

Protocols and materials databases

DNASUi12702.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000054002; ENSMUSP00000059129; ENSMUSG00000053113.
GeneIDi12702.
KEGGimmu:12702.
UCSCiuc007moi.2. mouse.

Organism-specific databases

CTDi9021.
MGIiMGI:1201791. Socs3.

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG105645.
InParanoidiO35718.
KOiK04696.
OMAiKRTYYIY.
OrthoDBiEOG091G0NEU.
PhylomeDBiO35718.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-1059683. Interleukin-6 signaling.
R-MMU-2586551. Signaling by Leptin.
R-MMU-2586552. Signaling by Leptin.
R-MMU-877300. Interferon gamma signaling.
R-MMU-877312. Regulation of IFNG signaling.
R-MMU-8849474. PTK6 Activates STAT3.
R-MMU-909733. Interferon alpha/beta signaling.
R-MMU-982772. Growth hormone receptor signaling.

Miscellaneous databases

EvolutionaryTraceiO35718.
PROiO35718.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000053113.
CleanExiMM_SOCS3.
GenevisibleiO35718. MM.

Family and domain databases

Gene3Di3.30.505.10. 2 hits.
InterProiIPR000980. SH2.
IPR028414. SOCS3.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF78. PTHR24369:SF78. 2 hits.
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 nameiSOCS3_MOUSE
AccessioniPrimary (citable) accession number: O35718
Secondary accession number(s): P97803, Q3U7X5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 154 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.