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Protein

Suppressor of cytokine signaling 3

Gene

Socs3

Organism
Rattus norvegicus (Rat)
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. Seems to recognize IL6ST (By similarity).By similarity

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

  • aging Source: RGD
  • animal organ regeneration Source: RGD
  • cytokine-mediated signaling pathway Source: GO_Central
  • intracellular signal transduction Source: RGD
  • JAK-STAT cascade Source: RGD
  • negative regulation of apoptotic process Source: InterPro
  • negative regulation of insulin receptor signaling pathway Source: GO_Central
  • negative regulation of JAK-STAT cascade Source: GO_Central
  • negative regulation of protein kinase activity Source: GO_Central
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of cell growth Source: RGD
  • response to bacterium Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to estradiol Source: RGD
  • response to food Source: RGD
  • response to gamma radiation Source: RGD
  • response to glucocorticoid Source: RGD
  • response to heat Source: RGD
  • response to hormone Source: RGD
  • response to hypoxia Source: RGD
  • response to insulin Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to peptide hormone Source: RGD
  • response to progesterone Source: RGD
  • signal transduction Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of cytokine signaling 3
Short name:
SOCS-3
Alternative name(s):
Cytokine-inducible SH2 protein 3
Gene namesi
Name:Socs3
Synonyms:Cish3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621087. Socs3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812451 – 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

PaxDbiO88583.

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. Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors. Interaction with CSNK1E stabilize SOCS3 protein. Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SOCS3. Interacts with CUL5, RNF7, TCEB1 and TCEB2. Interacts with FGFR3 (By similarity). Interacts with INSR (By similarity). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (By similarity). Interacts with NOD2 (via CARD domain); the interaction promotes NOD2 degradation (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi250151. 1 interactor.
STRINGi10116.ENSRNOP00000003940.

Structurei

3D structure databases

ProteinModelPortaliO88583.
ModBaseiSearch...
MobiDBiSearch...

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.
HOGENOMiHOG000236320.
HOVERGENiHBG105645.
InParanoidiO88583.
KOiK04696.
PhylomeDBiO88583.

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.

O88583-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVTHSKFPAA GMSRPLDTSL RLKTFSSKSE YQLVVNAVRK LQESGFYWSA
60 70 80 90 100
VTGGEANLLL SAEPAGTFLI RDSSDQRHFF TLSVETQSGT KNLRIQCEGG
110 120 130 140 150
SFSLQSDPRS TQPVPRFDCV LKLVHHYMPP PGAPSFSLPP TEPSFEVQEQ
160 170 180 190 200
PPAQALPGGT PKRAYYIYSG GEKIPLVLSR PLSSNVATLQ HLCRKTVNGH
210 220
LDSYEKVTQL PGPIREFLDQ YDAPL
Length:225
Mass (Da):24,808
Last modified:November 1, 1998 - v1
Checksum:iBC95FF2074125D8F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti75D → G in CAB56083 (Ref. 2) Curated1
Sequence conflicti85E → K in CAB56083 (Ref. 2) Curated1
Sequence conflicti145F → S in CAB56083 (Ref. 2) Curated1
Sequence conflicti164A → G in CAB56083 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF075383 mRNA. Translation: AAC26223.1.
AJ249240 Genomic DNA. Translation: CAB56083.1.
RefSeqiNP_446017.1. NM_053565.1.
UniGeneiRn.127801.

Genome annotation databases

GeneIDi89829.
KEGGirno:89829.
UCSCiRGD:621087. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF075383 mRNA. Translation: AAC26223.1.
AJ249240 Genomic DNA. Translation: CAB56083.1.
RefSeqiNP_446017.1. NM_053565.1.
UniGeneiRn.127801.

3D structure databases

ProteinModelPortaliO88583.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250151. 1 interactor.
STRINGi10116.ENSRNOP00000003940.

Proteomic databases

PaxDbiO88583.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi89829.
KEGGirno:89829.
UCSCiRGD:621087. rat.

Organism-specific databases

CTDi9021.
RGDi621087. Socs3.

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
HOGENOMiHOG000236320.
HOVERGENiHBG105645.
InParanoidiO88583.
KOiK04696.
PhylomeDBiO88583.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiO88583.

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_RAT
AccessioniPrimary (citable) accession number: O88583
Secondary accession number(s): Q9QYV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 117 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.