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Protein

Suppressor of cytokine signaling 2

Gene

SOCS2

Organism
Homo sapiens (Human)
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. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. 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.

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

  • growth hormone receptor binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: UniProtKB
  • JAK pathway signal transduction adaptor activity Source: ProtInc
  • protein kinase inhibitor activity Source: GO_Central
  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  • cellular response to hormone stimulus Source: BHF-UCL
  • cytokine-mediated signaling pathway Source: GO_Central
  • growth hormone receptor signaling pathway Source: BHF-UCL
  • JAK-STAT cascade Source: ProtInc
  • negative regulation of apoptotic process Source: ProtInc
  • 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: UniProtKB
  • regulation of signal transduction Source: UniProtKB
  • response to estradiol Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Signal transduction inhibitor

Keywords - Biological processi

Growth regulation, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000120833-MONOMER.
ReactomeiR-HSA-982772. Growth hormone receptor signaling.
SignaLinkiO14508.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of cytokine signaling 2
Short name:
SOCS-2
Alternative name(s):
Cytokine-inducible SH2 protein 2
Short name:
CIS-2
STAT-induced STAT inhibitor 2
Short name:
SSI-2
Gene namesi
Name:SOCS2
Synonyms:CIS2, SSI2, STATI2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:19382. SOCS2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi8835.
OpenTargetsiENSG00000120833.
PharmGKBiPA128394542.

Polymorphism and mutation databases

BioMutaiSOCS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812381 – 198Suppressor of cytokine signaling 2Add BLAST198

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO14508.
PaxDbiO14508.
PeptideAtlasiO14508.
PRIDEiO14508.

PTM databases

iPTMnetiO14508.
PhosphoSitePlusiO14508.

Expressioni

Tissue specificityi

High expression in heart, placenta, lung, kidney and prostate.

Inductioni

By a subset of cytokines, including EPO/erythropoietin and CSF2/GM-CSF.

Gene expression databases

BgeeiENSG00000120833.
CleanExiHS_SOCS2.
ExpressionAtlasiO14508. baseline and differential.
GenevisibleiO14508. HS.

Organism-specific databases

HPAiCAB010356.

Interactioni

Subunit structurei

Interacts with IGF1 receptor, prolactin receptor and growth hormone (GH) receptor. Associates with the Elongin BC complex.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
EPORP192353EBI-617737,EBI-617321
KITP107214EBI-617737,EBI-1379503
TCEB1Q153692EBI-617737,EBI-301231

GO - Molecular functioni

  • growth hormone receptor binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: UniProtKB
  • JAK pathway signal transduction adaptor activity Source: ProtInc
  • SH3/SH2 adaptor activity Source: ProtInc

Protein-protein interaction databases

BioGridi114362. 21 interactors.
DIPiDIP-29569N.
IntActiO14508. 10 interactors.
MINTiMINT-1459522.
STRINGi9606.ENSP00000339428.

Structurei

Secondary structure

1198
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 45Combined sources13
Helixi55 – 62Combined sources8
Beta strandi70 – 74Combined sources5
Beta strandi77 – 79Combined sources3
Beta strandi81 – 88Combined sources8
Beta strandi91 – 100Combined sources10
Beta strandi103 – 106Combined sources4
Turni108 – 112Combined sources5
Helixi113 – 115Combined sources3
Beta strandi119 – 121Combined sources3
Helixi122 – 132Combined sources11
Helixi163 – 174Combined sources12
Helixi178 – 180Combined sources3
Beta strandi181 – 183Combined sources3
Helixi185 – 192Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C9WX-ray1.90A32-198[»]
4JGHX-ray3.00A32-198[»]
5BO4X-ray2.90A/D/G/J/M/P32-198[»]
ProteinModelPortaliO14508.
SMRiO14508.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14508.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 156SH2PROSITE-ProRule annotationAdd BLAST109
Domaini151 – 197SOCS boxPROSITE-ProRule annotationAdd BLAST47

Domaini

The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.

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.
InParanoidiO14508.
KOiK04695.
OMAiHLYLNKP.
OrthoDBiEOG091G0J75.
PhylomeDBiO14508.
TreeFamiTF321368.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028410. SOCS2.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF75. PTHR24369:SF75. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
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.

O14508-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTLRCLEPSG NGGEGTRSQW GTAGSAEEPS PQAARLAKAL RELGQTGWYW
60 70 80 90 100
GSMTVNEAKE KLKEAPEGTF LIRDSSHSDY LLTISVKTSA GPTNLRIEYQ
110 120 130 140 150
DGKFRLDSII CVKSKLKQFD SVVHLIDYYV QMCKDKRTGP EAPRNGTVHL
160 170 180 190
YLTKPLYTSA PSLQHLCRLT INKCTGAIWG LPLPTRLKDY LEEYKFQV
Length:198
Mass (Da):22,172
Last modified:January 1, 1998 - v1
Checksum:iDAFC4AD97F8182BF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti2T → N in AAC98896 (Ref. 3) Curated1
Sequence conflicti5C → R in BAA22536 (PubMed:9344848).Curated1
Sequence conflicti31 – 39PQAARLAKA → RRRRVWRR in AAC98896 (Ref. 3) Curated9

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05203252S → N.Corresponds to variant rs3741676dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004903 mRNA. Translation: BAA22429.1.
AB006966 mRNA. Translation: BAA22536.1.
AF020590 mRNA. Translation: AAC98896.1.
AF037989 mRNA. Translation: AAC34745.1.
AK290546 mRNA. Translation: BAF83235.1.
AK313165 mRNA. Translation: BAG35983.1.
CH471054 Genomic DNA. Translation: EAW97492.1.
BC010399 mRNA. Translation: AAH10399.1.
AF132441 Genomic DNA. Translation: AAD27710.1.
CCDSiCCDS9047.1.
PIRiJC5626.
JC5760.
RefSeqiNP_001257396.1. NM_001270467.1.
NP_001257397.1. NM_001270468.1.
NP_001257398.1. NM_001270469.1.
NP_001257399.1. NM_001270470.1.
NP_001257400.1. NM_001270471.1.
NP_003868.1. NM_003877.4.
XP_016875645.1. XM_017020156.1.
UniGeneiHs.485572.
Hs.594327.
Hs.594374.
Hs.736572.
Hs.737206.

Genome annotation databases

EnsembliENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.
ENST00000622746; ENSP00000481249; ENSG00000120833.
GeneIDi8835.
KEGGihsa:8835.
UCSCiuc001tcw.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB004903 mRNA. Translation: BAA22429.1.
AB006966 mRNA. Translation: BAA22536.1.
AF020590 mRNA. Translation: AAC98896.1.
AF037989 mRNA. Translation: AAC34745.1.
AK290546 mRNA. Translation: BAF83235.1.
AK313165 mRNA. Translation: BAG35983.1.
CH471054 Genomic DNA. Translation: EAW97492.1.
BC010399 mRNA. Translation: AAH10399.1.
AF132441 Genomic DNA. Translation: AAD27710.1.
CCDSiCCDS9047.1.
PIRiJC5626.
JC5760.
RefSeqiNP_001257396.1. NM_001270467.1.
NP_001257397.1. NM_001270468.1.
NP_001257398.1. NM_001270469.1.
NP_001257399.1. NM_001270470.1.
NP_001257400.1. NM_001270471.1.
NP_003868.1. NM_003877.4.
XP_016875645.1. XM_017020156.1.
UniGeneiHs.485572.
Hs.594327.
Hs.594374.
Hs.736572.
Hs.737206.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C9WX-ray1.90A32-198[»]
4JGHX-ray3.00A32-198[»]
5BO4X-ray2.90A/D/G/J/M/P32-198[»]
ProteinModelPortaliO14508.
SMRiO14508.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114362. 21 interactors.
DIPiDIP-29569N.
IntActiO14508. 10 interactors.
MINTiMINT-1459522.
STRINGi9606.ENSP00000339428.

PTM databases

iPTMnetiO14508.
PhosphoSitePlusiO14508.

Polymorphism and mutation databases

BioMutaiSOCS2.

Proteomic databases

MaxQBiO14508.
PaxDbiO14508.
PeptideAtlasiO14508.
PRIDEiO14508.

Protocols and materials databases

DNASUi8835.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340600; ENSP00000339428; ENSG00000120833.
ENST00000536696; ENSP00000442898; ENSG00000120833.
ENST00000549122; ENSP00000447161; ENSG00000120833.
ENST00000549206; ENSP00000448815; ENSG00000120833.
ENST00000551556; ENSP00000449227; ENSG00000120833.
ENST00000622746; ENSP00000481249; ENSG00000120833.
GeneIDi8835.
KEGGihsa:8835.
UCSCiuc001tcw.3. human.

Organism-specific databases

CTDi8835.
DisGeNETi8835.
GeneCardsiSOCS2.
HGNCiHGNC:19382. SOCS2.
HPAiCAB010356.
MIMi605117. gene.
neXtProtiNX_O14508.
OpenTargetsiENSG00000120833.
PharmGKBiPA128394542.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4566. Eukaryota.
ENOG4111V4J. LUCA.
GeneTreeiENSGT00760000119136.
HOGENOMiHOG000236320.
HOVERGENiHBG002457.
InParanoidiO14508.
KOiK04695.
OMAiHLYLNKP.
OrthoDBiEOG091G0J75.
PhylomeDBiO14508.
TreeFamiTF321368.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000120833-MONOMER.
ReactomeiR-HSA-982772. Growth hormone receptor signaling.
SignaLinkiO14508.

Miscellaneous databases

ChiTaRSiSOCS2. human.
EvolutionaryTraceiO14508.
GeneWikiiSOCS2.
GenomeRNAii8835.
PROiO14508.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120833.
CleanExiHS_SOCS2.
ExpressionAtlasiO14508. baseline and differential.
GenevisibleiO14508. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR000980. SH2.
IPR028410. SOCS2.
IPR001496. SOCS_box.
[Graphical view]
PANTHERiPTHR24369:SF75. PTHR24369:SF75. 1 hit.
PfamiPF00017. SH2. 1 hit.
PF07525. SOCS_box. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
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 nameiSOCS2_HUMAN
AccessioniPrimary (citable) accession number: O14508
Secondary accession number(s): A8K3D1
, O14542, O95102, Q9UKS5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2002
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 152 of the entry and version 1 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.