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UniProtKB - O14508 (SOCS2_HUMAN)
Protein
Suppressor of cytokine signaling 2
Gene
SOCS2
Organism
Homo sapiens (Human)
Status
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.
: protein ubiquitination Pathwayi
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
- 1-phosphatidylinositol-3-kinase regulator activity Source: GO_Central
- growth hormone receptor binding Source: UniProtKB
- insulin-like growth factor receptor binding Source: UniProtKB
- JAK pathway signal transduction adaptor activity Source: ProtInc
GO - Biological processi
- cellular response to hormone stimulus Source: BHF-UCL
- growth hormone receptor signaling pathway Source: BHF-UCL
- intracellular signal transduction Source: Ensembl
- lactation Source: Ensembl
- mammary gland alveolus development Source: Ensembl
- negative regulation of apoptotic process Source: ProtInc
- negative regulation of multicellular organism growth Source: Ensembl
- negative regulation of receptor signaling pathway via JAK-STAT Source: Ensembl
- phosphatidylinositol phosphate biosynthetic process Source: GO_Central
- positive regulation of neuron differentiation Source: Ensembl
- protein ubiquitination Source: UniProtKB-UniPathway
- receptor signaling pathway via JAK-STAT Source: ProtInc
- regulation of cell growth Source: UniProtKB
- regulation of signal transduction Source: UniProtKB
- response to estradiol Source: BHF-UCL
Keywordsi
Molecular function | Signal transduction inhibitor |
Biological process | Growth regulation, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | O14508 |
Reactomei | R-HSA-1266695, Interleukin-7 signaling R-HSA-8951664, Neddylation R-HSA-9706369, Negative regulation of FLT3 R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | O14508 |
SIGNORi | O14508 |
UniPathwayi | UPA00143 |
Names & Taxonomyi
Protein namesi | Recommended name: Suppressor of cytokine signaling 2Short 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:19382, SOCS2 |
MIMi | 605117, gene |
neXtProti | NX_O14508 |
VEuPathDBi | HostDB:ENSG00000120833 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Other locations
- cytoplasm Source: UniProtKB
- phosphatidylinositol 3-kinase complex Source: GO_Central
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 87 | K → R: No effect on protein half-life. 1 Publication | 1 | |
Mutagenesisi | 154 | K → R: No effect on protein half-life. 1 Publication | 1 | |
Mutagenesisi | 173 | K → R: Increased protein half-life. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 8835 |
OpenTargetsi | ENSG00000120833 |
PharmGKBi | PA128394542 |
Miscellaneous databases
Pharosi | O14508, Tbio |
Genetic variation databases
BioMutai | SOCS2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000181238 | 1 – 198 | Suppressor of cytokine signaling 2Add BLAST | 198 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 30 | PhosphoserineCombined sources | 1 | |
Modified residuei | 52 | Phosphoserine; by PKC1 Publication | 1 | |
Cross-linki | 173 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication |
Post-translational modificationi
Ubiquitinated; mediated by AREL1 and leading to its subsequent proteasomal degradation (PubMed:31578312). Ubiquitination is dependent on its phosphorylation at Ser-52, by PKC (PubMed:31578312). Ubiquitination is stimulated by LPS (By similarity).By similarity1 Publication
Phosphorylation at Ser-52 by PKC facilitates its ubiquitination and proteosomal degradation.1 Publication
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O14508 |
MassIVEi | O14508 |
MaxQBi | O14508 |
PaxDbi | O14508 |
PeptideAtlasi | O14508 |
PRIDEi | O14508 |
ProteomicsDBi | 48046 |
PTM databases
iPTMneti | O14508 |
PhosphoSitePlusi | O14508 |
Expressioni
Tissue specificityi
High expression in heart, placenta, lung, kidney and prostate. Predominantly expressed in pulmonary epithelia cells, specifically type II pneumocytes.2 Publications
Inductioni
By a subset of cytokines, including EPO/erythropoietin and CSF2/GM-CSF.
Gene expression databases
Bgeei | ENSG00000120833, Expressed in ectocervix and 230 other tissues |
ExpressionAtlasi | O14508, baseline and differential |
Genevisiblei | O14508, HS |
Organism-specific databases
HPAi | ENSG00000120833, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
O14508
GO - Molecular functioni
- growth hormone receptor binding Source: UniProtKB
- insulin-like growth factor receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114362, 89 interactors |
DIPi | DIP-29569N |
IntActi | O14508, 13 interactors |
MINTi | O14508 |
STRINGi | 9606.ENSP00000481249 |
Miscellaneous databases
RNActi | O14508, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O14508 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O14508 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 48 – 156 | SH2PROSITE-ProRule annotationAdd BLAST | 109 | |
Domaini | 151 – 197 | SOCS boxPROSITE-ProRule annotationAdd BLAST | 47 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 75 | Interaction with AREL11 PublicationAdd BLAST | 75 | |
Regioni | 1 – 29 | DisorderedSequence analysisAdd BLAST | 29 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 12 – 26 | Polar residuesSequence analysisAdd BLAST | 15 |
Domaini
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
Keywords - Domaini
SH2 domainPhylogenomic databases
eggNOGi | KOG4566, Eukaryota |
GeneTreei | ENSGT00940000157983 |
InParanoidi | O14508 |
OMAi | RCRIAIN |
OrthoDBi | 1135696at2759 |
PhylomeDBi | O14508 |
TreeFami | TF321368 |
Family and domain databases
CDDi | cd10383, SH2_SOCS2, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
IDEALi | IID00523 |
InterProi | View protein in InterPro IPR000980, SH2 IPR036860, SH2_dom_sf IPR028410, SOCS2 IPR035862, SOCS2_SH2 IPR001496, SOCS_box IPR036036, SOCS_box-like_dom_sf |
PANTHERi | PTHR10155:SF7, PTHR10155:SF7, 1 hit |
Pfami | View protein in Pfam PF00017, SH2, 1 hit PF07525, SOCS_box, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00253, SOCS, 1 hit SM00969, SOCS_box, 1 hit |
SUPFAMi | SSF158235, SSF158235, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit PS50225, SOCS, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
O14508-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketS4R3W1 | S4R3W1_HUMAN | Suppressor of cytokine-signaling 2 | SOCS2 | 116 | Annotation score: | ||
S4R3Z4 | S4R3Z4_HUMAN | Suppressor of cytokine-signaling 2 | SOCS2 | 46 | Annotation score: | ||
F8VRV3 | F8VRV3_HUMAN | Suppressor of cytokine-signaling 2 | SOCS2 | 161 | Annotation score: | ||
F8VU91 | F8VU91_HUMAN | Suppressor of cytokine-signaling 2 | SOCS2 | 142 | Annotation score: | ||
F8VS53 | F8VS53_HUMAN | Suppressor of cytokine-signaling 2 | SOCS2 | 102 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 2 | T → N in AAC98896 (Ref. 3) Curated | 1 | |
Sequence conflicti | 5 | C → R in BAA22536 (PubMed:9344848).Curated | 1 | |
Sequence conflicti | 31 – 39 | PQAARLAKA → RRRRVWRR in AAC98896 (Ref. 3) Curated | 9 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052032 | 52 | S → N Increased protein half-life; reduced interaction with AREL1. 1 PublicationCorresponds to variant dbSNP:rs3741676Ensembl. | 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 |
CCDSi | CCDS9047.1 |
PIRi | JC5626 JC5760 |
RefSeqi | NP_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 |
Genome annotation databases
Ensembli | ENST00000340600; ENSP00000339428; ENSG00000120833 ENST00000536696; ENSP00000442898; ENSG00000120833 ENST00000549122; ENSP00000447161; ENSG00000120833 ENST00000549206; ENSP00000448815; ENSG00000120833 ENST00000551556; ENSP00000449227; ENSG00000120833 ENST00000622746; ENSP00000481249; ENSG00000120833 |
GeneIDi | 8835 |
KEGGi | hsa:8835 |
MANE-Selecti | ENST00000551556.2; ENSP00000449227.1; NM_001270471.2; NP_001257400.1 |
UCSCi | uc001tcw.3, human |
Similar proteinsi
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 |
CCDSi | CCDS9047.1 |
PIRi | JC5626 JC5760 |
RefSeqi | NP_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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2C9W | X-ray | 1.90 | A | 32-198 | [»] | |
4JGH | X-ray | 3.00 | A | 32-198 | [»] | |
5BO4 | X-ray | 2.90 | A/D/G/J/M/P | 32-198 | [»] | |
6I4X | X-ray | 2.69 | A | 30-198 | [»] | |
6I5J | X-ray | 2.80 | A/D | 30-198 | [»] | |
6I5N | X-ray | 1.98 | A/D | 30-198 | [»] | |
7M6T | X-ray | 3.19 | A | 32-198 | [»] | |
SMRi | O14508 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114362, 89 interactors |
DIPi | DIP-29569N |
IntActi | O14508, 13 interactors |
MINTi | O14508 |
STRINGi | 9606.ENSP00000481249 |
PTM databases
iPTMneti | O14508 |
PhosphoSitePlusi | O14508 |
Genetic variation databases
BioMutai | SOCS2 |
Proteomic databases
EPDi | O14508 |
MassIVEi | O14508 |
MaxQBi | O14508 |
PaxDbi | O14508 |
PeptideAtlasi | O14508 |
PRIDEi | O14508 |
ProteomicsDBi | 48046 |
Protocols and materials databases
Antibodypediai | 4158, 294 antibodies from 36 providers |
DNASUi | 8835 |
Genome annotation databases
Ensembli | ENST00000340600; ENSP00000339428; ENSG00000120833 ENST00000536696; ENSP00000442898; ENSG00000120833 ENST00000549122; ENSP00000447161; ENSG00000120833 ENST00000549206; ENSP00000448815; ENSG00000120833 ENST00000551556; ENSP00000449227; ENSG00000120833 ENST00000622746; ENSP00000481249; ENSG00000120833 |
GeneIDi | 8835 |
KEGGi | hsa:8835 |
MANE-Selecti | ENST00000551556.2; ENSP00000449227.1; NM_001270471.2; NP_001257400.1 |
UCSCi | uc001tcw.3, human |
Organism-specific databases
CTDi | 8835 |
DisGeNETi | 8835 |
GeneCardsi | SOCS2 |
HGNCi | HGNC:19382, SOCS2 |
HPAi | ENSG00000120833, Low tissue specificity |
MIMi | 605117, gene |
neXtProti | NX_O14508 |
OpenTargetsi | ENSG00000120833 |
PharmGKBi | PA128394542 |
VEuPathDBi | HostDB:ENSG00000120833 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4566, Eukaryota |
GeneTreei | ENSGT00940000157983 |
InParanoidi | O14508 |
OMAi | RCRIAIN |
OrthoDBi | 1135696at2759 |
PhylomeDBi | O14508 |
TreeFami | TF321368 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | O14508 |
Reactomei | R-HSA-1266695, Interleukin-7 signaling R-HSA-8951664, Neddylation R-HSA-9706369, Negative regulation of FLT3 R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | O14508 |
SIGNORi | O14508 |
Miscellaneous databases
BioGRID-ORCSi | 8835, 10 hits in 1084 CRISPR screens |
ChiTaRSi | SOCS2, human |
EvolutionaryTracei | O14508 |
GeneWikii | SOCS2 |
GenomeRNAii | 8835 |
Pharosi | O14508, Tbio |
PROi | PR:O14508 |
RNActi | O14508, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000120833, Expressed in ectocervix and 230 other tissues |
ExpressionAtlasi | O14508, baseline and differential |
Genevisiblei | O14508, HS |
Family and domain databases
CDDi | cd10383, SH2_SOCS2, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
IDEALi | IID00523 |
InterProi | View protein in InterPro IPR000980, SH2 IPR036860, SH2_dom_sf IPR028410, SOCS2 IPR035862, SOCS2_SH2 IPR001496, SOCS_box IPR036036, SOCS_box-like_dom_sf |
PANTHERi | PTHR10155:SF7, PTHR10155:SF7, 1 hit |
Pfami | View protein in Pfam PF00017, SH2, 1 hit PF07525, SOCS_box, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00252, SH2, 1 hit SM00253, SOCS, 1 hit SM00969, SOCS_box, 1 hit |
SUPFAMi | SSF158235, SSF158235, 1 hit SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit PS50225, SOCS, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SOCS2_HUMAN | |
Accessioni | O14508Primary (citable) accession number: O14508 Secondary accession number(s): A8K3D1 Q9UKS5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2002 |
Last sequence update: | January 1, 1998 | |
Last modified: | February 23, 2022 | |
This is version 190 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references