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SOCS4 suppressor of cytokine signaling 4 [ Homo sapiens (human) ]

Gene ID: 122809, updated on 2-Nov-2024

Summary

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Official Symbol
SOCS4provided by HGNC
Official Full Name
suppressor of cytokine signaling 4provided by HGNC
Primary source
HGNC:HGNC:19392
See related
Ensembl:ENSG00000180008 MIM:616337; AllianceGenome:HGNC:19392
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SOCS7
Summary
The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS), also known as STAT-induced STAT inhibitor (SSI), protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in appendix (RPKM 5.4), lymph node (RPKM 5.2) and 25 other tissues See more
Orthologs
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Genomic context

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See SOCS4 in Genome Data Viewer
Location:
14q22.3
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (55027236..55049489)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (49232425..49254678)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (55493954..55516207)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene GTP cyclohydrolase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8421 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:55364129-55364629 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5774 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5775 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5776 Neighboring gene farnesyl diphosphate synthase pseudogene 3 Neighboring gene Sharpr-MPRA regulatory region 2393 Neighboring gene WD repeat and HMG-box DNA binding protein 1 Neighboring gene ribosomal protein SA pseudogene 13 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr14:55493639-55494166 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr14:55494167-55494693 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:55517727-55518416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5779 Neighboring gene mitogen-activated protein kinase 1 interacting protein 1 like Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8423 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8424 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr14:55543983-55545182 Neighboring gene uncharacterized LOC124903318 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8425 Neighboring gene Sharpr-MPRA regulatory region 8345

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Suppressor of cytokine signaling 4 detected as a novel gastric cancer suppressor gene using double combination array analysis. Kobayashi D, et al. World J Surg, 2012 Feb. PMID 22127425
  2. A missense mutation underlies defective SOCS4 function in a family with autoimmunity. Arts P, et al. J Intern Med, 2015 Aug. PMID 25639832
  3. Negative regulation of cytokine signaling: STAT-induced STAT inhibitor. Naka T, et al. Trends Biochem Sci, 1999 Oct. PMID 10500304
  4. Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation. Bullock AN, et al. Structure, 2007 Nov. PMID 17997974, Free PMC Article
  5. Interleukin-23 Facilitates Thyroid Cancer Cell Migration and Invasion by Inhibiting SOCS4 Expression via MicroRNA-25. Mei Z, et al. PLoS One, 2015. PMID 26437444, Free PMC Article

See all (34) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4.
    Title: Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4.
  2. SOCS4 expression was lower in T-cell-mediated kidney allograft rejection group compared with non-rejected individuals
    Title: Suppressor of cytokine signaling genes in renal transplant receivers: Association with transplant fate.
  3. Mechanistic investigations demonstrated that TUSC7 can interact with miR-616 and decrease its expression, thereby upregulating the expression of miR-616's targets SOCS4 (SOCS5).
    Title: Long noncoding RNA TUSC7 inhibits cell proliferation, migration and invasion by regulating SOCS4 (SOCS5) expression through targeting miR-616 in endometrial carcinoma.
  4. In vitro significance of SOCS-3 and SOCS-4 and potential mechanistic links to wound healing have been presented.
    Title: In vitro significance of SOCS-3 and SOCS-4 and potential mechanistic links to wound healing.
  5. Significantly higher levels of suppressor of cytokine signalling proteins SOCS3 and SOCS4 in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level.
    Title: Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing.
  6. miR-25 promotes the migration and invasion of thyroid cancer cells by directly binding to the 3'-UTR of SOCS4 that leads to the inhibition of SOCS4.
    Title: Interleukin-23 Facilitates Thyroid Cancer Cell Migration and Invasion by Inhibiting SOCS4 Expression via MicroRNA-25.
  7. This study showed that increased protein levels of SOCS-4 and SOCS-7 in Alzheimer's disease brains.
    Title: Expression of suppressor of cytokine signaling genes in human elderly and Alzheimer's disease brains and human microglia.
  8. SOCS4 is a known inhibitor of epidermal growth factor (EGF) receptor signalling, and functional studies demonstrated specific upregulation of EGF-dependent immune stimulation in affected family members.
    Title: A missense mutation underlies defective SOCS4 function in a family with autoimmunity.
  9. Identified is a conserved region of about 70 residues in the N-terminal domains of SOCS4 and 5 that is predicted to be more ordered than the surrounding sequence.
    Title: The N-terminal domains of SOCS proteins: a conserved region in the disordered N-termini of SOCS4 and 5.
  10. The expression of SOCS4 seems to be controlled epigenetically and is often weakly expressed in gastric cancer tissue and cell lines. SOCS4 methylation status could be a predictor of gastric cancer prognosis.
    Title: Suppressor of cytokine signaling 4 detected as a novel gastric cancer suppressor gene using double combination array analysis.
Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp686J1568

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in cytokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of epidermal growth factor-activated receptor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in protein ubiquitination IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
suppressor of cytokine signaling 4
Names
SH2 domain containing SOCS box protein
SOCS-4
SOCS-7
suppressor of cytokine signaling 7

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_080867.3 → NP_543143.1  suppressor of cytokine signaling 4

    See identical proteins and their annotated locations for NP_543143.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5' region, as compared to variant 1.
    Source sequence(s)
    AK126195, BC060790, BX161418, BX648734
    Consensus CDS
    CCDS9722.1
    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    B3KW39, Q5H9R6
    Related
    ENSP00000378855.2, ENST00000395472.2
    Conserved Domains (3) summary
    cd10385
    Location:275 → 375
    SH2_SOCS4; Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins
    cd03738
    Location:384 → 439
    SOCS_SOCS4; SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the ...
    pfam12610
    Location:59 → 111
    SOCS; Suppressor of cytokine signalling

  2. NM_199421.2 → NP_955453.1  suppressor of cytokine signaling 4

    See identical proteins and their annotated locations for NP_955453.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is the longer transcript and it has an additional exon in the 5' region.
    Source sequence(s)
    AK126195, BC060790, BX648734, CD109883
    Consensus CDS
    CCDS9722.1
    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    B3KW39, Q5H9R6
    Related
    ENSP00000452522.1, ENST00000555846.2
    Conserved Domains (3) summary
    cd10385
    Location:275 → 375
    SH2_SOCS4; Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins
    cd03738
    Location:384 → 439
    SOCS_SOCS4; SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the ...
    pfam12610
    Location:59 → 111
    SOCS; Suppressor of cytokine signalling

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    55027236..55049489
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011536425.2 → XP_011534727.1  suppressor of cytokine signaling 4 isoform X1

    See identical proteins and their annotated locations for XP_011534727.1

    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    B3KW39, Q5H9R6
    Conserved Domains (3) summary
    cd10385
    Location:275 → 375
    SH2_SOCS4; Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins
    cd03738
    Location:384 → 439
    SOCS_SOCS4; SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the ...
    pfam12610
    Location:59 → 111
    SOCS; Suppressor of cytokine signalling

  2. XM_011536426.2 → XP_011534728.1  suppressor of cytokine signaling 4 isoform X1

    See identical proteins and their annotated locations for XP_011534728.1

    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    B3KW39, Q5H9R6
    Conserved Domains (3) summary
    cd10385
    Location:275 → 375
    SH2_SOCS4; Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins
    cd03738
    Location:384 → 439
    SOCS_SOCS4; SOCS (suppressors of cytokine signaling) box of SOCS4-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. The general function of the SOCS box is the ...
    pfam12610
    Location:59 → 111
    SOCS; Suppressor of cytokine signalling

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    49232425..49254678
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054375392.1 → XP_054231367.1  suppressor of cytokine signaling 4 isoform X1

    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    Q5H9R6

  2. XM_054375393.1 → XP_054231368.1  suppressor of cytokine signaling 4 isoform X1

    UniProtKB/Swiss-Prot
    Q8WXH5
    UniProtKB/TrEMBL
    Q5H9R6
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WXH5.1 GenPept UniProtKB/Swiss-Prot:Q8WXH5

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