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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
    mouse all
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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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    NEW Try the new Transcript table

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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