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    DOK4 docking protein 4 [ Homo sapiens (human) ]

    Gene ID: 55715, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DOK4provided by HGNC
    Official Full Name
    docking protein 4provided by HGNC
    Primary source
    HGNC:HGNC:19868
    See related
    Ensembl:ENSG00000125170 MIM:608333; AllianceGenome:HGNC:19868
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IRS5; IRS-5
    Summary
    Predicted to be involved in Ras protein signal transduction; cell surface receptor protein tyrosine kinase signaling pathway; and positive regulation of MAPK cascade. Predicted to act upstream of or within nervous system development. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in colon (RPKM 23.2), small intestine (RPKM 21.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DOK4 in Genome Data Viewer
    Location:
    16q21
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (57471922..57487322, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (63267111..63282532, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (57505834..57521234, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene cytokine induced apoptosis inhibitor 1 Neighboring gene Sharpr-MPRA regulatory region 5957 Neighboring gene Sharpr-MPRA regulatory region 83 Neighboring gene coenzyme Q9 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:57506902-57507423 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:57507424-57507944 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:57508610-57509398 Neighboring gene RNA polymerase II subunit C Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:57519658-57520454 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:57541954-57542946 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:57543642-57544142 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_43689 Neighboring gene coiled-coil domain containing 102A Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:57562855-57563355 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10896 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10897 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:57566372-57566931 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:57566932-57567490 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7531 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10898 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10899 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10900 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_43712 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7532 Neighboring gene adhesion G protein-coupled receptor G5 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10901 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:57598339-57598840 Neighboring gene uncharacterized LOC105371291 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_43740 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7533 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7534 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10902 Neighboring gene uncharacterized LOC107984889

    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. DOK4/IRS-5 expression is altered in clear cell renal cell carcinoma. Al-Sarraf N, et al. Int J Cancer, 2007 Sep 1. PMID 17443497
    2. Study of DOK4 gene expression and promoter methylation in sporadic breast cancer. Heidarizadi A, et al. Neoplasma, 2020 Jul. PMID 32386480
    3. Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells. Gray SG, et al. Clin Lung Cancer, 2008 Nov. PMID 19073520
    4. Dok-4 is a novel negative regulator of T cell activation. Gérard A, et al. J Immunol, 2009 Jun 15. PMID 19494292, Free PMC Article
    5. New insights into Dok-4 PTB domain structure and function. Hooker E, et al. Biochem Biophys Res Commun, 2012 Oct 12. PMID 22982678

    See all (27) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Study of DOK4 gene expression and promoter methylation in sporadic breast cancer.
      Title: Study of DOK4 gene expression and promoter methylation in sporadic breast cancer.
    2. the current study have explored in more detail the structure and function of the Dok-4 PTB domain.
      Title: New insights into Dok-4 PTB domain structure and function.
    3. Dok-4 represents a novel negative regulator of T cells
      Title: Dok-4 is a novel negative regulator of T cell activation.
    4. Results suggest that Dok-4, through activation of the Rap1-ERK1/2 pathway, regulates GDNF-mediated neurite outgrowth during neuronal development.
      Title: Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase.
    5. Epigenetic regulation of DOK4 expression is associated with non-small-cell lung cancer.
      Title: Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells.
    6. IRS-5 (DOK4) is significantly upregulated in 90% of examined clear cell RCCs. Studies on this gene has shown that it is regulated through chromatin remodeling in kidney cells
      Title: DOK4/IRS-5 expression is altered in clear cell renal cell carcinoma.
    7. IRS5/DOK4 and IRS6/DOK5 represent two new signaling proteins with potential roles in insulin and IGF-1 action
      Title: Two new substrates in insulin signaling, IRS5/DOK4 and IRS6/DOK5.
    8. DOK4 expression in human T cells has been demonstrated, and its genomic structure has been predicted.
      Title: DOK4 and DOK5: new Dok-related genes expressed in human T cells.
    Submit: New GeneRIF Correction

    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

    • FLJ10488

    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 Ras protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell surface receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in nervous system development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAPK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    docking protein 4
    Names
    downstream of tyrosine kinase 4
    insulin receptor substrate 5

    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_001330556.2 → NP_001317485.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Related
      ENSP00000455566.1, ENST00000566936.5
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    2. NM_001369618.1 → NP_001356547.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    3. NM_001369619.1 → NP_001356548.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    4. NM_001369620.1 → NP_001356549.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    5. NM_001369621.1 → NP_001356550.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Related
      ENSP00000455128.1, ENST00000569548.5
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    6. NM_001394652.1 → NP_001381581.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    7. NM_001394653.1 → NP_001381582.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    8. NM_001394654.1 → NP_001381583.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    9. NM_001394655.1 → NP_001381584.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    10. NM_001394656.1 → NP_001381585.1  docking protein 4 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS81986.1
      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    11. NM_001394657.1 → NP_001381586.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    12. NM_001394658.1 → NP_001381587.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    13. NM_001394659.1 → NP_001381588.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    14. NM_001394660.1 → NP_001381589.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    15. NM_001394661.1 → NP_001381590.1  docking protein 4 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    16. NM_018110.5 → NP_060580.2  docking protein 4 isoform 1

      See identical proteins and their annotated locations for NP_060580.2

      Status: VALIDATED

      Source sequence(s)
      AC009052
      Consensus CDS
      CCDS10783.1
      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3
      UniProtKB/TrEMBL
      B2RD67
      Related
      ENSP00000344277.4, ENST00000340099.10
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    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_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      57471922..57487322 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047434361.1 → XP_047290317.1  docking protein 4 isoform X2

      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3

    2. XM_024450347.2 → XP_024306115.1  docking protein 4 isoform X1

      UniProtKB/TrEMBL
      B2RD67, H3BQ19
      Conserved Domains (2) summary
      cd13164
      Location:133 → 235
      PTB_DOK4_DOK5_DOK6; Downstream of tyrosine kinase 4, 5, and 6 proteins phosphotyrosine-binding domain (PTBi)
      cd14678
      Location:9 → 113
      PH_DOK4_DOK5_DOK6; Pleckstrin homology (PH) domain of Downstream of tyrosine kinase 4, 5, and 6 proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      63267111..63282532 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054313463.1 → XP_054169438.1  docking protein 4 isoform X2

      UniProtKB/Swiss-Prot
      O75209, Q8TEW6, Q9BTP2, Q9NVV3

    2. XM_054313462.1 → XP_054169437.1  docking protein 4 isoform X1

      UniProtKB/TrEMBL
      H3BQ19
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TEW6.2 GenPept UniProtKB/Swiss-Prot:Q8TEW6

    Gene LinkOut

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

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