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DOK4 docking protein 4 [ Homo sapiens (human) ]

Gene ID: 55715, updated on 11-Apr-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 positive regulation of MAPK cascade and transmembrane receptor protein tyrosine kinase signaling pathway. 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, Apr 2022]
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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Location:
16q21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (57471922..57487322, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (63267111..63282532, complement)
105.20220307 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
  • 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. Study of DOK4 gene expression and promoter methylation in sporadic breast cancer. Heidarizadi A, et al. Neoplasma, 2020 Jul. PMID 32386480
  2. 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
  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. 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
  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 (25) 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_2023_10

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

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