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    DOK1 docking protein 1 [ Homo sapiens (human) ]

    Gene ID: 1796, updated on 14-Nov-2024

    Summary

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    Official Symbol
    DOK1provided by HGNC
    Official Full Name
    docking protein 1provided by HGNC
    Primary source
    HGNC:HGNC:2990
    See related
    Ensembl:ENSG00000115325 MIM:602919; AllianceGenome:HGNC:2990
    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
    pp62; P62DOK
    Summary
    The protein encoded by this gene is part of a signal transduction pathway downstream of receptor tyrosine kinases. The encoded protein is a scaffold protein that helps form a platform for the assembly of multiprotein signaling complexes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
    Expression
    Ubiquitous expression in fat (RPKM 6.6), spleen (RPKM 6.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DOK1 in Genome Data Viewer
    Location:
    2p13.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (74549105..74557551)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (74557671..74566117)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (74776232..74784678)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16070 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74756279-74757161 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16073 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16074 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16075 Neighboring gene DEAQ-box RNA dependent ATPase 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:74763605-74764106 Neighboring gene AUP1 lipid droplet regulating VLDL assembly factor Neighboring gene HtrA serine peptidase 2 Neighboring gene lysyl oxidase like 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16076 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11669 Neighboring gene Sharpr-MPRA regulatory regions 4995 and 13004 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11670 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:74781947-74782464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16078 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16079 Neighboring gene meiosis 1 associated protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16080 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16081 Neighboring gene TOR1B pseudogene 1 Neighboring gene TVP23B pseudogene 2

    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. IkappaB kinase beta phosphorylates Dok1 serines in response to TNF, IL-1, or gamma radiation. Lee S, et al. Proc Natl Acad Sci U S A, 2004 Dec 14. PMID 15574499, Free PMC Article
    2. Epstein-Barr virus down-regulates tumor suppressor DOK1 expression. Siouda M, et al. PLoS Pathog, 2014 May. PMID 24809689, Free PMC Article
    3. Inactivation of the putative suppressor gene DOK1 by promoter hypermethylation in primary human cancers. Saulnier A, et al. Int J Cancer, 2012 Jun 1. PMID 21796618, Free PMC Article
    4. Oncogenic tyrosine kinases target Dok-1 for ubiquitin-mediated proteasomal degradation to promote cell transformation. Janas JA, et al. Mol Cell Biol, 2011 Jul. PMID 21536658, Free PMC Article
    5. Targeted mass spectrometric analysis of N-terminally truncated isoforms generated via alternative translation initiation. Kobayashi R, et al. FEBS Lett, 2009 Jul 21. PMID 19481542

    See all (103) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
      Title: Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
    2. Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus.
      Title: Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus.
    3. Analysis of the DOK1 gene in breast cancer.
      Title: Analysis of the DOK1 gene in breast cancer.
    4. Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion.
      Title: Nck adapter proteins promote podosome biogenesis facilitating extracellular matrix degradation and cancer invasion.
    5. Decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML.
      Title: Methylation-associated DOK1 and DOK2 down-regulation: Potential biomarkers for predicting adverse prognosis in acute myeloid leukemia.
    6. Taken together, these results indicate that ATRA-enhanced expression of DOK1 activates PPARgamma leading to inhibition of cell proliferation and enhancement of cell apoptosis in MCF-7 cell.
      Title: DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells.
    7. DOK1 was identified as a prognostic factor for non-metastatic CRC, and, via its drugability by PPARgamma-agonist, may constitute a potential target for future cancer treatments.
      Title: Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer.
    8. DOK3 expression was not altered much in HTLV-1-infected T cells.
      Title: Expression of DOK1, 2, and 3 genes in HTLV-1-infected T cells.
    9. Results indicate that hypermethylation of tumor suppressor protein RASSF1A and docking protein 1 (DOK1) contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics.
      Title: RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients.
    10. Data show that residues Ser745 and Ser756 in the integrin beta2 tail, which are adjacent to the NxxF motif, are required for docking protein 1, docking protein 1, 62kDa (downstream of tyrosine kinase 1) (Dok1) interaction.
      Title: An Alternative Phosphorylation Switch in Integrin β2 (CD18) Tail for Dok1 Binding.
    Submit: New GeneRIF Correction See all GeneRIFs (45)

    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with docking protein 1 (DOK1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • MGC117395, MGC138860

    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 cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in macrophage colony-stimulating factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    docking protein 1
    Names
    Downstream of tyrosine kinase 1

    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.

    Genomic

    1. NG_050617.1 RefSeqGene

      Range
      11516..14347
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001197260.2 → NP_001184189.1  docking protein 1 isoform b

      See identical proteins and their annotated locations for NP_001184189.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b, also known as 2) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode the same isoform (b).
      Source sequence(s)
      AF035299, BQ575925, DA382785
      Consensus CDS
      CCDS56125.1
      UniProtKB/Swiss-Prot
      Q99704
      Related
      ENSP00000387016.1, ENST00000409429.5
      Conserved Domains (1) summary
      cd01203
      Location:12 → 114
      PTB_DOK1_DOK2_DOK3; Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi)

    2. NM_001318866.2 → NP_001305795.1  docking protein 1 isoform b

      Status: REVIEWED

      Source sequence(s)
      AK055944, AK314678, BQ575925
      Consensus CDS
      CCDS56125.1
      UniProtKB/TrEMBL
      B3KP83
      Conserved Domains (1) summary
      cd01203
      Location:12 → 114
      PTB_DOK1_DOK2_DOK3; Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi)

    3. NM_001318867.2 → NP_001305796.1  docking protein 1 isoform c

      Status: REVIEWED

      Source sequence(s)
      AK055944, AK296154, BQ575925
      UniProtKB/TrEMBL
      B3KP83, B4DJN1, Q53GP8
      Conserved Domains (3) summary
      cd01203
      Location:140 → 242
      PTB_DOK1_DOK2_DOK3; Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi)
      pfam00169
      Location:8 → 105
      PH; PH domain
      cl17171
      Location:11 → 108
      PH-like; Pleckstrin homology-like domain

    4. NM_001318868.2 → NP_001305797.1  docking protein 1 isoform d

      Status: REVIEWED

      Source sequence(s)
      AC005033, AK055944, BC111055, BQ575925
      Consensus CDS
      CCDS82474.1
      UniProtKB/Swiss-Prot
      Q99704
      UniProtKB/TrEMBL
      B3KP83, Q2TA81
      Related
      ENSP00000344330.6, ENST00000340004.6
      Conserved Domains (1) summary
      cl17171
      Location:6 → 119
      PH-like; Pleckstrin homology-like domain

    5. NM_001318869.2 → NP_001305798.1  docking protein 1 isoform e

      Status: REVIEWED

      Source sequence(s)
      AC005033, AK055944, BC114497, BQ575925
      UniProtKB/TrEMBL
      Q14CB2, Q2TA81
      Conserved Domains (1) summary
      cl17171
      Location:1 → 39
      PH-like; Pleckstrin homology-like domain

    6. NM_001381.5 → NP_001372.1  docking protein 1 isoform a

      See identical proteins and their annotated locations for NP_001372.1

      Status: REVIEWED

      Source sequence(s)
      AC005033, AK055944, BQ575925
      Consensus CDS
      CCDS1954.1
      UniProtKB/Swiss-Prot
      O43204, Q53TY2, Q99704, Q9UHG6
      UniProtKB/TrEMBL
      B3KP83, Q53GP8
      Related
      ENSP00000233668.5, ENST00000233668.10
      Conserved Domains (2) summary
      cd01203
      Location:151 → 253
      PTB_DOK1_DOK2_DOK3; Downstream of tyrosine kinase 1, 2, and 3 proteins phosphotyrosine-binding domain (PTBi)
      cl17171
      Location:6 → 119
      PH-like; Pleckstrin homology-like domain

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      74549105..74557551
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      74557671..74566117
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99704.1 GenPept UniProtKB/Swiss-Prot:Q99704

    Gene LinkOut

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

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