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] See more...

Aliases for DOK1 Gene

Aliases for DOK1 Gene

  • Docking Protein 1 2 3 4 5
  • Downstream Of Tyrosine Kinase 1 2 3 4
  • Pp62 3 4
  • Docking Protein 1, 62kDa (Downstream Of Tyrosine Kinase 1) 2
  • Docking Protein 1, 62kD (Downstream Of Tyrosine Kinase 1) 2
  • P62(Dok) 4
  • P62DOK 3
  • P62dok 2
  • DOK1 5

External Ids for DOK1 Gene

Previous GeneCards Identifiers for DOK1 Gene

  • GC02P074918
  • GC02P074988
  • GC02P074733
  • GC02P074755
  • GC02P074756
  • GC02P074692
  • GC02P074776
  • GC02P074518

Summaries for DOK1 Gene

Entrez Gene Summary for DOK1 Gene

  • 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]

GeneCards Summary for DOK1 Gene

DOK1 (Docking Protein 1) is a Protein Coding gene. Diseases associated with DOK1 include Dehydrated Hereditary Stomatocytosis 1 With Or Without Pseudohyperkalemia And/Or Perinatal Edema and Leukemia, Chronic Myeloid. Among its related pathways are GDNF-Family Ligands and Receptor Interactions and B cell receptor signaling pathway (KEGG). Gene Ontology (GO) annotations related to this gene include obsolete signal transducer activity, downstream of receptor and insulin receptor binding. An important paralog of this gene is DOK2.

UniProtKB/Swiss-Prot Summary for DOK1 Gene

  • DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3.

Gene Wiki entry for DOK1 Gene

Additional gene information for DOK1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DOK1 Gene

Genomics for DOK1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for DOK1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J074550 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 606 +4.7 4738 5.7 HNRNPL CREB1 ZBTB33 ATF7 TEAD4 PRDM10 ZNF629 IKZF1 ZNF692 BACH1 DOK1 HSALNG0016078 LOXL3 ACTG2 LBX2-AS1 AUP1 HTRA2 TLX2 PCGF1 DQX1
GH02J074548 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 +0.3 334 2.1 PRDM10 LEF1 POLR2A BACH1 JUND LARP7 RFX1 RBFOX2 PATZ1 REST DOK1 DQX1 MRPL53 WBP1 MOGS TLX2 PCGF1 M1AP INO80B LOXL3
GH02J074551 Enhancer 0.3 ENCODE dbSUPER 600.7 +1.8 1752 0 DOK1 AUP1 HTRA2 DQX1 MRPL53 WBP1 MOGS TLX2 PCGF1 HSALNG0016078
GH02J074575 Promoter/Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 18.1 +27.8 27810 2.9 GABPA PKNOX1 TCF12 EED CTCF CEBPB ZBTB40 ZBTB11 ELF1 NBN lnc-LOXL3-1 DOK1 LOXL3 AUP1 HTRA2 DQX1 TLX2 PCGF1 LBX2 CCDC142
GH02J074573 Promoter/Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 17.3 +25.0 24951 1.3 IKZF1 PKNOX1 IKZF2 POLR2A HDAC1 GABPA EP300 EED ZNF766 RUNX3 lnc-LOXL3-1 DOK1 HTRA2 AUP1 TLX2 PCGF1 MRPL53 MOGS LBX2 WBP1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DOK1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DOK1

Top Transcription factor binding sites by QIAGEN in the DOK1 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • E47
  • STAT1

Genomic Locations for DOK1 Gene

Genomic Locations for DOK1 Gene
chr2:74,549,020-74,557,554
(GRCh38/hg38)
Size:
8,535 bases
Orientation:
Plus strand
chr2:74,776,147-74,784,681
(GRCh37/hg19)
Size:
8,535 bases
Orientation:
Plus strand

Genomic View for DOK1 Gene

Genes around DOK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DOK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DOK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DOK1 Gene

Proteins for DOK1 Gene

  • Protein details for DOK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99704-DOK1_HUMAN
    Recommended name:
    Docking protein 1
    Protein Accession:
    Q99704
    Secondary Accessions:
    • O43204
    • Q53TY2
    • Q9UHG6

    Protein attributes for DOK1 Gene

    Size:
    481 amino acids
    Molecular mass:
    52392 Da
    Quaternary structure:
    • Interacts with ABL1 (By similarity). Interacts with RasGAP and INPP5D/SHIP1. Interacts directly with phosphorylated ITGB3. Interacts with SRMS (via the SH2 and SH3 domains).
    Miscellaneous:
    • [Isoform 3]: Produced by alternative initiation at Met-140 of isoform 1.

    Three dimensional structures from OCA and Proteopedia for DOK1 Gene

    Alternative splice isoforms for DOK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DOK1 Gene

Post-translational modifications for DOK1 Gene

  • Constitutively tyrosine-phosphorylated. Phosphorylated by TEC (By similarity). Phosphorylated by LYN (By similarity). Phosphorylated on tyrosine residues by the insulin receptor kinase. Results in the negative regulation of the insulin signaling pathway. Phosphorylated on tyrosine residues by SRMS.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for DOK1 Gene

Domains & Families for DOK1 Gene

Gene Families for DOK1 Gene

Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for DOK1 Gene

InterPro:
Blocks:
  • Pleckstrin-like
ProtoNet:

Suggested Antigen Peptide Sequences for DOK1 Gene

GenScript: Design optimal peptide antigens:
  • pp62 (DOK1_HUMAN)
  • DOK1 protein (Q14CB2_HUMAN)
  • cDNA FLJ60879, highly similar to Docking protein 1 (Downstream of tyrosinekinase 1) (Q2TA81_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q99704

UniProtKB/Swiss-Prot:

DOK1_HUMAN :
  • The PTB domain mediates receptor interaction.
  • Belongs to the DOK family. Type A subfamily.
Domain:
  • The PTB domain mediates receptor interaction.
Family:
  • Belongs to the DOK family. Type A subfamily.
genes like me logo Genes that share domains with DOK1: view

Function for DOK1 Gene

Molecular function for DOK1 Gene

UniProtKB/Swiss-Prot Function:
DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3.
GENATLAS Biochemistry:
phosphotyrosylprotein,62kDa,GAP-associated protein-kinase in chronic myelogenic leukemia progenitor cells

Phenotypes From GWAS Catalog for DOK1 Gene

Gene Ontology (GO) - Molecular Function for DOK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16273093
genes like me logo Genes that share ontologies with DOK1: view
genes like me logo Genes that share phenotypes with DOK1: view

Animal Models for DOK1 Gene

MGI Knock Outs for DOK1:

Animal Model Products

CRISPR Products

miRNA for DOK1 Gene

miRTarBase miRNAs that target DOK1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DOK1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DOK1 Gene

Localization for DOK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DOK1 Gene

[Isoform 1]: Cytoplasm. Nucleus.
[Isoform 3]: Cytoplasm, perinuclear region.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DOK1 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
endoplasmic reticulum 2
extracellular 1
cytoskeleton 1
mitochondrion 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for DOK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 23822091
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with DOK1: view

Pathways & Interactions for DOK1 Gene

PathCards logo

SuperPathways for DOK1 Gene

SuperPathway Contained pathways
1 GDNF-Family Ligands and Receptor Interactions
.41
.41
2 Developmental Biology
3 Signaling by PTK6
4 G-protein signaling TC21 regulation pathway
.71
.71
5 Kit receptor signaling pathway
genes like me logo Genes that share pathways with DOK1: view

Pathways by source for DOK1 Gene

5 GeneGo (Thomson Reuters) pathways for DOK1 Gene
  • Chemotaxis CXCR4 signaling pathway
  • Development GDNF family signaling
  • G-protein signaling M-RAS regulation pathway
  • G-protein signaling TC21 regulation pathway
  • G-protein signaling_H-RAS regulation pathway
2 Qiagen pathways for DOK1 Gene
  • Fc-Gamma-RIIB Signaling in B-Cells
  • GDNF-Family Ligands and Receptor Interactions
1 Cell Signaling Technology pathway for DOK1 Gene

SIGNOR curated interactions for DOK1 Gene

Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for DOK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction TAS 9008160
GO:0007166 cell surface receptor signaling pathway TAS 10799545
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway TAS,IEA --
GO:0007265 Ras protein signal transduction IEA --
GO:0007411 axon guidance TAS --
genes like me logo Genes that share ontologies with DOK1: view

Drugs & Compounds for DOK1 Gene

(2) Drugs for DOK1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for DOK1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with DOK1: view

Transcripts for DOK1 Gene

mRNA/cDNA for DOK1 Gene

6 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DOK1

Alternative Splicing Database (ASD) splice patterns (SP) for DOK1 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c
SP1:
SP2: - -
SP3: -
SP4:

Relevant External Links for DOK1 Gene

GeneLoc Exon Structure for
DOK1

Expression for DOK1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DOK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DOK1 Gene

This gene is overexpressed in Whole Blood (x9.0).

Protein differential expression in normal tissues from HIPED for DOK1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (30.6), Platelet (18.1), and Monocytes (11.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for DOK1 Gene



Protein tissue co-expression partners for DOK1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DOK1

SOURCE GeneReport for Unigene cluster for DOK1 Gene:

Hs.103854

mRNA Expression by UniProt/SwissProt for DOK1 Gene:

Q99704-DOK1_HUMAN
Tissue specificity: Expressed in pancreas, heart, leukocyte and spleen. Expressed in both resting and activated peripheral blood T-cells. Expressed in breast cancer.

Evidence on tissue expression from TISSUES for DOK1 Gene

  • Blood(4.5)
  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with DOK1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for DOK1 Gene

Orthologs for DOK1 Gene

This gene was present in the common ancestor of animals.

Orthologs for DOK1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia DOK1 30 31
  • 99.58 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia DOK1 30 31
  • 88.77 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia DOK1 30 31
  • 87.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Dok1 30
  • 83.82 (n)
Mouse
(Mus musculus)
Mammalia Dok1 30 17 31
  • 83.47 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia DOK1 31
  • 63 (a)
OneToOne
Chicken
(Gallus gallus)
Aves DOK1 31
  • 33 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia DOK1 31
  • 44 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC101730410 30
  • 56.62 (n)
Zebrafish
(Danio rerio)
Actinopterygii dok1b 30 31
  • 53.61 (n)
OneToMany
dok1a 31
  • 26 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Dok 31
  • 15 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.4936 31
  • 25 (a)
OneToMany
Species where no ortholog for DOK1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for DOK1 Gene

ENSEMBL:
Gene Tree for DOK1 (if available)
TreeFam:
Gene Tree for DOK1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DOK1: view image

Paralogs for DOK1 Gene

Paralogs for DOK1 Gene

(2) SIMAP similar genes for DOK1 Gene using alignment to 4 proteins:

  • DOK1_HUMAN
  • H7C093_HUMAN
  • Q14CB2_HUMAN
  • Q2TA81_HUMAN

Pseudogenes.org Pseudogenes for DOK1 Gene

genes like me logo Genes that share paralogs with DOK1: view

Variants for DOK1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DOK1 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
777996 Benign: not provided 74,550,345(+) C/A MISSENSE_VARIANT,INTRON_VARIANT
798647 Likely Benign: not provided 74,549,467(+) C/G SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT,INTRON_VARIANT
rs146972503 Benign/Likely Benign: not specified; not provided 74,552,556(+) G/C MISSENSE_VARIANT,INTRON_VARIANT
rs41295954 Uncertain Significance: not specified 74,556,738(+) A/G MISSENSE_VARIANT,THREE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for DOK1 Gene

Variation tolerance for DOK1 Gene

Residual Variation Intolerance Score: 46.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.87; 34.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DOK1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
DOK1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for DOK1 Gene

Disorders for DOK1 Gene

MalaCards: The human disease database

(2) MalaCards diseases for DOK1 Gene - From: DISEASES and Novoseek

- elite association - COSMIC cancer census association via MalaCards
Search DOK1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DOK1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with DOK1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DOK1 Gene

Publications for DOK1 Gene

  1. p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells. (PMID: 9008160) Carpino N … Clarkson B (Cell 1997) 2 3 4 23
  2. DOK1 mediates SHP-2 binding to the alphaVbeta3 integrin and thereby regulates insulin-like growth factor I signaling in cultured vascular smooth muscle cells. (PMID: 15546884) Ling Y … Clemmons DR (The Journal of biological chemistry 2005) 2 3 23
  3. Insulin receptor-mediated p62dok tyrosine phosphorylation at residues 362 and 398 plays distinct roles for binding GTPase-activating protein and Nck and is essential for inhibiting insulin-stimulated activation of Ras and Akt. (PMID: 11551902) Wick MJ … Liu F (The Journal of biological chemistry 2001) 3 4 23
  4. The unique N-terminal region of SRMS regulates enzymatic activity and phosphorylation of its novel substrate docking protein 1. (PMID: 23822091) Goel RK … Lukong KE (The FEBS journal 2013) 3 4
  5. Targeted mass spectrometric analysis of N-terminally truncated isoforms generated via alternative translation initiation. (PMID: 19481542) Kobayashi R … Vykoukal J (FEBS letters 2009) 3 4

Products for DOK1 Gene

Sources for DOK1 Gene