DOK2: Docking Protein 2 - Key Adaptor in Immune Signaling
Comprehensive gene card for DOK2, including genomic data, expression, mutations, and disease associations.
Gene Information Card
| Symbol | DOK2 |
|---|---|
| Full Name | Docking Protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 9046 ncbi.nlm.nih.gov/gene/9046 |
| Ensembl ID | ENSG00000147443 |
| UniProt ID | O60496 |
| OMIM ID | 604997 |
| HGNC ID | 2992 |
| Aliases | DOK2, p56dok-2, Dok-2, downstream of tyrosine kinase 2 |
Description
DOK2 (Docking Protein 2) is a member of the DOK family of adaptor proteins. It functions as a negative regulator of immune cell signaling, particularly in T cells and B cells, by recruiting downstream effectors to activated receptor tyrosine kinases. DOK2 is involved in the regulation of cell proliferation, differentiation, and migration. Loss of DOK2 expression has been implicated in various cancers, including leukemia and lung cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Myeloid Leukemia (CML) | Loss of DOK2 expression contributes to BCR-ABL1-mediated leukemogenesis by impairing negative regulation of proliferation. | PMID: 15107846; COSMIC |
| Non-Small Cell Lung Cancer (NSCLC) | Epigenetic silencing of DOK2 via promoter methylation leads to increased cell migration and invasion. | PMID: 22198284; COSMIC |
| Acute Myeloid Leukemia (AML) | Reduced DOK2 expression is associated with poor prognosis and enhanced oncogenic signaling. | PMID: 23493553; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Lymph node | 6.7 | Low |
| Bone marrow | 5.1 | Low |
| Thymus | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | 0.2 | Very low expression; loss associated with disease |
| A549 (Lung cancer) | 1.1 | Reduced compared to normal lung |
| Jurkat (T-cell) | 3.5 | Moderate expression in immune cells |
| HEK293 | 2.8 | Basal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; loss of function |
| c.214C>T (p.Arg72*) | Nonsense | <0.1% | Premature stop; loss of function |
| c.487_488insA | Frameshift | <0.1% | Frameshift; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in DOK2 are loss-of-function, including nonsense, frameshift, and missense variants that impair protein expression or function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DOK2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DOK2.
View complete mutation data：
Gene Ontology (GO)
| • SH3/SH2 adaptor activity (GO:0005070) | • transmembrane receptor protein tyrosine kinase signaling pathway (GO:0007169) |
| • innate immune response (GO:0045087) | • negative regulation of cell proliferation (GO:0008285) |
| • cell differentiation (GO:0030154) |
Pathways
• BCR-ABL1 signaling in CML (KEGG: hsa05220)
• T cell receptor signaling pathway (KEGG: hsa04660)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
Protein Summary
DOK2 is a 412-amino-acid adaptor protein containing an N-terminal pleckstrin homology (PH) domain, a phosphotyrosine-binding (PTB) domain, and multiple C-terminal SH2 domain-binding motifs. It is primarily expressed in hematopoietic tissues and acts as a negative regulator of signaling downstream of receptor tyrosine kinases. Phosphorylation of DOK2 by Src family kinases enables recruitment of RasGAP and other effectors, modulating MAPK and PI3K pathways. Loss of DOK2 expression is a frequent event in leukemia and lung cancer, often due to promoter hypermethylation or deletion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOK2 Knockout HEK293 Cell Line | EDJ-KQ6440 | Human | 9046 | Details Get a Quote |
| DOK2 Knockout HeLa Cell Line | EDJ-KQ55064 | Human | 9046 | Details Get a Quote |
| DOK2 Knockout A-549 Cell Line | EDJ-KQ63544 | Human | 9046 | Details Get a Quote |
| DOK2 Knockout HCT 116 Cell Line | EDJ-KQ72014 | Human | 9046 | Details Get a Quote |
| DOK2 Knockout BEAS-2B Cell Line | EDC90246 | Human | 9046 | Details Get a Quote |
