DOCK1: Dedicator of Cytokinesis 1
A key guanine nucleotide exchange factor (GEF) for Rac1, involved in cell migration, adhesion, and cancer metastasis.
Gene Information Card
| Symbol | DOCK1 |
|---|---|
| Full Name | Dedicator of cytokinesis 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.2 |
| NCBI Gene ID | 1793 ncbi.nlm.nih.gov/gene/1793 |
| Ensembl ID | ENSG00000150760 |
| UniProt ID | Q8N1I0 |
| OMIM ID | 601403 |
| HGNC ID | 2989 |
| Aliases | DOCK180, MGC133047 |
Description
DOCK1 (Dedicator of cytokinesis 1) encodes a member of the DOCK family of guanine nucleotide exchange factors (GEFs) that specifically activate the small GTPase Rac1. The protein plays a critical role in cell migration, adhesion, phagocytosis, and myoblast fusion. DOCK1 interacts with ELMO proteins to form a bipartite GEF complex. Aberrant DOCK1 expression and mutations are implicated in cancer metastasis, developmental disorders, and immune dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types, e.g., breast, lung, glioblastoma) | DOCK1 overexpression or gain-of-function mutations enhance Rac1 signaling, promoting cell migration, invasion, and metastasis. | COSMIC, PubMed |
| Intellectual disability / developmental delay | Rare loss-of-function variants in DOCK1 disrupt Rac1-mediated neuronal migration and synaptic function. | ClinVar, OMIM |
| Immunodeficiency | DOCK1 deficiency impairs phagocytosis and immune cell migration, leading to recurrent infections. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Heart | 6.1 | Low |
| Liver | 4.2 | Not detected |
| Kidney | 9.7 | Low |
| Testis | 15.8 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.2 | Embryonic kidney; moderate expression |
| HeLa | 11.5 | Cervical carcinoma; moderate expression |
| A549 | 9.8 | Lung carcinoma; low expression |
| MCF7 | 7.3 | Breast carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | <0.1% | Loss of GEF activity; associated with developmental delay (ClinVar) |
| c.2567A>G (p.Gln856Arg) | Missense | <0.1% | Reduced Rac1 binding; reported in cancer (COSMIC) |
| c.3456_3457insA (p.Glu1153Argfs*5) | Frameshift | <0.1% | Loss of function; truncation (ClinVar) |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the DHR2 domain abolish GEF activity, leading to reduced Rac1 activation and impaired cell migration.
Gain of Function (GOF)
Missense mutations in the DHR2 domain that enhance Rac1 binding or catalytic efficiency, promoting oncogenic signaling and metastasis.
Dominant Negative (DN)
Mutations that produce a truncated protein lacking the C-terminal domain but retaining the N-terminal ELMO-binding region, interfering with endogenous DOCK1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rac1 signaling pathway (Reactome: R-HSA-9013408)
• ELMO-DOCK signaling (Reactome: R-HSA-9013409)
• Integrin signaling (Reactome: R-HSA-354192)
• Axon guidance (Reactome: R-HSA-422475)
Protein Summary
DOCK1 is a 1865-amino acid protein containing a DHR2 (DOCK homology region 2) domain responsible for Rac1 GEF activity, and a DHR1 domain that binds phosphatidylinositol phosphates for membrane targeting. It forms a stable complex with ELMO proteins, which enhances its GEF activity and subcellular localization. DOCK1 is essential for Rac1-dependent processes such as cell spreading, lamellipodia formation, and myoblast fusion. Post-translational modifications include phosphorylation by Src family kinases, which modulates its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOCK1 Knockout HEK293 Cell Line | EDJ-KQ4467 | Human | 1793 | Details Get a Quote |
| DOCK11 Knockout HEK293 Cell Line | EDJ-KQ9613 | Human | 139818 | Details Get a Quote |
| DOCK10 Knockout HEK293 Cell Line | EDJ-KQ13195 | Human | 55619 | Details Get a Quote |
| DOCK1 Knockout A-549 Cell Line | EDJ-KQ27028 | Human | 1793 | Details Get a Quote |
| DOCK1 Knockout HCT 116 Cell Line | EDJ-KQ27029 | Human | 1793 | Details Get a Quote |
| DOCK1 Knockout HeLa Cell Line | EDJ-KQ27030 | Human | 1793 | Details Get a Quote |
| DOCK11 Knockout A-549 Cell Line | EDJ-KQ36437 | Human | 139818 | Details Get a Quote |
| DOCK11 Knockout HeLa Cell Line | EDJ-KQ36438 | Human | 139818 | Details Get a Quote |
| DOCK10 Knockout A-549 Cell Line | EDJ-KQ42563 | Human | 55619 | Details Get a Quote |
| DOCK10 Knockout HeLa Cell Line | EDJ-KQ42564 | Human | 55619 | Details Get a Quote |
| DOCK10 Knockout HCT 116 Cell Line | EDJ-KQ73557 | Human | 55619 | Details Get a Quote |
| DOCK11 Knockout HCT 116 Cell Line | EDJ-KQ75318 | Human | 139818 | Details Get a Quote |
