CYTH3: Cytohesin 3
A guanine nucleotide exchange factor for ARF GTPases involved in vesicle trafficking and cell signaling
Gene Information Card
| Symbol | CYTH3 |
|---|---|
| Full Name | cytohesin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 7p21.3 |
| NCBI Gene ID | 9265 ncbi.nlm.nih.gov/gene/9265 |
| Ensembl ID | ENSG00000106344 |
| UniProt ID | O43739 |
| OMIM ID | 605081 |
| HGNC ID | 9506 |
| Aliases | GRP1, PSCD3, ARNO3 |
Description
CYTH3 (cytohesin 3) encodes a member of the cytohesin family of guanine nucleotide exchange factors (GEFs) that activate ADP-ribosylation factor (ARF) GTPases. The protein contains a pleckstrin homology (PH) domain, a Sec7 domain, and a coiled-coil region. It regulates membrane trafficking, cell adhesion, and signal transduction. CYTH3 is ubiquitously expressed with highest levels in brain, lung, and immune cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | CYTH3 overexpression promotes ARF6-mediated cell migration and invasion | COSMIC; PMID: 21502544 |
| Lung adenocarcinoma | Somatic mutations (e.g., p.Glu49Lys) may alter GEF activity | COSMIC; PMID: 22980975 |
| Colorectal cancer | CYTH3 amplification associated with poor prognosis | COSMIC; PMID: 25691885 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 9.8 | Medium |
| Spleen | 8.2 | Medium |
| Liver | 4.1 | Low |
| Heart | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| A549 | 11.0 | Lung adenocarcinoma cell line |
| MCF7 | 7.8 | Breast cancer cell line |
| HepG2 | 5.3 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu49Lys | Missense | <0.1% | Unknown; predicted to affect Sec7 domain |
| p.Arg335Trp | Missense | <0.1% | Unknown; located in PH domain |
| p.Gln361* | Nonsense | <0.1% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Gln361*) lead to truncated protein lacking PH domain.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance GEF activity.
Dominant Negative (DN)
Not reported for CYTH3.
View complete mutation data：
Gene Ontology (GO)
| • ARF guanyl-nucleotide exchange factor activity (GO:0005086) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • regulation of ARF protein signal transduction (GO:0032012) |
| • vesicle-mediated transport (GO:0016192) |
Pathways
• ARF6 signaling pathway
• Endocytosis
• Fc gamma R-mediated phagocytosis
Protein Summary
Cytohesin 3 (GRP1) is a 398-amino acid protein with a Sec7 domain (GEF activity), a PH domain (phosphoinositide binding), and a coiled-coil region (dimerization). It activates ARF1 and ARF6, regulating endocytosis, cell spreading, and integrin signaling. The protein is predominantly cytosolic but translocates to the plasma membrane upon PI3K activation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYTH3 Knockout HEK293 Cell Line | EDJ-KQ1724 | Human | 9265 | Details Get a Quote |
| CYTH3 Knockout A-549 Cell Line | EDJ-KQ21556 | Human | 9265 | Details Get a Quote |
| CYTH3 Knockout HCT 116 Cell Line | EDJ-KQ21557 | Human | 9265 | Details Get a Quote |
| CYTH3 Knockout HeLa Cell Line | EDJ-KQ21558 | Human | 9265 | Details Get a Quote |
