PKMYT1: Membrane-Associated Tyrosine/Threonine Kinase 1
A key regulator of G2/M cell cycle checkpoint and potential therapeutic target in cancer
Gene Information Card
| Symbol | PKMYT1 |
|---|---|
| Full Name | Protein Kinase, Membrane Associated Tyrosine/Threonine 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 9088 ncbi.nlm.nih.gov/gene/9088 |
| Ensembl ID | ENSG00000127564 |
| UniProt ID | Q99640 |
| OMIM ID | 601882 |
| HGNC ID | 17870 |
| Aliases | MYT1, Myt1 kinase |
Description
PKMYT1 (Myt1) is a membrane-associated tyrosine/threonine kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating CDK1. It is a key component of the G2 DNA damage checkpoint. PKMYT1 is overexpressed in several cancers and is being investigated as a therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of PKMYT1 promotes cell cycle progression and resistance to DNA damage; inhibition sensitizes cells to chemotherapy | PMID: 31073079 |
| Ovarian cancer | High PKMYT1 expression correlates with poor prognosis; knockdown induces mitotic catastrophe | PMID: 31570780 |
| Colorectal cancer | PKMYT1 upregulation associated with tumor progression; targeting PKMYT1 enhances sensitivity to DNA-damaging agents | PMID: 32669304 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Lung | 6.1 | Low |
| Breast | 5.4 | Low |
| Ovary | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| MCF7 | 9.8 | Breast cancer cell line |
| A549 | 7.3 | Lung cancer cell line |
| HCT116 | 6.5 | Colorectal cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123G>A (p.Gly375Arg) | Missense | <0.1% (COSMIC) | Unknown functional effect |
| c.1450C>T (p.Arg484Trp) | Missense | <0.1% (COSMIC) | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in COSMIC or ClinVar.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity | • ATP binding |
| • cell cycle | • G2/M transition of mitotic cell cycle |
| • protein phosphorylation | • membrane |
Pathways
• Cell Cycle (G2/M Checkpoint)
• p53-Independent DNA Damage Response
Protein Summary
PKMYT1 is a 499-amino acid membrane-associated kinase that localizes to the endoplasmic reticulum and Golgi. It contains an N-terminal membrane-binding domain and a C-terminal serine/threonine kinase domain. PKMYT1 phosphorylates CDK1 on Thr14 and Tyr15, inhibiting its activity and preventing premature mitotic entry. It is regulated by PLK1-mediated degradation at the G2/M transition.
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