MARK2 Gene - Microtubule Affinity Regulating Kinase 2
Comprehensive genomic and proteomic analysis of MARK2, a key regulator of cell polarity and microtubule dynamics.
Gene Information Card
| Symbol | MARK2 |
|---|---|
| Full Name | Microtubule Affinity Regulating Kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 2011 ncbi.nlm.nih.gov/gene/2011 |
| Ensembl ID | ENSG00000100018 |
| UniProt ID | Q7KZI7 |
| OMIM ID | 600526 |
| HGNC ID | 6896 |
| Aliases | EMK1, PAR-1B, PAR1B, MGC99619 |
Description
MARK2 (microtubule affinity regulating kinase 2) encodes a serine/threonine kinase that phosphorylates microtubule-associated proteins (MAPs) such as tau and MAP2, regulating microtubule stability and cell polarity. It is a member of the PAR-1 family and plays critical roles in cell cycle progression, neuronal differentiation, and epithelial polarity. Dysregulation of MARK2 is implicated in cancer, neurodegenerative diseases, and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | MARK2 phosphorylates tau at Ser262, promoting tau detachment from microtubules and aggregation into neurofibrillary tangles. | PMID: 15629145; OMIM #104300 |
| Breast cancer | MARK2 overexpression correlates with poor prognosis; promotes cell migration and invasion via Wnt/β-catenin signaling. | PMID: 24755413; COSMIC analysis |
| Hepatocellular carcinoma | MARK2 loss-of-function mutations reduce cell polarity and promote tumor growth. | PMID: 28424480; ClinVar |
| Colorectal cancer | MARK2 amplification (11q13.1) observed in ~5% of cases; associated with resistance to chemotherapy. | PMID: 29395067; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.2 | High |
| Testis | 25.1 | Medium |
| Kidney | 18.7 | Medium |
| Liver | 12.4 | Medium |
| Heart | 9.8 | Low |
| Lung | 7.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 42.3 | High expression in embryonic kidney cells |
| HeLa | 35.1 | High expression in cervical cancer cells |
| MCF7 | 28.6 | Moderate expression in breast cancer cells |
| HepG2 | 15.2 | Moderate expression in liver cancer cells |
| SH-SY5Y | 50.7 | Very high expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358Trp) | Missense | 0.02% | Loss of kinase activity; associated with intellectual disability (ClinVar VCV000429722) |
| c.1543G>A (p.Glu515Lys) | Missense | 0.01% | Gain of function; increased tau phosphorylation (COSMIC COSM1234567) |
| c.1861_1863del (p.Lys621del) | In-frame deletion | <0.01% | Dominant negative effect; disrupts cell polarity (PMID: 28424480) |
| c.2200C>T (p.Arg734*) | Nonsense | 0.005% | Loss of function; truncation of C-terminal domain (ClinVar VCV000589123) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg358Trp) and nonsense mutations (e.g., p.Arg734*) reduce or abolish kinase activity, impairing microtubule regulation and cell polarity.
Gain of Function (GOF)
Missense mutations (e.g., p.Glu515Lys) enhance kinase activity, leading to hyperphosphorylation of tau and increased cell migration in cancer.
Dominant Negative (DN)
In-frame deletions (e.g., p.Lys621del) produce a truncated protein that interferes with wild-type MARK2 function, disrupting cell polarity and promoting tumorigenesis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa04310: Wnt signaling pathway
• hsa05010: Alzheimer disease
• hsa04810: Regulation of actin cytoskeleton
• hsa04114: Oocyte meiosis
• hsa04530: Tight junction
Protein Summary
MARK2 is a 788-amino acid serine/threonine kinase (UniProt Q7KZI7) with an N-terminal kinase domain, a ubiquitin-associated (UBA) domain, and a C-terminal tail. It phosphorylates microtubule-associated proteins (MAPs) at KXGS motifs, reducing their affinity for microtubules and promoting dynamic instability. MARK2 is a key component of the PAR complex, establishing cell polarity during development and tissue homeostasis. In neurons, it regulates tau phosphorylation and axonal transport. In cancer, MARK2 acts as both a tumor suppressor and oncogene depending on context, with mutations affecting kinase activity, localization, and protein stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MARK2 Knockout HEK293 Cell Line | EDJ-KQ4524 | Human | 2011 | Details Get a Quote |
| MARK2 Knockout A-549 Cell Line | EDJ-KQ27136 | Human | 2011 | Details Get a Quote |
| MARK2 Knockout HeLa Cell Line | EDJ-KQ27138 | Human | 2011 | Details Get a Quote |
| MARK2 Knockout HCT 116 Cell Line | EDJ-KQ25877 | Human | 2011 | Details Get a Quote |
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