ROCK2 Gene: Rho Associated Coiled-Coil Containing Protein Kinase 2
A key regulator of actin cytoskeleton dynamics, cell motility, and gene transcription, implicated in cancer, cardiovascular, and neurological disorders.
Gene Information Card
| Symbol | ROCK2 |
|---|---|
| Full Name | Rho associated coiled-coil containing protein kinase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2p24.1 |
| NCBI Gene ID | 9475 ncbi.nlm.nih.gov/gene/9475 |
| Ensembl ID | ENSG00000134318 |
| UniProt ID | O75116 |
| OMIM ID | 604002 |
| HGNC ID | 10252 |
| Aliases | ROCK-II, Rho kinase 2, Rho-associated protein kinase 2 |
Description
The ROCK2 gene encodes a serine/threonine kinase that is a downstream effector of the small GTPase RhoA. ROCK2 regulates actin cytoskeleton organization, cell contraction, adhesion, and migration. It also modulates gene transcription via phosphorylation of transcription factors and chromatin remodelers. ROCK2 is involved in various cellular processes including smooth muscle contraction, neurite outgrowth, and immune responses. Aberrant ROCK2 activity is linked to cancer progression, cardiovascular diseases, and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | ROCK2 overexpression/activation promotes tumor invasion, metastasis, and angiogenesis via actomyosin contractility and EMT. | COSMIC; PubMed studies |
| Cardiovascular diseases (e.g., hypertension, atherosclerosis) | ROCK2 contributes to vascular smooth muscle contraction, endothelial dysfunction, and inflammatory responses. | OMIM; PubMed |
| Neurological disorders (e.g., spinal cord injury, Alzheimer's) | ROCK2 inhibits axonal regeneration and promotes neuroinflammation. | PubMed |
| Pulmonary arterial hypertension | ROCK2 activation causes vasoconstriction and vascular remodeling. | PubMed |
| Fibrosis (liver, kidney, lung) | ROCK2 promotes myofibroblast differentiation and extracellular matrix deposition. | PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | Medium |
| Heart | 11.5 | Medium |
| Lung | 9.8 | Low |
| Liver | 7.3 | Low |
| Kidney | 10.1 | Medium |
| Skeletal muscle | 8.9 | Low |
| Testis | 12.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 15.3 | High expression |
| A549 (lung cancer) | 12.8 | Medium |
| MCF7 (breast cancer) | 14.0 | Medium |
| HepG2 (liver cancer) | 10.5 | Low |
| SH-SY5Y (neuroblastoma) | 16.1 | High |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | 0.01% (gnomAD) | Potential kinase activity alteration |
| c.4567G>A (p.Val1523Met) | Missense | 0.005% | Unknown |
| c.789_790insA (frameshift) | Insertion | Rare | Loss of function |
| c.2345A>G (p.Asn782Ser) | Missense | 0.02% | Unknown |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ROCK2 are rare and may impair kinase activity, leading to reduced cell motility and contractility. Such mutations could potentially be protective against cancer metastasis but may also affect normal physiological processes.
Gain of Function (GOF)
Gain-of-function mutations or overexpression of ROCK2 are more common in cancer, leading to hyperactivation of downstream signaling, promoting invasion, metastasis, and angiogenesis.
Dominant Negative (DN)
Dominant-negative mutations of ROCK2 have been engineered in research to inhibit kinase activity, but naturally occurring dominant-negative mutations are not well documented.
View complete mutation data:
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • actin binding | • signal transduction |
| • regulation of cell migration | • cytoskeleton organization |
| • cell adhesion | • apoptotic process |
| • response to hypoxia | • positive regulation of gene expression |
Pathways
• RhoA signaling pathway
• Actin cytoskeleton regulation
• VEGF signaling pathway
• TGF-beta signaling pathway
• Axon guidance
• Smooth muscle contraction
Protein Summary
ROCK2 is a 160 kDa serine/threonine kinase composed of an N-terminal kinase domain, a coiled-coil region, and a C-terminal pleckstrin homology (PH) domain. It is activated by binding to GTP-bound RhoA, leading to autophosphorylation and conformational changes. ROCK2 phosphorylates various substrates including myosin light chain (MLC), MLC phosphatase, LIM kinases, and ezrin/radixin/moesin proteins, thereby regulating actin dynamics and cell contractility. It also phosphorylates transcription factors such as SRF and NF-κB, influencing gene expression. ROCK2 is ubiquitously expressed but enriched in brain, heart, and immune cells. Its dysregulation is implicated in multiple diseases, making it a promising therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Rock2 Knockout CFSC-8B Cell Line | EDJ-KQ14 | Rat | 25537 | Details Get a Quote |
| ROCK2 Knockout HEK293 Cell Line | EDJ-KQ326 | Human | 9475 | Details Get a Quote |
| ROCK2 Knockout HeLa Cell Line | EDJ-KQ17971 | Human | 9475 | Details Get a Quote |
| ROCK2 Knockout A-549 Cell Line | EDJ-KQ18489 | Human | 9475 | Details Get a Quote |
| ROCK2 Knockout HCT 116 Cell Line | EDJ-KQ18490 | Human | 9475 | Details Get a Quote |
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