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.

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 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
Displaying Records 1 To 5 Of 5 Records
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