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FLASH GENE

Symbol

ROCK2

contributors: mct - updated : 12-04-2014

HGNC name	Rho-associated, coiled-coil containing protein kinase 2
HGNC id	10252

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004850 33 - 6401 NP_004841 161 1388 - 2007 17596509

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately   vessel       highly Digestive intestine large intestine colon   highly   intestine small intestine     moderately Endocrine thyroid       moderately Lymphoid/Immune lymph node       highly Nervous nerve       highly Reproductive female system uterus     moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     moderately Connective adipose     highly Epithelial barrier/lining

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a tyrosine kinase catalytic domain
	an AGC-kinase C-terminal domain
	a REM (Hr1) repeat
	a PH domain
	a phorbol-ester/DAG-type zinc finger
	C-terminus acting as a coincidence detector for spatial regulatory signal

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to rattus Rock2 (96.4 pc)
	homolog to murine Rock2 (96.6 pc)

intraspecies

homolog to ROCK1

Homologene

FAMILY	protein kinase superfamily
	AGC Ser/Thr protein kinase family

CATEGORY

regulatory , structural protein

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus
text	actin cytoskeleton

basic FUNCTION	phosphorylating a large number of important signaling proteins
	regulating the assembly of the actin cytoskeleton
	promoting formation of stress fibers and of focal adhesion complexes
	playing a role in smooth muscle contraction
	plays an important role in the process of atherosclerosis
	key factor in regulation of motility/invasion of breast cancer cells
	playing a central role in the disassembly of apical junctional complex in epithelial cells
	plays important roles in many cellular processes, including signal transduction, vesicle trafficking, and cytoskeletal organization
	ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation
	ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in epidermal keratinocytes
	ROCK1, ROCK2 are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation
	ROCK1 and ROCK2, negatively regulate CD1D-mediated Ag presentation
	ROCK2-mediated intrinsic rhythm of vascular contractility may underlie the diurnal variation of the incidence of cardiovascular diseases
	ROCK2 is required for stabilizing actin cytoskeleton through regulating cofilin phosphorylation
	ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant
	is required for stabilizing the actin cytoskeleton and cell adhesion
	important role for RHOA-ROCK2 signaling to maintain apico-basal polarity in retinal progenitor cells, which is essential for subsequent cellular differentiation, morphology and eventually organ function

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complex consisting of BRCA2, NPM, and ROCK2 maintains . the numerical integrity of centrosomes and accurate cell division and dysfunction of this regulation might be involved in the tumorigenesis of breast cancer
	SORL1 and ROCK2 form a stable complex in human cells and tissues

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	ATP
	Zn2+

protein	binding to RHOA (activated by GTP binding)
	binding to IRS1, RHOB and RHOC
	with ARHGEF11 and PTK2, cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts
	dynamically associate with OLR1 in the presence of Oxidatively modified low-density lipoprotein (OxLDL)
	RHOA and RHOC are both required for the ROCK2-dependent promotion of centrosome duplication
	interacting with SORL1 (ROCK2 may phosphorylate SORL1, and increases SORL1 ectodomain shedding)
	PTPN11 acts via ROCK2 to regulate the cardiac actin cytoskeleton
	ROCK1 and ROCK2 could promote vascular smooth muscle cells (VSMC) proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein
	ARHGEF18 is a key regulator of RHOA-ROCK2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium
	ROCK2 is a target of junctional PTK7-SRC signaling
	CDKN3 binds and activates ROCK2 (RNA-mediated downregulation of CDKN3 leads to decreased ROCK2 activity and this, in turn, increases RAC1-mediated invasion)
	MEF2D and ROCK2 are RBFOX2 splicing targets
	ROCK2, PLK2 and PLK4 are all essential for centrosomes to re-duplicate in the cells arrested by exposure to DNA synthesis inhibitor

cell & other

REGULATION

activated by

RHOA binding

repressed by

PTPN11, that mediates dephosphorylation of ROCK2 and, therefore, regulates RhoA-induced cell rounding

Other

kinase activity requires association between the hydrophobic motif of ROCK2 with the N-terminal extension

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

up-regulation of Fhl2 may contribute to the antihypertrophic phenotype that is observed in cardiac-specific Rock2-deficient mice