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FLASH GENE

Symbol

ROCK1

contributors: mct/pgu - updated : 21-05-2016

HGNC name	Rho-associated, coiled-coil containing protein kinase 1
HGNC id	10251

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_005406 33 - 6650 NP_005397 158 1354 - 2008 19036714

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 Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune lymph node       highly Nervous nerve       highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal serine/threonine kinase domain
	a long alpha-helix
	a cysteine rich zing finger-like motif, phorbol-ester/DAG-type zinc finger
	a REM (hr1) repeat
	a central coiled-coil region containing a Rho binding site
	a protein kinase domain
	a C terminal pleckstrin homology domain (PH), and a RhoA-binding domain
	auto-inhibitory domain interfering with kinase activity

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	AGC Ser/Thr protein kinase family

CATEGORY

enzyme , regulatory , receptor nuclear membrane

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic

basic FUNCTION	serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions and the activation of the c-fos serum response element
	required for centromere positioning and centromere- dependent exit from mitosis
	phosphorylating the C-terminal residues Ser1131, Ser1137, and Thr1141 of FHOD1
	plays an important role in the process of atherosclerosis
	in bone marrow -derived cells mediates neointima formation following vascular injury
	functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer
	key factor in regulation of motility/invasion of breast cancer cells
	novel regulator of glucose homeostasis and insulin sensitivity, which could lead to new treatment approaches for obesity and type 2 diabetes
	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
	involved in controlling embryonic stem (ES) cell renewal and differentiation
	promote embryonic stem cell colony formation, maintain them at undifferentiated state, and prevent them from neural differentiation at high seeding density, and its inhibition represents a new strategy for preparing large numbers of neural progenitor cells
	participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation
	functional role in ameloblast differentiation
	ROCK1 and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma
	ROCK1/MARK2-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland
	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
	is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction
	ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant
	is involved in destabilizing the actin cytoskeleton and cell detachment
	role of the ROCK1 pathway during early stages of human neurogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

NOTCH1-ROCK1 pathway critical for cellular differentiation and loss of self-renewal capacity in a subset of immature cells

a component

FRMD6/PARD3-PRKCI-ROCK1 pathway that controls epithelial apical morphology

INTERACTION

DNA

RNA

small molecule

protein	phosphorylating and activating LIMK1
	downstream effector of RHO, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity
	direct cleavage substrate of activated caspase-3 (CASP3), which is associated with heart failure (in promoting apoptotic signals in myocardial hypertrophy and/or failure)
	activity of ROCK1 was required for TAOK1 to induce cell contraction and membrane blebbing
	RND3 binds to the N-terminal 420 AAs of ROCK1, which includes the kinase domain as well as N-terminal and C-terminal extensions
	SHROOM3-ROCK1 interaction is crucial for the regulation of epithelial and neuroepithelial cell arrangement and remodeling
	PFN1 interacts with HTT, as being a direct target of the ROCK1 isoform
	MAPK8IP3 scaffolding protein is an interacting partner of ROCK1 (phosphorylation of MAPK8IP3 by ROCK1 was crucial for the recruitment of JNK)
	KRIT1-CCM2 interaction regulates vascular barrier function by suppressing RHO/ROCK1 signaling and that this pathway is dysregulated in human CCM endothelium
	physical interaction between CTNND1 and Rho-associated protein kinase 1 (ROCK1), a major effector of RHOA
	MAPK8 activation is required for GNA12-induced invasion of breast cancer cells and MAPK8 is downstream of ROCK1 on this pathway
	SHROOM2-ROCK1 interaction is sufficient to direct ROCK1 subcellular localization and the subsequent assembly of contractile actomyosin networks in defined subcellular locales
	involvement of RHOA and ROCK1 in F11R relocalization
	ROCK1 and ROCK2 could promote vascular smooth muscle cells (VSMC) proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein
	cleavage of Rho associated Coiled Coil kinase I (ROCK 1) by CASP3 contributes to membrane blebbing
	ROCK1 via LIMK1, LIMK2 regulates growth, maturation and actin based functions in mast cells
	may promote cancer cell proliferation in prostate carcinoma by upregulating ROCK1

cell & other

REGULATION

activated by	RHOA binding
	by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis

inhibited by

MYBPH, that inhibited ROCK1 and negatively regulated actomyosin organization, which in turn reduced single cell motility and increased collective cell migration, resulting in decreased cancer invasion and metastasis

Phosphorylated by

PRKCI, that phosphorylates ROCK1 and suppresses its junctional localization, thereby allowing cells to retain normally shaped apical domains

Other

ACTG1 regulates cell migration and modulates the ROCK1 signaling pathway

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function causes whole body insulin resistance by impairing insulin signaling in skeletal muscle, suggesting that activation of ROCK1 is essential for the normal actions of insulin on glucose transport in skeletal muscle tumoral somatic mutation     gain of function three somatic mutations leading to elevated kinase activity and driving actin cytoskeleton rearrangements that promote increased motility and decreased adhesion (characteristics of cancer progression) tumoral     --over   in various tumor cell lines and tumor tissues from osteosarcoma patients

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast potential target in breast cancer immunology inflammatory   may represent a promising therapeutic target in vascular inflammatory diseases cancer bone   may be a promising therapeutic target for the treatment of osteosarcoma patients. neuromuscular spinal muscular atrophy   therapeutic potential of ROCK1 inhibition in SMA neurology neurodegenerative huntington chorea A signaling pathway from ROCK1 to profilin thus controls polyglutamine protein aggregation and is targeted by a promising therapeutic lead for HD

ANIMAL & CELL MODELS

ROCK1-deficient mice exhibited insulin resistance, as revealed by the failure of blood glucose levels to decrease after insulin injection