Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ROCK1 (Q13464) - Overview - Molecular Target Synopsis

Protein


ROCK1, Rho-associated protein kinase 1
Enzyme Classification 2.7.11.1
UniProt Q13464

Also Known as ROCK1_HUMAN, ROCK1

Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN. Interacts with ITGB1BP1 (via N-terminus and PTB domain) (By similarity). Interacts with RHOA (activated by GTP), CHORDC1, DAPK3, GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101. Interacts with FHOD1 in a Src-dependent manner.

2V55
MECHANISM OF MULTI-SITE PHOSPHORYLATION FROM A ROCK-I:RHOE COMPLEX STRUCTURE
RCSB/PDB
Inspect Structure
See all 3D Structures for ROCK1

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1354ENSG00000067900ENST00000399799ENSP00000382697Q13464-1
99ENSG00000067900ENST00000578051ENSP00000462004

Sub-cellular localization


UniProt: ROCK1 is active in the following subcellular-locations: bleb, cell membrane, cell projection, centriole, centrosome, cytoplasm, cytoskeleton, golgi apparatus membrane, lamellipodium, microtubule organizing center, ruffle.
GO terms: ROCK1 is active in the following subcellular-locations: bleb, centriole, cytoplasm, cytoplasmic stress granule, cytoskeleton, cytosol, extracellular region, Golgi membrane, lamellipodium, plasma membrane, ruffle, secretory granule lumen.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ROCK1 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 956 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HL_60, HS578T, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SNU-398, NCI-H209, WSU-FSCCL

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, MCF-7

(see details)

RNA Interference


ROCK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: BXPC3, H23. (see details)

3D Structures


For ROCK1 there are:
27 structures (80 chains) solved
23 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ROCK1 has been screened with 2193 compounds (3163 bioactivities), 689 compounds have bioactivities that show binding affinity of <= 500nM (869 bioactivities). (see details)