Rho-associated protein kinase 1
Also known as: ROCK1
Function
Protein kinase which is a key regulator of the 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, TPPP, 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 (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation. Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity).
Classification
- Family (Pfam)
- PF25346 PH_MRCK, PF00069 Pkinase, PF08912 Rho_Binding
- InterPro
- AGC-kinase_C, C1-like_sf, HR1_rho-bd, Kinase-like_dom_sf, MRCK/ROCK_PH, PH-like_dom_sf, PH_domain, PKC_DAG/PE, Prot_kinase_dom, Protein_kinase_ATP_BS, Rho-assoc_Ser/Thr_Kinase, ROCK1/ROCK2, ROCK1_HR1, ROCK_Rho-bd_dom, Ser/Thr_kinase_AS
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 32
- 1S1C X-ray 2.60A
- 2ESM X-ray 3.20A
- 2ETK X-ray 2.96A
- 2ETR X-ray 2.60A
- 2V55 X-ray 3.70A
- 3D9V X-ray 3.30A
- 3NCZ X-ray 3.00A
- 3NDM X-ray 3.30A
- 3O0Z X-ray 2.33A
- 3TV7 X-ray 2.75A
- 3TWJ X-ray 2.90A
- 3V8S X-ray 2.29A
- … and 20 more
A predicted model is available from AlphaFold.
Gene Ontology · 76
- GO:0032059 bleb
- GO:0005814 centriole
- GO:0005737 cytoplasm
- GO:0010494 cytoplasmic stress granule
- GO:0005856 cytoskeleton
- GO:0005829 cytosol
- GO:0005576 extracellular region
- GO:0000139 Golgi membrane
- GO:0030027 lamellipodium
- GO:0005886 plasma membrane
- GO:0001726 ruffle
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0034774 secretory granule lumen
- GO:0005524 ATP binding
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0072518 Rho-dependent protein serine/threonine kinase activity
- GO:0031267 small GTPase binding
- GO:0048156 tau protein binding
- GO:0050321 tau-protein kinase activity
- GO:0008270 zinc ion binding
- GO:0030036 actin cytoskeleton organization
- GO:0031032 actomyosin structure organization
- GO:0003180 aortic valve morphogenesis
- GO:0006915 apoptotic process
- GO:0097746 blood vessel diameter maintenance
- GO:0030866 cortical actin cytoskeleton organization
- GO:0048598 embryonic morphogenesis
- GO:0001837 epithelial to mesenchymal transition
- GO:0035556 intracellular signal transduction
- GO:0007159 leukocyte cell-cell adhesion
- GO:0050900 leukocyte migration
- GO:0050901 leukocyte tethering or rolling
- GO:0022614 membrane to membrane docking
- GO:0000281 mitotic cytokinesis
- GO:0061157 mRNA destabilization
- GO:0051451 myoblast migration
- GO:1902992 negative regulation of amyloid precursor protein catabolic process
- GO:1902430 negative regulation of amyloid-beta formation
- GO:0016525 negative regulation of angiogenesis
- GO:1903347 negative regulation of bicellular tight junction assembly
- GO:0070168 negative regulation of biomineral tissue development
- GO:0051045 negative regulation of membrane protein ectodomain proteolysis
- GO:0032091 negative regulation of protein binding
- GO:0140058 neuron projection arborization
- GO:0031175 neuron projection development
- GO:0018105 peptidyl-serine phosphorylation
- GO:0090521 podocyte cell migration
- GO:1900223 positive regulation of amyloid-beta clearance
- GO:0010508 positive regulation of autophagy
- GO:0010613 positive regulation of cardiac muscle hypertrophy
- GO:1905205 positive regulation of connective tissue replacement
- GO:0051894 positive regulation of focal adhesion assembly
- GO:0010628 positive regulation of gene expression
- GO:0043410 positive regulation of MAPK cascade
- GO:0072659 protein localization to plasma membrane
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0110061 regulation of angiotensin-activated signaling pathway
- GO:0030155 regulation of cell adhesion
- GO:1901888 regulation of cell junction assembly
- GO:0030334 regulation of cell migration
- GO:2000145 regulation of cell motility
- GO:2000114 regulation of establishment of cell polarity
- GO:1903140 regulation of establishment of endothelial barrier
- GO:0051893 regulation of focal adhesion assembly
- GO:0045616 regulation of keratinocyte differentiation
- GO:0070507 regulation of microtubule cytoskeleton organization
- GO:0045664 regulation of neuron differentiation
- GO:0051492 regulation of stress fiber assembly
- GO:0090128 regulation of synapse maturation
- GO:1900242 regulation of synaptic vesicle endocytosis
- GO:1990776 response to angiotensin
- GO:0071559 response to transforming growth factor beta
- GO:0007266 Rho protein signal transduction
- GO:0007165 signal transduction
- GO:0006939 smooth muscle contraction
Drugs targeting this protein · 9
- RIPASUDIL inhibitor
- AT-13148 inhibitor
- VEROSUDIL inhibitor
- SAR-407899 inhibitor
- FASUDIL inhibitor
- NETARSUDIL DIMESYLATE inhibitor
- RIPASUDIL HYDROCHLORIDE DIHYDRATE inhibitor
- BELUMOSUDIL MESYLATE inhibitor
- Y-39983 inhibitor
Related proteins · sequence + function similarity
- Rho-associated protein kinase 1 1.00
- Rho-associated protein kinase 1 1.00
- Rho-associated protein kinase 1 1.00
- Rho-associated protein kinase 2 0.97
- Rho-associated protein kinase 2 0.97
- Rho-associated protein kinase 2 0.97
- Rho-associated protein kinase 2 0.96
- Rho-associated protein kinase 2 0.96
- Serine/threonine-protein kinase MRCK alpha 0.91
- Serine/threonine-protein kinase MRCK alpha 0.90
- Serine/threonine-protein kinase MRCK alpha 0.90
- Rho-associated protein kinase 1 0.88
Co-cited proteins · studied together in the literature
- FH1/FH2 domain-containing protein 1 1 shared papers
- Rho-associated protein kinase 2 6 shared papers
- LIM domain kinase 2 2 shared papers
- GTP-binding protein GEM 1 shared papers
- Rho-related GTP-binding protein RhoE 1 shared papers
- Protein phosphatase 1 regulatory subunit 12A 4 shared papers
- Myosin regulatory light polypeptide 9 1 shared papers
- LIM domain kinase 1 2 shared papers
- Rho-associated protein kinase 1 3 shared papers
- Tubulin polymerization-promoting protein 2 shared papers
- C-Jun-amino-terminal kinase-interacting protein 3 1 shared papers
- Death-associated protein kinase 3 1 shared papers
Literature · 38 cited papers
- A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. Oncogene · 2017
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Tubulin polymerization promoting protein 1 (Tppp1) phosphorylation by Rho-associated coiled-coil kinase (rock) and cyclin-dependent kinase 1 (Cdk1) inhibits microtubule dynamics to increase cell proliferation. J. Biol. Chem. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration. J. Biol. Chem. · 2012
- N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
- Structure of Shroom domain 2 reveals a three-segmented coiled-coil required for dimerization, Rock binding, and apical constriction. Mol. Biol. Cell · 2012
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Caspase-activated ROCK-1 allows erythroblast terminal maturation independently of cytokine-induced Rho signaling. Cell Death Differ. · 2011
- Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton · 2010
- Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and tumorigenesis. Dev. Cell · 2010
- … and 26 more in the literature graph