Rho-associated protein kinase 2
Also known as: KIAA0619, ROCK2
Function
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 ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.
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, ROCK2_cat, ROCK2_HR1, ROCK_Rho-bd_dom, Ser/Thr_kinase_AS
- Functional cluster
- ATP Synthase Gamma Subunit & related
Experimental structures · PDB · 21
- 4L6Q X-ray 2.79A
- 4WOT X-ray 2.93A
- 5U7Q X-ray 3.15A
- 5U7R X-ray 3.33A
- 6ED6 X-ray 2.86A
- 6P5M X-ray 2.65A
- 6P5P X-ray 3.30A
- 7JNT X-ray 2.21A
- 7JOV X-ray 2.59A
- 7P6N X-ray 3.00A
- 7P6O X-ray 2.75A
- 7P6P X-ray 2.82A
- … and 9 more
A predicted model is available from AlphaFold.
Gene Ontology · 70
- GO:0005813 centrosome
- GO:0005737 cytoplasm
- GO:0036464 cytoplasmic ribonucleoprotein granule
- GO:0005856 cytoskeleton
- GO:0005829 cytosol
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0005524 ATP binding
- GO:0061133 endopeptidase activator activity
- GO:0002020 protease binding
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0072518 Rho-dependent protein serine/threonine kinase activity
- GO:0003723 RNA binding
- GO:0031267 small GTPase binding
- GO:0005198 structural molecule activity
- 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:0097746 blood vessel diameter maintenance
- GO:1905145 cellular response to acetylcholine
- GO:0051298 centrosome duplication
- GO:0030866 cortical actin cytoskeleton organization
- GO:0048598 embryonic morphogenesis
- GO:0001837 epithelial to mesenchymal transition
- GO:0044788 host-mediated perturbation of viral process
- GO:0000281 mitotic cytokinesis
- GO:0061157 mRNA destabilization
- GO:0016525 negative regulation of angiogenesis
- GO:1903347 negative regulation of bicellular tight junction assembly
- GO:0070168 negative regulation of biomineral tissue development
- GO:0010629 negative regulation of gene expression
- GO:0045019 negative regulation of nitric oxide biosynthetic process
- GO:0150033 negative regulation of protein localization to lysosome
- GO:1902993 positive regulation of amyloid precursor protein catabolic process
- GO:1902004 positive regulation of amyloid-beta formation
- GO:0010613 positive regulation of cardiac muscle hypertrophy
- GO:0030335 positive regulation of cell migration
- GO:0010825 positive regulation of centrosome duplication
- GO:0032723 positive regulation of connective tissue growth factor production
- GO:1905205 positive regulation of connective tissue replacement
- GO:0090271 positive regulation of fibroblast growth factor production
- GO:0010628 positive regulation of gene expression
- GO:0043410 positive regulation of MAPK cascade
- GO:1902966 positive regulation of protein localization to early endosome
- GO:0051496 positive regulation of stress fiber assembly
- GO:0072659 protein localization to plasma membrane
- GO:0006468 protein phosphorylation
- 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:2000145 regulation of cell motility
- GO:1900037 regulation of cellular response to hypoxia
- GO:0042752 regulation of circadian rhythm
- 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:0031644 regulation of nervous system process
- GO:0051492 regulation of stress fiber assembly
- GO:1990776 response to angiotensin
- GO:0002931 response to ischemia
- GO:0071559 response to transforming growth factor beta
- GO:0007266 Rho protein signal transduction
- GO:0048511 rhythmic process
- GO:0006939 smooth muscle contraction
Drugs targeting this protein · 10
- BELUMOSUDIL inhibitor
- 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 2 1.00
- Rho-associated protein kinase 2 1.00
- Rho-associated protein kinase 2 1.00
- Rho-associated protein kinase 2 1.00
- Rho-associated protein kinase 1 0.97
- Rho-associated protein kinase 1 0.96
- Rho-associated protein kinase 1 0.96
- Rho-associated protein kinase 1 0.96
- Serine/threonine-protein kinase MRCK alpha 0.92
- Serine/threonine-protein kinase MRCK alpha 0.91
- Serine/threonine-protein kinase MRCK alpha 0.91
- Rho-associated protein kinase 1 0.88
Co-cited proteins · studied together in the literature
- Rho-associated protein kinase 1 6 shared papers
- Protein phosphatase 1 regulatory subunit 12A 2 shared papers
- Myosin regulatory light polypeptide 9 1 shared papers
- Rho-associated protein kinase 2 2 shared papers
- Rho-associated protein kinase 2 1 shared papers
- Cysteine and histidine-rich domain-containing protein 1 1 shared papers
- Sortilin-related receptor 1 shared papers
- Nucleophosmin 2 shared papers
- Tyrosine-protein phosphatase non-receptor type 11 1 shared papers
- Forkhead box protein M1 1 shared papers
- Protein phosphatase 1 regulatory subunit 12A 2 shared papers
- Cysteine and histidine-rich domain-containing protein morgana 1 shared papers
Literature · 27 cited papers
- A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. Oncogene · 2017
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- 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
- Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production. J. Biol. Chem. · 2011
- BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2. Cancer Res. · 2011
- Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics. J. Cell Sci. · 2010
- 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
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- … and 15 more in the literature graph