Rho-associated protein kinase 2 (ROCK2)
The protein contains 1388 amino acids for an estimated molecular weight of 160900 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Actomyosin structure organization
Aortic valve morphogenesis
Axon guidance
Blood vessel diameter maintenance
Cellular response to acetylcholine
Cellular response to testosterone stimulus
Centrosome duplication
Cortical actin cytoskeleton organization
Cytokinesis
Dendrite morphogenesis
Embryonic morphogenesis
Ephrin receptor signaling pathway
Epithelial to mesenchymal transition
Extrinsic apoptotic signaling pathway via death domain receptors
G protein-coupled receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
Mitotic cytokinesis
MRNA destabilization
Negative regulation of angiogenesis
Negative regulation of bicellular tight junction assembly
Negative regulation of biomineral tissue development
Negative regulation of gene expression
Negative regulation of myosin-light-chain-phosphatase activity
Negative regulation of nitric oxide biosynthetic process
Negative regulation of protein localization to lysosome
Neural tube closure
Peptidyl-serine phosphorylation
Peptidyl-threonine phosphorylation
Positive regulation of amyloid precursor protein catabolic process
Positive regulation of amyloid-beta formation
Positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process
Positive regulation of cardiac muscle hypertrophy
Positive regulation of cell migration
Positive regulation of centrosome duplication
Positive regulation of connective tissue growth factor production
Positive regulation of connective tissue replacement
Positive regulation of endothelial cell migration
Positive regulation of fibroblast growth factor production
Positive regulation of gene expression
Positive regulation of MAPK cascade
Positive regulation of protein localization to early endosome
Positive regulation of protein phosphorylation
Positive regulation of stress fiber assembly
Protein localization to plasma membrane
Protein phosphorylation
Regulation of actin cytoskeleton organization
Regulation of angiotensin-activated signaling pathway
Regulation of cell adhesion
Regulation of cell junction assembly
Regulation of cell motility
Regulation of cellular response to hypoxia
Regulation of circadian rhythm
Regulation of establishment of cell polarity
Regulation of establishment of endothelial barrier
Regulation of focal adhesion assembly
Regulation of keratinocyte differentiation
Regulation of nervous system process
Regulation of protein metabolic process
Regulation of stress fiber assembly
Response to angiotensin
Response to ischemia
Response to transforming growth factor beta
Rho protein signal transduction
Rhythmic process
Smooth muscle contraction
Vascular endothelial growth factor receptor signaling pathway
Viral RNA genome replication
Cellular Component
Centrosome
Cytoplasm
Cytoplasmic ribonucleoprotein granule
Cytoskeleton
Cytosol
Nucleus
Plasma membrane
Spindle pole centrosome
Molecular Function
ATP binding
GTP-Rho binding
Metal ion binding
Poly(A) RNA binding
Protein serine kinase activity
Protein serine/threonine kinase activity
Protein threonine kinase activity
Rho GTPase binding
Rho-dependent protein serine/threonine kinase activity
RNA binding
Small GTPase binding
Structural molecule activity
Tau protein binding
Tau-protein kinase activity
The reference OMIM entry for this protein is 604002
Rho-associated coiled-coil-containing protein kinase 2; rock2
DESCRIPTION
ROCK2 is a 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 (164810) serum response element. ROCK2, which is an isozyme of ROCK1 (601702), is a target for the small GTPase Rho (e.g., 165390).CLONING
By screening human brain cDNAs for the potential to encode proteins larger than 50 kD, Ishikawa et al. (1998) identified a ROCK2 cDNA, which they called KIAA0619. RT-PCR detected ROCK2 expression in all human tissues examined. By PCR of human cDNA using oligonucleotides based on the sequence of a bovine ROCK2 cDNA, followed by screening of a human brain cDNA library, Takahashi et al. (1999) isolated a human ROCK2 cDNA. The deduced 1,388-amino acid human ROCK2 protein is 97% and 96% identical to bovine ROCK2 and mouse Rock2, respectively.GENE FUNCTION
Nakamura et al. (2001) studied the role of Rho in the migration of corneal epithelial cells in rabbit. They detected both ROCK1 and ROCK2 in the corneal epithelium at protein and mRNA levels. They found that exoenzyme C3, a Rho inhibitor, inhibits corneal epithelial migration in a dose-dependent manner and prevents the stimulatory effect of the Rho activator lysophosphatidic acid (LPA). Both cytochalasin B, an inhibitor of actin filament assembly, and ML7, an inhibitor of myosin light chain kinase, also prevent LPA stimulation of epithelial migration. The authors suggested that Rho mediates corneal epithelial migration in response to external stimuli by regulating the organization of the actin cytoskeleton. Rao et al. (2001) investigated the role of Rho kinase in the modulation of aqueous humor outflow facility. The treatment of human trabecular meshwork and canal of Schlemm cells with a Rho kinase-specific inhibitor led to significant but reversible changes in cell shape and decreased actin stress fibers, focal adhesions, and protein phosphotyrosine staining. Based on the Rho kinase inhibitor-induced changes in myosin light chain phosphorylation and actomyosin organization, the authors suggested that cellular relaxation and loss of cell-substratum adhesions in the human trabecular meshwork and canal of Schlemm cells could result in either increased paracellular fluid flow across the canal of Schlemm or altered flow pathway through the juxtacanalicular tissue, thereby lowering resistance to outflow. They suggested Rho kinase as a potential target for the development of drugs to modulate intraocular pressure in glaucoma patients. Using human, mouse, and fish constructs expressed in human cell lines, Zhang et al. (2009) identified a conserved role for ROCK2 in the internalization of cell surface TGF-beta receptors (see TGFBR1, 190181), leading to their lysosomal degradation. The kinase activity of ROCK2 was required to downregulate TGF-beta (TGFB1; 190180) signaling. Zebrafish rock2a and endogenous human ROCK2 coimmunoprecipitated with mouse Dpr2 (DACT2; 608966) in transfected HEK293T cells. The Dpr2-ROCK2 interaction did not require ROCK2 kinase activity, but downregulation of TGF-beta signaling by Dpr2 was dependent on ROCK2 kinase activity.MAPPING
Ishikawa et al. (1998) mapped the ROCK2 gene to chromosome 2 using a radiation hybrid mapping panel. By FISH and radiation hybrid mapping, Takahashi et al. (1999) localized the ROCK2 gene to 2p24.MOLECULAR GENETICS
- Role in Left-Right Patterning By high-resolutio ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604002 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed