Rho-associated protein kinase 1 (ROCK1)

The protein contains 1354 amino acids for an estimated molecular weight of 158175 Da.

 

Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). 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 (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579, PubMed:23093407, PubMed:23355470). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). 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 (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641) (updated: Feb. 10, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 32%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs55811609
dbSNP:rs45562542
dbSNP:rs35881519
a lung neuroendocrine carcinoma sample
dbSNP:rs2847092
dbSNP:rs1045142
dbSNP:rs2663698

Biological Process

Actin cytoskeleton organization GO Logo
Actomyosin structure organization GO Logo
Aortic valve morphogenesis GO Logo
Apical constriction GO Logo
Apoptotic process GO Logo
Axon guidance GO Logo
Bleb assembly GO Logo
Blood vessel diameter maintenance GO Logo
Cellular component disassembly involved in execution phase of apoptosis GO Logo
Cortical actin cytoskeleton organization GO Logo
Embryonic morphogenesis GO Logo
Ephrin receptor signaling pathway GO Logo
Epithelial to mesenchymal transition GO Logo
Execution phase of apoptosis GO Logo
G protein-coupled receptor signaling pathway GO Logo
Glomerular visceral epithelial cell migration GO Logo
I-kappaB kinase/NF-kappaB signaling GO Logo
Leukocyte cell-cell adhesion GO Logo
Leukocyte migration GO Logo
Leukocyte tethering or rolling GO Logo
Membrane to membrane docking GO Logo
Mitotic cytokinesis GO Logo
MRNA destabilization GO Logo
Myoblast migration GO Logo
Negative regulation of amyloid precursor protein catabolic process GO Logo
Negative regulation of amyloid-beta formation GO Logo
Negative regulation of angiogenesis GO Logo
Negative regulation of bicellular tight junction assembly GO Logo
Negative regulation of biomineral tissue development GO Logo
Negative regulation of membrane protein ectodomain proteolysis GO Logo
Negative regulation of myosin-light-chain-phosphatase activity GO Logo
Negative regulation of neuron apoptotic process GO Logo
Negative regulation of phosphorylation GO Logo
Negative regulation of protein binding GO Logo
Neuron projection arborization GO Logo
Neuron projection development GO Logo
Neutrophil degranulation GO Logo
Peptidyl-serine phosphorylation GO Logo
Peptidyl-threonine phosphorylation GO Logo
Positive regulation of amyloid-beta clearance GO Logo
Positive regulation of autophagy GO Logo
Positive regulation of cardiac muscle hypertrophy GO Logo
Positive regulation of connective tissue replacement GO Logo
Positive regulation of focal adhesion assembly GO Logo
Positive regulation of gene expression GO Logo
Positive regulation of MAPK cascade GO Logo
Protein localization to plasma membrane GO Logo
Protein phosphorylation GO Logo
Regulation of actin cytoskeleton organization GO Logo
Regulation of amyloid-beta formation GO Logo
Regulation of angiotensin-activated signaling pathway GO Logo
Regulation of autophagy GO Logo
Regulation of cell adhesion GO Logo
Regulation of cell junction assembly GO Logo
Regulation of cell migration GO Logo
Regulation of cell motility GO Logo
Regulation of establishment of cell polarity GO Logo
Regulation of establishment of endothelial barrier GO Logo
Regulation of focal adhesion assembly GO Logo
Regulation of keratinocyte differentiation GO Logo
Regulation of microtubule cytoskeleton organization GO Logo
Regulation of neuron differentiation GO Logo
Regulation of stress fiber assembly GO Logo
Regulation of synaptic vesicle endocytosis GO Logo
Response to angiotensin GO Logo
Response to transforming growth factor beta GO Logo
Rho protein signal transduction GO Logo
Signal transduction GO Logo
Smooth muscle contraction GO Logo
Vascular endothelial growth factor receptor signaling pathway GO Logo

The reference OMIM entry for this protein is 601702

Rho-associated coiled-coil-containing protein kinase 1; rock1
P160-rock
Rho kinase

DESCRIPTION

The protein serine/threonine kinase ROCK1 is a downstream effector for the small GTPase Rho (RHOA; 165390). ROCK1 is involved in a wide range of physiologic and pathologic processes that require remodeling of the actin cytoskeleton and the formation of actomyosin bundles, including cell contractility and migration (summary by Shimizu et al., 2005).

CLONING

The small GTPase Rho regulates formation of focal adhesions and stress fibers of fibroblasts, as well as adhesion and aggregation of platelets and lymphocytes by shuttling between the inactive GDP-bound form and the active GTP-bound form. Rho is also essential in cytokinesis and plays a role in transcriptional activation by serum response factor (600589). Ishizaki et al. (1996) identified the protein serine/threonine kinase ROCK1, which they called p160-ROCK, that is activated when bound to the GTP-bound form of Rho. Fujisawa et al. (1996) reported that the full-length 1,354-amino acid human ROCK1 protein has an N-terminal kinase domain, followed by a 600-amino acid alpha-helical region, a pleckstrin (PLEK; 173570) homology domain, and a C-terminal cysteine-rich region. The alpha-helical region includes a cysteine-rich zinc finger. Fujisawa et al. (1996) localized the Rho-binding domain of ROCK1 to residues 934 to 1015, near the C-terminal end of the alpha-helical region. By X-gal staining of Rock1 +/- mouse embryos, Shimizu et al. (2005) found widespread Rock1 expression, with staining detected in skin, heart, aorta, umbilical blood vessels, and dorsal root ganglia.

MAPPING

Hartz (2014) mapped the ROCK1 gene to chromosome 18q11.1 based on an alignment of the ROCK1 sequence (GenBank GENBANK AB208965) and the genomic sequence (GRCh37).

GENE FUNCTION

Maekawa et al. (1999) demonstrated that ROCK1 phosphorylates and activates LIM kinase (see 601329) which, in turn, phosphorylates cofilin (601442), inhibiting its actin-depolymerizing activity. They diagrammed proposed signaling pathways for Rho-induced remodeling of the actin cytoskeleton in their Figure 3C. Bito et al. (2000) found that up- and downregulation of Rock1 in cultured mouse cerebellar granule neurons during the first day in vitro affected axon numbers and growth cone size. Inhibition of endogenous Rock1 was sufficient to initiate formation of axonal processes and to facilitate axonal maturation during early stages of axonogenesis, with little effect on axon elongation. Rock1 also negatively controlled the size and motility of growth cones at the tip of extending axons. Anderson and SundarRaj (2001) noted that increased expression of ROCK1 is associated with limbal to corneal epithelial transition on the ocular surface. In a study of the expression of ROCK1 during the cell cycle of the corneal epithelium, they found that levels of ROCK1 were significantly lower in the G1 phase than in the S and G0 phases. Downregulation of ROCK1 during the G1 phase is due in part to the decreased levels of its mRNA. The authors concluded that ROCK1 may have a role in the progression of the cell cycle in the corneal epithelial cells as they migrate centripetally from the limbus across the corneal surface. Nakamura et al. (2001) studied the role of Rho in the migration of corneal epithelial cells in rabbit. They detected both ROCK1 and ROCK2 (604002) in the corneal epithelium at protein and mRNA levels. They found that exoenzyme C3, a Rho inhibitor, inhibits corneal epithelial migration in a ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Dec. 2, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

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 601702 was added.