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ROCK2 (Rho-associated, coiled-coil containing protein kinase 2)

Written2012-12Carmen Chak-Lui Wong, Irene Oi-Lin Ng
Department of Pathology, State Key Laboratory for Liver Research, The University of, Hong Kong, Hong Kong, China

(Note : for Links provided by Atlas : click)

Identity

Other aliasROCK-II
HGNC (Hugo) ROCK2
LocusID (NCBI) 9475
Atlas_Id 43474
Location 2p25.1  [Link to chromosome band 2p25]
Location_base_pair Starts at 11179759 and ends at 11345407 bp from pter ( according to hg19-Feb_2009)  [Mapping ROCK2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
PIWIL2 (8p21.3) / ROCK2 (2p25.1)ROCK2 (2p25.1) / CC2D2A (4p15.32)ROCK2 (2p25.1) / CMKLR1 (12q23.3)
ROCK2 (2p25.1) / DTNB (2p23.3)ROCK2 (2p25.1) / NBAS (2p24.3)ROCK2 (2p25.1) / NTSR2 (2p25.1)
ROCK2 (2p25.1) / SH3YL1 (2p25.3)

DNA/RNA

Note ROCK2 was first identified as a target of active RhoA in an expression screening assay from a rat brain cDNA library (Leung et al. 1995).
Description The ROCK2 gene is 4164 bp long which encodes 1388 amino acids producing a protein of 160 kDa (UniGene: Hs.681743). The ROCK2 gene comprises 33 exons.

Protein

Note ROCK2 is a 160 kDa serine/threonine kinase which is composed of a kinase domain (44-415 aa) at the amino-terminus, a rho-binding domain (981-1046 aa), and a pleckstrin homology (PH) domain with a cysteine-rich region at the carboxyl-terminus (1152-1350 aa). A coiled-coil inhibitory structure was predicted to form between the kinase domain and the PH domain. ROCK2 exists in an auto-inhibitory form which could be released when active form of RhoA (RhoA-GTP) binds to the RBD domain of ROCK2. The functional domains of ROCK2 have unique roles such as protein-protein interaction, cellular localization, and regulation of ROCK2 activity. Kinase domain of ROCK2 is the key domain conferring the most important function of ROCK2 which is the phosphorylation and activation of its downstream substrates (Leung et al., 1995). PH domain of ROCK2 is responsible for lipid binding and membrane localization of ROCK2 (Miyazaki et al., 2006). PH domain of a ROCK2 homolog also facilitates the interaction with other proteins such as filamin A, a protein critical to actin cytoskeleton remodeling (Ueda et al., 2003).
 
  Schematic diagram of ROCK2. RBD: rho-binding domain; PH: pleckstrin homology; C1: cysteine-rich region.
Expression Very few studies have demonstrated the distinctive roles of ROCK1 and ROCK2; however, their differential tissue distribution indicates that they participate in different physiological functions. ROCK1 and ROCK2 are ubiquitously expressed in all tissues. Earlier studies using Northern blot analysis demonstrated that ROCK1 mRNA expression was especially abundant in testis, liver, and lung while ROCK2 mRNA expression was especially abundant in brain and muscle (Leung et al., 1996).
Regulation: The most common regulatory mechanism of ROCK2 is mediated by RhoGTPases whose activity exchanges between a GTP-bound active form and a GDP-bound inactive form. RhoA-GTP binds to the RBD domain of ROCK and releases the kinase domain of ROCK leading to the activation of ROCK (Leung et al., 1995). In addition to this classical model of activity regulation, ROCK2 can also be activated by lipids such as arachidonic acid (Feng et al., 1999). The ROCK2 kinase domain can also be released when the C-terminus of ROCK2 is cleaved by granzyme B (Sebbagh et al., 2005). Furthermore, Polo-like kinase-1 (Plk1) interacts with and phosphorylates ROCK2 at Threonine 967, Serine 1099, Serine 1133, and S1374 and activates ROCK2 (Lowery et al., 2007).
Recent studies have demonstrated that ROCK2 is also regulated at the expression level. Two microRNAs (miRNAs), miR-139 and miR-124, have independently been shown to interact with the 3'untranslated region of ROCK2 and subsequently suppress ROCK2 expression in hepatocellular carcinoma (HCC) cell lines (Wong et al., 2011; Zheng et al., 2012). MiR-139 and miR-124 have been shown to be downregulated in human HCCs and their expression levels inversely correlated with ROCK2 protein expression in human HCC samples (Wong et al., 2011; Zheng et al., 2012).
Localisation ROCK2 is mainly found in the cytoplasm in most cell types. It was reported that overexpression of a dominant-active form of RhoA re-localized ROCK2 to the membranous actin filaments in a cervical cancer cell line, HeLa (Leung et al., 1995). A study has also shown that ROCK2 could be found in the nuclei in multiple cell types such as human keratinocytes, mouse mammary epithelial cells, osteoblasts, and mouse fibroblasts (Tanaka et al., 2006). ROCK2 was also found to be located in the centrosome in fibroblasts (Ma et al., 2006; Wang et al., 2011).
Function ROCK2 are responsible for many key cellular processes including cell migration and invasion (Croft et al., 2004), apoptosis (Sebbagh et al., 2005), centrosome duplication (Ma et al., 2006), and cytokinesis (Lowery et al., 2007).
The best well-characterized function of ROCK is contributed by the kinase domain for its ability to phosphorylate the serine/threonine residues of downstream substrates that are important for actin cytoskeleton organization. The most well-known substrates of ROCK include myosin light chain 2 (MLC2) and myosin phosphatase 1 (MYPT1) which regulate actomyosin contractility in cells (Amano et al., 1996). Other ROCK substrates include cofilin and LIM kinases, responsible for actin polymerization and depolymerization (Yang et al., 1998; Sumi et al., 1999; Ohashi et al., 2000; Sumi et al., 2001); vimentin (Goto et al., 1998), responsible for actin filament formation; adducin, responsible for membrane ruffles formation (Fukata et al., 1999); calponin, responsible for actin filament binding (Kaneko et al., 2000); ezrin, responsible for anchoring the cytoskeleton to the cell membrane and the formation of focal adhesion molecules (Matsui et al., 1998; Tran Quang et al., 2000).
In addition to cell movement, ROCK2 was shown to be important in keratinocyte differentiation (McMullan et al., 2003). Also, Plk1-mediated phosphorylation and activation of ROCK2 induced cytokinesis (Lowery et al., 2007). Nuclear function of ROCK2 was first reported when ROCK2 was found to be a binding partner of p300 acetyltransferase (Tanaka et al., 2006). Nuclear ROCK2 phosphorylated p300 and activated p300-mediated transcription (Tanaka et al., 2006). Centrosomal ROCK2 interacted with nucleophosmin/B23 and BRCA2 proteins for centrosome duplication (Ma et al., 2006; Wang et al., 2011).
ROCK2 also regulates the extracellular matrix. Expression of conditional active ROCK2 construct has been shown to activate MYPT and MLC and drive actomyosin contraction in mouse skin, thereby modifying the ECM through increased collagen deposition and tissue stiffness (Samuel et al., 2011). Along with the ECM modification, activation of ROCK2 may also increase nuclear accumulation and activity of β-catenin. Activation of β-catenin can elevate epidermal cell proliferation rate, subsequently contributing to epidermal hyperplasia and tumor growth (Samuel et al., 2011).
Homology ROCK2 shares close homology with another protein called ROCK1. ROCK1 and ROCK2 are 65% homologous in human; particularly, their kinase domains are 87% homologous (Leung et al., 1996). Due to their high degree of homology, ROCK1 and ROCK2 are regulated by common mechanisms and share many common substrates.

Implicated in

Note
  
Entity Solid cancers
Note ROCK, in general, has been shown to be implicated in various cancer cell line models; however, only a few studies focus on the expression and roles of ROCK2 in cancers.
  
  
Entity Colorectal cancer
Note In a subcutaneous tumor model in nude mice, conditional expression of active ROCK2 construct in colorectal cancer cell lines has been demonstrated to enhance angiogenesis and cancer cell invasion into the surrounding stromal tissues (Croft et al., 2004).
  
  
Entity Hepatocellular carcinoma
Note ROCK2 protein was shown to be over-expressed in 54% (22/41 cases) of human hepatocellular carcinoma (HCC) as compared with their corresponding non-tumorous liver tissues by Western blot analysis (Wong et al., 2009). Over-expression of ROCK2 in HCC was associated with the presence of tumor microsatellite formation, an important clinicopathological feature of aggressive HCC and an indicator of intrahepatic metastasis in human HCC (Wong et al., 2009). Knockdown of ROCK2 in human HCC cell lines suppressed stress fiber and focal adhesion formation, as well as actomyosin contractility in HCC cells, thereby retarding HCC cell invasion in vitro and in vivo (Wong et al., 2009).
  
  
Entity Squamous skin carcinomas
Note Immunohistochemical study using an antibody with reactivity towards both ROCK1 and ROCK2 indicates that high ROCK expression was detected in 40 cases of human squamous skin carcinomas (Samuel et al., 2011). Along with this finding, phosphorylation of MYPT, as a reflection of ROCK activity, was also detected in these cases of carcinoma (Samuel et al., 2011).
  
  
Entity Testicular cancer
Note ROCK2 protein was shown in Western blot analysis to be overexpressed in testicular cancers as compared to non-tumorous tissues in a cohort of 57 patients (Kamai et al., 2004). ROCK2 protein expression was significantly higher in patients with recurrent testicular cancers than those without sign of recurrence after treatment (Kamai et al., 2004).
  
  
Entity Breast cancer
Note It has long been challenging to detect the ROCK activity in human clinical specimens owing to the fact that ROCK activity declines rapidly in clinical specimens after resection. Also, the phosphorylation sites in ROCK, which truly reflect its activity status, have not been identified or extensively studied. Recently, a study has demonstrated that the activity status of ROCK2 can be reflected by the phosphorylation level of ROCK2 at Ser1366. Immunohistochemical staining shows that phosphorylation of ROCK2 at Ser1366 was increased in 2 cases of breast cancer tissues as compared to their normal counterparts (Chuang et al., 2012).
  

To be noted

Drugs
Multiple ROCK inhibitors are available; but none of these inhibitors specifically discriminate the two homologs. The common commercially available ROCK inhibitors are pyridine or isoquinoline-based small molecule inhibitors. Both inhibitors compete for the ATP-binding sites of ROCK. Y27632 is the most commonly used pyridine-based ROCK inhibitor and has been shown to possess significant selectivity towards ROCK than other protein kinases (Davies et al., 2000; Ishizaki et al., 2000). Fasudil, the most common isoquinoline-based ROCK inhibitor, was first used in the clinic in 1993 for the treatment of cerebral vasospasm in Japan and was later discovered to possess inhibitory effect on ROCK (Shibuya and Suzuki, 1993). Clinical experience of fasudil shows that it is well tolerated in the human body; however, it is less selective than Y27632. Therefore, Y27632 is more widely used in basic research whilst fasudil is more widely used in the clinic. The half-life of Y27632 in vivo is around 2 hours (Takamura et al., 2001). Studies have demonstrated that continuous delivery of Y27632 by osmotic pump profoundly suppressed the formation of metastases in syngeneic rats that were peritoneally implanted with rat hepatoma cells or in SCID mice that were orthotopically implanted with human HCC cells (Itoh et al., 1999; Takamura et al., 2001). So far, ROCK inhibitors have not been used in the clinic for cancer treatment. Further investigation on the efficacy of ROCK inhibitors in cancer treatments is much warranted.

Bibliography

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Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis.
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Rho-associated kinase of chicken gizzard smooth muscle.
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PMID 9920927
 
Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility.
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J Cell Biol. 1999 Apr 19;145(2):347-61.
PMID 10209029
 
Phosphorylation of vimentin by Rho-associated kinase at a unique amino-terminal site that is specifically phosphorylated during cytokinesis.
Goto H, Kosako H, Tanabe K, Yanagida M, Sakurai M, Amano M, Kaibuchi K, Inagaki M.
J Biol Chem. 1998 May 8;273(19):11728-36.
PMID 9565595
 
Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases.
Ishizaki T, Uehata M, Tamechika I, Keel J, Nonomura K, Maekawa M, Narumiya S.
Mol Pharmacol. 2000 May;57(5):976-83.
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An essential part for Rho-associated kinase in the transcellular invasion of tumor cells.
Itoh K, Yoshioka K, Akedo H, Uehata M, Ishizaki T, Narumiya S.
Nat Med. 1999 Feb;5(2):221-5.
PMID 9930872
 
Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer.
Kamai T, Yamanishi T, Shirataki H, Takagi K, Asami H, Ito Y, Yoshida K.
Clin Cancer Res. 2004 Jul 15;10(14):4799-805.
PMID 15269155
 
Identification of calponin as a novel substrate of Rho-kinase.
Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, Kaibuchi K.
Biochem Biophys Res Commun. 2000 Jun 24;273(1):110-6.
PMID 10873572
 
The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton.
Leung T, Chen XQ, Manser E, Lim L.
Mol Cell Biol. 1996 Oct;16(10):5313-27.
PMID 8816443
 
A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes.
Leung T, Manser E, Tan L, Lim L.
J Biol Chem. 1995 Dec 8;270(49):29051-4.
PMID 7493923
 
Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate.
Lowery DM, Clauser KR, Hjerrild M, Lim D, Alexander J, Kishi K, Ong SE, Gammeltoft S, Carr SA, Yaffe MB.
EMBO J. 2007 May 2;26(9):2262-73. Epub 2007 Apr 19.
PMID 17446864
 
Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication.
Ma Z, Kanai M, Kawamura K, Kaibuchi K, Ye K, Fukasawa K.
Mol Cell Biol. 2006 Dec;26(23):9016-34. Epub 2006 Oct 2.
PMID 17015463
 
Rho-kinase phosphorylates COOH-terminal threonines of ezrin/radixin/moesin (ERM) proteins and regulates their head-to-tail association.
Matsui T, Maeda M, Doi Y, Yonemura S, Amano M, Kaibuchi K, Tsukita S, Tsukita S.
J Cell Biol. 1998 Feb 9;140(3):647-57.
PMID 9456324
 
Keratinocyte differentiation is regulated by the Rho and ROCK signaling pathway.
McMullan R, Lax S, Robertson VH, Radford DJ, Broad S, Watt FM, Rowles A, Croft DR, Olson MF, Hotchin NA.
Curr Biol. 2003 Dec 16;13(24):2185-9.
PMID 14680635
 
Dynamics of RhoA and ROKalpha translocation in single living cells.
Miyazaki K, Komatsu S, Ikebe M.
Cell Biochem Biophys. 2006;45(3):243-54.
PMID 16845171
 
Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop.
Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K.
J Biol Chem. 2000 Feb 4;275(5):3577-82.
PMID 10652353
 
Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth.
Samuel MS, Lopez JI, McGhee EJ, Croft DR, Strachan D, Timpson P, Munro J, Schroder E, Zhou J, Brunton VG, Barker N, Clevers H, Sansom OJ, Anderson KI, Weaver VM, Olson MF.
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Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner.
Sebbagh M, Hamelin J, Bertoglio J, Solary E, Breard J.
J Exp Med. 2005 Feb 7;201(3):465-71.
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Treatment of cerebral vasospasm by a protein kinase inhibitor AT 877.
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No To Shinkei. 1993 Sep;45(9):819-24.
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Specific activation of LIM kinase 2 via phosphorylation of threonine 505 by ROCK, a Rho-dependent protein kinase.
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Inhibition of intrahepatic metastasis of human hepatocellular carcinoma by Rho-associated protein kinase inhibitor Y-27632.
Takamura M, Sakamoto M, Genda T, Ichida T, Asakura H, Hirohashi S.
Hepatology. 2001 Mar;33(3):577-81.
PMID 11230737
 
Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.
Tanaka T, Nishimura D, Wu RC, Amano M, Iso T, Kedes L, Nishida H, Kaibuchi K, Hamamori Y.
J Biol Chem. 2006 Jun 2;281(22):15320-9. Epub 2006 Mar 30.
PMID 16574662
 
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Tran Quang C, Gautreau A, Arpin M, Treisman R.
EMBO J. 2000 Sep 1;19(17):4565-76.
PMID 10970850
 
The carboxy-terminal pleckstrin homology domain of ROCK interacts with filamin-A.
Ueda K, Ohta Y, Hosoya H.
Biochem Biophys Res Commun. 2003 Feb 21;301(4):886-90.
PMID 12589795
 
BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2.
Wang HF, Takenaka K, Nakanishi A, Miki Y.
Cancer Res. 2011 Jan 1;71(1):68-77. doi: 10.1158/0008-5472.CAN-10-0030. Epub 2010 Nov 16.
PMID 21084279
 
The microRNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulating Rho-kinase 2.
Wong CC, Wong CM, Tung EK, Au SL, Lee JM, Poon RT, Man K, Ng IO.
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Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization.
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PMID 9655398
 
The putative tumour suppressor microRNA-124 modulates hepatocellular carcinoma cell aggressiveness by repressing ROCK2 and EZH2.
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PMID 21672940
 

Citation

This paper should be referenced as such :
Wong, CCL ; Ng, IOL
ROCK2 (Rho-associated, coiled-coil containing protein kinase 2)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(7):441-444.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/ROCK2ID43474ch2p25.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Squamous Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)ROCK2   10252
Cards
AtlasROCK2ID43474ch2p25
Entrez_Gene (NCBI)ROCK2  9475  Rho associated coiled-coil containing protein kinase 2
AliasesROCK-II
GeneCards (Weizmann)ROCK2
Ensembl hg19 (Hinxton)ENSG00000134318 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000134318 [Gene_View]  chr2:11179759-11345407 [Contig_View]  ROCK2 [Vega]
ICGC DataPortalENSG00000134318
TCGA cBioPortalROCK2
AceView (NCBI)ROCK2
Genatlas (Paris)ROCK2
WikiGenes9475
SOURCE (Princeton)ROCK2
Genetics Home Reference (NIH)ROCK2
Genomic and cartography
GoldenPath hg38 (UCSC)ROCK2  -     chr2:11179759-11345407 -  2p25.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ROCK2  -     2p25.1   [Description]    (hg19-Feb_2009)
EnsemblROCK2 - 2p25.1 [CytoView hg19]  ROCK2 - 2p25.1 [CytoView hg38]
Mapping of homologs : NCBIROCK2 [Mapview hg19]  ROCK2 [Mapview hg38]
OMIM604002   
Gene and transcription
Genbank (Entrez)AB014519 AK299296 AK310358 AL049383 BC111801
RefSeq transcript (Entrez)NM_001321643 NM_004850
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)ROCK2
Cluster EST : UnigeneHs.681743 [ NCBI ]
CGAP (NCI)Hs.681743
Alternative Splicing GalleryENSG00000134318
Gene ExpressionROCK2 [ NCBI-GEO ]   ROCK2 [ EBI - ARRAY_EXPRESS ]   ROCK2 [ SEEK ]   ROCK2 [ MEM ]
Gene Expression Viewer (FireBrowse)ROCK2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9475
GTEX Portal (Tissue expression)ROCK2
Human Protein AtlasENSG00000134318-ROCK2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO75116   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO75116  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO75116
Splice isoforms : SwissVarO75116
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusO75116
Domaine pattern : Prosite (Expaxy)AGC_KINASE_CTER (PS51285)    PH_DOMAIN (PS50003)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    ZF_DAG_PE_2 (PS50081)   
Domains : Interpro (EBI)AGC-kinase_C    Kinase-like_dom    PE/DAG-bd    PH_dom-like    PH_domain    Prot_kinase_dom    Protein_kinase_ATP_BS    Rho-bd_dom    ROCK1/ROCK2    ROCK2    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)    Rho_Binding (PF08912)   
Domain families : Pfam (NCBI)pfam00069    pfam08912   
Domain families : Smart (EMBL)C1 (SM00109)  PH (SM00233)  S_TK_X (SM00133)  S_TKc (SM00220)  
Conserved Domain (NCBI)ROCK2
DMDM Disease mutations9475
Blocks (Seattle)ROCK2
PDB (SRS)4L6Q    4WOT   
PDB (PDBSum)4L6Q    4WOT   
PDB (IMB)4L6Q    4WOT   
PDB (RSDB)4L6Q    4WOT   
Structural Biology KnowledgeBase4L6Q    4WOT   
SCOP (Structural Classification of Proteins)4L6Q    4WOT   
CATH (Classification of proteins structures)4L6Q    4WOT   
SuperfamilyO75116
Human Protein Atlas [tissue]ENSG00000134318-ROCK2 [tissue]
Peptide AtlasO75116
HPRD04922
IPIIPI00307155   IPI00894514   IPI00894377   IPI00894264   
Protein Interaction databases
DIP (DOE-UCLA)O75116
IntAct (EBI)O75116
FunCoupENSG00000134318
BioGRIDROCK2
STRING (EMBL)ROCK2
ZODIACROCK2
Ontologies - Pathways
QuickGOO75116
Ontology : AmiGOcytokinesis  positive regulation of protein phosphorylation  RNA binding  protein serine/threonine kinase activity  structural molecule activity  protein binding  ATP binding  nucleus  centrosome  cytosol  cytosol  plasma membrane  protein phosphorylation  smooth muscle contraction  I-kappaB kinase/NF-kappaB signaling  Rho protein signal transduction  positive regulation of endothelial cell migration  positive regulation of gene expression  positive regulation of centrosome duplication  negative regulation of angiogenesis  Rho GTPase binding  regulation of cell adhesion  cortical actin cytoskeleton organization  cortical actin cytoskeleton organization  regulation of actin cytoskeleton organization  negative regulation of myosin-light-chain-phosphatase activity  negative regulation of myosin-light-chain-phosphatase activity  cytoplasmic ribonucleoprotein granule  viral RNA genome replication  regulation of circadian rhythm  regulation of keratinocyte differentiation  metal ion binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  rhythmic process  centrosome duplication  regulation of stress fiber assembly  regulation of focal adhesion assembly  cellular response to testosterone stimulus  Rho-dependent protein serine/threonine kinase activity  establishment of protein localization to plasma membrane  establishment of protein localization to plasma membrane  regulation of establishment of endothelial barrier  regulation of establishment of endothelial barrier  negative regulation of bicellular tight junction assembly  regulation of establishment of cell polarity  regulation of cell motility  
Ontology : EGO-EBIcytokinesis  positive regulation of protein phosphorylation  RNA binding  protein serine/threonine kinase activity  structural molecule activity  protein binding  ATP binding  nucleus  centrosome  cytosol  cytosol  plasma membrane  protein phosphorylation  smooth muscle contraction  I-kappaB kinase/NF-kappaB signaling  Rho protein signal transduction  positive regulation of endothelial cell migration  positive regulation of gene expression  positive regulation of centrosome duplication  negative regulation of angiogenesis  Rho GTPase binding  regulation of cell adhesion  cortical actin cytoskeleton organization  cortical actin cytoskeleton organization  regulation of actin cytoskeleton organization  negative regulation of myosin-light-chain-phosphatase activity  negative regulation of myosin-light-chain-phosphatase activity  cytoplasmic ribonucleoprotein granule  viral RNA genome replication  regulation of circadian rhythm  regulation of keratinocyte differentiation  metal ion binding  vascular endothelial growth factor receptor signaling pathway  ephrin receptor signaling pathway  rhythmic process  centrosome duplication  regulation of stress fiber assembly  regulation of focal adhesion assembly  cellular response to testosterone stimulus  Rho-dependent protein serine/threonine kinase activity  establishment of protein localization to plasma membrane  establishment of protein localization to plasma membrane  regulation of establishment of endothelial barrier  regulation of establishment of endothelial barrier  negative regulation of bicellular tight junction assembly  regulation of establishment of cell polarity  regulation of cell motility  
Pathways : BIOCARTACCR3 signaling in Eosinophils [Genes]   
Pathways : KEGG   
REACTOMEO75116 [protein]
REACTOME PathwaysR-HSA-5627117 [pathway]   
NDEx NetworkROCK2
Atlas of Cancer Signalling NetworkROCK2
Wikipedia pathwaysROCK2
Orthology - Evolution
OrthoDB9475
GeneTree (enSembl)ENSG00000134318
Phylogenetic Trees/Animal Genes : TreeFamROCK2
HOVERGENO75116
HOGENOMO75116
Homologs : HomoloGeneROCK2
Homology/Alignments : Family Browser (UCSC)ROCK2
Gene fusions - Rearrangements
Fusion : MitelmanROCK2/DTNB [2p25.1/2p23.3]  
Fusion : MitelmanROCK2/NTSR2 [2p25.1/2p25.1]  [t(2;2)(p25;p25)]  
Fusion : MitelmanROCK2/SH3YL1 [2p25.1/2p25.3]  [t(2;2)(p25;p25)]  
Fusion: TCGA_MDACCROCK2 2p25.1 DTNB 2p23.3 LUAD
Fusion: TCGA_MDACCROCK2 2p25.1 NTSR2 2p25.1 PRAD
Tumor Fusion PortalROCK2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerROCK2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ROCK2
dbVarROCK2
ClinVarROCK2
1000_GenomesROCK2 
Exome Variant ServerROCK2
ExAC (Exome Aggregation Consortium)ENSG00000134318
GNOMAD BrowserENSG00000134318
Genetic variants : HAPMAP9475
Genomic Variants (DGV)ROCK2 [DGVbeta]
DECIPHERROCK2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisROCK2 
Mutations
ICGC Data PortalROCK2 
TCGA Data PortalROCK2 
Broad Tumor PortalROCK2
OASIS PortalROCK2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICROCK2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDROCK2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch ROCK2
DgiDB (Drug Gene Interaction Database)ROCK2
DoCM (Curated mutations)ROCK2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)ROCK2 (select a term)
intoGenROCK2
NCG5 (London)ROCK2
Cancer3DROCK2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604002   
Orphanet
DisGeNETROCK2
MedgenROCK2
Genetic Testing Registry ROCK2
NextProtO75116 [Medical]
TSGene9475
GENETestsROCK2
Target ValidationROCK2
Huge Navigator ROCK2 [HugePedia]
snp3D : Map Gene to Disease9475
BioCentury BCIQROCK2
ClinGenROCK2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9475
Chemical/Pharm GKB GenePA34624
Clinical trialROCK2
Miscellaneous
canSAR (ICR)ROCK2 (select the gene name)
Probes
Litterature
PubMed150 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineROCK2
EVEXROCK2
GoPubMedROCK2
iHOPROCK2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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