ROCK2_MOUSE
ID ROCK2_MOUSE Reviewed; 1388 AA.
AC P70336; A5XDA7; Q8BR64; Q8CBR0;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Rho-associated protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 2;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase II;
DE Short=ROCK-II;
DE AltName: Full=p164 ROCK-2;
GN Name=Rock2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=8772201; DOI=10.1016/0014-5793(96)00811-3;
RA Nakagawa O., Fujisawa K., Ishizaki T., Saito Y., Nakao K., Narumiya S.;
RT "ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming
RT protein serine/threonine kinase in mice.";
RL FEBS Lett. 392:189-193(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1144 (ISOFORM 2), PHOSPHORYLATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=17606625; DOI=10.1128/mcb.01735-06;
RA Pelosi M., Marampon F., Zani B.M., Prudente S., Perlas E., Caputo V.,
RA Cianetti L., Berno V., Narumiya S., Kang S.W., Musaro A., Rosenthal N.;
RT "ROCK2 and its alternatively spliced isoform ROCK2m positively control the
RT maturation of the myogenic program.";
RL Mol. Cell. Biol. 27:6163-6176(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 633-1388 AND 677-1388.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12832488; DOI=10.1128/mcb.23.14.5043-5055.2003;
RA Thumkeo D., Keel J., Ishizaki T., Hirose M., Nonomura K., Oshima H.,
RA Oshima M., Taketo M.M., Narumiya S.;
RT "Targeted disruption of the mouse rho-associated kinase 2 gene results in
RT intrauterine growth retardation and fetal death.";
RL Mol. Cell. Biol. 23:5043-5055(2003).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15753128; DOI=10.1083/jcb.200411179;
RA Shimizu Y., Thumkeo D., Keel J., Ishizaki T., Oshima H., Oshima M.,
RA Noda Y., Matsumura F., Taketo M.M., Narumiya S.;
RT "ROCK-I regulates closure of the eyelids and ventral body wall by inducing
RT assembly of actomyosin bundles.";
RL J. Cell Biol. 168:941-953(2005).
RN [6]
RP CLEAVAGE BY GRANZYME B.
RX PubMed=15699075; DOI=10.1084/jem.20031877;
RA Sebbagh M., Hamelin J., Bertoglio J., Solary E., Breard J.;
RT "Direct cleavage of ROCK II by granzyme B induces target cell membrane
RT blebbing in a caspase-independent manner.";
RL J. Exp. Med. 201:465-471(2005).
RN [7]
RP FUNCTION.
RX PubMed=19181962; DOI=10.1152/ajpheart.01038.2008;
RA Kroll J., Epting D., Kern K., Dietz C.T., Feng Y., Hammes H.P., Wieland T.,
RA Augustin H.G.;
RT "Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven
RT retinal neovascularization and sprouting angiogenesis.";
RL Am. J. Physiol. 296:H893-H899(2009).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18718479; DOI=10.1016/j.neuropharm.2008.07.031;
RA Zhou Z., Meng Y., Asrar S., Todorovski Z., Jia Z.;
RT "A critical role of Rho-kinase ROCK2 in the regulation of spine and
RT synaptic function.";
RL Neuropharmacology 56:81-89(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137 AND SER-1374, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION.
RX PubMed=20697158; DOI=10.1172/jci42856;
RA Biswas P.S., Gupta S., Chang E., Song L., Stirzaker R.A., Liao J.K.,
RA Bhagat G., Pernis A.B.;
RT "Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and
RT the development of autoimmunity in mice.";
RL J. Clin. Invest. 120:3280-3295(2010).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=23172836; DOI=10.1161/circulationaha.112.135608;
RA Saito T., Hirano M., Ide T., Ichiki T., Koibuchi N., Sunagawa K.,
RA Hirano K.;
RT "Pivotal role of Rho-associated kinase 2 in generating the intrinsic
RT circadian rhythm of vascular contractility.";
RL Circulation 127:104-114(2013).
RN [12]
RP INTERACTION WITH PJVK.
RX PubMed=28089576; DOI=10.1016/j.neuroscience.2016.12.055;
RA Harris S.L., Kazmierczak M., Pangrsic T., Shah P., Chuchvara N.,
RA Barrantes-Freer A., Moser T., Schwander M.;
RT "Conditional deletion of pejvakin in adult outer hair cells causes
RT progressive hearing loss in mice.";
RL Neuroscience 344:380-393(2017).
CC -!- FUNCTION: Protein kinase which is a key regulator of actin cytoskeleton
CC and cell polarity. Involved in regulation of smooth muscle contraction,
CC actin cytoskeleton organization, stress fiber and focal adhesion
CC formation, neurite retraction, cell adhesion and motility via
CC phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN,
CC MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4.
CC Acts as a negative regulator of VEGF-induced angiogenic endothelial
CC cell activation. Positively regulates the activation of p42/MAPK1-
CC p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays
CC an important role in the timely initiation of centrosome duplication.
CC Inhibits keratinocyte terminal differentiation. May regulate closure of
CC the eyelids and ventral body wall through organization of actomyosin
CC bundles. Plays a critical role in the regulation of spine and synaptic
CC properties in the hippocampus. Plays a role in placental homeostasis
CC during the perinatal period. Plays an important role in generating the
CC circadian rhythm of the aortic myofilament Ca(2+) sensitivity and
CC vascular contractility by modulating the myosin light chain
CC phosphorylation. {ECO:0000269|PubMed:12832488,
CC ECO:0000269|PubMed:18718479, ECO:0000269|PubMed:19181962,
CC ECO:0000269|PubMed:20697158, ECO:0000269|PubMed:23172836}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by RHOA binding. Inhibited by Y-27632
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with IRS1. Interacts with
CC RAF1 (By similarity). Interacts with RHOA (activated by GTP), RHOB and
CC RHOC (By similarity). Interacts with PPP1R12A (By similarity).
CC Interacts with EP300 (By similarity). Interacts with CHORDC1 (By
CC similarity). Interacts with BRCA2 (By similarity). Interacts with NPM1;
CC this interaction enhances ROCK2 activity (By similarity). Interacts
CC with SORL1 (By similarity). Interacts with PJVK (PubMed:28089576).
CC {ECO:0000250|UniProtKB:O75116, ECO:0000250|UniProtKB:Q28021,
CC ECO:0000250|UniProtKB:Q62868, ECO:0000269|PubMed:28089576}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Cell membrane; Peripheral
CC membrane protein. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome {ECO:0000250}.
CC Note=Cytoplasmic, and associated with actin microfilaments and the
CC plasma membrane. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Cell membrane; Peripheral
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P70336-1; Sequence=Displayed;
CC Name=2; Synonyms=ROCK2m;
CC IsoId=P70336-2; Sequence=VSP_041818, VSP_041819;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, heart, lung, liver,
CC stomach, spleen, kidney, testis, muscle, embryo and placenta. Isoform 2
CC is expressed predominantly in the skeletal muscle.
CC {ECO:0000269|PubMed:17606625, ECO:0000269|PubMed:8772201}.
CC -!- INDUCTION: Expression oscillates in a circadian manner in the aorta.
CC {ECO:0000269|PubMed:23172836}.
CC -!- DOMAIN: An interaction between Thr-414 and Asp-48 is essential for
CC kinase activity and dimerization. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding
CC to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation
CC by PTPN11 stimulates its RHOA binding activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Cleaved by granzyme B during apoptosis. This leads to constitutive
CC activation of the kinase and membrane blebbing.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit both EOB (eyes open at birth) and
CC omphalocele phenotypes as a result of disorganization of actomyosin
CC cables in the eyelid epithelium and defective actin assembly in the
CC umbilical ring. Mice are impaired in both basal synaptic transmission
CC and hippocampal long-term potentiation (LTP). Embryos manifest
CC extensive thrombus formation in the placenta, resulting in placental
CC dysfunction, intrauterine growth retardation, and fetal death.
CC {ECO:0000269|PubMed:12832488, ECO:0000269|PubMed:15753128,
CC ECO:0000269|PubMed:18718479}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; U58513; AAC53133.1; -; mRNA.
DR EMBL; DQ864977; ABI75318.1; -; mRNA.
DR EMBL; AK045517; BAC32403.1; -; mRNA.
DR EMBL; AK035509; BAC29084.1; -; mRNA.
DR CCDS; CCDS36410.1; -. [P70336-1]
DR PIR; S74245; S74245.
DR RefSeq; NP_033098.2; NM_009072.2.
DR AlphaFoldDB; P70336; -.
DR SMR; P70336; -.
DR BioGRID; 202951; 47.
DR CORUM; P70336; -.
DR IntAct; P70336; 7.
DR MINT; P70336; -.
DR STRING; 10090.ENSMUSP00000020904; -.
DR GlyConnect; 2685; 7 N-Linked glycans (1 site).
DR GlyGen; P70336; 1 site, 7 N-linked glycans (1 site).
DR iPTMnet; P70336; -.
DR PhosphoSitePlus; P70336; -.
DR SwissPalm; P70336; -.
DR EPD; P70336; -.
DR jPOST; P70336; -.
DR MaxQB; P70336; -.
DR PaxDb; P70336; -.
DR PeptideAtlas; P70336; -.
DR PRIDE; P70336; -.
DR ProteomicsDB; 300567; -. [P70336-1]
DR ProteomicsDB; 301592; -. [P70336-2]
DR DNASU; 19878; -.
DR GeneID; 19878; -.
DR KEGG; mmu:19878; -.
DR UCSC; uc007ncg.1; mouse. [P70336-2]
DR CTD; 9475; -.
DR MGI; MGI:107926; Rock2.
DR eggNOG; KOG0612; Eukaryota.
DR InParanoid; P70336; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; P70336; -.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-MMU-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR Reactome; R-MMU-9013422; RHOBTB1 GTPase cycle.
DR BioGRID-ORCS; 19878; 8 hits in 76 CRISPR screens.
DR ChiTaRS; Rock2; mouse.
DR PRO; PR:P70336; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P70336; protein.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0031616; C:spindle pole centrosome; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:ARUK-UCL.
DR GO; GO:0072518; F:Rho-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IGI:BHF-UCL.
DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IMP:ARUK-UCL.
DR GO; GO:1905145; P:cellular response to acetylcholine; IMP:ARUK-UCL.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; ISO:MGI.
DR GO; GO:0051298; P:centrosome duplication; IMP:MGI.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IGI:MGI.
DR GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IGI:BHF-UCL.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IGI:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0000281; P:mitotic cytokinesis; IBA:GO_Central.
DR GO; GO:0044788; P:modulation by host of viral process; ISO:MGI.
DR GO; GO:0061157; P:mRNA destabilization; IMP:ARUK-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISO:MGI.
DR GO; GO:0001843; P:neural tube closure; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:1902993; P:positive regulation of amyloid precursor protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; IMP:ARUK-UCL.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0010825; P:positive regulation of centrosome duplication; IMP:MGI.
DR GO; GO:0032723; P:positive regulation of connective tissue growth factor production; ISO:MGI.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; IMP:ARUK-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0090271; P:positive regulation of fibroblast growth factor production; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:ARUK-UCL.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:MGI.
DR GO; GO:0098974; P:postsynaptic actin cytoskeleton organization; IDA:SynGO.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0110061; P:regulation of angiotensin-activated signaling pathway; IMP:ARUK-UCL.
DR GO; GO:1901888; P:regulation of cell junction assembly; IBA:GO_Central.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; IMP:ARUK-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:MGI.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; ISO:MGI.
DR GO; GO:0031644; P:regulation of nervous system process; IMP:ARUK-UCL.
DR GO; GO:0051246; P:regulation of protein metabolic process; IMP:ARUK-UCL.
DR GO; GO:1990776; P:response to angiotensin; IGI:ARUK-UCL.
DR GO; GO:0002931; P:response to ischemia; IMP:ARUK-UCL.
DR GO; GO:0071559; P:response to transforming growth factor beta; IGI:ARUK-UCL.
DR GO; GO:0007266; P:Rho protein signal transduction; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006939; P:smooth muscle contraction; IEA:InterPro.
DR CDD; cd00029; C1; 1.
DR CDD; cd11638; HR1_ROCK2; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020684; ROCK1/ROCK2.
DR InterPro; IPR037311; ROCK2_HR1.
DR InterPro; IPR015008; ROCK_Rho-bd_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08912; Rho_Binding; 1.
DR PIRSF; PIRSF037568; Rho_kinase; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51860; REM_1; 1.
DR PROSITE; PS51859; RHO_BD; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Biological rhythms; Cell membrane;
KW Coiled coil; Cytoplasm; Cytoskeleton; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..1388
FT /note="Rho-associated protein kinase 2"
FT /id="PRO_0000086626"
FT DOMAIN 92..354
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 357..425
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 497..573
FT /note="REM-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 979..1047
FT /note="RhoBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01206"
FT DOMAIN 1150..1349
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 1260..1315
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..784
FT /note="Interaction with PPP1R12A"
FT /evidence="ECO:0000250"
FT REGION 373..420
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000250"
FT REGION 512..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 979..1047
FT /note="RHOA binding"
FT /evidence="ECO:0000250"
FT REGION 1345..1388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 439..1131
FT /evidence="ECO:0000255"
FT COMPBIAS 1363..1388
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 214
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 98..106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 1131..1132
FT /note="Cleavage; by granzyme B"
FT MOD_RES 414
FT /note="Phosphothreonine; by ROCK2"
FT /evidence="ECO:0000250|UniProtKB:Q62868"
FT MOD_RES 722
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1149
FT /note="P -> PVHITQSHTMESMSFTYQRSSTSLSIATKPSSSHTLLDFDSEEDSLP
FT YLPSSSEPIST (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17606625"
FT /id="VSP_041818"
FT VAR_SEQ 1388
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17606625"
FT /id="VSP_041819"
SQ SEQUENCE 1388 AA; 160586 MW; 7A4F331165038161 CRC64;
MSRPPPTGKM PGAPEAAPGD GAGAGRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP
ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM
KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFCAFQ DDRYLYMVME YMPGGDLVNL
MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD
ETGMVHCDTA VGTPDYISPE VLKSQGGDGY YGRECDWWSV GVFLFEMLVG DTPFYADSLV
GTYSKIMDHK NSLCFPEDTE ISKHAKNLIC AFLTDREVRL GRNGVEEIKQ HPFFKNDQWN
WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYFRENL
LLSDSPPCRE NDAIQTRKSE ESQEIQKKLY ALEEHLSSEV QAKEELEQKC KSINTRLEKT
AKELEEEITL RKSVESTLRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL
EDLKKRNQSS QISTEKVNQL QKQLDEANAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRISG LEEDLKTGKA
LLAKVELEKR QLQEKLTDLE KEKSNMEIDM TYQLKVIQQS LEQEEAEHKT TKARLADKNK
IYESIEEAKS EAMKEMEKKL LEERSLKQKV ENLLLEAEKR CSILDCDLKQ SQQKLNELLK
QKDVLNEDVR NLTLKIEQET QKRCLMQNDL KMQTQQVNTL KMSEKQIKQE NNHLMEMKMN
LEKQNTELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEENEEK TKLCKELQQK
KQDLQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE
LTEKDTTIAS LEETNRTLTS DVANLANEKE ELNNKLKDSQ EQLSKLKDEE MSAAAIKAQF
EKQLLNERTL KTQAVNKLAE IMNRKEPVKR GSDTDVRRKE KENRKLHMEL KSEREKLTQQ
MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGM DSSSIGSGPG
DAEPDDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EPEFPVEPVG EKSNYICHKG
HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECRRCHIKC HKDHMDKKEE IIAPCKVYYD
ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR
QLAPNKPS
