ID ROCK1_HUMAN Reviewed; 1354 AA. AC Q13464; B0YJ91; Q2KHM4; Q59GZ4; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 229. DE RecName: Full=Rho-associated protein kinase 1; DE EC=2.7.11.1 {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470}; DE AltName: Full=Renal carcinoma antigen NY-REN-35; DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 1; DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase I; DE Short=ROCK-I; DE AltName: Full=p160 ROCK-1; DE Short=p160ROCK; GN Name=ROCK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 187-195; 281-288; 465-473; RP 818-828; 885-893 AND 934-945, FUNCTION, PHOSPHORYLATION, INTERACTION WITH RP RHOA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Leukemia; RX PubMed=8617235; DOI=10.1002/j.1460-2075.1996.tb00539.x; RA Ishizaki T., Maekawa M., Fujisawa K., Okawa K., Iwamatsu A., Fujita A., RA Watanabe N., Saito Y., Kakizuka A., Morii N., Narumiya S.; RT "The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr RT protein kinase homologous to myotonic dystrophy kinase."; RL EMBO J. 15:1885-1893(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 2-13; 85-94; 327-334; 405-415 AND 546-563, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Ramsay A., Leung H.Y.; RL Submitted (MAR-2009) to UniProtKB. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 323-1027. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP ROLE IN SMOOTH MUSCLE CONTRACTION. RX PubMed=9722579; DOI=10.1074/jbc.273.36.23433; RA Van Eyk J.E., Arrell D.K., Foster D.B., Strauss J.D., Heinonen T.Y., RA Furmaniak-Kazmierczak E., Cote G.P., Mak A.S.; RT "Different molecular mechanisms for Rho family GTPase-dependent, Ca2+- RT independent contraction of smooth muscle."; RL J. Biol. Chem. 273:23433-23439(1998). RN [7] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LIMK1 AND LIMK2, AND RP INHIBITION BY Y-27632. RX PubMed=10436159; DOI=10.1126/science.285.5429.895; RA Maekawa M., Ishizaki T., Boku S., Watanabe N., Fujita A., Iwamatsu A., RA Obinata T., Ohashi K., Mizuno K., Narumiya S.; RT "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK RT and LIM-kinase."; RL Science 285:895-898(1999). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH LIMK1. RX PubMed=10652353; DOI=10.1074/jbc.275.5.3577; RA Ohashi K., Nagata K., Maekawa M., Ishizaki T., Narumiya S., Mizuno K.; RT "Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at RT threonine 508 within the activation loop."; RL J. Biol. Chem. 275:3577-3582(2000). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH LIMK2. RX PubMed=11018042; DOI=10.1074/jbc.m007074200; RA Sumi T., Matsumoto K., Nakamura T.; RT "Specific activation of LIM kinase 2 via phosphorylation of threonine 505 RT by ROCK, a Rho-dependent protein kinase."; RL J. Biol. Chem. 276:670-676(2001). RN [11] RP CLEAVAGE BY CASPASE-3, MUTAGENESIS OF ASP-1113, INTERACTION WITH PPP1R12A, RP AND FUNCTION. RX PubMed=11283607; DOI=10.1038/35070019; RA Sebbagh M., Renvoize C., Hamelin J., Riche N., Bertoglio J., Breard J.; RT "Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and RT apoptotic membrane blebbing."; RL Nat. Cell Biol. 3:346-352(2001). RN [12] RP INTERACTION WITH GEM. RX PubMed=11956230; DOI=10.1083/jcb.200111026; RA Ward Y., Yap S.-F., Ravichandran V., Matsumura F., Ito M., Spinelli B., RA Kelly K.; RT "The GTP binding proteins Gem and Rad are negative regulators of the Rho- RT Rho kinase pathway."; RL J. Cell Biol. 157:291-302(2002). RN [13] RP INTERACTION WITH RHOE AND PPP1R12A, AND SUBCELLULAR LOCATION. RX PubMed=12773565; DOI=10.1128/mcb.23.12.4219-4229.2003; RA Riento K., Guasch R.M., Garg R., Jin B., Ridley A.J.; RT "RhoE binds to ROCK I and inhibits downstream signaling."; RL Mol. Cell. Biol. 23:4219-4229(2003). RN [14] RP REVIEW. RX PubMed=12778124; DOI=10.1038/nrm1128; RA Riento K., Ridley A.J.; RT "Rocks: multifunctional kinases in cell behaviour."; RL Nat. Rev. Mol. Cell Biol. 4:446-456(2003). RN [15] RP INTERACTION WITH TSG101. RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850; RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K., RA Sundquist W.I.; RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and RT function in cytokinesis."; RL EMBO J. 26:4215-4227(2007). RN [16] RP FUNCTION, AND INTERACTION WITH DAPK3. RX PubMed=17158456; DOI=10.1074/jbc.m609990200; RA Hagerty L., Weitzel D.H., Chambers J., Fortner C.N., Brush M.H., RA Loiselle D., Hosoya H., Haystead T.A.; RT "ROCK1 phosphorylates and activates zipper-interacting protein kinase."; RL J. Biol. Chem. 282:4884-4893(2007). RN [17] RP FUNCTION, INTERACTION WITH FHOD1, AND SUBCELLULAR LOCATION. RX PubMed=18694941; DOI=10.1074/jbc.m801800200; RA Hannemann S., Madrid R., Stastna J., Kitzing T., Gasteier J., RA Schoenichen A., Bouchet J., Jimenez A., Geyer M., Grosse R., Benichou S., RA Fackler O.T.; RT "The diaphanous-related formin FHOD1 associates with ROCK1 and promotes RT Src-dependent plasma membrane blebbing."; RL J. Biol. Chem. 283:27891-27903(2008). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [19] RP FUNCTION, AND INTERACTION WITH PFN1. RX PubMed=18573880; DOI=10.1128/mcb.00079-08; RA Shao J., Welch W.J., Diprospero N.A., Diamond M.I.; RT "Phosphorylation of profilin by ROCK1 regulates polyglutamine RT aggregation."; RL Mol. Cell. Biol. 28:5196-5208(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [21] RP FUNCTION, AND INTERACTION WITH JIP3. RX PubMed=19036714; DOI=10.1126/scisignal.1161938; RA Ongusaha P.P., Qi H.H., Raj L., Kim Y.B., Aaronson S.A., Davis R.J., RA Shi Y., Liao J.K., Lee S.W.; RT "Identification of ROCK1 as an upstream activator of the JIP-3 to JNK RT signaling axis in response to UVB damage."; RL Sci. Signal. 1:RA14-RA14(2008). RN [22] 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 [23] RP FUNCTION, AND INTERACTION WITH PPP1R12A. RX PubMed=19131646; DOI=10.1161/circresaha.108.188524; RA Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X., Surks H.K.; RT "ROCK isoform regulation of myosin phosphatase and contractility in RT vascular smooth muscle cells."; RL Circ. Res. 104:531-540(2009). RN [24] RP FUNCTION. RX PubMed=19997641; DOI=10.1371/journal.pone.0008190; RA Lock F.E., Hotchin N.A.; RT "Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte RT differentiation."; RL PLoS ONE 4:E8190-E8190(2009). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1105, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-647, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [27] RP INTERACTION WITH CHORDC1. RX PubMed=20230755; DOI=10.1016/j.devcel.2009.12.020; RA Ferretti R., Palumbo V., Di Savino A., Velasco S., Sbroggio M., RA Sportoletti P., Micale L., Turco E., Silengo L., Palumbo G., Hirsch E., RA Teruya-Feldstein J., Bonaccorsi S., Pandolfi P.P., Gatti M., Tarone G., RA Brancaccio M.; RT "Morgana/chp-1, a ROCK inhibitor involved in centrosome duplication and RT tumorigenesis."; RL Dev. Cell 18:486-495(2010). RN [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [29] RP FUNCTION, AND CLEAVAGE BY CASPASE-3. RX PubMed=21072057; DOI=10.1038/cdd.2010.140; RA Gabet A.S., Coulon S., Fricot A., Vandekerckhove J., Chang Y., Ribeil J.A., RA Lordier L., Zermati Y., Asnafi V., Belaid Z., Debili N., Vainchenker W., RA Varet B., Hermine O., Courtois G.; RT "Caspase-activated ROCK-1 allows erythroblast terminal maturation RT independently of cytokine-induced Rho signaling."; RL Cell Death Differ. 18:678-689(2011). RN [30] RP REVIEW. RX PubMed=20803696; DOI=10.1002/cm.20472; RA Amano M., Nakayama M., Kaibuchi K.; RT "Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity."; RL Cytoskeleton 67:545-554(2010). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [32] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23093407; DOI=10.1074/jbc.m112.394965; RA Schofield A.V., Steel R., Bernard O.; RT "Rho-associated coiled-coil kinase (ROCK) protein controls microtubule RT dynamics in a novel signaling pathway that regulates cell migration."; RL J. Biol. Chem. 287:43620-43629(2012). RN [33] RP INTERACTION WITH SHROOM3. RX PubMed=22493320; DOI=10.1091/mbc.e11-11-0937; RA Mohan S., Rizaldy R., Das D., Bauer R.J., Heroux A., Trakselis M.A., RA Hildebrand J.D., VanDemark A.P.; RT "Structure of Shroom domain 2 reveals a three-segmented coiled-coil RT required for dimerization, Rock binding, and apical constriction."; RL Mol. Biol. Cell 23:2131-2142(2012). RN [34] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [35] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23355470; DOI=10.1074/jbc.m112.441048; RA Schofield A.V., Gamell C., Suryadinata R., Sarcevic B., Bernard O.; RT "Tubulin polymerization promoting protein 1 (Tppp1) phosphorylation by Rho- RT associated coiled-coil kinase (rock) and cyclin-dependent kinase 1 (Cdk1) RT inhibits microtubule dynamics to increase cell proliferation."; RL J. Biol. Chem. 288:7907-7917(2013). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1328, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 947-1015 IN COMPLEX WITH RHOA. RX PubMed=14660612; DOI=10.1074/jbc.m311911200; RA Dvorsky R., Blumenstein L., Vetter I.R., Ahmadian M.R.; RT "Structural insights into the interaction of ROCKI with the switch regions RT of RhoA."; RL J. Biol. Chem. 279:7098-7104(2004). RN [39] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 6-415, AND SUBUNIT. RX PubMed=16249185; DOI=10.1074/jbc.m508847200; RA Jacobs M., Hayakawa K., Swenson L., Bellon S., Fleming M., Taslimi P., RA Doran J.; RT "The structure of dimeric ROCK I reveals the mechanism for ligand RT selectivity."; RL J. Biol. Chem. 281:260-268(2006). RN [40] RP VARIANTS [LARGE SCALE ANALYSIS] ASN-108; SER-773; PRO-1112; SER-1193; RP GLU-1217; GLN-1262 AND ARG-1264. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Protein kinase which is a key regulator of the actin CC cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, CC PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, CC PubMed:19131646, PubMed:8617235, PubMed:9722579). Involved in CC regulation of smooth muscle contraction, actin cytoskeleton CC organization, stress fiber and focal adhesion formation, neurite CC retraction, cell adhesion and motility via phosphorylation of DAPK3, CC GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A CC (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, CC PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, CC PubMed:9722579, PubMed:23093407, PubMed:23355470). Phosphorylates FHOD1 CC and acts synergistically with it to promote SRC-dependent non-apoptotic CC plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and CC regulates the recruitment of JNK to JIP3 upon UVB-induced stress CC (PubMed:19036714). Acts as a suppressor of inflammatory cell migration CC by regulating PTEN phosphorylation and stability (By similarity). Acts CC as a negative regulator of VEGF-induced angiogenic endothelial cell CC activation (PubMed:19181962). Required for centrosome positioning and CC centrosome-dependent exit from mitosis (By similarity). Plays a role in CC terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte CC motility via regulation of actin cytoskeletal dynamics and CC phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal CC differentiation (PubMed:19997641). Involved in osteoblast compaction CC through the fibronectin fibrillogenesis cell-mediated matrix assembly CC process, essential for osteoblast mineralization (By similarity). May CC regulate closure of the eyelids and ventral body wall by inducing the CC assembly of actomyosin bundles (By similarity). CC {ECO:0000250|UniProtKB:P70335, ECO:0000250|UniProtKB:Q8MIT6, CC ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, CC ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18573880, CC ECO:0000269|PubMed:18694941, ECO:0000269|PubMed:19036714, CC ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19181962, CC ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21072057, CC ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, CC ECO:0000269|PubMed:8617235, ECO:0000269|PubMed:9722579}. 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 Evidence={ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:23093407, CC ECO:0000269|PubMed:23355470}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:23093407, CC ECO:0000269|PubMed:23355470}; 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; Evidence={ECO:0000269|PubMed:10436159, CC ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, CC ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:23093407, CC ECO:0000269|PubMed:23355470}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ACTIVITY REGULATION: Activated by RHOA binding. Inhibited by Y-27632. CC -!- SUBUNIT: Homodimer. Interacts with RHOB, RHOC, MYLC2B and PTEN. CC Interacts with ITGB1BP1 (via N-terminus and PTB domain) (By CC similarity). Interacts with RHOA (activated by GTP), CHORDC1, DAPK3, CC GEM, JIP3, RHOE, PPP1R12A, PFN1, LIMK1, LIMK2 and TSG101. Interacts CC with FHOD1 in a Src-dependent manner. Interacts with SHROOM3 CC (PubMed:22493320). {ECO:0000250|UniProtKB:P70335, CC ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, CC ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, CC ECO:0000269|PubMed:11956230, ECO:0000269|PubMed:12773565, CC ECO:0000269|PubMed:14660612, ECO:0000269|PubMed:16249185, CC ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:17853893, CC ECO:0000269|PubMed:18573880, ECO:0000269|PubMed:18694941, CC ECO:0000269|PubMed:19036714, ECO:0000269|PubMed:19131646, CC ECO:0000269|PubMed:20230755, ECO:0000269|PubMed:22493320, CC ECO:0000269|PubMed:8617235}. CC -!- INTERACTION: CC Q13464; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-876651, EBI-749051; CC Q13464; Q86V42: FAM124A; NbExp=3; IntAct=EBI-876651, EBI-744506; CC Q13464; Q7Z6J6: FRMD5; NbExp=4; IntAct=EBI-876651, EBI-727282; CC Q13464; P25791: LMO2; NbExp=3; IntAct=EBI-876651, EBI-739696; CC Q13464; O15481: MAGEB4; NbExp=4; IntAct=EBI-876651, EBI-751857; CC Q13464; Q13203: MYBPH; NbExp=2; IntAct=EBI-876651, EBI-5655165; CC Q13464; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-876651, EBI-5452779; CC Q13464; P61586: RHOA; NbExp=4; IntAct=EBI-876651, EBI-446668; CC Q13464; Q99816: TSG101; NbExp=4; IntAct=EBI-876651, EBI-346882; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8617235}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, CC centriole {ECO:0000250|UniProtKB:P70335}. Golgi apparatus membrane CC {ECO:0000269|PubMed:12773565}; Peripheral membrane protein CC {ECO:0000269|PubMed:12773565}. Cell projection, bleb CC {ECO:0000269|PubMed:18694941}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:P70335}. Cell membrane CC {ECO:0000250|UniProtKB:P70335}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:P70335}. Cell projection, ruffle CC {ECO:0000250|UniProtKB:P70335}. Note=A small proportion is associated CC with Golgi membranes (PubMed:12773565). Associated with the mother CC centriole and an intercentriolar linker (By similarity). Colocalizes CC with ITGB1BP1 and ITGB1 at the cell membrane predominantly in CC lamellipodia and membrane ruffles, but also in retraction fibers (By CC similarity). Localizes at the cell membrane in an ITGB1BP1-dependent CC manner (By similarity). {ECO:0000250|UniProtKB:P70335, CC ECO:0000269|PubMed:12773565}. CC -!- TISSUE SPECIFICITY: Detected in blood platelets. CC {ECO:0000269|PubMed:8617235}. CC -!- DOMAIN: The C-terminal auto-inhibitory domain interferes with kinase CC activity. RHOA binding leads to a conformation change and activation of CC the kinase. Truncated ROCK1 is constitutively activated. CC -!- PTM: Autophosphorylated on serine and threonine residues. CC {ECO:0000269|PubMed:8617235}. CC -!- PTM: Cleaved by caspase-3 during apoptosis. This leads to constitutive CC activation of the kinase and membrane blebbing. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U43195; AAB02814.1; -; mRNA. DR EMBL; EF445027; ACA06069.1; -; Genomic_DNA. DR EMBL; BC113114; AAI13115.1; -; mRNA. DR EMBL; AB208965; BAD92202.1; -; mRNA. DR CCDS; CCDS11870.2; -. DR PIR; S69211; S69211. DR RefSeq; NP_005397.1; NM_005406.2. DR PDB; 1S1C; X-ray; 2.60 A; X/Y=947-1015. DR PDB; 2ESM; X-ray; 3.20 A; A/B=6-415. DR PDB; 2ETK; X-ray; 2.96 A; A/B=6-415. DR PDB; 2ETR; X-ray; 2.60 A; A/B=6-415. DR PDB; 2V55; X-ray; 3.70 A; A/C=1-406. DR PDB; 3D9V; X-ray; 3.30 A; A/B=6-415. DR PDB; 3NCZ; X-ray; 3.00 A; A/B/C/D=6-415. DR PDB; 3NDM; X-ray; 3.30 A; A/B/C/D=6-415. DR PDB; 3O0Z; X-ray; 2.33 A; A/B/C/D=535-700. DR PDB; 3TV7; X-ray; 2.75 A; A/B/C/D=6-415. DR PDB; 3TWJ; X-ray; 2.90 A; A/B/C/D=6-415. DR PDB; 3V8S; X-ray; 2.29 A; A/B/C/D=6-415. DR PDB; 4L2W; X-ray; 2.49 A; A/B/C/D=834-914. DR PDB; 4W7P; X-ray; 2.80 A; A/B/C/D=2-410. DR PDB; 4YVC; X-ray; 3.20 A; A/B=6-415. DR PDB; 4YVE; X-ray; 3.40 A; A/B=6-415. DR PDB; 5BML; X-ray; 2.95 A; A/B=6-415. DR PDB; 5F5P; X-ray; 3.57 A; C/D/E/F=834-913. DR PDB; 5HVU; X-ray; 2.80 A; A/B=6-415. DR PDB; 5KKS; X-ray; 3.30 A; A/B=6-415. DR PDB; 5KKT; X-ray; 2.80 A; A/B=6-415. DR PDB; 5UZJ; X-ray; 3.30 A; A/B=6-415. DR PDB; 5WNE; X-ray; 2.60 A; A/B/C/D=6-415. DR PDB; 5WNF; X-ray; 2.45 A; A/B/C/D=6-415. DR PDB; 5WNG; X-ray; 2.90 A; A/B/C/D=6-415. DR PDB; 5WNH; X-ray; 3.10 A; A/B/C/D=6-415. DR PDB; 6E9W; X-ray; 2.96 A; A/B=6-415. DR PDB; 7JOU; X-ray; 3.32 A; A=6-415. DR PDB; 7S25; X-ray; 2.34 A; A/B/C/D=7-402. DR PDB; 7S26; X-ray; 2.74 A; A/B/C/D=6-402. DR PDB; 8P0S; X-ray; 2.20 A; A/B=420-550. DR PDBsum; 1S1C; -. DR PDBsum; 2ESM; -. DR PDBsum; 2ETK; -. DR PDBsum; 2ETR; -. DR PDBsum; 2V55; -. DR PDBsum; 3D9V; -. DR PDBsum; 3NCZ; -. DR PDBsum; 3NDM; -. DR PDBsum; 3O0Z; -. DR PDBsum; 3TV7; -. DR PDBsum; 3TWJ; -. DR PDBsum; 3V8S; -. DR PDBsum; 4L2W; -. DR PDBsum; 4W7P; -. DR PDBsum; 4YVC; -. DR PDBsum; 4YVE; -. DR PDBsum; 5BML; -. DR PDBsum; 5F5P; -. DR PDBsum; 5HVU; -. DR PDBsum; 5KKS; -. DR PDBsum; 5KKT; -. DR PDBsum; 5UZJ; -. DR PDBsum; 5WNE; -. DR PDBsum; 5WNF; -. DR PDBsum; 5WNG; -. DR PDBsum; 5WNH; -. DR PDBsum; 6E9W; -. DR PDBsum; 7JOU; -. DR PDBsum; 7S25; -. DR PDBsum; 7S26; -. DR PDBsum; 8P0S; -. DR AlphaFoldDB; Q13464; -. DR SMR; Q13464; -. DR BioGRID; 112020; 164. DR CORUM; Q13464; -. DR DIP; DIP-35645N; -. DR ELM; Q13464; -. DR IntAct; Q13464; 42. DR MINT; Q13464; -. DR STRING; 9606.ENSP00000382697; -. DR BindingDB; Q13464; -. DR ChEMBL; CHEMBL3231; -. DR DrugBank; DB07876; (S)-2-METHYL-1-[(4-METHYL-5-ISOQUINOLINE)SULFONYL]-HOMOPIPERAZINE. DR DrugBank; DB16703; Belumosudil. DR DrugBank; DB08162; Fasudil. DR DrugBank; DB04707; Hydroxyfasudil. DR DrugBank; DB13931; Netarsudil. DR DrugBank; DB13165; Ripasudil. DR DrugBank; DB08756; Y-27632. DR DrugCentral; Q13464; -. DR GuidetoPHARMACOLOGY; 1503; -. DR GlyCosmos; Q13464; 1 site, 1 glycan. DR GlyGen; Q13464; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13464; -. DR MetOSite; Q13464; -. DR PhosphoSitePlus; Q13464; -. DR SwissPalm; Q13464; -. DR BioMuta; ROCK1; -. DR DMDM; 47605999; -. DR CPTAC; CPTAC-2877; -. DR EPD; Q13464; -. DR jPOST; Q13464; -. DR MassIVE; Q13464; -. DR MaxQB; Q13464; -. DR PaxDb; 9606-ENSP00000382697; -. DR PeptideAtlas; Q13464; -. DR ProteomicsDB; 59461; -. DR Pumba; Q13464; -. DR Antibodypedia; 1128; 798 antibodies from 46 providers. DR DNASU; 6093; -. DR Ensembl; ENST00000399799.3; ENSP00000382697.1; ENSG00000067900.9. DR GeneID; 6093; -. DR KEGG; hsa:6093; -. DR MANE-Select; ENST00000399799.3; ENSP00000382697.1; NM_005406.3; NP_005397.1. DR UCSC; uc002kte.4; human. DR AGR; HGNC:10251; -. DR CTD; 6093; -. DR DisGeNET; 6093; -. DR GeneCards; ROCK1; -. DR HGNC; HGNC:10251; ROCK1. DR HPA; ENSG00000067900; Low tissue specificity. DR MIM; 601702; gene. DR neXtProt; NX_Q13464; -. DR OpenTargets; ENSG00000067900; -. DR PharmGKB; PA34623; -. DR VEuPathDB; HostDB:ENSG00000067900; -. DR eggNOG; KOG0612; Eukaryota. DR GeneTree; ENSGT01030000234517; -. DR HOGENOM; CLU_000288_140_0_1; -. DR InParanoid; Q13464; -. DR OMA; XETLATQ; -. DR OrthoDB; 4221785at2759; -. DR PhylomeDB; Q13464; -. DR TreeFam; TF313551; -. DR PathwayCommons; Q13464; -. DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-3928663; EPHA-mediated growth cone collapse. DR Reactome; R-HSA-416482; G alpha (12/13) signalling events. DR Reactome; R-HSA-416572; Sema4D induced cell migration and growth-cone collapse. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-5627117; RHO GTPases Activate ROCKs. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8980692; RHOA GTPase cycle. DR Reactome; R-HSA-9013026; RHOB GTPase cycle. DR Reactome; R-HSA-9013106; RHOC GTPase cycle. DR Reactome; R-HSA-9013407; RHOH GTPase cycle. DR Reactome; R-HSA-9013422; RHOBTB1 GTPase cycle. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9696264; RND3 GTPase cycle. DR SABIO-RK; Q13464; -. DR SignaLink; Q13464; -. DR SIGNOR; Q13464; -. DR BioGRID-ORCS; 6093; 26 hits in 1191 CRISPR screens. DR ChiTaRS; ROCK1; human. DR EvolutionaryTrace; Q13464; -. DR GeneWiki; ROCK1; -. DR GenomeRNAi; 6093; -. DR Pharos; Q13464; Tclin. DR PRO; PR:Q13464; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; Q13464; Protein. DR Bgee; ENSG00000067900; Expressed in calcaneal tendon and 97 other cell types or tissues. DR ExpressionAtlas; Q13464; baseline and differential. DR GO; GO:0032059; C:bleb; IEA:UniProtKB-SubCell. DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:ARUK-UCL. DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0001726; C:ruffle; ISS:UniProtKB. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IMP:ARUK-UCL. 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; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0072518; F:Rho-dependent protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0050321; F:tau-protein kinase activity; NAS:ARUK-UCL. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:BHF-UCL. DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central. DR GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0003383; P:apical constriction; IEA:Ensembl. DR GO; GO:0032060; P:bleb assembly; IEA:Ensembl. DR GO; GO:0097746; P:blood vessel diameter maintenance; ISS:ARUK-UCL. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:BHF-UCL. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0050900; P:leukocyte migration; IDA:BHF-UCL. DR GO; GO:0050901; P:leukocyte tethering or rolling; IDA:BHF-UCL. DR GO; GO:0022614; P:membrane to membrane docking; IDA:BHF-UCL. DR GO; GO:0000281; P:mitotic cytokinesis; IBA:GO_Central. DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0061157; P:mRNA destabilization; ISS:ARUK-UCL. DR GO; GO:0051451; P:myoblast migration; ISS:UniProtKB. DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; IMP:ARUK-UCL. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; IMP:ARUK-UCL. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; IGI:UniProtKB. DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:BHF-UCL. DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; TAS:ARUK-UCL. DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; IMP:UniProtKB. DR GO; GO:0042326; P:negative regulation of phosphorylation; ISS:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB. DR GO; GO:0140058; P:neuron projection arborization; IGI:ARUK-UCL. DR GO; GO:0031175; P:neuron projection development; IGI:ARUK-UCL. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0090521; P:podocyte cell migration; ISS:UniProtKB. DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; IGI:ARUK-UCL. DR GO; GO:0010508; P:positive regulation of autophagy; IGI:ARUK-UCL. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:ARUK-UCL. DR GO; GO:1905205; P:positive regulation of connective tissue replacement; IMP:ARUK-UCL. DR GO; GO:0035306; P:positive regulation of dephosphorylation; IMP:ARUK-UCL. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB. 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:0010922; P:positive regulation of phosphatase activity; IMP:ARUK-UCL. DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IDA:UniProtKB. DR GO; GO:1902003; P:regulation of amyloid-beta formation; TAS:ARUK-UCL. DR GO; GO:0110061; P:regulation of angiotensin-activated signaling pathway; IMP:ARUK-UCL. DR GO; GO:0010506; P:regulation of autophagy; TAS:ARUK-UCL. DR GO; GO:0030155; P:regulation of cell adhesion; TAS:UniProtKB. DR GO; GO:1901888; P:regulation of cell junction assembly; IBA:GO_Central. DR GO; GO:0030334; P:regulation of cell migration; IDA:UniProtKB. DR GO; GO:2000145; P:regulation of cell motility; TAS:UniProtKB. DR GO; GO:2000114; P:regulation of establishment of cell polarity; TAS:UniProtKB. DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; IMP:UniProtKB. DR GO; GO:0051893; P:regulation of focal adhesion assembly; TAS:UniProtKB. DR GO; GO:0045616; P:regulation of keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IDA:UniProtKB. DR GO; GO:0045664; P:regulation of neuron differentiation; IGI:ARUK-UCL. DR GO; GO:0051492; P:regulation of stress fiber assembly; TAS:UniProtKB. DR GO; GO:0090128; P:regulation of synapse maturation; IEA:Ensembl. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; IGI:ARUK-UCL. DR GO; GO:1990776; P:response to angiotensin; ISS:ARUK-UCL. DR GO; GO:0071559; P:response to transforming growth factor beta; ISS:ARUK-UCL. DR GO; GO:0007266; P:Rho protein signal transduction; IGI:ARUK-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006939; P:smooth muscle contraction; TAS:UniProtKB. DR CDD; cd20874; C1_ROCK1; 1. DR CDD; cd11639; HR1_ROCK1; 1. DR CDD; cd01242; PH_ROCK; 1. DR CDD; cd22250; ROCK_SBD; 1. DR CDD; cd05622; STKc_ROCK1; 1. DR DisProt; DP02365; -. DR Gene3D; 1.20.5.340; -; 1. DR Gene3D; 3.30.60.20; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.20.5.730; Single helix bin; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; IPR037310; ROCK1_HR1. DR InterPro; IPR015008; ROCK_Rho-bd_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR22988; MYOTONIC DYSTROPHY S/T KINASE-RELATED; 1. DR PANTHER; PTHR22988:SF33; RHO-ASSOCIATED PROTEIN KINASE 1; 1. 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; SSF57889; Cysteine-rich domain; 1. DR SUPFAM; SSF103652; G protein-binding domain; 1. DR SUPFAM; SSF90257; Myosin rod fragments; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q13464; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; ATP-binding; Cell membrane; KW Cell projection; Coiled coil; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Golgi apparatus; Kinase; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:22814378" FT CHAIN 2..1354 FT /note="Rho-associated protein kinase 1" FT /id="PRO_0000086619" FT DOMAIN 76..338 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 341..409 FT /note="AGC-kinase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618" FT DOMAIN 479..556 FT /note="REM-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207" FT DOMAIN 949..1015 FT /note="RhoBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01206" FT DOMAIN 1118..1317 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT ZN_FING 1228..1281 FT /note="Phorbol-ester/DAG-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 368..727 FT /note="Interaction with FHOD1" FT /evidence="ECO:0000269|PubMed:18694941" FT REGION 707..946 FT /note="SHROOM3 binding" FT /evidence="ECO:0000269|PubMed:22493320" FT REGION 998..1010 FT /note="RHOA binding" FT REGION 1115..1354 FT /note="Auto-inhibitory" FT REGION 1320..1354 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 422..692 FT /evidence="ECO:0000255" FT COILED 1011..1102 FT /evidence="ECO:0000255" FT COMPBIAS 1326..1354 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 198 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 82..90 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 105 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 1113..1114 FT /note="Cleavage; by caspase-3" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:22814378" FT MOD_RES 647 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1105 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1108 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P70335" FT MOD_RES 1328 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 108 FT /note="S -> N (in dbSNP:rs55811609)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041055" FT VARIANT 773 FT /note="T -> S (in dbSNP:rs45562542)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041056" FT VARIANT 1112 FT /note="T -> P (in dbSNP:rs35881519)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041057" FT VARIANT 1193 FT /note="P -> S (in a lung neuroendocrine carcinoma sample; FT somatic mutation; dbSNP:rs1057520015)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041058" FT VARIANT 1217 FT /note="Q -> E (in dbSNP:rs201390233)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041059" FT VARIANT 1262 FT /note="R -> Q (in dbSNP:rs1045142)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041060" FT VARIANT 1264 FT /note="C -> R (in dbSNP:rs2663698)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041061" FT MUTAGEN 1113 FT /note="D->A: Abolishes cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:11283607" FT CONFLICT 170 FT /note="V -> A (in Ref. 3; AAI13115)" FT /evidence="ECO:0000305" FT CONFLICT 197 FT /note="R -> G (in Ref. 3; AAI13115)" FT /evidence="ECO:0000305" FT CONFLICT 220 FT /note="C -> R (in Ref. 3; AAI13115)" FT /evidence="ECO:0000305" FT CONFLICT 323..325 FT /note="RLG -> GTR (in Ref. 5; BAD92202)" FT /evidence="ECO:0000305" FT CONFLICT 521 FT /note="D -> N (in Ref. 3; AAI13115)" FT /evidence="ECO:0000305" FT CONFLICT 965 FT /note="K -> R (in Ref. 3; AAI13115)" FT /evidence="ECO:0000305" FT CONFLICT 1354 FT /note="S -> R (in Ref. 2; ACA06069)" FT /evidence="ECO:0000305" FT HELIX 9..19 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:5WNG" FT HELIX 27..41 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 50..69 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 73..75 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 76..84 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 86..95 FT /evidence="ECO:0007829|PDB:3V8S" FT TURN 96..98 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 101..108 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 109..114 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 121..130 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 139..144 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 157..160 FT /evidence="ECO:0007829|PDB:3NDM" FT HELIX 161..167 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 172..191 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 204..206 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:5KKS" FT STRAND 227..230 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 238..240 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 243..247 FT /evidence="ECO:0007829|PDB:3V8S" FT TURN 248..252 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 258..273 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 283..291 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 293..296 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 307..316 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:3V8S" FT TURN 324..327 FT /evidence="ECO:0007829|PDB:7S25" FT HELIX 329..333 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 336..338 FT /evidence="ECO:0007829|PDB:3V8S" FT TURN 345..347 FT /evidence="ECO:0007829|PDB:7S25" FT HELIX 348..350 FT /evidence="ECO:0007829|PDB:3V8S" FT HELIX 365..367 FT /evidence="ECO:0007829|PDB:3NCZ" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:3V8S" FT STRAND 399..402 FT /evidence="ECO:0007829|PDB:2ETR" FT HELIX 535..540 FT /evidence="ECO:0007829|PDB:3O0Z" FT HELIX 544..691 FT /evidence="ECO:0007829|PDB:3O0Z" FT HELIX 840..902 FT /evidence="ECO:0007829|PDB:4L2W" FT HELIX 947..982 FT /evidence="ECO:0007829|PDB:1S1C" FT HELIX 984..1011 FT /evidence="ECO:0007829|PDB:1S1C" SQ SEQUENCE 1354 AA; 158175 MW; 93078CBB009A6F27 CRC64; MSTGDSFETR FEKMDNLLRD PKSEVNSDCL LDGLDALVYD LDFPALRKNK NIDNFLSRYK DTINKIRDLR MKAEDYEVVK VIGRGAFGEV QLVRHKSTRK VYAMKLLSKF EMIKRSDSAF FWEERDIMAF ANSPWVVQLF YAFQDDRYLY MVMEYMPGGD LVNLMSNYDV PEKWARFYTA EVVLALDAIH SMGFIHRDVK PDNMLLDKSG HLKLADFGTC MKMNKEGMVR CDTAVGTPDY ISPEVLKSQG GDGYYGRECD WWSVGVFLYE MLVGDTPFYA DSLVGTYSKI MNHKNSLTFP DDNDISKEAK NLICAFLTDR EVRLGRNGVE EIKRHLFFKN DQWAWETLRD TVAPVVPDLS SDIDTSNFDD LEEDKGEEET FPIPKAFVGN QLPFVGFTYY SNRRYLSSAN PNDNRTSSNA DKSLQESLQK TIYKLEEQLH NEMQLKDEME QKCRTSNIKL DKIMKELDEE GNQRRNLEST VSQIEKEKML LQHRINEYQR KAEQENEKRR NVENEVSTLK DQLEDLKKVS QNSQLANEKL SQLQKQLEEA NDLLRTESDT AVRLRKSHTE MSKSISQLES LNRELQERNR ILENSKSQTD KDYYQLQAIL EAERRDRGHD SEMIGDLQAR ITSLQEEVKH LKHNLEKVEG ERKEAQDMLN HSEKEKNNLE IDLNYKLKSL QQRLEQEVNE HKVTKARLTD KHQSIEEAKS VAMCEMEKKL KEEREAREKA ENRVVQIEKQ CSMLDVDLKQ SQQKLEHLTG NKERMEDEVK NLTLQLEQES NKRLLLQNEL KTQAFEADNL KGLEKQMKQE INTLLEAKRL LEFELAQLTK QYRGNEGQMR ELQDQLEAEQ YFSTLYKTQV KELKEEIEEK NRENLKKIQE LQNEKETLAT QLDLAETKAE SEQLARGLLE EQYFELTQES KKAASRNRQE ITDKDHTVSR LEEANSMLTK DIEILRRENE ELTEKMKKAE EEYKLEKEEE ISNLKAAFEK NINTERTLKT QAVNKLAEIM NRKDFKIDRK KANTQDLRKK EKENRKLQLE LNQEREKFNQ MVVKHQKELN DMQAQLVEEC AHRNELQMQL ASKESDIEQL RAKLLDLSDS TSVASFPSAD ETDGNLPESR IEGWLSVPNR GNIKRYGWKK QYVVVSSKKI LFYNDEQDKE QSNPSMVLDI DKLFHVRPVT QGDVYRAETE EIPKIFQILY ANEGECRKDV EMEPVQQAEK TNFQNHKGHE FIPTLYHFPA NCDACAKPLW HVFKPPPALE CRRCHVKCHR DHLDKKEDLI CPCKVSYDVT SARDMLLLAC SQDEQKKWVT HLVKKIPKNP PSGFVRASPR TLSTRSTANQ SFRKVVKNTS GKTS //