ROCK1_HUMAN
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 03-AUG-2022, entry version 220.
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 ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; Q13464; -.
DR SMR; Q13464; -.
DR BioGRID; 112020; 120.
DR CORUM; Q13464; -.
DR DIP; DIP-35645N; -.
DR ELM; Q13464; -.
DR IntAct; Q13464; 37.
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 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 EPD; Q13464; -.
DR jPOST; Q13464; -.
DR MassIVE; Q13464; -.
DR MaxQB; Q13464; -.
DR PaxDb; Q13464; -.
DR PeptideAtlas; Q13464; -.
DR PRIDE; Q13464; -.
DR ProteomicsDB; 59461; -.
DR Antibodypedia; 1128; 703 antibodies from 46 providers.
DR DNASU; 6093; -.
DR Ensembl; ENST00000399799.3; ENSP00000382697.1; ENSG00000067900.8.
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 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; 759391at2759; -.
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; 24 hits in 1109 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 95 other tissues.
DR ExpressionAtlas; Q13464; baseline and differential.
DR Genevisible; Q13464; HS.
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: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: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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
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:0018107; P:peptidyl-threonine phosphorylation; IBA:GO_Central.
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:0032970; P:regulation of actin filament-based process; IEA:Ensembl.
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: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; cd00029; C1; 1.
DR CDD; cd11639; HR1_ROCK1; 1.
DR DisProt; DP02365; -.
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; IPR037310; ROCK1_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 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:rs2847092)"
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:5WNF"
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:5WNE"
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
