ROCK2_HUMAN
ID ROCK2_HUMAN Reviewed; 1388 AA.
AC O75116; Q53QZ0; Q53SJ7; Q9UQN5;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 4.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Rho-associated protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=Rho kinase 2;
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; Synonyms=KIAA0619;
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], AND VARIANT ASN-431.
RC TISSUE=Brain;
RX PubMed=9933571; DOI=10.1006/geno.1998.5344;
RA Takahashi N., Tuiki H., Saya H., Kaibuchi K.;
RT "Localization of the gene coding for ROCK II/Rho kinase on human chromosome
RT 2p24.";
RL Genomics 55:235-237(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-431.
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP FUNCTION, AND INTERACTION WITH PPP1R12A.
RX PubMed=10579722; DOI=10.1083/jcb.147.5.1023;
RA Kawano Y., Fukata Y., Oshiro N., Amano M., Nakamura T., Ito M.,
RA Matsumura F., Inagaki M., Kaibuchi K.;
RT "Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by
RT Rho-kinase in vivo.";
RL J. Cell Biol. 147:1023-1038(1999).
RN [5]
RP CLEAVAGE BY GRANZYME B, MUTAGENESIS OF ASP-1131, AND FUNCTION.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH EP300.
RX PubMed=16574662; DOI=10.1074/jbc.m510954200;
RA Tanaka T., Nishimura D., Wu R.C., Amano M., Iso T., Kedes L., Nishida H.,
RA Kaibuchi K., Hamamori Y.;
RT "Nuclear Rho kinase, ROCK2, targets p300 acetyltransferase.";
RL J. Biol. Chem. 281:15320-15329(2006).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NPM1.
RX PubMed=17015463; DOI=10.1128/mcb.01383-06;
RA Ma Z., Kanai M., Kawamura K., Kaibuchi K., Ye K., Fukasawa K.;
RT "Interaction between ROCK II and nucleophosmin/B23 in the regulation of
RT centrosome duplication.";
RL Mol. Cell. Biol. 26:9016-9034(2006).
RN [8]
RP PHOSPHORYLATION AT TYR-722, AND DEPHOSPHORYLATION.
RX PubMed=18559669; DOI=10.1083/jcb.200710187;
RA Lee H.H., Chang Z.F.;
RT "Regulation of RhoA-dependent ROCKII activation by Shp2.";
RL J. Cell Biol. 181:999-1012(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, AND IDENTIFICATION BY
RP 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 [11]
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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, 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 [14]
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 [15]
RP PHOSPHORYLATION AT TYR-722.
RX PubMed=20826462; DOI=10.1242/jcs.071555;
RA Lee H.H., Tien S.C., Jou T.S., Chang Y.C., Jhong J.G., Chang Z.F.;
RT "Src-dependent phosphorylation of ROCK participates in regulation of focal
RT adhesion dynamics.";
RL J. Cell Sci. 123:3368-3377(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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 [18]
RP FUNCTION, AND INTERACTION WITH BRCA2.
RX PubMed=21084279; DOI=10.1158/0008-5472.can-10-0030;
RA Wang H.F., Takenaka K., Nakanishi A., Miki Y.;
RT "BRCA2 and nucleophosmin coregulate centrosome amplification and form a
RT complex with the Rho effector kinase ROCK2.";
RL Cancer Res. 71:68-77(2011).
RN [19]
RP FUNCTION, INTERACTION WITH SORL1, AND TISSUE SPECIFICITY.
RX PubMed=21147781; DOI=10.1074/jbc.m110.167239;
RA Herskowitz J.H., Seyfried N.T., Gearing M., Kahn R.A., Peng J., Levey A.I.,
RA Lah J.J.;
RT "Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA
RT alters amyloid-beta production.";
RL J. Biol. Chem. 286:6117-6127(2011).
RN [20]
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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1137, AND IDENTIFICATION BY
RP 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1212; SER-1362 AND SER-1374,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [24]
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 [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [26]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-431; VAL-601 AND PRO-1194.
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 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 an important role in generating
CC the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and
CC vascular contractility by modulating the myosin light chain
CC phosphorylation. {ECO:0000269|PubMed:10579722,
CC ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662,
CC ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646,
CC ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279,
CC ECO:0000269|PubMed:21147781}.
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 (By
CC similarity). Interacts with RAF1 (By similarity). Interacts with RHOA
CC (activated by GTP), RHOB and RHOC (By similarity). Interacts with
CC PPP1R12A (PubMed:10579722, PubMed:19131646). Interacts with EP300
CC (PubMed:16574662). Interacts with CHORDC1 (PubMed:20230755). Interacts
CC with BRCA2 (PubMed:21084279). Interacts with NPM1; this interaction
CC enhances ROCK2 activity (PubMed:17015463). Interacts with SORL1
CC (PubMed:21147781). Interacts with PJVK (By similarity).
CC {ECO:0000250|UniProtKB:P70336, ECO:0000250|UniProtKB:Q28021,
CC ECO:0000250|UniProtKB:Q62868, ECO:0000269|PubMed:10579722,
CC ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463,
CC ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:20230755,
CC ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}.
CC -!- INTERACTION:
CC O75116; P05067: APP; NbExp=6; IntAct=EBI-366288, EBI-77613;
CC O75116; O60674: JAK2; NbExp=2; IntAct=EBI-366288, EBI-518647;
CC O75116; P40763: STAT3; NbExp=3; IntAct=EBI-366288, EBI-518675;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Nucleus. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome.
CC Note=Cytoplasmic, and associated with actin microfilaments and the
CC plasma membrane. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level).
CC {ECO:0000269|PubMed:21147781}.
CC -!- DOMAIN: An interaction between Thr-414 and Asp-48 is essential for
CC kinase activity and dimerization. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Tyr-722 reduces its binding to RHOA and is
CC crucial for focal adhesion dynamics. Dephosphorylation by PTPN11
CC stimulates its RHOA binding activity. {ECO:0000269|PubMed:18559669,
CC ECO:0000269|PubMed:20826462}.
CC -!- PTM: Cleaved by granzyme B 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 -!- SEQUENCE CAUTION:
CC Sequence=AAX93049.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA31594.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ROCK2ID43474ch2p25.html";
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DR EMBL; D87931; BAA75636.1; -; mRNA.
DR EMBL; AB014519; BAA31594.2; ALT_INIT; mRNA.
DR EMBL; AC018463; AAX93049.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AC099344; AAY14825.1; -; Genomic_DNA.
DR CCDS; CCDS42654.1; -.
DR RefSeq; NP_001308572.1; NM_001321643.1.
DR RefSeq; NP_004841.2; NM_004850.4.
DR PDB; 4L6Q; X-ray; 2.79 A; A/B=19-417.
DR PDB; 4WOT; X-ray; 2.93 A; A/B/C/D=22-417.
DR PDB; 5U7Q; X-ray; 3.15 A; A/B/C/D=23-417.
DR PDB; 5U7R; X-ray; 3.33 A; A/B/C/D=23-417.
DR PDB; 6ED6; X-ray; 2.86 A; A/B=27-417.
DR PDB; 6P5M; X-ray; 2.65 A; A/B/C/D=18-417.
DR PDB; 6P5P; X-ray; 3.30 A; A/B/C/D=18-417.
DR PDB; 7JNT; X-ray; 2.21 A; A/B/C/D/E/F/G/H=19-417.
DR PDB; 7JOV; X-ray; 2.59 A; A/B/C/D/E/F/G/H=23-417.
DR PDBsum; 4L6Q; -.
DR PDBsum; 4WOT; -.
DR PDBsum; 5U7Q; -.
DR PDBsum; 5U7R; -.
DR PDBsum; 6ED6; -.
DR PDBsum; 6P5M; -.
DR PDBsum; 6P5P; -.
DR PDBsum; 7JNT; -.
DR PDBsum; 7JOV; -.
DR AlphaFoldDB; O75116; -.
DR SMR; O75116; -.
DR BioGRID; 114860; 118.
DR CORUM; O75116; -.
DR IntAct; O75116; 36.
DR MINT; O75116; -.
DR STRING; 9606.ENSP00000317985; -.
DR BindingDB; O75116; -.
DR ChEMBL; CHEMBL2973; -.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB08162; Fasudil.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB13931; Netarsudil.
DR DrugBank; DB13165; Ripasudil.
DR DrugBank; DB08756; Y-27632.
DR DrugCentral; O75116; -.
DR GuidetoPHARMACOLOGY; 1504; -.
DR GlyGen; O75116; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75116; -.
DR MetOSite; O75116; -.
DR PhosphoSitePlus; O75116; -.
DR SwissPalm; O75116; -.
DR BioMuta; ROCK2; -.
DR EPD; O75116; -.
DR jPOST; O75116; -.
DR MassIVE; O75116; -.
DR MaxQB; O75116; -.
DR PaxDb; O75116; -.
DR PeptideAtlas; O75116; -.
DR PRIDE; O75116; -.
DR ProteomicsDB; 49773; -.
DR Antibodypedia; 2077; 728 antibodies from 45 providers.
DR DNASU; 9475; -.
DR Ensembl; ENST00000315872.11; ENSP00000317985.6; ENSG00000134318.15.
DR GeneID; 9475; -.
DR KEGG; hsa:9475; -.
DR MANE-Select; ENST00000315872.11; ENSP00000317985.6; NM_004850.5; NP_004841.2.
DR UCSC; uc002rbd.2; human.
DR CTD; 9475; -.
DR DisGeNET; 9475; -.
DR GeneCards; ROCK2; -.
DR HGNC; HGNC:10252; ROCK2.
DR HPA; ENSG00000134318; Low tissue specificity.
DR MIM; 604002; gene.
DR neXtProt; NX_O75116; -.
DR OpenTargets; ENSG00000134318; -.
DR PharmGKB; PA34624; -.
DR VEuPathDB; HostDB:ENSG00000134318; -.
DR eggNOG; KOG0612; Eukaryota.
DR GeneTree; ENSGT01030000234517; -.
DR HOGENOM; CLU_000288_140_0_1; -.
DR InParanoid; O75116; -.
DR OMA; WTFENLR; -.
DR OrthoDB; 759391at2759; -.
DR PhylomeDB; O75116; -.
DR TreeFam; TF313551; -.
DR PathwayCommons; O75116; -.
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-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 SignaLink; O75116; -.
DR SIGNOR; O75116; -.
DR BioGRID-ORCS; 9475; 41 hits in 1129 CRISPR screens.
DR ChiTaRS; ROCK2; human.
DR GenomeRNAi; 9475; -.
DR Pharos; O75116; Tclin.
DR PRO; PR:O75116; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O75116; protein.
DR Bgee; ENSG00000134318; Expressed in calcaneal tendon and 198 other tissues.
DR ExpressionAtlas; O75116; baseline and differential.
DR Genevisible; O75116; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; IMP:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; NAS:ProtInc.
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:0097746; P:blood vessel diameter maintenance; ISS:ARUK-UCL.
DR GO; GO:1905145; P:cellular response to acetylcholine; ISS:ARUK-UCL.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IMP:UniProtKB.
DR GO; GO:0051298; P:centrosome duplication; 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:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; IBA:GO_Central.
DR GO; GO:0044788; P:modulation by host of viral process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061157; P:mRNA destabilization; ISS: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:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; IMP:UniProtKB.
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; IMP:ARUK-UCL.
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; ISS:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL.
DR GO; GO:0010825; P:positive regulation of centrosome duplication; IEA:InterPro.
DR GO; GO:0032723; P:positive regulation of connective tissue growth factor production; ISS:ARUK-UCL.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; ISS:ARUK-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0090271; P:positive regulation of fibroblast growth factor production; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:ARUK-UCL.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; IMP:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:BHF-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; TAS:UniProtKB.
DR GO; GO:0110061; P:regulation of angiotensin-activated signaling pathway; ISS: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:2000145; P:regulation of cell motility; TAS:UniProtKB.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; ISS:ARUK-UCL.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS: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:0031644; P:regulation of nervous system process; ISS:ARUK-UCL.
DR GO; GO:0051246; P:regulation of protein metabolic process; ISS:ARUK-UCL.
DR GO; GO:0051492; P:regulation of stress fiber assembly; TAS:UniProtKB.
DR GO; GO:1990776; P:response to angiotensin; ISS:ARUK-UCL.
DR GO; GO:0002931; P:response to ischemia; 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; IBA:GO_Central.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006939; P:smooth muscle contraction; TAS:UniProtKB.
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 3D-structure; ATP-binding; Biological rhythms; Cell membrane; Coiled coil;
KW Cytoplasm; Cytoskeleton; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1388
FT /note="Rho-associated protein kinase 2"
FT /id="PRO_0000086625"
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..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..784
FT /note="Interaction with PPP1R12A"
FT REGION 373..420
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000269|PubMed:17015463"
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 429..1024
FT /evidence="ECO:0000255"
FT COILED 1053..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:0000269|PubMed:18559669,
FT ECO:0000269|PubMed:20826462"
FT MOD_RES 1137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1212
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 431
FT /note="T -> N (in dbSNP:rs2230774)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9734811, ECO:0000269|PubMed:9933571"
FT /id="VAR_041062"
FT VARIANT 601
FT /note="D -> V (in dbSNP:rs35768389)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041063"
FT VARIANT 1083
FT /note="K -> M (in dbSNP:rs34945852)"
FT /id="VAR_057110"
FT VARIANT 1194
FT /note="S -> P (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041064"
FT MUTAGEN 1131
FT /note="D->A: Abolishes cleavage by granzyme B."
FT /evidence="ECO:0000269|PubMed:15699075"
FT CONFLICT 83
FT /note="R -> K (in Ref. 1; BAA75636)"
FT /evidence="ECO:0000305"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 43..57
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 66..85
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 92..100
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 125..130
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 137..146
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 162..169
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 177..183
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 188..207
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:7JNT"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:5U7Q"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:6P5M"
FT HELIX 274..289
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 299..307
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:6P5M"
FT HELIX 323..332
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 336..338
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 340..343
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 346..349
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:7JNT"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:7JNT"
FT HELIX 408..410
FT /evidence="ECO:0007829|PDB:7JNT"
SQ SEQUENCE 1388 AA; 160900 MW; 876240F410C2487E CRC64;
MSRPPPTGKM PGAPETAPGD GAGASRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP
ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM
KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFYAFQ DDRYLYMVME YMPGGDLVNL
MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD
ETGMVHCDTA VGTPDYISPE VLKSQGGDGF YGRECDWWSV GVFLYEMLVG DTPFYADSLV
GTYSKIMDHK NSLCFPEDAE ISKHAKNLIC AFLTDREVRL GRNGVEEIRQ HPFFKNDQWH
WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYYRENL
LLSDSPSCRE TDSIQSRKNE ESQEIQKKLY TLEEHLSNEM QAKEELEQKC KSVNTRLEKT
AKELEEEITL RKSVESALRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL
EDLKKRNQNS QISTEKVNQL QRQLDETNAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRICG LEEDLKNGKI
LLAKVELEKR QLQERFTDLE KEKSNMEIDM TYQLKVIQQS LEQEEAEHKA TKARLADKNK
IYESIEEAKS EAMKEMEKKL LEERTLKQKV ENLLLEAEKR CSLLDCDLKQ SQQKINELLK
QKDVLNEDVR NLTLKIEQET QKRCLTQNDL KMQTQQVNTL KMSEKQLKQE NNHLMEMKMN
LEKQNAELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEECEEK TKLGKELQQK
KQELQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE
LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDVQ EQLSRLKDEE ISAAAIKAQF
EKQLLTERTL KTQAVNKLAE IMNRKEPVKR GNDTDVRRKE KENRKLHMEL KSEREKLTQQ
MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGL DSSSIGSGPG
DAEADDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EQEFPVEPVG EKSNYICHKG
HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECRRCHIKC HKDHMDKKEE IIAPCKVYYD
ISTAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR
QLAPNKPS
