ROCK2_RAT
ID ROCK2_RAT Reviewed; 1388 AA.
AC Q62868;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Rho-associated protein kinase 2;
DE EC=2.7.11.1;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase 2;
DE AltName: Full=Rho-associated, coiled-coil-containing protein kinase II;
DE Short=ROCK-II;
DE AltName: Full=RhoA-binding kinase 2;
DE AltName: Full=p150 ROK-alpha;
DE Short=ROKalpha;
DE AltName: Full=p164 ROCK-2;
GN Name=Rock2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH
RP RHOA, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=7493923; DOI=10.1074/jbc.270.49.29051;
RA Leung T., Manser E., Tan L., Lim L.;
RT "A novel serine/threonine kinase binding the Ras-related RhoA GTPase which
RT translocates the kinase to peripheral membranes.";
RL J. Biol. Chem. 270:29051-29054(1995).
RN [2]
RP FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH RHOA; RHOB AND RHOC,
RP MUTAGENESIS OF LYS-121, AND TISSUE SPECIFICITY.
RX PubMed=8816443; DOI=10.1128/mcb.16.10.5313;
RA Leung T., Chen X.-Q., Manser E., Lim L.;
RT "The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and
RT is involved in the reorganization of the cytoskeleton.";
RL Mol. Cell. Biol. 16:5313-5327(1996).
RN [3]
RP FUNCTION, ROLE IN HYPERTENSION, AND INHIBITION BY Y-27632.
RX PubMed=9353125; DOI=10.1038/40187;
RA Uehata M., Ishizaki T., Satoh H., Ono T., Kawahara T., Morishita T.,
RA Tamakawa H., Yamagami K., Inui J., Maekawa M., Narumiya S.;
RT "Calcium sensitization of smooth muscle mediated by a Rho-associated
RT protein kinase in hypertension.";
RL Nature 389:990-994(1997).
RN [4]
RP INTERACTION WITH IRS1.
RX PubMed=11739394; DOI=10.1074/jbc.m110508200;
RA Begum N., Sandu O.A., Ito M., Lohmann S.M., Smolenski A.;
RT "Active Rho kinase (ROK-alpha) associates with insulin receptor substrate-1
RT and inhibits insulin signaling in vascular smooth muscle cells.";
RL J. Biol. Chem. 277:6214-6222(2002).
RN [5]
RP INTERACTION WITH RAF1.
RX PubMed=15753127; DOI=10.1083/jcb.200409162;
RA Ehrenreiter K., Piazzolla D., Velamoor V., Sobczak I., Small J.V.,
RA Takeda J., Leung T., Baccarini M.;
RT "Raf-1 regulates Rho signaling and cell migration.";
RL J. Cell Biol. 168:955-964(2005).
RN [6]
RP CLEAVAGE BY GRANZYME B.
RX PubMed=15699075; DOI=10.1084/jem.20031877;
RA Sebbagh M., Hamelin J., Bertoglio J., Solary E., Breard J.;
RT "Direct cleavage of ROCK II by granzyme B induces target cell membrane
RT blebbing in a caspase-independent manner.";
RL J. Exp. Med. 201:465-471(2005).
RN [7]
RP DOMAIN, PHOSPHORYLATION AT THR-414, AND MUTAGENESIS OF ASP-48; LYS-121;
RP THR-414 AND TRP-1170.
RX PubMed=19099536; DOI=10.1042/bj20081376;
RA Couzens A.L., Saridakis V., Scheid M.P.;
RT "The hydrophobic motif of ROCK2 requires association with the N-terminal
RT extension for kinase activity.";
RL Biochem. J. 419:141-148(2009).
RN [8]
RP FUNCTION, INTERACTION WITH PPP1R12A, AND SUBCELLULAR LOCATION.
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 [9]
RP FUNCTION IN PHOSPHORYLATION OF MYL9/MLC2 AND PPP1R12A.
RX PubMed=21457715; DOI=10.1016/j.febslet.2011.03.054;
RA Tan I., Lai J., Yong J., Li S.F., Leung T.;
RT "Chelerythrine perturbs lamellar actomyosin filaments by selective
RT inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase.";
RL FEBS Lett. 585:1260-1268(2011).
CC -!- FUNCTION: Protein kinase which is a key regulator of actin cytoskeleton
CC and cell polarity. Involved in regulation of smooth muscle contraction,
CC actin cytoskeleton organization, stress fiber and focal adhesion
CC formation, neurite retraction, cell adhesion and motility via
CC phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN,
CC MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4.
CC Acts as a negative regulator of VEGF-induced angiogenic endothelial
CC cell activation. Positively regulates the activation of p42/MAPK1-
CC p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays
CC an important role in the timely initiation of centrosome duplication.
CC Inhibits keratinocyte terminal differentiation. May regulate closure of
CC the eyelids and ventral body wall through organization of actomyosin
CC bundles. Plays a critical role in the regulation of spine and synaptic
CC properties in the hippocampus. Plays a role in placental homeostasis
CC during the perinatal period. Plays an important role in generating the
CC circadian rhythm of the aortic myofilament Ca(2+) sensitivity and
CC vascular contractility by modulating the myosin light chain
CC phosphorylation. {ECO:0000269|PubMed:19131646,
CC ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:7493923,
CC ECO:0000269|PubMed:8816443, ECO:0000269|PubMed:9353125}.
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 -!- SUBUNIT: Homodimer (By similarity). Interacts with IRS1
CC (PubMed:11739394). Interacts with RAF1 (PubMed:15753127). Interacts
CC with RHOA (activated by GTP), RHOB, RHOC (PubMed:7493923,
CC PubMed:8816443). Interacts with PPP1R12A (PubMed:19131646). Interacts
CC with EP300 (By similarity). Interacts with CHORDC1 (By similarity).
CC Interacts with BRCA2 (By similarity). Interacts with NPM1; this
CC interaction enhances its activity (By similarity). Interacts with SORL1
CC (By similarity). Interacts with PJVK (By similarity).
CC {ECO:0000250|UniProtKB:O75116, ECO:0000250|UniProtKB:P70336,
CC ECO:0000250|UniProtKB:Q28021, ECO:0000269|PubMed:11739394,
CC ECO:0000269|PubMed:15753127, ECO:0000269|PubMed:19131646,
CC ECO:0000269|PubMed:7493923, ECO:0000269|PubMed:8816443}.
CC -!- INTERACTION:
CC Q62868; P19105: MYL12A; Xeno; NbExp=2; IntAct=EBI-1569209, EBI-354418;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC protein. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250}. Note=Cytoplasmic, and
CC associated with actin microfilaments and the plasma membrane.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, lung, liver, skeletal
CC muscle, kidney and testis. {ECO:0000269|PubMed:8816443}.
CC -!- DOMAIN: An interaction between Thr-414 and Asp-48 is essential for
CC kinase activity and dimerization. {ECO:0000269|PubMed:19099536}.
CC -!- PTM: Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding
CC to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation
CC by PTPN11 stimulates its RHOA binding activity (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Cleaved by granzyme B during apoptosis. This leads to constitutive
CC activation of the kinase and membrane blebbing.
CC -!- DISEASE: Note=May play a role in hypertension. ROCK-inhibitors lower
CC the blood pressure in spontaneous hypertensive, renal hypertensive and
CC deoxycorticosterone acetate-induced hypertensive rats, but not in
CC normal rats.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB37540.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U38481; AAB37540.1; ALT_INIT; mRNA.
DR RefSeq; NP_037154.2; NM_013022.2.
DR PDB; 2ROV; NMR; -; A=1151-1351.
DR PDB; 2ROW; NMR; -; A=1237-1320.
DR PDBsum; 2ROV; -.
DR PDBsum; 2ROW; -.
DR AlphaFoldDB; Q62868; -.
DR SMR; Q62868; -.
DR BioGRID; 247569; 3.
DR IntAct; Q62868; 5.
DR MINT; Q62868; -.
DR STRING; 10116.ENSRNOP00000006403; -.
DR BindingDB; Q62868; -.
DR ChEMBL; CHEMBL5490; -.
DR DrugCentral; Q62868; -.
DR GuidetoPHARMACOLOGY; 1504; -.
DR iPTMnet; Q62868; -.
DR PhosphoSitePlus; Q62868; -.
DR jPOST; Q62868; -.
DR PaxDb; Q62868; -.
DR PRIDE; Q62868; -.
DR GeneID; 25537; -.
DR KEGG; rno:25537; -.
DR CTD; 9475; -.
DR RGD; 3590; Rock2.
DR eggNOG; KOG0612; Eukaryota.
DR InParanoid; Q62868; -.
DR OrthoDB; 759391at2759; -.
DR Reactome; R-RNO-3928662; EPHB-mediated forward signaling.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-416572; Sema4D induced cell migration and growth-cone collapse.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-5627117; RHO GTPases Activate ROCKs.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013407; RHOH GTPase cycle.
DR Reactome; R-RNO-9013422; RHOBTB1 GTPase cycle.
DR EvolutionaryTrace; Q62868; -.
DR PRO; PR:Q62868; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:RGD.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
DR GO; GO:0031616; C:spindle pole centrosome; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; TAS:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0072518; F:Rho-dependent protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central.
DR GO; GO:0097746; P:blood vessel diameter maintenance; ISO:RGD.
DR GO; GO:1905145; P:cellular response to acetylcholine; ISO:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; ISO:RGD.
DR GO; GO:0051298; P:centrosome duplication; ISO:RGD.
DR GO; GO:0030261; P:chromosome condensation; TAS:RGD.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0048813; P:dendrite morphogenesis; ISO:RGD.
DR GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0000281; P:mitotic cytokinesis; IBA:GO_Central.
DR GO; GO:0061157; P:mRNA destabilization; ISO:RGD.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR GO; GO:1903347; P:negative regulation of bicellular tight junction assembly; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0035509; P:negative regulation of myosin-light-chain-phosphatase activity; ISO:RGD.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISO:RGD.
DR GO; GO:0150033; P:negative regulation of protein localization to lysosome; ISO:RGD.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:1902993; P:positive regulation of amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:1902004; P:positive regulation of amyloid-beta formation; ISO:RGD.
DR GO; GO:1902961; P:positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:ARUK-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0010825; P:positive regulation of centrosome duplication; ISO:RGD.
DR GO; GO:0032723; P:positive regulation of connective tissue growth factor production; IMP:ARUK-UCL.
DR GO; GO:1905205; P:positive regulation of connective tissue replacement; IMP:ARUK-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0090271; P:positive regulation of fibroblast growth factor production; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0098974; P:postsynaptic actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0110061; P:regulation of angiotensin-activated signaling pathway; ISO:RGD.
DR GO; GO:1901888; P:regulation of cell junction assembly; IBA:GO_Central.
DR GO; GO:1900037; P:regulation of cellular response to hypoxia; ISO:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:1903140; P:regulation of establishment of endothelial barrier; ISO:RGD.
DR GO; GO:0045616; P:regulation of keratinocyte differentiation; ISO:RGD.
DR GO; GO:0031644; P:regulation of nervous system process; ISO:RGD.
DR GO; GO:0051246; P:regulation of protein metabolic process; ISO:RGD.
DR GO; GO:1990776; P:response to angiotensin; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; ISO:RGD.
DR GO; GO:0071559; P:response to transforming growth factor beta; IGI:ARUK-UCL.
DR GO; GO:0007266; P:Rho protein signal transduction; IMP:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0006939; P:smooth muscle contraction; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; ISO:RGD.
DR CDD; cd00029; C1; 1.
DR CDD; cd11638; HR1_ROCK2; 1.
DR Gene3D; 2.30.29.30; -; 2.
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_0000086627"
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..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 363..784
FT /note="Interaction with PPP1R12A"
FT /evidence="ECO:0000269|PubMed:19131646"
FT REGION 373..420
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000250"
FT REGION 513..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 979..1047
FT /note="RHOA binding"
FT /evidence="ECO:0000250"
FT REGION 1345..1388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 439..1024
FT /evidence="ECO:0000255"
FT COILED 1052..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:0000269|PubMed:19099536"
FT MOD_RES 722
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75116"
FT MUTAGEN 48
FT /note="D->A: Loss of kinase activity; autophosphorylation
FT and dimerization."
FT /evidence="ECO:0000269|PubMed:19099536"
FT MUTAGEN 121
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:19099536,
FT ECO:0000269|PubMed:8816443"
FT MUTAGEN 121
FT /note="K->M: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19099536,
FT ECO:0000269|PubMed:8816443"
FT MUTAGEN 414
FT /note="T->A: Loss of kinase activity; autophosphorylation
FT and dimerization."
FT /evidence="ECO:0000269|PubMed:19099536"
FT MUTAGEN 1170
FT /note="W->A: Increased activity and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:19099536"
FT STRAND 1153..1158
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1163..1166
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1172..1178
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1181..1186
FT /evidence="ECO:0007829|PDB:2ROV"
FT HELIX 1188..1192
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1197..1200
FT /evidence="ECO:0007829|PDB:2ROV"
FT HELIX 1202..1204
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1205..1210
FT /evidence="ECO:0007829|PDB:2ROV"
FT TURN 1213..1215
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1217..1219
FT /evidence="ECO:0007829|PDB:2ROV"
FT TURN 1221..1223
FT /evidence="ECO:0007829|PDB:2ROV"
FT HELIX 1224..1226
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1227..1232
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1234..1236
FT /evidence="ECO:0007829|PDB:2ROV"
FT STRAND 1256..1258
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1261..1266
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1275..1281
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1284..1286
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1290..1296
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1299..1301
FT /evidence="ECO:0007829|PDB:2ROW"
FT HELIX 1302..1307
FT /evidence="ECO:0007829|PDB:2ROW"
FT TURN 1317..1319
FT /evidence="ECO:0007829|PDB:2ROW"
FT STRAND 1325..1330
FT /evidence="ECO:0007829|PDB:2ROV"
FT HELIX 1334..1347
FT /evidence="ECO:0007829|PDB:2ROV"
SQ SEQUENCE 1388 AA; 160387 MW; B23672CA8645067C CRC64;
MSRPPPTGKM PGAPEAAAGD GAGAGRQRKL EALIRDPRSP INVESLLDGL NSLVLDLDFP
ALRKNKNIDN FLNRYEKIVK KIRGLQMKAE DYDVVKVIGR GAFGEVQLVR HKASQKVYAM
KLLSKFEMIK RSDSAFFWEE RDIMAFANSP WVVQLFCAFQ DDRYLYMVME YMPGGDLVNL
MSNYDVPEKW AKFYTAEVVL ALDAIHSMGL IHRDVKPDNM LLDKHGHLKL ADFGTCMKMD
ETGMVHCDTA VGTPDYISPE VLKSQGGDGY YGRECDWWSV GVFLFEMLVG DTPFYADSLV
GTYSKIMDHK NSLCFPEDTE ISKHAKNLIC AFLTDREVRL GRNGVEEIKS ASFFKNDQWN
WDNIRETAAP VVPELSSDID SSNFDDIEDD KGDVETFPIP KAFVGNQLPF IGFTYFRENL
LLSDSPPCRE NDAIQTRKSE ESQEIQKKLY ALEEHLSSEV QAKEELEQKC KSINTRLEKT
AKELEEEITF RKNVESTLRQ LEREKALLQH KNAEYQRKAD HEADKKRNLE NDVNSLKDQL
EDLKKRNQSS QISTEKVNQL QKQLDEANAL LRTESDTAAR LRKTQAESSK QIQQLESNNR
DLQDKNCLLE TAKLKLEKEF INLQSALESE RRDRTHGSEI INDLQGRISG LEEDLKTGKT
LLAKVELEKR QLQEKLTDLE KEKSNMEIDM TYQLKVIQQS LEQEEAEHKT TKARLADKNK
IYESIEEAKS EAMKEMEKKL LEERSLKQKV ENLLLEAEKR CSILDCDLKQ SQQKLNELLK
QKDVLNEDVR NLTLKIEQET QKRCLMQNDL KMQTQQVNTL KMSEKQIKQE NNHLMEMKMN
LEKQNAELRK ERQDADGQMK ELQDQLEAEQ YFSTLYKTQV RELKEENEEK TKLCKELQQK
KQDLQDERDS LAAQLEITLT KADSEQLARS IAEEQYSDLE KEKIMKELEI KEMMARHKQE
LTEKDATIAS LEETNRTLTS DVANLANEKE ELNNKLKDTQ EQLSKLKDEE ISAAAIKAQF
EKQLLTERTL KTQAVNKLAE IMNRKEPVKR GSDTDVRRKE KENRKLHMEL KSEREKLTQQ
MIKYQKELNE MQAQIAEESQ IRIELQMTLD SKDSDIEQLR SQLQALHIGM DSSSIGSGPG
DAEPDDGFPE SRLEGWLSLP VRNNTKKFGW VKKYVIVSSK KILFYDSEQD KEQSNPYMVL
DIDKLFHVRP VTQTDVYRAD AKEIPRIFQI LYANEGESKK EPEFPVEPVG EKSNYICHKG
HEFIPTLYHF PTNCEACMKP LWHMFKPPPA LECSRCHIKC HKDHMDKKEE IIAPCKVYYD
ISSAKNLLLL ANSTEEQQKW VSRLVKKIPK KPPAPDPFAR SSPRTSMKIQ QNQSIRRPSR
QLAPNKPS
