366:
343:
265:
240:
3190:
3223:
372:
271:
29:
3241:
3205:
5421:
1837:
Increased expression of RhoA and ROCK1 in endothelial cell migration pathways can cause an increase in angiogenesis and metastatic behavior in tumor cells. It has been suggested that ROCK1 either regulates the expression of angiogenic factors or ROCK1 activation facilitates angiogenesis by increasing
1623:
There is one other isoform of ROCK known as ROCK2. ROCK2 is located at 2p24 and is highly homologous with ROCK1 with an overall amino acid sequence identity of 65%. The identity in the Rho-binding domain is 58% and approximately 92% in the kinase domain. The ROCK isoforms are encoded by two different
1596:
independently bind to the N-terminus kinase domain. When a substrate such as GTP-bound RhoA binds to the Rho-binding region of the coiled-coil domain, the interactions between the N-terminus and the C-terminus are disrupted, thus activating the protein. Cleavage of the C-terminal inhibitory domain by
1819:
In humans, the main function of ROCK1 is actomyosin contractility. As mentioned before, this contributes to many proximal progresses such as regulation of morphology, motility, and cellâcell and cellâmatrix adhesion. In addition, ROCK kinases influence more distal cellular processes including gene
1828:
Recent studies have explored the role of ROCK1 in cancer with particular attention focused on cell motility, metastasis, and angiogenesis. Rho GTPases such as RhoA are highly involved in morphologic changes in cells. When a tumor progresses from invasive to metastatic form it requires that they
1723:. These contribute to many progresses such as regulation of morphology, gene transcription, proliferation, differentiation, apoptosis and oncogenic transformation. Other functions involve smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation,
1846:
Overexpression of ROCK1 and RhoA is often seen in breast cancer. Activated ROCK1 phosphorylates MLC involved in actin-myosin contractility. RhoA also activates focal adhesion kinase activity. Together, these two pathways create the motile and invasive phenotype of cancer cells.
55:
1829:
undergo these dramatic morphologic changes. Therefore, increased expression of RhoA and its downstream effector ROCK1 is often observed in human cancers. These cancers are typically more invasive and metastatic phenotypes.
1658:
ROCK1 phosphorylation sites are at RXXS/T or RXS/T. More than 15 ROCK1 substrates have been identified and activation from these substrates most often leads to actin filament formation and cytoskeleton rearrangements.
1667:
contraction. When ROCK1 is activated by binding of GTPase RhoA it produces multiple signaling cascades. For example, RhoA is one of the downstream signaling cascades activated by vascular endothelial growth factor
379:
278:
1820:
transcription, proliferation, differentiation, apoptosis and oncogenic transformation. Given this diverse range of functions, it is not surprising that ROCK1 has been implicated in numerous aspects of cancer.
1838:
the plasticity of the tumor. By reducing the strength of cell-cell interactions and aiding the movement of tumor cells, ROCK1 may enable endothelial cells to penetrate the tumor mass more easily.
1525:
ROCK1 is also the name of the gene that encodes the protein ROCK1, a serine/threonine kinase. ROCK1 is activated when bound to the GTP-bound form of RhoA. The human ROCK1 gene is located on human
3284:
3569:
1572:
The ROCK1 structure is a serine/threonine kinase with molecular weight of 158 kDa. It is a homodimer composed of a catalytic kinase domain (residues76-338) located at the amino or
2842:
Croft DR, Sahai E, Mavria G, Li S, Tsai J, Lee WM, Marshall CJ, Olson MF (December 2004). "Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis".
3189:
3042:
Dahal BK, Kosanovic D, Pamarthi PK, Sydykov A, Lai YJ, Kast R, Schirok H, Stasch JP, Ghofrani HA, Weissmann N, Grimminger F, Seeger W, Schermuly RT (October 2010).
2499:"Sphingosylphosphorylcholine is a novel messenger for Rho-kinase-mediated Ca2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C"
3277:
1608:
This view of autoinhibition released by RhoA binding has been challenged by low resolution electron microscopy data showing ROCK to be a constitutive linear
3131:
2497:
Shirao S, Kashiwagi S, Sato M, Miwa S, Nakao F, Kurokawa T, Todoroki-Ikeda N, Mogami K, Mizukami Y, Kuriyama S, Haze K, Suzuki M, Kobayashi S (July 2002).
1912:. Fasudil has been used to characterize the role of ROCK1 in vascular function in clinical studies and has been approved for use in Japan for treatment of
1221:
201:
3270:
1635:
can increase ROCK1 activity 5- to 6-fold. These two lipids interact with the pleckstrin-homology domain, thus disrupting its ability to inhibit ROCK1.
1202:
1855:). HIFs have been shown to activate transcription of RhoA and ROCK1 leading to cytoskeletal changes that underlie the invasive cancer cell phenotype.
3477:
3232:
4822:
1684:(MLC) and an increase in contractility, which plays a crucial role in tumor cell migration and metastasis. This activated ROCK1 also activates
2596:
Kroll, Jens; Epting, Daniel; Kern, Katrin; Dietz, Christian T.; Feng, Yuxi; Hammes, Hans-Peter; Wieland, Thomas; Augustin, Hellmut G. (2009).
2036:
2018:
4864:
4025:
3328:
4973:
3711:
3598:
2995:"Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson's disease"
1421:
3986:
1428:
4959:
4778:
4424:
4020:
4010:
4005:
3315:
3297:
2456:
Feng J, Ito M, Kureishi Y, Ichikawa K, Amano M, Isaka N, Okawa K, Iwamatsu A, Kaibuchi K, Hartshorne DJ, Nakano T (February 1999).
5061:
4942:
3222:
2749:"The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton"
2635:
2958:
1696:
activity. This depolymerization results in stabilization of actin filaments and decreased branching which promotes contraction.
4648:
3517:
5441:
4712:
3687:
3169:
1588:
domain. When a substrate is absent, ROCK1 is an autoinhibited loop structure. Enzyme activity of ROCK1 is inhibited when the
2001:
4968:
2598:"Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis"
52:
3240:
3204:
3502:
1980:
4700:
5025:
3138:
1719:
ROCK1 has a diverse range of functions in the body. It is a key regulator of actin-myosin contraction, stability, and
365:
5140:
3957:
3947:
3632:
3262:
4639:
342:
4908:
4580:
3942:
3933:
2005:
1984:
1736:
2257:"ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice"
1266:
2798:"Identification of the Rho-binding domain of p160ROCK, a Rho-associated coiled-coil containing protein kinase"
5296:
4323:
3820:
3811:
3468:
3414:
2993:
Tönges L, Frank T, Tatenhorst L, Saal KA, Koch JC, Szego ĂM, BĂ€hr M, Weishaupt JH, Lingor P (November 2012).
1941:
1529:
with specific location of 18q11.1. The location of the base pair starts at 18,529,703 and ends at 18,691,812
264:
239:
1247:
3511:
1889:
1627:
GTPase-RhoA binding can increase the activity of ROCK1 by 1.5-2-fold. Without RhoA binding, lipids such as
181:
2892:"Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells"
2597:
1908:
for the kinase activation site. Experiments with Y27632 show it is a promising candidate as a therapeutic
1776:
1693:
1642:
binds to the N-terminus of ROCK1 and inhibits its activity by preventing RhoA binding. Small G-proteins,
378:
277:
5411:
4535:
4353:
3849:
1933:
1589:
1564:
cytoskeleton organization. In rats, ROCK1 is expressed in the lung, liver, spleen, kidney, and testis.
371:
270:
5397:
5384:
5371:
5358:
5345:
5332:
5319:
5281:
4525:
4520:
4515:
4505:
4500:
4495:
4485:
4280:
4055:
3651:
3162:
1852:
168:
2538:
Amano M, Fukata Y, Kaibuchi K (November 2000). "Regulation and functions of Rho-associated kinase".
5291:
5245:
5188:
4748:
4739:
4690:
3456:
3301:
1545:
189:
5193:
5048:
4471:
1917:
1484:
2123:"ROCK1 Rho-associated, coiled-coil containing protein kinase 1 [ Homo sapiens (human) ]"
1650:, have been shown to bind and inhibit ROCK1 function, but their mechanism of action is unclear.
1612:
120 nm in length. According to this new data ROCK does not need to be activated by RhoA or
1404:
1383:
1357:
1336:
3198:: Crystal structure of the complex between the human RhoA and Rho-binding domain of human ROCKI
1945:
1937:
1905:
1851:
often contain regions of reduced O2 which increases the activity of hypoxia-inducible factors (
1491:. Other common names are ROKÎČ and P160ROCK. ROCK1 is a major downstream effector of the small
5214:
5133:
3747:
2651:"RhoA/ROCK regulation of neuritogenesis via profilin IIa-mediated control of actin stability"
1909:
1767:. It is also required for centrosome positioning and centrosome-dependent exit from mitosis.
1534:
253:
2075:"Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy"
1703:
is another ROCK1 substrate that upon phosphorylation causes reduction in tension in cardiac
1505:
which promotes contractile force generation. ROCK1 plays a role in cancer and in particular
5286:
4314:
3155:
2903:
2409:
2141:
1664:
209:
8:
5250:
4423:
2352:
Jacobs M, Hayakawa K, Swenson L, Bellon S, Fleming M, Taslimi P, Doran J (January 2006).
1764:
3314:
2907:
2890:
Gilkes DM, Xiang L, Lee SJ, Chaturvedi P, Hubbi ME, Wirtz D, Semenza GL (January 2014).
2413:
2181:
2156:
1763:
and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane
5446:
5183:
4925:
4879:
3112:
3019:
2994:
2975:
2967:
2926:
2891:
2867:
2675:
2650:
2515:
2498:
2430:
2397:
2286:
2237:
2194:
2099:
2074:
1913:
1681:
1617:
213:
2773:
2748:
2724:
2699:
1896:
ROCK1 inhibition for cancer treatment has not been approved for standard therapy use.
1616:
because it is always active, and whether ROCK will phosphorylate its substrates (e.g.
1136:
1131:
1126:
1121:
1116:
1111:
1106:
1101:
1096:
1091:
1086:
1081:
1076:
1071:
1066:
1061:
1056:
1051:
1046:
1041:
1036:
1031:
1026:
1021:
1016:
1011:
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996:
991:
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981:
976:
971:
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951:
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941:
936:
931:
926:
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674:
669:
664:
659:
654:
649:
4185:
3894:
3292:
3104:
3087:
Riento K, Ridley AJ (June 2003). "Rocks: multifunctional kinases in cell behaviour".
3065:
3024:
2950:
2931:
2859:
2819:
2778:
2729:
2715:
2680:
2617:
2555:
2520:
2479:
2435:
2375:
2336:
2278:
2273:
2256:
2229:
2212:
Riento K, Ridley AJ (June 2003). "Rocks: multifunctional kinases in cell behaviour".
2186:
2104:
1676:
activation and angiogenesis. ROCK1 activation by RhoA also promotes stabilization of
161:
45:
3116:
2241:
5229:
5224:
5198:
5126:
3923:
3914:
3844:
3835:
3781:
3772:
3429:
3096:
3055:
3014:
3006:
2942:
2921:
2911:
2871:
2851:
2809:
2768:
2760:
2719:
2711:
2670:
2662:
2609:
2547:
2510:
2469:
2425:
2417:
2365:
2290:
2268:
2221:
2198:
2176:
2168:
2157:"Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity"
2094:
2086:
1673:
1628:
458:
389:
333:
288:
193:
2855:
2649:
Da Silva JS, Medina M, Zuliani C, Di Nardo A, Witke W, Dotti CG (September 2003).
5276:
5260:
5173:
4604:
3675:
3670:
3665:
3142:
1613:
433:
217:
2613:
2255:
Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S (August 1996).
2041:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2023:
National Center for
Biotechnology Information, U.S. National Library of Medicine
5425:
5314:
5255:
2896:
Proceedings of the
National Academy of Sciences of the United States of America
1848:
1707:. ROCK1 also acts as a suppressor of inflammatory cell migration by regulating
1553:
534:
3060:
3043:
2354:"The structure of dimeric ROCK I reveals the mechanism for ligand selectivity"
2172:
5435:
5219:
5178:
3660:
2814:
2797:
1868:
1728:
1720:
1632:
1609:
1526:
1506:
636:
3728:
3044:"Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension"
2946:
2916:
2636:"Entrez Gene: ROCK1 Rho-associated, coiled-coil containing protein kinase 1"
594:
472:
5168:
4599:
3424:
3135:
3108:
3069:
3028:
3010:
2954:
2935:
2863:
2764:
2733:
2684:
2621:
2559:
2551:
2524:
2474:
2457:
2439:
2379:
2370:
2353:
2233:
2190:
2108:
2090:
1514:
1502:
451:
230:
2964:. If this is an intentional citation to a retracted paper, please replace
2823:
2782:
2666:
2483:
2282:
1468:
1463:
172:, P160ROCK, ROCK-I, Rho associated coiled-coil containing protein kinase 1
5392:
5327:
5163:
4805:
4437:
4377:
4260:
4180:
3904:
2582:
2398:"A molecular ruler regulates cytoskeletal remodelling by the Rho kinases"
2122:
1872:
1708:
1647:
1577:
1549:
1538:
1311:
1292:
28:
2796:
Fujisawa K, Fujita A, Ishizaki T, Saito Y, Narumiya S (September 1996).
2421:
4893:
3367:
1957:
1928:
The ROCK1 signaling plays an important role in many diseases including
1904:
are examples of ROCK1 inhibitors. Both inhibit ROCK1 by competing with
1878:
1685:
1643:
1593:
1585:
1581:
1573:
1557:
1510:
1499:
350:
247:
197:
138:
134:
130:
126:
122:
118:
114:
110:
106:
102:
98:
94:
90:
86:
82:
78:
74:
5366:
5340:
3854:
1636:
1602:
1598:
1530:
1166:
417:
404:
316:
303:
205:
3100:
2225:
5420:
4210:
4105:
4100:
4095:
1929:
1795:
1756:
1704:
1700:
1660:
1452:
3570:
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase
1731:
and motility. These functions are activated by phosphorylation of
1092:
negative regulation of amyloid precursor protein catabolic process
4869:
4847:
4842:
4832:
4827:
4629:
4624:
4619:
4614:
4609:
4594:
4589:
4240:
4205:
3444:
3439:
3434:
3250:
3214:
1901:
1724:
1689:
1677:
1278:
1233:
1151:
1147:
2602:
American
Journal of Physiology. Heart and Circulatory Physiology
185:
5379:
5149:
5099:
5094:
5089:
5084:
5079:
5074:
5069:
5020:
5015:
5010:
5005:
5000:
4983:
4978:
4852:
4837:
4788:
4783:
4768:
4763:
4758:
4753:
4727:
4722:
4717:
4705:
4683:
4678:
4570:
4545:
4220:
4045:
4040:
4035:
4030:
4015:
3859:
3796:
3791:
3786:
3762:
3588:
3583:
3557:
3552:
3547:
3537:
3532:
3522:
3362:
3293:
1897:
1584:, and a pleckstrin-homology domain (residues 1118-1317) with a
1492:
1436:
1188:
3147:
1047:
negative regulation of membrane protein ectodomain proteolysis
927:
negative regulation of myosin-light-chain-phosphatase activity
5353:
4995:
4988:
4898:
4795:
4695:
4673:
4668:
4663:
4658:
4653:
4565:
4560:
4555:
4550:
4540:
4510:
4490:
4367:
4362:
4343:
4338:
4328:
4304:
4299:
4294:
4270:
4265:
4255:
4250:
4245:
4235:
4215:
4200:
4195:
4190:
4170:
4165:
4155:
4150:
4145:
4140:
4135:
4125:
4120:
4115:
4110:
4090:
4085:
4080:
4075:
4070:
4065:
4050:
4000:
3995:
3889:
3884:
3879:
3874:
3869:
3864:
3825:
3757:
3752:
3701:
3696:
3622:
3617:
3612:
3578:
3357:
3352:
3347:
3342:
3337:
3041:
2648:
2395:
2254:
1783:
1760:
1744:
1740:
1732:
1561:
1552:. This is consistent with its function as a key modulator of
882:
vascular endothelial growth factor receptor signaling pathway
2396:
Truebestein L, Elsner DJ, Fuchs E, Leonard TA (2015-12-01).
4888:
4815:
4810:
4800:
4773:
4530:
4480:
4461:
4456:
4451:
4446:
4401:
4396:
4391:
4386:
4333:
4289:
4230:
4225:
4175:
4160:
4130:
4060:
3976:
3971:
3966:
3899:
3801:
3742:
3737:
3641:
3607:
3492:
3487:
3482:
3451:
3419:
3407:
3402:
3397:
3387:
3382:
2795:
2698:
Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (June 2003).
2351:
1882:
1807:
1801:
1789:
1752:
1748:
1669:
1639:
1495:
5118:
4857:
3392:
3377:
2992:
2142:"Rho-Associated, Coiled-Coil Containing Protein Kinase 1"
877:
negative regulation of bicellular tight junction assembly
5047:
2889:
2700:"RhoE binds to ROCK I and inhibits downstream signaling"
2458:"Rho-associated kinase of chicken gizzard smooth muscle"
441:
2496:
2455:
1489:
rho-associated, coiled-coil-containing protein kinase 1
1863:
ROCK1 inhibitors might be used in cancer therapy for:
700:
Rho-dependent protein serine/threonine kinase activity
5409:
1858:
1062:
regulation of angiotensin-activated signaling pathway
606:
2595:
1097:
positive regulation of connective tissue replacement
1052:
negative regulation of biomineral tissue development
2697:
2537:
2841:
2747:Leung T, Chen XQ, Manser E, Lim L (October 1996).
2746:
1997:
1995:
1993:
1976:
1974:
1972:
1620:) depends only on their subcellular localization.
952:regulation of establishment of endothelial barrier
2068:
2066:
2064:
2062:
2060:
2058:
2056:
2054:
2052:
2050:
1624:identified genes and are ubiquitously expressed.
1017:positive regulation of cardiac muscle hypertrophy
388:
287:
5433:
2154:
1544:ROCK1 has a ubiquitous tissue distribution, but
1990:
1969:
807:negative regulation of neuron apoptotic process
2885:
2883:
2881:
2047:
2002:GRCm38: Ensembl release 89: ENSMUSG00000024290
1672:). ROCK1 acts as a negative regulator of VEGF
1653:
922:positive regulation of focal adhesion assembly
5134:
3329:Non-specific serine/threonine protein kinases
3278:
3163:
2837:
2835:
2833:
2338:Chapter 7Rho Kinase in Vascular Smooth Muscle
1888:treating haematological malignancies such as
1087:negative regulation of amyloid-beta formation
1072:positive regulation of amyloid-beta clearance
832:regulation of actin cytoskeleton organization
3086:
3035:
2986:
2691:
2642:
2451:
2449:
2341:. Morgan & Claypool Life Sciences. 2010.
2211:
997:G protein-coupled receptor signaling pathway
937:regulation of establishment of cell polarity
2878:
2789:
2740:
2345:
2248:
2205:
2148:
1981:GRCh38: Ensembl release 89: ENSG00000067900
1567:
1057:response to transforming growth factor beta
5141:
5127:
3712:Goodpasture-antigen-binding protein kinase
3285:
3271:
3170:
3156:
2978:|...|intentional=yes}}
2830:
2531:
1580:region (residues 425-1100) containing the
1077:regulation of synaptic vesicle endocytosis
917:regulation of keratinocyte differentiation
857:regulation of actin filament-based process
4425:Serine/threonine-specific protein kinases
3599:(isocitrate dehydrogenase (NADP+)) kinase
3316:Serine/threonine-specific protein kinases
3298:Serine/threonine-specific protein kinases
3059:
3018:
2925:
2915:
2813:
2772:
2723:
2674:
2577:
2575:
2573:
2571:
2569:
2514:
2473:
2446:
2429:
2369:
2330:
2328:
2326:
2324:
2322:
2320:
2272:
2180:
2098:
2072:
4960:Receptor protein serine/threonine kinase
2335:"Rho Kinase in Vascular Smooth Muscle".
2318:
2316:
2314:
2312:
2310:
2308:
2306:
2304:
2302:
2300:
1814:
942:cortical actin cytoskeleton organization
675:protein serine/threonine kinase activity
4943:Low-density-lipoprotein receptor kinase
3249:: Crystal Structure of ROCK I bound to
3231:: Crystal Structure of ROCK 1 bound to
3213:: Crystal Structure of ROCK 1 bound to
2155:Hahmann C, Schroeter T (January 2010).
2136:
2134:
2132:
992:protein localization to plasma membrane
972:regulation of cytoskeleton organization
5434:
2589:
2566:
1520:
1022:positive regulation of gene expression
852:negative regulation of protein binding
5122:
5046:
4422:
3688:Fas-activated serine/threonine kinase
3313:
3266:
3151:
3089:Nature Reviews Molecular Cell Biology
2490:
2391:
2389:
2297:
2214:Nature Reviews Molecular Cell Biology
1759:. Additionally, ROCK1 phosphorylates
1548:it is thought to colocalize with the
907:regulation of focal adhesion assembly
393:
354:
349:
292:
251:
246:
5060:
4969:Bone morphogenetic protein receptors
2161:Cellular and Molecular Life Sciences
2129:
2115:
1137:regulation of cell junction assembly
1082:regulation of amyloid-beta formation
1042:regulation of neuron differentiation
3503:Dephospho-(reductase kinase) kinase
2802:The Journal of Biological Chemistry
2462:The Journal of Biological Chemistry
2358:The Journal of Biological Chemistry
1037:positive regulation of MAPK cascade
932:I-kappaB kinase/NF-kappaB signaling
912:negative regulation of angiogenesis
862:regulation of stress fiber assembly
13:
3958:G-protein coupled receptor kinases
3079:
2516:10.1161/01.res.0000026057.13161.42
2386:
1859:ROCK1 inhibitors in cancer therapy
1122:peptidyl-threonine phosphorylation
14:
5458:
3948:Beta adrenergic receptor kinase-2
3633:(tyrosine 3-monooxygenase) kinase
3125:
2073:Rath N, Olson MF (October 2012).
1923:
1877:concomitant blocking of ROCK and
1823:
1127:actomyosin structure organization
1112:blood vessel diameter maintenance
842:ephrin receptor signaling pathway
827:intracellular signal transduction
5419:
4640:Mitogen-activated protein kinase
3239:
3221:
3203:
3188:
3048:The European Respiratory Journal
2716:10.1128/mcb.23.12.4219-4229.2003
1841:
1680:, phosphorylation of regulatory
1012:positive regulation of autophagy
377:
370:
364:
341:
276:
269:
263:
238:
27:
5026:Anti-MĂŒllerian hormone receptor
4909:(acetyl-CoA carboxylase) kinase
4581:(RNA-polymerase)-subunit kinase
3943:Beta adrenergic receptor kinase
3934:Beta adrenergic receptor kinase
3177:
2628:
1832:
1770:
1711:phosphorylation and stability.
1592:and Rho-binding domains in the
1027:peptidyl-serine phosphorylation
957:actin cytoskeleton organization
892:Rho protein signal transduction
4649:Extracellular signal-regulated
2753:Molecular and Cellular Biology
2704:Molecular and Cellular Biology
2029:
2011:
1605:can also activate the kinase.
1067:neuron projection arborization
902:leukocyte tethering or rolling
595:More reference expression data
1:
4713:P38 mitogen-activated protein
3812:cGMP-dependent protein kinase
3773:cAMP-dependent protein kinase
3469:Pyruvate dehydrogenase kinase
3415:Ataxia telangiectasia mutated
2856:10.1158/0008-5472.CAN-04-2052
1963:
1942:amyotrophic lateral sclerosis
1663:is involved in a pathway for
1633:sphingosine phosphorylcholine
1618:myosin regulatory light chain
1032:neuron projection development
545:tunica media of zone of aorta
362:
261:
5442:Genes on human chromosome 18
3512:AMP-activated protein kinase
2274:10.1016/0014-5793(96)00811-3
1890:chronic myelogenous leukemia
987:execution phase of apoptosis
897:membrane to membrane docking
812:leukocyte cell-cell adhesion
7:
5148:
4427:(EC 2.7.11.21-EC 2.7.11.30)
2655:The Journal of Cell Biology
2614:10.1152/ajpheart.01038.2008
1951:
1714:
1654:Substrates and interactions
887:regulation of cell adhesion
867:regulation of cell motility
695:tau-protein kinase activity
10:
5463:
4354:Elongation factor 2 kinase
3318:(EC 2.7.11.1-EC 2.7.11.20)
2540:Experimental Cell Research
1934:neurodegenerative diseases
1498:and is a regulator of the
1002:aortic valve morphogenesis
786:cytoplasmic stress granule
5305:
5297:MichaelisâMenten kinetics
5269:
5238:
5207:
5156:
5056:
5042:
4958:
4941:
4924:
4907:
4878:
4749:MAP kinase kinase kinases
4738:
4638:
4579:
4470:
4436:
4432:
4418:
4376:
4352:
4313:
4281:Myosin light-chain kinase
4279:
3987:Ca2+/calmodulin-dependent
3985:
3956:
3932:
3913:
3834:
3810:
3771:
3727:
3710:
3686:
3652:Myosin-heavy-chain kinase
3650:
3631:
3597:
3568:
3501:
3467:
3327:
3323:
3309:
3183:
3061:10.1183/09031936.00140309
2173:10.1007/s00018-009-0189-x
2037:"Mouse PubMed Reference:"
2019:"Human PubMed Reference:"
1467:
1462:
1458:
1451:
1435:
1416:
1401:
1397:
1380:
1376:
1369:
1354:
1350:
1333:
1329:
1322:
1309:
1305:
1290:
1286:
1277:
1264:
1260:
1245:
1241:
1232:
1219:
1215:
1200:
1196:
1187:
1172:
1165:
1161:
1145:
817:smooth muscle contraction
635:
631:
619:
614:
605:
592:
541:
532:
511:Descending thoracic aorta
479:
470:
440:
432:
428:
411:
398:
361:
340:
331:
327:
310:
297:
260:
237:
228:
224:
179:
176:
166:
159:
154:
71:
66:
49:
44:
39:
35:
26:
21:
5189:Diffusion-limited enzyme
5049:Dual-specificity kinases
2815:10.1074/jbc.271.38.23022
1775:ROCK1 has been shown to
1688:, which, phosphorylates
1568:Structure and regulation
1429:Chr 18: 10.06 â 10.18 Mb
1422:Chr 18: 20.95 â 21.11 Mb
982:neutrophil degranulation
549:Rostral migratory stream
4472:Cyclin-dependent kinase
3134:Info with links in the
2947:10.1073/pnas.2213288119
2917:10.1073/pnas.1321510111
1918:subarachnoid hemorrhage
1485:serine/threonine kinase
1132:embryonic morphogenesis
1102:response to angiotensin
1007:regulation of autophagy
872:protein phosphorylation
781:secretory granule lumen
655:protein kinase activity
3136:Cell Migration Gateway
2765:10.1128/mcb.16.10.5313
2583:"Q13464 (ROCK1_HUMAN)"
2552:10.1006/excr.2000.5046
2475:10.1074/jbc.274.6.3744
2371:10.1074/jbc.M508847200
2091:10.1038/embor.2012.127
1946:pulmonary hypertension
1910:antihypertensive agent
5282:EadieâHofstee diagram
5215:Allosteric regulation
2970:|...}}
2941:(Retracted, see
2667:10.1083/jcb.200304021
2402:Nature Communications
1885:âdriven lung cancers
1815:Clinical significance
499:right coronary artery
356:Chromosome 18 (mouse)
254:Chromosome 18 (human)
5292:LineweaverâBurk plot
4315:Phosphorylase kinase
3011:10.1093/brain/aws254
2503:Circulation Research
1694:actin-depolymerizing
1107:mRNA destabilization
791:amyloid-beta complex
776:extracellular region
650:transferase activity
507:left coronary artery
67:List of PDB id codes
40:Available structures
2908:2014PNAS..111E.384G
2422:10.1038/ncomms10029
2414:2015NatCo...610029T
1938:Parkinson's disease
1590:pleckstrin-homology
1558:tumor cell invasion
1521:Gene and expression
1117:mitotic cytokinesis
967:signal transduction
962:leukocyte migration
947:apical constriction
690:tau protein binding
519:epithelium of colon
5251:Enzyme superfamily
5184:Enzyme promiscuity
4926:Tropomyosin kinase
4880:Tau-protein kinase
3141:2014-12-11 at the
3005:(Pt 11): 3355â70.
1914:cerebral vasospasm
1682:myosin light chain
1582:Rho-binding domain
1576:of the protein, a
1267:ENSMUSG00000024290
822:myoblast migration
800:Biological process
709:Cellular component
660:nucleotide binding
643:Molecular function
5407:
5406:
5116:
5115:
5112:
5111:
5108:
5107:
5038:
5037:
5034:
5033:
4414:
4413:
4410:
4409:
3895:Protein kinase N1
3850:Protein kinase Cζ
3260:
3259:
2850:(24): 8994â9001.
1692:, inhibiting its
1478:
1477:
1474:
1473:
1447:
1446:
1412:
1411:
1391:
1390:
1365:
1364:
1344:
1343:
1318:
1317:
1299:
1298:
1273:
1272:
1254:
1253:
1228:
1227:
1209:
1208:
1157:
1156:
977:apoptotic process
665:metal ion binding
627:
626:
623:
622:
601:
600:
588:
587:
526:
525:
503:bone marrow cells
424:
423:
323:
322:
218:ROCK1 - orthologs
150:
149:
146:
145:
50:Ortholog search:
5454:
5424:
5423:
5415:
5287:HanesâWoolf plot
5230:Enzyme activator
5225:Enzyme inhibitor
5199:Enzyme catalysis
5143:
5136:
5129:
5120:
5119:
5058:
5057:
5044:
5043:
4691:C-Jun N-terminal
4434:
4433:
4420:
4419:
3924:Rhodopsin kinase
3915:Rhodopsin kinase
3845:Protein kinase C
3836:Protein kinase C
3821:Protein kinase G
3782:Protein kinase A
3393:Protein kinase B
3325:
3324:
3311:
3310:
3287:
3280:
3273:
3264:
3263:
3243:
3225:
3207:
3192:
3172:
3165:
3158:
3149:
3148:
3120:
3074:
3073:
3063:
3039:
3033:
3032:
3022:
2990:
2984:
2983:
2981:
2979:
2971:
2960:Retraction Watch
2939:
2929:
2919:
2887:
2876:
2875:
2839:
2828:
2827:
2817:
2793:
2787:
2786:
2776:
2744:
2738:
2737:
2727:
2695:
2689:
2688:
2678:
2646:
2640:
2639:
2632:
2626:
2625:
2608:(3): H893âH899.
2593:
2587:
2586:
2579:
2564:
2563:
2535:
2529:
2528:
2518:
2494:
2488:
2487:
2477:
2453:
2444:
2443:
2433:
2393:
2384:
2383:
2373:
2349:
2343:
2342:
2332:
2295:
2294:
2276:
2252:
2246:
2245:
2209:
2203:
2202:
2184:
2152:
2146:
2145:
2138:
2127:
2126:
2119:
2113:
2112:
2102:
2070:
2045:
2044:
2033:
2027:
2026:
2015:
2009:
1999:
1988:
1978:
1674:endothelial cell
1629:arachidonic acid
1460:
1459:
1431:
1424:
1407:
1395:
1394:
1386:
1374:
1373:
1370:RefSeq (protein)
1360:
1348:
1347:
1339:
1327:
1326:
1303:
1302:
1284:
1283:
1258:
1257:
1239:
1238:
1213:
1212:
1194:
1193:
1163:
1162:
633:
632:
612:
611:
597:
557:secondary oocyte
537:
535:Top expressed in
530:
529:
487:popliteal artery
475:
473:Top expressed in
468:
467:
447:
446:
430:
429:
420:
407:
396:
381:
374:
368:
357:
345:
329:
328:
319:
306:
295:
280:
273:
267:
256:
242:
226:
225:
220:
171:
164:
141:
64:
63:
58:
37:
36:
31:
19:
18:
5462:
5461:
5457:
5456:
5455:
5453:
5452:
5451:
5432:
5431:
5430:
5418:
5410:
5408:
5403:
5315:Oxidoreductases
5301:
5277:Enzyme kinetics
5265:
5261:List of enzymes
5234:
5203:
5174:Catalytic triad
5152:
5147:
5117:
5104:
5052:
5030:
4954:
4937:
4920:
4903:
4874:
4734:
4634:
4605:P70-S6 Kinase 1
4575:
4466:
4428:
4406:
4372:
4348:
4309:
4275:
3981:
3952:
3928:
3909:
3830:
3806:
3767:
3723:
3706:
3682:
3676:Aurora C kinase
3671:Aurora B kinase
3666:Aurora A kinase
3646:
3627:
3593:
3564:
3497:
3463:
3319:
3305:
3291:
3261:
3256:
3253:
3244:
3235:
3226:
3217:
3208:
3199:
3193:
3179:
3176:
3143:Wayback Machine
3128:
3123:
3101:10.1038/nrm1128
3082:
3080:Further reading
3077:
3040:
3036:
2991:
2987:
2973:
2965:
2963:
2940:
2888:
2879:
2844:Cancer Research
2840:
2831:
2808:(38): 23022â8.
2794:
2790:
2759:(10): 5313â27.
2745:
2741:
2710:(12): 4219â29.
2696:
2692:
2647:
2643:
2634:
2633:
2629:
2594:
2590:
2581:
2580:
2567:
2536:
2532:
2495:
2491:
2454:
2447:
2394:
2387:
2350:
2346:
2334:
2333:
2298:
2253:
2249:
2226:10.1038/nrm1128
2210:
2206:
2153:
2149:
2140:
2139:
2130:
2121:
2120:
2116:
2071:
2048:
2035:
2034:
2030:
2017:
2016:
2012:
2000:
1991:
1979:
1970:
1966:
1954:
1926:
1861:
1844:
1835:
1826:
1817:
1773:
1717:
1656:
1614:phosphorylation
1570:
1523:
1469:View/Edit Mouse
1464:View/Edit Human
1427:
1420:
1417:Location (UCSC)
1403:
1382:
1356:
1335:
1248:ENSG00000067900
1141:
837:phosphorylation
795:
751:plasma membrane
731:cell projection
726:Golgi apparatus
704:
680:protein binding
670:kinase activity
593:
584:
579:
575:
571:
567:
565:ascending aorta
563:
559:
555:
551:
547:
533:
522:
517:
515:ascending aorta
513:
509:
505:
501:
497:
493:
491:tibial arteries
489:
485:
483:Achilles tendon
471:
415:
402:
394:
384:
383:
382:
375:
355:
332:Gene location (
314:
301:
293:
283:
282:
281:
274:
252:
229:Gene location (
180:
167:
160:
73:
51:
17:
12:
11:
5:
5460:
5450:
5449:
5444:
5429:
5428:
5405:
5404:
5402:
5401:
5388:
5375:
5362:
5349:
5336:
5323:
5309:
5307:
5303:
5302:
5300:
5299:
5294:
5289:
5284:
5279:
5273:
5271:
5267:
5266:
5264:
5263:
5258:
5253:
5248:
5242:
5240:
5239:Classification
5236:
5235:
5233:
5232:
5227:
5222:
5217:
5211:
5209:
5205:
5204:
5202:
5201:
5196:
5191:
5186:
5181:
5176:
5171:
5166:
5160:
5158:
5154:
5153:
5146:
5145:
5138:
5131:
5123:
5114:
5113:
5110:
5109:
5106:
5105:
5103:
5102:
5097:
5092:
5087:
5082:
5077:
5072:
5066:
5064:
5054:
5053:
5040:
5039:
5036:
5035:
5032:
5031:
5029:
5028:
5023:
5018:
5013:
5008:
5003:
4998:
4993:
4992:
4991:
4986:
4981:
4976:
4965:
4963:
4962:(EC 2.7.11.30)
4956:
4955:
4953:
4952:
4948:
4946:
4945:(EC 2.7.11.29)
4939:
4938:
4936:
4935:
4931:
4929:
4928:(EC 2.7.11.28)
4922:
4921:
4919:
4918:
4914:
4912:
4911:(EC 2.7.11.27)
4905:
4904:
4902:
4901:
4896:
4891:
4885:
4883:
4882:(EC 2.7.11.26)
4876:
4875:
4873:
4872:
4867:
4862:
4861:
4860:
4855:
4850:
4845:
4840:
4835:
4830:
4820:
4819:
4818:
4813:
4808:
4803:
4793:
4792:
4791:
4786:
4781:
4776:
4771:
4766:
4761:
4756:
4745:
4743:
4742:(EC 2.7.11.25)
4736:
4735:
4733:
4732:
4731:
4730:
4725:
4720:
4710:
4709:
4708:
4703:
4698:
4688:
4687:
4686:
4681:
4676:
4671:
4666:
4661:
4656:
4645:
4643:
4642:(EC 2.7.11.24)
4636:
4635:
4633:
4632:
4627:
4622:
4617:
4612:
4607:
4602:
4597:
4592:
4586:
4584:
4583:(EC 2.7.11.23)
4577:
4576:
4574:
4573:
4568:
4563:
4558:
4553:
4548:
4543:
4538:
4533:
4528:
4523:
4518:
4513:
4508:
4503:
4498:
4493:
4488:
4483:
4477:
4475:
4474:(EC 2.7.11.22)
4468:
4467:
4465:
4464:
4459:
4454:
4449:
4443:
4441:
4440:(EC 2.7.11.21)
4430:
4429:
4416:
4415:
4412:
4411:
4408:
4407:
4405:
4404:
4399:
4394:
4389:
4383:
4381:
4380:(EC 2.7.11.21)
4374:
4373:
4371:
4370:
4365:
4359:
4357:
4356:(EC 2.7.11.20)
4350:
4349:
4347:
4346:
4341:
4336:
4331:
4326:
4320:
4318:
4317:(EC 2.7.11.19)
4311:
4310:
4308:
4307:
4302:
4297:
4292:
4286:
4284:
4283:(EC 2.7.11.18)
4277:
4276:
4274:
4273:
4268:
4263:
4258:
4253:
4248:
4243:
4238:
4233:
4228:
4223:
4218:
4213:
4208:
4203:
4198:
4193:
4188:
4183:
4178:
4173:
4168:
4163:
4158:
4153:
4148:
4143:
4138:
4133:
4128:
4123:
4118:
4113:
4108:
4103:
4098:
4093:
4088:
4083:
4078:
4073:
4068:
4063:
4058:
4053:
4048:
4043:
4038:
4033:
4028:
4023:
4018:
4013:
4008:
4003:
3998:
3992:
3990:
3989:(EC 2.7.11.17)
3983:
3982:
3980:
3979:
3974:
3969:
3963:
3961:
3960:(EC 2.7.11.16)
3954:
3953:
3951:
3950:
3945:
3939:
3937:
3936:(EC 2.7.11.15)
3930:
3929:
3927:
3926:
3920:
3918:
3917:(EC 2.7.11.14)
3911:
3910:
3908:
3907:
3902:
3897:
3892:
3887:
3882:
3877:
3872:
3867:
3862:
3857:
3852:
3847:
3841:
3839:
3838:(EC 2.7.11.13)
3832:
3831:
3829:
3828:
3823:
3817:
3815:
3814:(EC 2.7.11.12)
3808:
3807:
3805:
3804:
3799:
3794:
3789:
3784:
3778:
3776:
3775:(EC 2.7.11.11)
3769:
3768:
3766:
3765:
3760:
3755:
3750:
3745:
3740:
3734:
3732:
3731:(EC 2.7.11.10)
3725:
3724:
3722:
3721:
3717:
3715:
3708:
3707:
3705:
3704:
3699:
3693:
3691:
3684:
3683:
3681:
3680:
3679:
3678:
3673:
3668:
3657:
3655:
3648:
3647:
3645:
3644:
3638:
3636:
3629:
3628:
3626:
3625:
3620:
3615:
3610:
3604:
3602:
3595:
3594:
3592:
3591:
3586:
3581:
3575:
3573:
3566:
3565:
3563:
3562:
3561:
3560:
3555:
3550:
3542:
3541:
3540:
3535:
3527:
3526:
3525:
3520:
3508:
3506:
3499:
3498:
3496:
3495:
3490:
3485:
3480:
3474:
3472:
3465:
3464:
3462:
3461:
3460:
3459:
3449:
3448:
3447:
3442:
3437:
3432:
3422:
3417:
3412:
3411:
3410:
3405:
3400:
3390:
3385:
3380:
3375:
3370:
3365:
3360:
3355:
3350:
3345:
3340:
3334:
3332:
3321:
3320:
3307:
3306:
3290:
3289:
3282:
3275:
3267:
3258:
3257:
3255:
3254:
3245:
3238:
3236:
3233:hydroxyfasudil
3227:
3220:
3218:
3209:
3202:
3200:
3194:
3187:
3184:
3181:
3180:
3175:
3174:
3167:
3160:
3152:
3146:
3145:
3127:
3126:External links
3124:
3122:
3121:
3083:
3081:
3078:
3076:
3075:
3034:
2985:
2902:(3): E384â93.
2877:
2829:
2788:
2739:
2690:
2661:(7): 1267â79.
2641:
2627:
2588:
2565:
2530:
2489:
2468:(6): 3744â52.
2445:
2385:
2344:
2296:
2247:
2204:
2147:
2128:
2114:
2046:
2028:
2010:
1989:
1967:
1965:
1962:
1961:
1960:
1953:
1950:
1925:
1924:Other diseases
1922:
1894:
1893:
1886:
1875:
1860:
1857:
1849:Breast cancers
1843:
1840:
1834:
1831:
1825:
1824:Role in cancer
1822:
1816:
1813:
1812:
1811:
1805:
1799:
1793:
1787:
1772:
1769:
1716:
1713:
1655:
1652:
1569:
1566:
1522:
1519:
1487:also known as
1476:
1475:
1472:
1471:
1466:
1456:
1455:
1449:
1448:
1445:
1444:
1442:
1440:
1433:
1432:
1425:
1418:
1414:
1413:
1410:
1409:
1399:
1398:
1392:
1389:
1388:
1378:
1377:
1371:
1367:
1366:
1363:
1362:
1352:
1351:
1345:
1342:
1341:
1331:
1330:
1324:
1320:
1319:
1316:
1315:
1307:
1306:
1300:
1297:
1296:
1288:
1287:
1281:
1275:
1274:
1271:
1270:
1262:
1261:
1255:
1252:
1251:
1243:
1242:
1236:
1230:
1229:
1226:
1225:
1217:
1216:
1210:
1207:
1206:
1198:
1197:
1191:
1185:
1184:
1179:
1174:
1170:
1169:
1159:
1158:
1155:
1154:
1143:
1142:
1140:
1139:
1134:
1129:
1124:
1119:
1114:
1109:
1104:
1099:
1094:
1089:
1084:
1079:
1074:
1069:
1064:
1059:
1054:
1049:
1044:
1039:
1034:
1029:
1024:
1019:
1014:
1009:
1004:
999:
994:
989:
984:
979:
974:
969:
964:
959:
954:
949:
944:
939:
934:
929:
924:
919:
914:
909:
904:
899:
894:
889:
884:
879:
874:
869:
864:
859:
854:
849:
844:
839:
834:
829:
824:
819:
814:
809:
803:
801:
797:
796:
794:
793:
788:
783:
778:
773:
768:
763:
758:
753:
748:
746:Golgi membrane
743:
738:
733:
728:
723:
718:
712:
710:
706:
705:
703:
702:
697:
692:
687:
682:
677:
672:
667:
662:
657:
652:
646:
644:
640:
639:
629:
628:
625:
624:
621:
620:
617:
616:
609:
603:
602:
599:
598:
590:
589:
586:
585:
583:
582:
581:left lung lobe
578:
574:
573:lacrimal gland
570:
569:primary oocyte
566:
562:
558:
554:
550:
546:
542:
539:
538:
527:
524:
523:
521:
520:
516:
512:
508:
504:
500:
496:
492:
488:
484:
480:
477:
476:
464:
463:
455:
444:
438:
437:
434:RNA expression
426:
425:
422:
421:
413:
409:
408:
400:
397:
392:
386:
385:
376:
369:
363:
359:
358:
353:
347:
346:
338:
337:
325:
324:
321:
320:
312:
308:
307:
299:
296:
291:
285:
284:
275:
268:
262:
258:
257:
250:
244:
243:
235:
234:
222:
221:
178:
174:
173:
165:
157:
156:
152:
151:
148:
147:
144:
143:
69:
68:
60:
59:
48:
42:
41:
33:
32:
24:
23:
15:
9:
6:
4:
3:
2:
5459:
5448:
5445:
5443:
5440:
5439:
5437:
5427:
5422:
5417:
5416:
5413:
5399:
5395:
5394:
5389:
5386:
5382:
5381:
5376:
5373:
5369:
5368:
5363:
5360:
5356:
5355:
5350:
5347:
5343:
5342:
5337:
5334:
5330:
5329:
5324:
5321:
5317:
5316:
5311:
5310:
5308:
5304:
5298:
5295:
5293:
5290:
5288:
5285:
5283:
5280:
5278:
5275:
5274:
5272:
5268:
5262:
5259:
5257:
5256:Enzyme family
5254:
5252:
5249:
5247:
5244:
5243:
5241:
5237:
5231:
5228:
5226:
5223:
5221:
5220:Cooperativity
5218:
5216:
5213:
5212:
5210:
5206:
5200:
5197:
5195:
5192:
5190:
5187:
5185:
5182:
5180:
5179:Oxyanion hole
5177:
5175:
5172:
5170:
5167:
5165:
5162:
5161:
5159:
5155:
5151:
5144:
5139:
5137:
5132:
5130:
5125:
5124:
5121:
5101:
5098:
5096:
5093:
5091:
5088:
5086:
5083:
5081:
5078:
5076:
5073:
5071:
5068:
5067:
5065:
5063:
5059:
5055:
5050:
5045:
5041:
5027:
5024:
5022:
5019:
5017:
5014:
5012:
5009:
5007:
5004:
5002:
4999:
4997:
4994:
4990:
4987:
4985:
4982:
4980:
4977:
4975:
4972:
4971:
4970:
4967:
4966:
4964:
4961:
4957:
4950:
4949:
4947:
4944:
4940:
4933:
4932:
4930:
4927:
4923:
4916:
4915:
4913:
4910:
4906:
4900:
4897:
4895:
4892:
4890:
4887:
4886:
4884:
4881:
4877:
4871:
4868:
4866:
4863:
4859:
4856:
4854:
4851:
4849:
4846:
4844:
4841:
4839:
4836:
4834:
4831:
4829:
4826:
4825:
4824:
4821:
4817:
4814:
4812:
4809:
4807:
4804:
4802:
4799:
4798:
4797:
4794:
4790:
4787:
4785:
4782:
4780:
4777:
4775:
4772:
4770:
4767:
4765:
4762:
4760:
4757:
4755:
4752:
4751:
4750:
4747:
4746:
4744:
4741:
4737:
4729:
4726:
4724:
4721:
4719:
4716:
4715:
4714:
4711:
4707:
4704:
4702:
4699:
4697:
4694:
4693:
4692:
4689:
4685:
4682:
4680:
4677:
4675:
4672:
4670:
4667:
4665:
4662:
4660:
4657:
4655:
4652:
4651:
4650:
4647:
4646:
4644:
4641:
4637:
4631:
4628:
4626:
4623:
4621:
4618:
4616:
4613:
4611:
4608:
4606:
4603:
4601:
4598:
4596:
4593:
4591:
4588:
4587:
4585:
4582:
4578:
4572:
4569:
4567:
4564:
4562:
4559:
4557:
4554:
4552:
4549:
4547:
4544:
4542:
4539:
4537:
4534:
4532:
4529:
4527:
4524:
4522:
4519:
4517:
4514:
4512:
4509:
4507:
4504:
4502:
4499:
4497:
4494:
4492:
4489:
4487:
4484:
4482:
4479:
4478:
4476:
4473:
4469:
4463:
4460:
4458:
4455:
4453:
4450:
4448:
4445:
4444:
4442:
4439:
4435:
4431:
4426:
4421:
4417:
4403:
4400:
4398:
4395:
4393:
4390:
4388:
4385:
4384:
4382:
4379:
4375:
4369:
4366:
4364:
4361:
4360:
4358:
4355:
4351:
4345:
4342:
4340:
4337:
4335:
4332:
4330:
4327:
4325:
4322:
4321:
4319:
4316:
4312:
4306:
4303:
4301:
4298:
4296:
4293:
4291:
4288:
4287:
4285:
4282:
4278:
4272:
4269:
4267:
4264:
4262:
4259:
4257:
4254:
4252:
4249:
4247:
4244:
4242:
4239:
4237:
4234:
4232:
4229:
4227:
4224:
4222:
4219:
4217:
4214:
4212:
4209:
4207:
4204:
4202:
4199:
4197:
4194:
4192:
4189:
4187:
4184:
4182:
4179:
4177:
4174:
4172:
4169:
4167:
4164:
4162:
4159:
4157:
4154:
4152:
4149:
4147:
4144:
4142:
4139:
4137:
4134:
4132:
4129:
4127:
4124:
4122:
4119:
4117:
4114:
4112:
4109:
4107:
4104:
4102:
4099:
4097:
4094:
4092:
4089:
4087:
4084:
4082:
4079:
4077:
4074:
4072:
4069:
4067:
4064:
4062:
4059:
4057:
4054:
4052:
4049:
4047:
4044:
4042:
4039:
4037:
4034:
4032:
4029:
4027:
4024:
4022:
4019:
4017:
4014:
4012:
4009:
4007:
4004:
4002:
3999:
3997:
3994:
3993:
3991:
3988:
3984:
3978:
3975:
3973:
3970:
3968:
3965:
3964:
3962:
3959:
3955:
3949:
3946:
3944:
3941:
3940:
3938:
3935:
3931:
3925:
3922:
3921:
3919:
3916:
3912:
3906:
3903:
3901:
3898:
3896:
3893:
3891:
3888:
3886:
3883:
3881:
3878:
3876:
3873:
3871:
3868:
3866:
3863:
3861:
3858:
3856:
3853:
3851:
3848:
3846:
3843:
3842:
3840:
3837:
3833:
3827:
3824:
3822:
3819:
3818:
3816:
3813:
3809:
3803:
3800:
3798:
3795:
3793:
3790:
3788:
3785:
3783:
3780:
3779:
3777:
3774:
3770:
3764:
3761:
3759:
3756:
3754:
3751:
3749:
3746:
3744:
3741:
3739:
3736:
3735:
3733:
3730:
3726:
3719:
3718:
3716:
3714:(EC 2.7.11.9)
3713:
3709:
3703:
3700:
3698:
3695:
3694:
3692:
3690:(EC 2.7.11.8)
3689:
3685:
3677:
3674:
3672:
3669:
3667:
3664:
3663:
3662:
3661:Aurora kinase
3659:
3658:
3656:
3654:(EC 2.7.11.7)
3653:
3649:
3643:
3640:
3639:
3637:
3635:(EC 2.7.11.6)
3634:
3630:
3624:
3621:
3619:
3616:
3614:
3611:
3609:
3606:
3605:
3603:
3601:(EC 2.7.11.5)
3600:
3596:
3590:
3587:
3585:
3582:
3580:
3577:
3576:
3574:
3572:(EC 2.7.11.4)
3571:
3567:
3559:
3556:
3554:
3551:
3549:
3546:
3545:
3543:
3539:
3536:
3534:
3531:
3530:
3528:
3524:
3521:
3519:
3516:
3515:
3513:
3510:
3509:
3507:
3505:(EC 2.7.11.3)
3504:
3500:
3494:
3491:
3489:
3486:
3484:
3481:
3479:
3476:
3475:
3473:
3471:(EC 2.7.11.2)
3470:
3466:
3458:
3455:
3454:
3453:
3450:
3446:
3443:
3441:
3438:
3436:
3433:
3431:
3428:
3427:
3426:
3425:EIF-2 kinases
3423:
3421:
3418:
3416:
3413:
3409:
3406:
3404:
3401:
3399:
3396:
3395:
3394:
3391:
3389:
3386:
3384:
3381:
3379:
3376:
3374:
3371:
3369:
3366:
3364:
3361:
3359:
3356:
3354:
3351:
3349:
3346:
3344:
3341:
3339:
3336:
3335:
3333:
3331:(EC 2.7.11.1)
3330:
3326:
3322:
3317:
3312:
3308:
3303:
3299:
3295:
3288:
3283:
3281:
3276:
3274:
3269:
3268:
3265:
3252:
3248:
3242:
3237:
3234:
3230:
3224:
3219:
3216:
3212:
3206:
3201:
3197:
3191:
3186:
3185:
3182:
3173:
3168:
3166:
3161:
3159:
3154:
3153:
3150:
3144:
3140:
3137:
3133:
3130:
3129:
3118:
3114:
3110:
3106:
3102:
3098:
3095:(6): 446â56.
3094:
3090:
3085:
3084:
3071:
3067:
3062:
3057:
3054:(4): 808â18.
3053:
3049:
3045:
3038:
3030:
3026:
3021:
3016:
3012:
3008:
3004:
3000:
2996:
2989:
2977:
2969:
2962:
2961:
2956:
2952:
2948:
2944:
2937:
2933:
2928:
2923:
2918:
2913:
2909:
2905:
2901:
2897:
2893:
2886:
2884:
2882:
2873:
2869:
2865:
2861:
2857:
2853:
2849:
2845:
2838:
2836:
2834:
2825:
2821:
2816:
2811:
2807:
2803:
2799:
2792:
2784:
2780:
2775:
2770:
2766:
2762:
2758:
2754:
2750:
2743:
2735:
2731:
2726:
2721:
2717:
2713:
2709:
2705:
2701:
2694:
2686:
2682:
2677:
2672:
2668:
2664:
2660:
2656:
2652:
2645:
2637:
2631:
2623:
2619:
2615:
2611:
2607:
2603:
2599:
2592:
2584:
2578:
2576:
2574:
2572:
2570:
2561:
2557:
2553:
2549:
2545:
2541:
2534:
2526:
2522:
2517:
2512:
2508:
2504:
2500:
2493:
2485:
2481:
2476:
2471:
2467:
2463:
2459:
2452:
2450:
2441:
2437:
2432:
2427:
2423:
2419:
2415:
2411:
2407:
2403:
2399:
2392:
2390:
2381:
2377:
2372:
2367:
2363:
2359:
2355:
2348:
2340:
2339:
2331:
2329:
2327:
2325:
2323:
2321:
2319:
2317:
2315:
2313:
2311:
2309:
2307:
2305:
2303:
2301:
2292:
2288:
2284:
2280:
2275:
2270:
2267:(2): 189â93.
2266:
2262:
2258:
2251:
2243:
2239:
2235:
2231:
2227:
2223:
2220:(6): 446â56.
2219:
2215:
2208:
2200:
2196:
2192:
2188:
2183:
2178:
2174:
2170:
2166:
2162:
2158:
2151:
2143:
2137:
2135:
2133:
2124:
2118:
2110:
2106:
2101:
2096:
2092:
2088:
2085:(10): 900â8.
2084:
2080:
2076:
2069:
2067:
2065:
2063:
2061:
2059:
2057:
2055:
2053:
2051:
2042:
2038:
2032:
2024:
2020:
2014:
2007:
2003:
1998:
1996:
1994:
1986:
1982:
1977:
1975:
1973:
1968:
1959:
1956:
1955:
1949:
1947:
1943:
1939:
1935:
1931:
1921:
1919:
1915:
1911:
1907:
1903:
1899:
1891:
1887:
1884:
1880:
1876:
1874:
1870:
1867:targeting of
1866:
1865:
1864:
1856:
1854:
1850:
1842:Breast cancer
1839:
1830:
1821:
1809:
1806:
1803:
1800:
1797:
1794:
1791:
1788:
1785:
1782:
1781:
1780:
1778:
1768:
1766:
1762:
1758:
1754:
1750:
1746:
1742:
1738:
1734:
1730:
1729:cell adhesion
1726:
1722:
1721:cell polarity
1712:
1710:
1706:
1702:
1697:
1695:
1691:
1687:
1683:
1679:
1675:
1671:
1666:
1665:smooth muscle
1662:
1651:
1649:
1645:
1641:
1638:
1634:
1630:
1625:
1621:
1619:
1615:
1611:
1606:
1604:
1600:
1595:
1591:
1587:
1586:cysteine-rich
1583:
1579:
1575:
1565:
1563:
1559:
1555:
1554:cell motility
1551:
1547:
1546:subcellularly
1542:
1540:
1536:
1532:
1528:
1527:chromosome 18
1518:
1516:
1512:
1508:
1507:cell motility
1504:
1501:
1497:
1494:
1490:
1486:
1483:is a protein
1482:
1470:
1465:
1461:
1457:
1454:
1450:
1443:
1441:
1438:
1434:
1430:
1426:
1423:
1419:
1415:
1408:
1406:
1400:
1396:
1393:
1387:
1385:
1379:
1375:
1372:
1368:
1361:
1359:
1353:
1349:
1346:
1340:
1338:
1332:
1328:
1325:
1323:RefSeq (mRNA)
1321:
1314:
1313:
1308:
1304:
1301:
1295:
1294:
1289:
1285:
1282:
1280:
1276:
1269:
1268:
1263:
1259:
1256:
1250:
1249:
1244:
1240:
1237:
1235:
1231:
1224:
1223:
1218:
1214:
1211:
1205:
1204:
1199:
1195:
1192:
1190:
1186:
1183:
1180:
1178:
1175:
1171:
1168:
1164:
1160:
1153:
1149:
1144:
1138:
1135:
1133:
1130:
1128:
1125:
1123:
1120:
1118:
1115:
1113:
1110:
1108:
1105:
1103:
1100:
1098:
1095:
1093:
1090:
1088:
1085:
1083:
1080:
1078:
1075:
1073:
1070:
1068:
1065:
1063:
1060:
1058:
1055:
1053:
1050:
1048:
1045:
1043:
1040:
1038:
1035:
1033:
1030:
1028:
1025:
1023:
1020:
1018:
1015:
1013:
1010:
1008:
1005:
1003:
1000:
998:
995:
993:
990:
988:
985:
983:
980:
978:
975:
973:
970:
968:
965:
963:
960:
958:
955:
953:
950:
948:
945:
943:
940:
938:
935:
933:
930:
928:
925:
923:
920:
918:
915:
913:
910:
908:
905:
903:
900:
898:
895:
893:
890:
888:
885:
883:
880:
878:
875:
873:
870:
868:
865:
863:
860:
858:
855:
853:
850:
848:
847:bleb assembly
845:
843:
840:
838:
835:
833:
830:
828:
825:
823:
820:
818:
815:
813:
810:
808:
805:
804:
802:
799:
798:
792:
789:
787:
784:
782:
779:
777:
774:
772:
771:lamellipodium
769:
767:
764:
762:
759:
757:
754:
752:
749:
747:
744:
742:
739:
737:
734:
732:
729:
727:
724:
722:
719:
717:
714:
713:
711:
708:
707:
701:
698:
696:
693:
691:
688:
686:
683:
681:
678:
676:
673:
671:
668:
666:
663:
661:
658:
656:
653:
651:
648:
647:
645:
642:
641:
638:
637:Gene ontology
634:
630:
618:
613:
610:
608:
604:
596:
591:
580:
576:
572:
568:
564:
560:
556:
552:
548:
544:
543:
540:
536:
531:
528:
518:
514:
510:
506:
502:
498:
494:
490:
486:
482:
481:
478:
474:
469:
466:
465:
462:
460:
456:
454:
453:
449:
448:
445:
443:
439:
435:
431:
427:
419:
414:
410:
406:
401:
395:18|18 A1
391:
387:
380:
373:
367:
360:
352:
348:
344:
339:
335:
330:
326:
318:
313:
309:
305:
300:
290:
286:
279:
272:
266:
259:
255:
249:
245:
241:
236:
232:
227:
223:
219:
215:
211:
207:
203:
199:
195:
191:
187:
183:
175:
170:
163:
158:
153:
142:
140:
136:
132:
128:
124:
120:
116:
112:
108:
104:
100:
96:
92:
88:
84:
80:
76:
70:
65:
62:
61:
57:
54:
47:
43:
38:
34:
30:
25:
20:
5393:Translocases
5390:
5377:
5364:
5351:
5338:
5328:Transferases
5325:
5312:
5169:Binding site
4600:P70S6 kinase
3372:
3246:
3228:
3210:
3195:
3092:
3088:
3051:
3047:
3037:
3002:
2998:
2988:
2974:{{
2966:{{
2959:
2957:,
2899:
2895:
2847:
2843:
2805:
2801:
2791:
2756:
2752:
2742:
2707:
2703:
2693:
2658:
2654:
2644:
2630:
2605:
2601:
2591:
2546:(1): 44â51.
2543:
2539:
2533:
2509:(2): 112â9.
2506:
2502:
2492:
2465:
2461:
2405:
2401:
2364:(1): 260â8.
2361:
2357:
2347:
2337:
2264:
2261:FEBS Letters
2260:
2250:
2217:
2213:
2207:
2167:(2): 171â7.
2164:
2160:
2150:
2117:
2082:
2079:EMBO Reports
2078:
2040:
2031:
2022:
2013:
1927:
1895:
1881:activity in
1871:rather than
1862:
1845:
1836:
1833:Angiogenesis
1827:
1818:
1774:
1771:Interactions
1727:retraction,
1718:
1698:
1657:
1626:
1622:
1607:
1571:
1543:
1524:
1515:angiogenesis
1503:cytoskeleton
1488:
1480:
1479:
1402:
1381:
1355:
1334:
1310:
1291:
1265:
1246:
1220:
1201:
1181:
1176:
766:cytoskeleton
577:aortic valve
561:ciliary body
457:
450:
177:External IDs
72:
5164:Active site
5051:(EC 2.7.12)
4438:Polo kinase
4378:Polo kinase
3178:PDB gallery
1944:(ALS), and
1873:tumor cells
1578:coiled-coil
1550:centrosomes
1539:amino acids
685:ATP binding
416:10,182,045
403:10,064,401
315:21,111,813
302:20,946,906
155:Identifiers
5436:Categories
5367:Isomerases
5341:Hydrolases
5208:Regulation
3729:IÎșB kinase
3304:2.7.11-12)
2008:, May 2017
1987:, May 2017
1964:References
1958:Rho kinase
1916:following
1879:proteasome
1686:LIM kinase
1594:C-terminus
1574:N-terminus
1537:into 1354
1535:translates
1511:metastasis
1500:actomyosin
461:(ortholog)
198:HomoloGene
5447:EC 2.7.11
5246:EC number
3855:PKC alpha
2976:retracted
2968:retracted
2408:: 10029.
1749:MYL9/MLC2
1637:G-protein
1603:apoptosis
1599:caspase-3
1405:NP_033097
1384:NP_005397
1358:NM_009071
1337:NM_005406
1167:Orthologs
761:centriole
716:cytoplasm
206:GeneCards
5270:Kinetics
5194:Cofactor
5157:Activity
4211:KIAA0999
4106:MAPKAPK5
4101:MAPKAPK3
4096:MAPKAPK2
3139:Archived
3117:40665081
3109:12778124
3070:20530035
3029:23087045
2955:36053739
2936:24324133
2864:15604264
2734:12773565
2685:14517206
2622:19181962
2560:11082274
2525:12142343
2440:26620183
2380:16249185
2242:40665081
2234:12778124
2191:19907920
2182:11115778
2109:22964758
2004:–
1983:–
1952:See also
1936:such as
1930:diabetes
1777:interact
1765:blebbing
1757:PPP1R12A
1715:Function
1705:myocytes
1701:troponin
1699:Cardiac
1453:Wikidata
1146:Sources:
736:membrane
495:monocyte
5426:Biology
5380:Ligases
5150:Enzymes
4870:MAP3K14
4848:MAP3K11
4843:MAP3K10
4833:MAP3K13
4828:MAP3K12
4630:RPS6KC1
4625:RPS6KA1
4620:RPS6KA3
4615:RPS6KA2
4610:RPS6KB2
4595:RPS6KA4
4590:RPS6KA5
4241:Kalirin
4206:SNF1LK2
3445:EIF2AK4
3440:EIF2AK3
3294:Kinases
3251:Y-27632
3215:fasudil
3020:3501973
2927:3903228
2904:Bibcode
2872:8380551
2824:8798490
2783:8816443
2676:2173969
2484:9920927
2431:4686654
2410:Bibcode
2291:6684411
2283:8772201
2199:6445354
2100:3463970
2006:Ensembl
1985:Ensembl
1902:Fasudil
1869:stromal
1725:neurite
1690:cofilin
1678:F-actin
1601:during
1279:UniProt
1234:Ensembl
1173:Species
1152:QuickGO
721:cytosol
436:pattern
294:18q11.1
162:Aliases
16:Protein
5412:Portal
5354:Lyases
5100:MAP2K7
5095:MAP2K6
5090:MAP2K5
5085:MAP2K4
5080:MAP2K3
5075:MAP2K2
5070:MAP2K1
5021:ACVRL1
5016:ACVR2B
5011:ACVR2A
5006:ACVR1C
5001:ACVR1B
4984:BMPR1B
4979:BMPR1A
4853:MAP3K7
4838:MAP3K9
4789:MAP3K8
4784:MAP3K7
4779:MAP3K6
4774:MAP3K5
4769:MAP3K4
4764:MAP3K3
4759:MAP3K2
4754:MAP3K1
4728:MAPK14
4723:MAPK13
4718:MAPK11
4706:MAPK10
4684:MAPK15
4679:MAPK12
4571:CDC2L1
4546:CDC2L5
4221:SNF1LK
4046:CAMK2G
4041:CAMK2D
4036:CAMK2B
4031:CAMK2A
4021:CAMK1G
4016:CAMK1D
4011:CAMK1B
4006:CAMK1A
3860:PRKCB1
3797:PRKACA
3792:PRKACB
3787:PRKACG
3763:IKBKAP
3589:BCKDHB
3584:BCKDHA
3558:PRKAG3
3553:PRKAG2
3548:PRKAG1
3538:PRKAB2
3533:PRKAB1
3523:PRKAA2
3518:PRKAA1
3363:STK38L
3115:
3107:
3068:
3027:
3017:
2953:
2949:,
2934:
2924:
2870:
2862:
2822:
2781:
2774:231530
2771:
2732:
2725:156133
2722:
2683:
2673:
2620:
2558:
2523:
2482:
2438:
2428:
2378:
2289:
2281:
2240:
2232:
2197:
2189:
2179:
2107:
2097:
1898:Y27632
1779:with:
1661:MYPT-1
1560:, and
1513:, and
1493:GTPase
1439:search
1437:PubMed
1312:P70335
1293:Q13464
1189:Entrez
741:ruffle
607:BioGPS
553:zygote
194:107927
186:601702
5306:Types
5062:MAP2K
4996:ACVR1
4989:BMPR2
4974:BMPR1
4899:GSK-3
4740:MAP3K
4701:MAPK9
4696:MAPK8
4674:MAPK7
4669:MAPK6
4664:MAPK4
4659:MAPK3
4654:MAPK1
4566:PFTK1
4561:PCTK3
4556:PCTK2
4551:PCTK1
4541:CDK12
4536:CDK10
4511:CDKL5
4491:CDKL2
4368:STK19
4363:EEF2K
4344:PHKG2
4339:PHKG1
4329:PHKA2
4324:PHKA1
4305:MYLK4
4300:MYLK3
4295:MYLK2
4271:DCLK1
4266:Titin
4256:TRIB3
4251:TRIB2
4246:TRIB1
4236:TSSK2
4216:STK40
4201:PSKH1
4196:PRKD3
4191:PRKD2
4171:PHKG2
4166:PHKG1
4156:OBSCN
4151:NUAK2
4146:NUAK1
4141:MKNK2
4136:MKNK1
4126:MARK4
4121:MARK3
4116:MARK2
4111:MARK1
4091:STK11
4086:DAPK3
4081:DAPK2
4076:DAPK1
4071:CHEK2
4066:CHEK1
4051:CAMK4
4026:CAMK2
4001:CAMK1
3996:BRSK2
3890:PRKCQ
3885:PRKCI
3880:PRKCG
3875:PRKCH
3870:PRKCE
3865:PRKCD
3826:PRKG1
3758:IKBKG
3753:IKBKE
3702:STK10
3697:FASTK
3623:IDH3G
3618:IDH3B
3613:IDH3A
3579:BCKDK
3373:ROCK1
3358:STK38
3353:MAST2
3348:MAST1
3343:LATS2
3338:LATS1
3132:ROCK1
3113:S2CID
2999:Brain
2972:with
2868:S2CID
2287:S2CID
2238:S2CID
2195:S2CID
1892:(CML)
1883:KâRas
1804:, and
1796:MYPT1
1784:LIMK1
1761:FHOD1
1745:LIMK2
1741:LIMK1
1733:DAPK3
1610:dimer
1562:actin
1481:ROCK1
1222:19877
1182:Mouse
1177:Human
1148:Amigo
459:Mouse
452:Human
399:Start
334:Mouse
298:Start
231:Human
210:ROCK1
202:55899
169:ROCK1
22:ROCK1
5398:list
5391:EC7
5385:list
5378:EC6
5372:list
5365:EC5
5359:list
5352:EC4
5346:list
5339:EC3
5333:list
5326:EC2
5320:list
5313:EC1
4889:TPK1
4865:CDC7
4823:MLKs
4816:KSR2
4811:KSR1
4806:BRAF
4801:ARAF
4796:RAFs
4531:CDK9
4526:CDK8
4521:CDK7
4516:CDK6
4506:CDK5
4501:CDK4
4496:CDK3
4486:CDK2
4481:CDK1
4462:PLK4
4457:PLK3
4452:PLK2
4447:PLK1
4402:PLK4
4397:PLK3
4392:PLK2
4387:PLK1
4334:PHKB
4290:MYLK
4261:TRIO
4231:SPEG
4226:SNRK
4186:PKD1
4181:PIM2
4176:PIM1
4161:PASK
4131:MELK
4061:CASK
4056:MLCK
3977:GRK6
3972:GRK5
3967:GRK4
3905:PKN3
3900:PKN2
3802:PRKY
3748:TBK1
3743:IKK2
3738:CHUK
3642:STK4
3608:IDH2
3493:PDK4
3488:PDK3
3483:PDK2
3478:PDK1
3457:WEE1
3452:Wee1
3420:mTOR
3408:AKT3
3403:AKT2
3398:AKT1
3388:SGK3
3383:SGK2
3247:2etr
3229:2etk
3211:2esm
3196:1s1c
3105:PMID
3066:PMID
3025:PMID
2951:PMID
2932:PMID
2860:PMID
2820:PMID
2779:PMID
2730:PMID
2681:PMID
2618:PMID
2556:PMID
2521:PMID
2480:PMID
2436:PMID
2376:PMID
2279:PMID
2230:PMID
2187:PMID
2105:PMID
1940:and
1900:and
1853:HIFs
1808:RHOA
1802:PFN2
1755:and
1753:PFN1
1737:GFAP
1709:PTEN
1670:VEGF
1646:and
1640:RhoE
1533:and
1496:RhoA
1203:6093
756:bleb
442:Bgee
390:Band
351:Chr.
289:Band
248:Chr.
182:OMIM
139:5BML
135:4YVE
131:4YVC
127:4W7P
123:4L2W
119:3V8S
115:3TWJ
111:3TV7
107:3O0Z
103:3NDM
99:3NCZ
95:3D9V
91:2V55
87:2ETR
83:2ETK
79:2ESM
75:1S1C
56:RCSB
53:PDBe
4894:TTK
4858:ZAK
3435:HRI
3430:PKR
3378:SGK
3368:CIT
3097:doi
3056:doi
3015:PMC
3007:doi
3003:135
2943:doi
2922:PMC
2912:doi
2900:111
2852:doi
2810:doi
2806:271
2769:PMC
2761:doi
2720:PMC
2712:doi
2671:PMC
2663:doi
2659:162
2610:doi
2606:296
2548:doi
2544:261
2511:doi
2470:doi
2466:274
2426:PMC
2418:doi
2366:doi
2362:281
2269:doi
2265:392
2222:doi
2177:PMC
2169:doi
2095:PMC
2087:doi
1906:ATP
1790:MLC
1648:Rad
1644:Gem
1631:or
615:n/a
412:End
311:End
214:OMA
190:MGI
46:PDB
5438::
3544:Îł
3529:ÎČ
3514:α
3302:EC
3296::
3111:.
3103:.
3091:.
3064:.
3052:36
3050:.
3046:.
3023:.
3013:.
3001:.
2997:.
2930:.
2920:.
2910:.
2898:.
2894:.
2880:^
2866:.
2858:.
2848:64
2846:.
2832:^
2818:.
2804:.
2800:.
2777:.
2767:.
2757:16
2755:.
2751:.
2728:.
2718:.
2708:23
2706:.
2702:.
2679:.
2669:.
2657:.
2653:.
2616:.
2604:.
2600:.
2568:^
2554:.
2542:.
2519:.
2507:91
2505:.
2501:.
2478:.
2464:.
2460:.
2448:^
2434:.
2424:.
2416:.
2404:.
2400:.
2388:^
2374:.
2360:.
2356:.
2299:^
2285:.
2277:.
2263:.
2259:.
2236:.
2228:.
2216:.
2193:.
2185:.
2175:.
2165:67
2163:.
2159:.
2131:^
2103:.
2093:.
2083:13
2081:.
2077:.
2049:^
2039:.
2021:.
1992:^
1971:^
1948:.
1932:,
1920:.
1751:,
1747:,
1743:,
1739:,
1735:,
1556:,
1541:.
1531:bp
1517:.
1509:,
1150:/
418:bp
405:bp
317:bp
304:bp
212:;
208::
204:;
200::
196:;
192::
188:;
184::
137:,
133:,
129:,
125:,
121:,
117:,
113:,
109:,
105:,
101:,
97:,
93:,
89:,
85:,
81:,
77:,
5414::
5400:)
5396:(
5387:)
5383:(
5374:)
5370:(
5361:)
5357:(
5348:)
5344:(
5335:)
5331:(
5322:)
5318:(
5142:e
5135:t
5128:v
4951:-
4934:-
4917:-
3720:-
3300:(
3286:e
3279:t
3272:v
3171:e
3164:t
3157:v
3119:.
3099::
3093:4
3072:.
3058::
3031:.
3009::
2982:)
2980:.
2945::
2938:.
2914::
2906::
2874:.
2854::
2826:.
2812::
2785:.
2763::
2736:.
2714::
2687:.
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