316:
293:
215:
190:
1367:. This gene product stimulates the motility of tumor cells, has angiogenic properties, and its expression is up-regulated in several kinds of tumours. Also, autotaxin and LPA are involved in numerous inflammatory-driven diseases such as asthma and arthritis. Physiologically, LPA helps promote wound healing responses to tissue damage. Under normal circumstances, LPA negatively regulates autotaxin transcription, but in the context of wound repair, cytokines induce autotaxin expression to increase overall LPA concentrations.
567:
574:
322:
221:
3678:
1387:
inflammation and neurological diseases, since autotaxin is responsible of LPA generation, a key lipid mediator involved in numerous diseases and physiological processes. However, clinical trials need to be performed in order to assess the importance of ATX inhibition by THC during medicinal cannabis consumption. Development of cannabinoid inspired autotaxin inhibitors could also be an option in the future.
31:
1351:. Autotaxin is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants have been identified. Autotaxin is able to cleave the phosphodiester bond between the α and the β position of triphosphate nucleotides, acting as an ectonucleotide phosphodiesterase producing
1386:
Recently, it has been shown that THC is also a partial autotaxin inhibitor, with an apparent IC50 of 407 ± 67 nM for the ATX-gamma isoform. THC was also co-crystallized with autotaxin, deciphering the binding interface of the complex. These results might explain some of the effects of THC on
57:
2409:
Koh E, Clair T, Woodhouse EC, Schiffmann E, Liotta L, Stracke M (May 2003). "Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities".
1363:. The physiological function of autotaxin is the production of the signalling lipid lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and
1533:
Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, et al. (November 1995). "Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)".
329:
228:
1407:-like (SMB) domains which may be involved in cell-surface localisation. The catalytic domain follows and contains a deep hydrophobic pocket in which the lipid substrate binds. At the
1800:
Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, et al. (February 2011). "Crystal structure of autotaxin and insight into GPCR activation by lipid mediators".
2193:
Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, et al. (September 2001). "Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor".
3159:
3105:
2431:
Kehlen A, Englert N, Seifert A, Klonisch T, Dralle H, Langner J, et al. (May 2004). "Expression, regulation and function of autotaxin in thyroid carcinomas".
2335:
Yang SY, Lee J, Park CG, Kim S, Hong S, Chung HC, et al. (2003). "Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells".
1708:
Kato K, Ikeda H, Miyakawa S, Futakawa S, Nonaka Y, Fujiwara M, et al. (May 2016). "Structural basis for specific inhibition of
Autotaxin by a DNA aptamer".
2372:
Gijsbers R, Aoki J, Arai H, Bollen M (March 2003). "The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site".
972:
953:
151:
1596:
Benesch MG, Ko YM, McMullen TP, Brindley DN (August 2014). "Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions".
2470:"Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression"
2259:"Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase"
1850:"Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase"
2767:
2928:
1515:
1497:
2585:
1360:
3024:
1220:
2519:
1403:
has been solved along with those of product- or inhibitor-bound complexes. Both proteins consist of 4 domains, including 2 N-terminal
1227:
2735:
2752:
1582:
2999:
1480:
3698:
2913:
2525:
1375:
Various small molecule inhibitors of autotaxin have been developed for clinical applications. A specific inhibitor against
54:
2216:"Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production"
1885:"Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production"
3014:
3008:
2809:
2559:
1459:
2857:
1963:"Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility"
315:
3397:
2968:
2757:
2004:"cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases"
292:
3075:
2963:
1484:
1463:
2107:"Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities"
1928:"Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein"
2884:
2794:
2747:
1017:
3553:
3306:
3247:
1376:
1344:
product of the reaction catalyzed by autotaxin, which is responsible for its effects on cell-proliferation.
998:
122:, ATX, ATX-X, AUTOTAXIN, LysoPLD, NPP2, PD-IALPHA, PDNP2, ectonucleotide pyrophosphatase/phosphodiesterase 2
3351:
2918:
2908:
214:
189:
131:
1695:
for "Study to Assess Safety, Tolerability, Pharmacokinetic and
Pharmacodynamic Properties of GLPG1690" at
1332:
Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be
3311:
3203:
2828:
2140:
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000).
2039:"Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells"
328:
227:
3668:
2897:
2893:
2889:
2805:
2638:
321:
220:
3654:
3641:
3628:
3615:
3602:
3589:
3576:
3538:
3065:
2621:
1926:
Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, et al. (February 1992).
1425:
1337:
118:
3548:
3502:
3445:
2813:
2662:
2576:
1641:"Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate"
1199:
1195:
1191:
1166:
1162:
1158:
1132:
1128:
1120:
1099:
1091:
1087:
139:
2070:
Lee HY, Clair T, Mulvaney PT, Woodhouse EC, Aznavoorian S, Liotta LA, et al. (October 1996).
3450:
2682:
2552:
2294:"Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells"
1203:
1170:
1124:
1095:
3238:
2877:
2037:
Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, et al. (January 1996).
3471:
3390:
3173:
3070:
2862:
2823:
2687:
2609:
1420:
1396:
1333:
1326:
1314:
2257:
Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, et al. (October 2002).
2072:"Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin"
1848:
Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, et al. (October 2002).
3543:
3356:
3191:
3186:
3119:
2779:
2604:
2153:
2002:
Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, et al. (December 1994).
203:
159:
2468:
Boucher J, Quilliot D, Pradères JP, Simon MF, Grès S, Guigné C, et al. (March 2005).
8:
3507:
3211:
3181:
2985:
2980:
2904:
2840:
2626:
2531:
1322:
2157:
3440:
3344:
3196:
2677:
2667:
2545:
2494:
2469:
2456:
2397:
2360:
2323:
2240:
2215:
1990:
1909:
1884:
1825:
1777:
1752:
1733:
1696:
1667:
1640:
1621:
163:
2385:
2310:
2293:
2020:
2003:
1944:
1927:
887:
882:
877:
872:
867:
862:
857:
852:
847:
842:
837:
832:
827:
822:
817:
812:
807:
802:
797:
792:
787:
782:
777:
772:
767:
762:
757:
752:
747:
742:
737:
732:
716:
711:
706:
701:
696:
691:
675:
670:
665:
660:
655:
650:
640:
635:
630:
625:
620:
615:
3703:
3145:
3090:
3058:
2933:
2652:
2499:
2448:
2419:
2389:
2352:
2315:
2280:
2245:
2202:
2181:
2176:
2141:
2128:
2093:
2058:
2025:
1982:
1978:
1949:
1914:
1871:
1817:
1782:
1725:
1672:
1613:
1561:
1348:
111:
47:
2460:
2401:
2364:
2327:
2214:
Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, et al. (July 2002).
1883:
Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, et al. (July 2002).
1737:
1625:
143:
3486:
3481:
3455:
3383:
3221:
2801:
2706:
2701:
2657:
2489:
2481:
2440:
2381:
2344:
2305:
2270:
2235:
2227:
2171:
2161:
2118:
2083:
2050:
2015:
1994:
1974:
1939:
1904:
1896:
1861:
1829:
1809:
1772:
1764:
1717:
1662:
1652:
1605:
1583:"Entrez Gene: ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin)"
1551:
1543:
408:
339:
283:
238:
1691:
1609:
3533:
3517:
3430:
3323:
3137:
3053:
3048:
3043:
2956:
2951:
2711:
2589:
1556:
1430:
1341:
1318:
1310:
383:
167:
2537:
2142:"Shotgun sequencing of the human transcriptome with ORF expressed sequence tags"
1520:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1502:
National Center for
Biotechnology Information, U.S. National Library of Medicine
3682:
3571:
3512:
3296:
3291:
3286:
2672:
2647:
2643:
2616:
2599:
2292:
Jung ID, Lee J, Yun SY, Park CG, Choi WS, Lee HW, et al. (December 2002).
2146:
Proceedings of the
National Academy of Sciences of the United States of America
484:
2485:
2348:
566:
3692:
3476:
3435:
3037:
2946:
2696:
2088:
2071:
1435:
1411:
is the inactive nuclease domain which may function to aid protein stability.
1404:
1400:
1356:
1352:
602:
573:
544:
422:
3425:
3164:
3095:
2818:
2739:
2503:
2452:
2423:
2393:
2356:
2319:
2284:
2275:
2258:
2249:
2206:
2185:
2166:
2054:
1918:
1875:
1866:
1849:
1821:
1786:
1768:
1729:
1676:
1617:
1547:
1379:
showed promising results in a phase II trial that ended in May 2018. A DNA
401:
180:
2231:
2132:
2123:
2106:
2097:
2062:
2029:
1986:
1953:
1900:
1565:
1355:, as most members of the ENPP family. Importantly, autotaxin also acts as
1267:
1262:
3649:
3584:
3420:
3339:
3110:
3004:
2867:
2833:
2771:
1753:"Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling"
1062:
1043:
1657:
645:
3316:
2139:
1961:
Stracke ML, Arestad A, Levine M, Krutzsch HC, Liotta LA (August 1995).
1408:
1364:
300:
197:
147:
2444:
1813:
1721:
1639:
Benesch MG, Zhao YY, Curtis JM, McMullen TP, Brindley DN (June 2015).
88:
84:
80:
76:
3623:
3597:
3229:
3028:
2568:
917:
367:
354:
266:
253:
155:
2038:
1962:
3677:
3274:
3269:
3264:
3085:
2720:
2572:
1251:
873:
positive regulation of substrate adhesion-dependent cell spreading
3281:
3259:
3254:
2872:
1380:
1029:
984:
902:
898:
1284:
ectonucleotide pyrophosphatase/phosphodiesterase family member 2
135:
3636:
3406:
3301:
3234:
3127:
2725:
2633:
1399:
of rat and mouse autotaxin have been solved. In each case, the
1291:
1235:
939:
582:
1925:
3610:
3243:
2994:
2990:
2467:
2430:
2256:
2036:
1960:
1847:
1309:
Autotaxin is a secreted enzyme important for generating the
2975:
2852:
2845:
2789:
2784:
2408:
1799:
1298:
3375:
651:
alkylglycerophosphoethanolamine phosphodiesterase activity
2069:
1707:
1638:
1595:
2213:
1882:
1532:
783:
positive regulation of peptidyl-tyrosine phosphorylation
391:
2105:
Clair T, Lee HY, Liotta LA, Stracke ML (January 1997).
30:
2371:
2001:
1750:
1359:, catalyzing the removal of the head group of various
848:
positive regulation of oligodendrocyte differentiation
3666:
2104:
556:
1751:
Eymery MC, McCarthy AA, Hausmann J (February 2023).
828:
positive regulation of cell population proliferation
2192:
2043:
1476:
1474:
1472:
1455:
1453:
1451:
743:positive regulation of lamellipodium morphogenesis
2863:Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
2567:
338:
237:
3690:
1383:inhibitor of Autotaxin has also been described.
1347:The protein encoded by this gene functions as a
753:positive regulation of epithelial cell migration
1469:
1448:
788:phosphate-containing compound metabolic process
18:Protein-coding gene in the species Homo sapiens
2334:
2291:
1481:GRCm38: Ensembl release 89: ENSMUSG00000022425
853:positive regulation of focal adhesion assembly
3391:
2553:
1793:
733:G protein-coupled receptor signaling pathway
1460:GRCh38: Ensembl release 89: ENSG00000136960
823:negative regulation of cell-matrix adhesion
808:nucleic acid phosphodiester bond hydrolysis
3398:
3384:
2560:
2546:
1526:
2493:
2309:
2274:
2239:
2175:
2165:
2122:
2087:
2019:
1943:
1908:
1865:
1802:Nature Structural & Molecular Biology
1776:
1710:Nature Structural & Molecular Biology
1666:
1656:
1555:
1577:
1575:
2753:Ubiquitin carboxy-terminal hydrolase L1
868:cellular response to estradiol stimulus
3691:
2337:Clinical & Experimental Metastasis
3379:
3333:either deoxy- or ribo-
2541:
1572:
803:phosphatidylcholine catabolic process
697:integral component of plasma membrane
343:
304:
299:
242:
201:
196:
2914:Protein serine/threonine phosphatase
3015:Cyclic nucleotide phosphodiesterase
3009:Clostridium perfringens alpha toxin
2810:Tartrate-resistant acid phosphatase
2263:The Journal of Biological Chemistry
2111:The Journal of Biological Chemistry
2076:The Journal of Biological Chemistry
2008:The Journal of Biological Chemistry
1932:The Journal of Biological Chemistry
1854:The Journal of Biological Chemistry
1370:
13:
2858:Pyruvate dehydrogenase phosphatase
1840:
507:choroid plexus of fourth ventricle
14:
3715:
2758:4-hydroxybenzoyl-CoA thioesterase
2512:
1294:that in humans is encoded by the
616:nucleotide diphosphatase activity
3676:
1979:10.1097/00008390-199508000-00001
863:cellular response to cadmium ion
572:
565:
441:inferior ganglion of vagus nerve
327:
320:
314:
291:
226:
219:
213:
188:
29:
3076:N-acetylglucosamine-6-sulfatase
2964:Sphingomyelin phosphodiesterase
2433:International Journal of Cancer
1744:
1701:
2885:Inositol-phosphate phosphatase
2748:Palmitoyl protein thioesterase
1683:
1632:
1589:
1508:
1490:
818:phospholipid metabolic process
778:phospholipid catabolic process
583:More reference expression data
545:More reference expression data
1:
3248:RNA-induced silencing complex
2386:10.1016/S0014-5793(03)00133-9
2311:10.1016/S0014-5793(02)03698-0
2021:10.1016/S0021-9258(18)43838-0
1945:10.1016/S0021-9258(18)45911-X
1610:10.1016/j.febslet.2014.02.009
1441:
1377:idiopathic pulmonary fibrosis
763:receptor-mediated endocytosis
312:
211:
3352:Serratia marcescens nuclease
2919:Dual-specificity phosphatase
2909:Protein tyrosine phosphatase
1390:
878:response to polycyclic arene
738:regulation of cell migration
626:transcription factor binding
621:phosphodiesterase I activity
495:Epithelium of choroid plexus
437:Epithelium of choroid plexus
7:
3699:Genes on human chromosome 8
3405:
2829:Fructose 1,6-bisphosphatase
2220:The Journal of Cell Biology
1889:The Journal of Cell Biology
1414:
1321:activity that converts lyso
1304:
641:scavenger receptor activity
527:nucleus of stria terminalis
461:superior vestibular nucleus
10:
3720:
2530:gene details page in the
1426:Lysophospholipid receptors
1338:lysophospholipid receptors
1317:(LPA). Autotaxin has lyso
883:vesicle-mediated transport
758:regulation of angiogenesis
671:lysophospholipase activity
499:retinal pigment epithelium
433:retinal pigment epithelium
3562:
3554:Michaelis–Menten kinetics
3526:
3495:
3464:
3413:
3332:
3220:
3172:
3158:
3136:
3118:
3104:
3084:
3066:Galactosamine-6 sulfatase
3023:
2927:
2766:
2734:
2622:6-phosphogluconolactonase
2584:
2486:10.1007/s00125-004-1660-8
1645:Journal of Lipid Research
1516:"Mouse PubMed Reference:"
1498:"Human PubMed Reference:"
1266:
1261:
1257:
1250:
1234:
1221:Chr 8: 119.56 – 119.67 Mb
1215:
1188:
1184:
1155:
1151:
1144:
1117:
1113:
1084:
1080:
1073:
1060:
1056:
1041:
1037:
1028:
1015:
1011:
996:
992:
983:
970:
966:
951:
947:
938:
923:
916:
912:
896:
601:
597:
580:
564:
555:
542:
491:
482:
429:
420:
390:
382:
378:
361:
348:
311:
290:
281:
277:
260:
247:
210:
187:
178:
174:
129:
126:
116:
109:
104:
73:
68:
51:
46:
41:
37:
28:
23:
3446:Diffusion-limited enzyme
2814:Purple acid phosphatases
2089:10.1074/jbc.271.40.24408
1228:Chr 15: 54.84 – 54.95 Mb
833:diencephalon development
469:external globus pallidus
2349:10.1023/A:1020950420196
1336:(which signals through
768:lipid catabolic process
3239:Microprocessor complex
2878:Beta-propeller phytase
2276:10.1074/jbc.M205623200
2167:10.1073/pnas.97.7.3491
2055:10.1006/bbrc.1996.0127
1867:10.1074/jbc.M205623200
1769:10.26508/lsa.202201595
1689:Clinical trial number
1548:10.1006/geno.1995.0036
631:polysaccharide binding
519:mesenteric lymph nodes
511:deep cerebellar nuclei
3539:Eadie–Hofstee diagram
3472:Allosteric regulation
3174:Endodeoxyribonuclease
3071:Iduronate-2-sulfatase
2824:Glucose 6-phosphatase
2610:Butyrylcholinesterase
2232:10.1083/jcb.200204026
2124:10.1074/jbc.272.2.996
1901:10.1083/jcb.200204026
1757:Life Science Alliance
1557:20.500.14094/D1001481
1421:Lysophosphatidic acid
1315:lysophosphatidic acid
838:forebrain development
306:Chromosome 15 (mouse)
3549:Lineweaver–Burk plot
3357:Micrococcal nuclease
3192:Deoxyribonuclease IV
3187:Deoxyribonuclease II
3120:Exodeoxyribonuclease
2780:Alkaline phosphatase
2605:Acetylcholinesterase
2524:genome location and
843:midbrain development
702:extracellular region
656:nucleic acid binding
465:middle frontal gyrus
204:Chromosome 8 (human)
69:List of PDB id codes
42:Available structures
3212:UvrABC endonuclease
3182:Deoxyribonuclease I
2905:Protein phosphatase
2841:Protein phosphatase
2639:Bile salt-dependent
2627:PAF acetylhydrolase
2532:UCSC Genome Browser
2158:2000PNAS...97.3491D
1658:10.1194/jlr.M057661
1323:phosphatidylcholine
707:extracellular space
666:calcium ion binding
453:subthalamic nucleus
3508:Enzyme superfamily
3441:Enzyme promiscuity
3345:Mung bean nuclease
3204:Restriction enzyme
3197:Restriction enzyme
1697:ClinicalTrials.gov
1397:crystal structures
1018:ENSMUSG00000022425
726:Biological process
685:Cellular component
661:hydrolase activity
646:catalytic activity
609:Molecular function
3664:
3663:
3373:
3372:
3369:
3368:
3365:
3364:
3154:
3153:
3146:Oligonucleotidase
3091:deoxyribonuclease
3059:Steroid sulfatase
2934:Phosphodiesterase
2663:Hormone-sensitive
2445:10.1002/ijc.20022
1967:Melanoma Research
1814:10.1038/nsmb.1998
1763:(2): e202201595.
1722:10.1038/nsmb.3200
1349:phosphodiesterase
1277:
1276:
1273:
1272:
1246:
1245:
1211:
1210:
1178:
1177:
1140:
1139:
1107:
1106:
1069:
1068:
1050:
1049:
1024:
1023:
1005:
1004:
979:
978:
960:
959:
908:
907:
636:metal ion binding
593:
592:
589:
588:
551:
550:
538:
537:
476:
475:
374:
373:
273:
272:
168:ENPP2 - orthologs
100:
99:
96:
95:
52:Ortholog search:
3711:
3681:
3680:
3672:
3544:Hanes–Woolf plot
3487:Enzyme activator
3482:Enzyme inhibitor
3456:Enzyme catalysis
3400:
3393:
3386:
3377:
3376:
3222:Endoribonuclease
3208:
3202:
3170:
3169:
3116:
3115:
3102:
3101:
2802:Acid phosphatase
2683:Monoacylglycerol
2593:ester hydrolases
2562:
2555:
2548:
2539:
2538:
2507:
2497:
2464:
2427:
2405:
2368:
2331:
2313:
2288:
2278:
2269:(42): 39436–42.
2253:
2243:
2210:
2189:
2179:
2169:
2136:
2126:
2101:
2091:
2082:(40): 24408–12.
2066:
2033:
2023:
2014:(48): 30479–84.
1998:
1957:
1947:
1922:
1912:
1879:
1869:
1860:(42): 39436–42.
1834:
1833:
1797:
1791:
1790:
1780:
1748:
1742:
1741:
1705:
1699:
1687:
1681:
1680:
1670:
1660:
1636:
1630:
1629:
1593:
1587:
1586:
1579:
1570:
1569:
1559:
1530:
1524:
1523:
1512:
1506:
1505:
1494:
1488:
1478:
1467:
1457:
1371:As a drug target
1282:, also known as
1259:
1258:
1230:
1223:
1206:
1182:
1181:
1173:
1149:
1148:
1145:RefSeq (protein)
1135:
1111:
1110:
1102:
1078:
1077:
1054:
1053:
1035:
1034:
1009:
1008:
990:
989:
964:
963:
945:
944:
914:
913:
748:lipid metabolism
676:zinc ion binding
599:
598:
585:
576:
569:
562:
561:
547:
503:fourth ventricle
487:
485:Top expressed in
480:
479:
449:endothelial cell
425:
423:Top expressed in
418:
417:
397:
396:
380:
379:
370:
357:
346:
331:
324:
318:
307:
295:
279:
278:
269:
256:
245:
230:
223:
217:
206:
192:
176:
175:
170:
121:
114:
91:
66:
65:
60:
39:
38:
33:
21:
20:
3719:
3718:
3714:
3713:
3712:
3710:
3709:
3708:
3689:
3688:
3687:
3675:
3667:
3665:
3660:
3572:Oxidoreductases
3558:
3534:Enzyme kinetics
3522:
3518:List of enzymes
3491:
3460:
3431:Catalytic triad
3409:
3404:
3374:
3361:
3328:
3216:
3206:
3200:
3163:
3150:
3138:Exoribonuclease
3132:
3109:
3093:
3089:
3080:
3054:Arylsulfatase L
3049:Arylsulfatase B
3044:Arylsulfatase A
3019:
2932:
2923:
2762:
2730:
2592:
2580:
2566:
2515:
2510:
2412:Cancer Research
2201:(18): 6938–44.
2195:Cancer Research
2117:(2): 996–1001.
1843:
1841:Further reading
1838:
1837:
1798:
1794:
1749:
1745:
1706:
1702:
1688:
1684:
1637:
1633:
1604:(16): 2712–27.
1594:
1590:
1581:
1580:
1573:
1531:
1527:
1514:
1513:
1509:
1496:
1495:
1491:
1479:
1470:
1458:
1449:
1444:
1431:Lipid signaling
1417:
1393:
1373:
1319:phospholipase D
1311:lipid signaling
1307:
1268:View/Edit Mouse
1263:View/Edit Human
1226:
1219:
1216:Location (UCSC)
1202:
1198:
1194:
1190:
1169:
1165:
1161:
1157:
1131:
1127:
1123:
1119:
1098:
1094:
1090:
1086:
999:ENSG00000136960
892:
858:cell chemotaxis
773:immune response
721:
717:Golgi apparatus
692:plasma membrane
680:
581:
571:
570:
543:
534:
529:
525:
523:globus pallidus
521:
517:
513:
509:
505:
501:
497:
483:
472:
467:
463:
459:
455:
451:
447:
445:corpus callosum
443:
439:
435:
421:
365:
352:
344:
334:
333:
332:
325:
305:
282:Gene location (
264:
251:
243:
233:
232:
231:
224:
202:
179:Gene location (
130:
117:
110:
75:
53:
19:
12:
11:
5:
3717:
3707:
3706:
3701:
3686:
3685:
3662:
3661:
3659:
3658:
3645:
3632:
3619:
3606:
3593:
3580:
3566:
3564:
3560:
3559:
3557:
3556:
3551:
3546:
3541:
3536:
3530:
3528:
3524:
3523:
3521:
3520:
3515:
3510:
3505:
3499:
3497:
3496:Classification
3493:
3492:
3490:
3489:
3484:
3479:
3474:
3468:
3466:
3462:
3461:
3459:
3458:
3453:
3448:
3443:
3438:
3433:
3428:
3423:
3417:
3415:
3411:
3410:
3403:
3402:
3395:
3388:
3380:
3371:
3370:
3367:
3366:
3363:
3362:
3360:
3359:
3354:
3349:
3348:
3347:
3336:
3334:
3330:
3329:
3327:
3326:
3321:
3320:
3319:
3314:
3309:
3304:
3294:
3289:
3284:
3279:
3278:
3277:
3272:
3267:
3262:
3252:
3251:
3250:
3241:
3226:
3224:
3218:
3217:
3215:
3214:
3209:
3194:
3189:
3184:
3178:
3176:
3167:
3156:
3155:
3152:
3151:
3149:
3148:
3142:
3140:
3134:
3133:
3131:
3130:
3124:
3122:
3113:
3099:
3082:
3081:
3079:
3078:
3073:
3068:
3063:
3062:
3061:
3056:
3051:
3046:
3033:
3031:
3021:
3020:
3018:
3017:
3012:
3002:
2997:
2988:
2983:
2978:
2973:
2972:
2971:
2961:
2960:
2959:
2954:
2944:
2938:
2936:
2925:
2924:
2922:
2921:
2916:
2911:
2902:
2901:
2900:
2882:
2881:
2880:
2870:
2865:
2860:
2855:
2850:
2849:
2848:
2838:
2837:
2836:
2826:
2821:
2816:
2799:
2798:
2797:
2792:
2787:
2776:
2774:
2764:
2763:
2761:
2760:
2755:
2750:
2744:
2742:
2732:
2731:
2729:
2728:
2723:
2717:
2716:
2715:
2714:
2709:
2704:
2693:
2692:
2691:
2690:
2688:Diacylglycerol
2685:
2680:
2675:
2670:
2665:
2660:
2655:
2650:
2641:
2630:
2629:
2624:
2619:
2617:Pectinesterase
2614:
2613:
2612:
2607:
2600:Cholinesterase
2596:
2594:
2582:
2581:
2565:
2564:
2557:
2550:
2542:
2536:
2535:
2514:
2513:External links
2511:
2509:
2508:
2465:
2428:
2406:
2369:
2332:
2289:
2254:
2211:
2190:
2137:
2102:
2067:
2034:
1999:
1958:
1923:
1880:
1844:
1842:
1839:
1836:
1835:
1792:
1743:
1716:(5): 395–401.
1700:
1682:
1651:(6): 1134–44.
1631:
1588:
1571:
1525:
1507:
1489:
1468:
1446:
1445:
1443:
1440:
1439:
1438:
1436:Phospholipases
1433:
1428:
1423:
1416:
1413:
1392:
1389:
1372:
1369:
1306:
1303:
1275:
1274:
1271:
1270:
1265:
1255:
1254:
1248:
1247:
1244:
1243:
1241:
1239:
1232:
1231:
1224:
1217:
1213:
1212:
1209:
1208:
1186:
1185:
1179:
1176:
1175:
1153:
1152:
1146:
1142:
1141:
1138:
1137:
1115:
1114:
1108:
1105:
1104:
1082:
1081:
1075:
1071:
1070:
1067:
1066:
1058:
1057:
1051:
1048:
1047:
1039:
1038:
1032:
1026:
1025:
1022:
1021:
1013:
1012:
1006:
1003:
1002:
994:
993:
987:
981:
980:
977:
976:
968:
967:
961:
958:
957:
949:
948:
942:
936:
935:
930:
925:
921:
920:
910:
909:
906:
905:
894:
893:
891:
890:
885:
880:
875:
870:
865:
860:
855:
850:
845:
840:
835:
830:
825:
820:
815:
810:
805:
800:
795:
790:
785:
780:
775:
770:
765:
760:
755:
750:
745:
740:
735:
729:
727:
723:
722:
720:
719:
714:
709:
704:
699:
694:
688:
686:
682:
681:
679:
678:
673:
668:
663:
658:
653:
648:
643:
638:
633:
628:
623:
618:
612:
610:
606:
605:
595:
594:
591:
590:
587:
586:
578:
577:
559:
553:
552:
549:
548:
540:
539:
536:
535:
533:
532:
528:
524:
520:
516:
512:
508:
504:
500:
496:
492:
489:
488:
477:
474:
473:
471:
470:
466:
462:
458:
454:
450:
446:
442:
438:
434:
430:
427:
426:
414:
413:
405:
394:
388:
387:
384:RNA expression
376:
375:
372:
371:
363:
359:
358:
350:
347:
342:
336:
335:
326:
319:
313:
309:
308:
303:
297:
296:
288:
287:
275:
274:
271:
270:
262:
258:
257:
249:
246:
241:
235:
234:
225:
218:
212:
208:
207:
200:
194:
193:
185:
184:
172:
171:
128:
124:
123:
115:
107:
106:
102:
101:
98:
97:
94:
93:
71:
70:
62:
61:
50:
44:
43:
35:
34:
26:
25:
17:
9:
6:
4:
3:
2:
3716:
3705:
3702:
3700:
3697:
3696:
3694:
3684:
3679:
3674:
3673:
3670:
3656:
3652:
3651:
3646:
3643:
3639:
3638:
3633:
3630:
3626:
3625:
3620:
3617:
3613:
3612:
3607:
3604:
3600:
3599:
3594:
3591:
3587:
3586:
3581:
3578:
3574:
3573:
3568:
3567:
3565:
3561:
3555:
3552:
3550:
3547:
3545:
3542:
3540:
3537:
3535:
3532:
3531:
3529:
3525:
3519:
3516:
3514:
3513:Enzyme family
3511:
3509:
3506:
3504:
3501:
3500:
3498:
3494:
3488:
3485:
3483:
3480:
3478:
3477:Cooperativity
3475:
3473:
3470:
3469:
3467:
3463:
3457:
3454:
3452:
3449:
3447:
3444:
3442:
3439:
3437:
3436:Oxyanion hole
3434:
3432:
3429:
3427:
3424:
3422:
3419:
3418:
3416:
3412:
3408:
3401:
3396:
3394:
3389:
3387:
3382:
3381:
3378:
3358:
3355:
3353:
3350:
3346:
3343:
3342:
3341:
3338:
3337:
3335:
3331:
3325:
3322:
3318:
3315:
3313:
3310:
3308:
3305:
3303:
3300:
3299:
3298:
3295:
3293:
3290:
3288:
3285:
3283:
3280:
3276:
3273:
3271:
3268:
3266:
3263:
3261:
3258:
3257:
3256:
3253:
3249:
3245:
3242:
3240:
3236:
3233:
3232:
3231:
3228:
3227:
3225:
3223:
3219:
3213:
3210:
3205:
3198:
3195:
3193:
3190:
3188:
3185:
3183:
3180:
3179:
3177:
3175:
3171:
3168:
3166:
3161:
3157:
3147:
3144:
3143:
3141:
3139:
3135:
3129:
3126:
3125:
3123:
3121:
3117:
3114:
3112:
3107:
3103:
3100:
3097:
3092:
3087:
3083:
3077:
3074:
3072:
3069:
3067:
3064:
3060:
3057:
3055:
3052:
3050:
3047:
3045:
3042:
3041:
3040:
3039:
3038:arylsulfatase
3035:
3034:
3032:
3030:
3026:
3022:
3016:
3013:
3010:
3006:
3003:
3001:
2998:
2996:
2992:
2989:
2987:
2984:
2982:
2979:
2977:
2974:
2970:
2967:
2966:
2965:
2962:
2958:
2955:
2953:
2950:
2949:
2948:
2947:Phospholipase
2945:
2943:
2940:
2939:
2937:
2935:
2930:
2926:
2920:
2917:
2915:
2912:
2910:
2906:
2903:
2899:
2895:
2891:
2888:
2887:
2886:
2883:
2879:
2876:
2875:
2874:
2871:
2869:
2866:
2864:
2861:
2859:
2856:
2854:
2851:
2847:
2844:
2843:
2842:
2839:
2835:
2832:
2831:
2830:
2827:
2825:
2822:
2820:
2817:
2815:
2811:
2807:
2803:
2800:
2796:
2793:
2791:
2788:
2786:
2783:
2782:
2781:
2778:
2777:
2775:
2773:
2769:
2765:
2759:
2756:
2754:
2751:
2749:
2746:
2745:
2743:
2741:
2737:
2733:
2727:
2724:
2722:
2719:
2718:
2713:
2710:
2708:
2705:
2703:
2700:
2699:
2698:
2697:Phospholipase
2695:
2694:
2689:
2686:
2684:
2681:
2679:
2676:
2674:
2671:
2669:
2666:
2664:
2661:
2659:
2656:
2654:
2651:
2649:
2645:
2642:
2640:
2637:
2636:
2635:
2632:
2631:
2628:
2625:
2623:
2620:
2618:
2615:
2611:
2608:
2606:
2603:
2602:
2601:
2598:
2597:
2595:
2591:
2587:
2583:
2578:
2574:
2570:
2563:
2558:
2556:
2551:
2549:
2544:
2543:
2540:
2533:
2529:
2528:
2523:
2522:
2517:
2516:
2505:
2501:
2496:
2491:
2487:
2483:
2480:(3): 569–77.
2479:
2475:
2471:
2466:
2462:
2458:
2454:
2450:
2446:
2442:
2438:
2434:
2429:
2425:
2421:
2418:(9): 2042–5.
2417:
2413:
2407:
2403:
2399:
2395:
2391:
2387:
2383:
2380:(1–3): 60–4.
2379:
2375:
2370:
2366:
2362:
2358:
2354:
2350:
2346:
2342:
2338:
2333:
2329:
2325:
2321:
2317:
2312:
2307:
2303:
2299:
2295:
2290:
2286:
2282:
2277:
2272:
2268:
2264:
2260:
2255:
2251:
2247:
2242:
2237:
2233:
2229:
2226:(2): 227–33.
2225:
2221:
2217:
2212:
2208:
2204:
2200:
2196:
2191:
2187:
2183:
2178:
2173:
2168:
2163:
2159:
2155:
2152:(7): 3491–6.
2151:
2147:
2143:
2138:
2134:
2130:
2125:
2120:
2116:
2112:
2108:
2103:
2099:
2095:
2090:
2085:
2081:
2077:
2073:
2068:
2064:
2060:
2056:
2052:
2048:
2044:
2040:
2035:
2031:
2027:
2022:
2017:
2013:
2009:
2005:
2000:
1996:
1992:
1988:
1984:
1980:
1976:
1972:
1968:
1964:
1959:
1955:
1951:
1946:
1941:
1938:(4): 2524–9.
1937:
1933:
1929:
1924:
1920:
1916:
1911:
1906:
1902:
1898:
1895:(2): 227–33.
1894:
1890:
1886:
1881:
1877:
1873:
1868:
1863:
1859:
1855:
1851:
1846:
1845:
1831:
1827:
1823:
1819:
1815:
1811:
1808:(2): 205–12.
1807:
1803:
1796:
1788:
1784:
1779:
1774:
1770:
1766:
1762:
1758:
1754:
1747:
1739:
1735:
1731:
1727:
1723:
1719:
1715:
1711:
1704:
1698:
1694:
1693:
1686:
1678:
1674:
1669:
1664:
1659:
1654:
1650:
1646:
1642:
1635:
1627:
1623:
1619:
1615:
1611:
1607:
1603:
1599:
1592:
1584:
1578:
1576:
1567:
1563:
1558:
1553:
1549:
1545:
1541:
1537:
1529:
1521:
1517:
1511:
1503:
1499:
1493:
1486:
1482:
1477:
1475:
1473:
1465:
1461:
1456:
1454:
1452:
1447:
1437:
1434:
1432:
1429:
1427:
1424:
1422:
1419:
1418:
1412:
1410:
1406:
1405:somatomedin-B
1402:
1401:apo structure
1398:
1388:
1384:
1382:
1378:
1368:
1366:
1362:
1358:
1357:phospholipase
1354:
1353:pyrophosphate
1350:
1345:
1343:
1339:
1335:
1330:
1328:
1324:
1320:
1316:
1312:
1302:
1300:
1297:
1293:
1289:
1285:
1281:
1269:
1264:
1260:
1256:
1253:
1249:
1242:
1240:
1237:
1233:
1229:
1225:
1222:
1218:
1214:
1207:
1205:
1201:
1197:
1193:
1187:
1183:
1180:
1174:
1172:
1168:
1164:
1160:
1154:
1150:
1147:
1143:
1136:
1134:
1130:
1126:
1122:
1116:
1112:
1109:
1103:
1101:
1097:
1093:
1089:
1083:
1079:
1076:
1074:RefSeq (mRNA)
1072:
1065:
1064:
1059:
1055:
1052:
1046:
1045:
1040:
1036:
1033:
1031:
1027:
1020:
1019:
1014:
1010:
1007:
1001:
1000:
995:
991:
988:
986:
982:
975:
974:
969:
965:
962:
956:
955:
950:
946:
943:
941:
937:
934:
931:
929:
926:
922:
919:
915:
911:
904:
900:
895:
889:
886:
884:
881:
879:
876:
874:
871:
869:
866:
864:
861:
859:
856:
854:
851:
849:
846:
844:
841:
839:
836:
834:
831:
829:
826:
824:
821:
819:
816:
814:
813:cell motility
811:
809:
806:
804:
801:
799:
796:
794:
791:
789:
786:
784:
781:
779:
776:
774:
771:
769:
766:
764:
761:
759:
756:
754:
751:
749:
746:
744:
741:
739:
736:
734:
731:
730:
728:
725:
724:
718:
715:
713:
710:
708:
705:
703:
700:
698:
695:
693:
690:
689:
687:
684:
683:
677:
674:
672:
669:
667:
664:
662:
659:
657:
654:
652:
649:
647:
644:
642:
639:
637:
634:
632:
629:
627:
624:
622:
619:
617:
614:
613:
611:
608:
607:
604:
603:Gene ontology
600:
596:
584:
579:
575:
568:
563:
560:
558:
554:
546:
541:
530:
526:
522:
518:
514:
510:
506:
502:
498:
494:
493:
490:
486:
481:
478:
468:
464:
460:
456:
452:
448:
444:
440:
436:
432:
431:
428:
424:
419:
416:
415:
412:
410:
406:
404:
403:
399:
398:
395:
393:
389:
385:
381:
377:
369:
364:
360:
356:
351:
345:15|15 D1
341:
337:
330:
323:
317:
310:
302:
298:
294:
289:
285:
280:
276:
268:
263:
259:
255:
250:
240:
236:
229:
222:
216:
209:
205:
199:
195:
191:
186:
182:
177:
173:
169:
165:
161:
157:
153:
149:
145:
141:
137:
133:
125:
120:
113:
108:
103:
92:
90:
86:
82:
78:
72:
67:
64:
63:
59:
56:
49:
45:
40:
36:
32:
27:
22:
16:
3650:Translocases
3647:
3634:
3621:
3608:
3595:
3585:Transferases
3582:
3569:
3426:Binding site
3207:}}
3201:{{
3165:Endonuclease
3096:ribonuclease
3036:
2941:
2819:Nucleotidase
2740:Thioesterase
2526:
2520:
2477:
2474:Diabetologia
2473:
2439:(6): 833–8.
2436:
2432:
2415:
2411:
2377:
2374:FEBS Letters
2373:
2343:(7): 603–8.
2340:
2336:
2304:(3): 351–6.
2301:
2298:FEBS Letters
2297:
2266:
2262:
2223:
2219:
2198:
2194:
2149:
2145:
2114:
2110:
2079:
2075:
2049:(3): 714–9.
2046:
2042:
2011:
2007:
1973:(4): 203–9.
1970:
1966:
1935:
1931:
1892:
1888:
1857:
1853:
1805:
1801:
1795:
1760:
1756:
1746:
1713:
1709:
1703:
1690:
1685:
1648:
1644:
1634:
1601:
1598:FEBS Letters
1597:
1591:
1542:(2): 380–4.
1539:
1535:
1528:
1519:
1510:
1501:
1492:
1394:
1385:
1374:
1346:
1331:
1308:
1295:
1287:
1283:
1279:
1278:
1200:NP_001272924
1196:NP_001272923
1192:NP_001129549
1189:
1167:NP_001317529
1163:NP_001124335
1159:NP_001035181
1156:
1133:NM_001285995
1129:NM_001285994
1121:NM_001136077
1118:
1100:NM_001330600
1092:NM_001130863
1088:NM_001040092
1085:
1061:
1042:
1016:
997:
971:
952:
932:
927:
407:
400:
265:119,673,453
252:119,557,086
127:External IDs
74:
15:
3421:Active site
3340:Nuclease S1
3111:Exonuclease
3005:Lecithinase
2834:Calcineurin
2772:Phosphatase
2678:Lipoprotein
2668:Endothelial
1692:NCT02738801
888:endocytosis
366:54,952,892
353:54,838,901
105:Identifiers
3693:Categories
3624:Isomerases
3598:Hydrolases
3465:Regulation
2653:Pancreatic
2590:Carboxylic
1487:, May 2017
1466:, May 2017
1442:References
1409:C-terminus
1365:chemotaxis
1361:lysolipids
798:chemotaxis
793:metabolism
411:(ortholog)
148:HomoloGene
3503:EC number
3230:RNase III
3088:(includes
3029:Sulfatase
2942:Autotaxin
2806:Prostatic
2658:Lysosomal
2573:esterases
2569:Hydrolase
1391:Structure
1313:molecule
1290:), is an
1280:Autotaxin
1204:NP_056559
1171:NP_006200
1125:NM_015744
1096:NM_006209
918:Orthologs
712:cytoplasm
156:GeneCards
3704:EC 3.1.4
3527:Kinetics
3451:Cofactor
3414:Activity
3324:RNase T1
3086:Nuclease
2721:Cutinase
2504:15700135
2461:25281125
2453:15027116
2424:12727817
2402:38206060
2394:12633853
2365:25181446
2357:12498389
2328:19821754
2320:12482591
2285:12176993
2250:12119361
2207:11559573
2186:10737800
1919:12119361
1876:12176993
1822:21240269
1787:36623871
1738:24948842
1730:27043297
1677:25896349
1626:35544825
1618:24560789
1536:Genomics
1483:–
1462:–
1415:See also
1305:Function
1252:Wikidata
897:Sources:
531:habenula
3683:Biology
3637:Ligases
3407:Enzymes
3297:RNase E
3292:RNase Z
3287:RNase A
3282:RNase P
3255:RNase H
2873:Phytase
2673:Hepatic
2648:Lingual
2644:Gastric
2495:1885462
2241:2173129
2154:Bibcode
2133:8995394
2098:8798697
2063:8579579
2030:7982964
1995:8300784
1987:7496154
1954:1733949
1910:2173129
1830:6336916
1778:9834664
1668:4442871
1566:8586446
1485:Ensembl
1464:Ensembl
1381:aptamer
1340:), the
1288:E-NPP 2
1030:UniProt
985:Ensembl
924:Species
903:QuickGO
386:pattern
244:8q24.12
144:1321390
112:Aliases
3669:Portal
3611:Lyases
3235:Drosha
3160:3.1.21
3128:RecBCD
3106:3.1.11
2726:PETase
2634:Lipase
2518:Human
2502:
2492:
2459:
2451:
2422:
2400:
2392:
2363:
2355:
2326:
2318:
2283:
2248:
2238:
2205:
2184:
2174:
2131:
2096:
2061:
2028:
1993:
1985:
1952:
1917:
1907:
1874:
1828:
1820:
1785:
1775:
1736:
1728:
1675:
1665:
1624:
1616:
1564:
1292:enzyme
1238:search
1236:PubMed
1063:Q9R1E6
1044:Q13822
940:Entrez
557:BioGPS
136:601060
3563:Types
3244:Dicer
3199:;see
3025:3.1.6
2995:PDE4B
2991:PDE4A
2929:3.1.4
2898:IMPA3
2894:IMPA2
2890:IMPA1
2768:3.1.3
2736:3.1.2
2586:3.1.1
2527:ENPP2
2521:ENPP2
2457:S2CID
2398:S2CID
2361:S2CID
2324:S2CID
2177:16267
1991:S2CID
1826:S2CID
1734:S2CID
1622:S2CID
1342:lipid
1325:into
1296:ENPP2
973:18606
933:Mouse
928:Human
899:Amigo
409:Mouse
402:Human
349:Start
284:Mouse
248:Start
181:Human
160:ENPP2
119:ENPP2
24:ENPP2
3655:list
3648:EC7
3642:list
3635:EC6
3629:list
3622:EC5
3616:list
3609:EC4
3603:list
3596:EC3
3590:list
3583:EC2
3577:list
3570:EC1
3162:-31:
3108:-16:
3094:and
3000:PDE5
2986:PDE3
2981:PDE2
2976:PDE1
2868:PTEN
2853:OCRL
2846:PP2A
2795:ALPP
2790:ALPL
2785:ALPI
2579:3.1)
2500:PMID
2449:PMID
2420:PMID
2390:PMID
2353:PMID
2316:PMID
2281:PMID
2246:PMID
2203:PMID
2182:PMID
2129:PMID
2094:PMID
2059:PMID
2026:PMID
1983:PMID
1950:PMID
1915:PMID
1872:PMID
1818:PMID
1783:PMID
1726:PMID
1673:PMID
1614:PMID
1562:PMID
1395:The
1299:gene
954:5168
515:iris
457:pons
392:Bgee
340:Band
301:Chr.
239:Band
198:Chr.
152:4526
132:OMIM
89:4ZG7
85:4ZG9
81:4ZG6
77:4ZGA
58:RCSB
55:PDBe
3317:4/5
2490:PMC
2482:doi
2441:doi
2437:109
2382:doi
2378:538
2345:doi
2306:doi
2302:532
2271:doi
2267:277
2236:PMC
2228:doi
2224:158
2172:PMC
2162:doi
2119:doi
2115:272
2084:doi
2080:271
2051:doi
2047:218
2016:doi
2012:269
1975:doi
1940:doi
1936:267
1905:PMC
1897:doi
1893:158
1862:doi
1858:277
1810:doi
1773:PMC
1765:doi
1718:doi
1663:PMC
1653:doi
1606:doi
1602:588
1552:hdl
1544:doi
1334:LPA
1327:LPA
362:End
261:End
164:OMA
140:MGI
48:PDB
3695::
3275:2C
3270:2B
3265:2A
3246::
3237::
3027::
2907::
2896:,
2892:,
2808:)/
2770::
2738::
2707:A2
2702:A1
2588::
2577:EC
2571::
2498:.
2488:.
2478:48
2476:.
2472:.
2455:.
2447:.
2435:.
2416:63
2414:.
2396:.
2388:.
2376:.
2359:.
2351:.
2341:19
2339:.
2322:.
2314:.
2300:.
2296:.
2279:.
2265:.
2261:.
2244:.
2234:.
2222:.
2218:.
2199:61
2197:.
2180:.
2170:.
2160:.
2150:97
2148:.
2144:.
2127:.
2113:.
2109:.
2092:.
2078:.
2074:.
2057:.
2045:.
2041:.
2024:.
2010:.
2006:.
1989:.
1981:.
1969:.
1965:.
1948:.
1934:.
1930:.
1913:.
1903:.
1891:.
1887:.
1870:.
1856:.
1852:.
1824:.
1816:.
1806:18
1804:.
1781:.
1771:.
1759:.
1755:.
1732:.
1724:.
1714:23
1712:.
1671:.
1661:.
1649:56
1647:.
1643:.
1620:.
1612:.
1600:.
1574:^
1560:.
1550:.
1540:30
1538:.
1518:.
1500:.
1471:^
1450:^
1329:.
1301:.
901:/
368:bp
355:bp
267:bp
254:bp
162:;
158::
154:;
150::
146:;
142::
138:;
134::
87:,
83:,
79:,
3671::
3657:)
3653:(
3644:)
3640:(
3631:)
3627:(
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3614:(
3605:)
3601:(
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3588:(
3579:)
3575:(
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3385:v
3312:3
3307:2
3302:1
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3011:)
3007:(
2993:/
2969:1
2957:D
2952:C
2931::
2812:/
2804:(
2712:B
2646:/
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2404:.
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2330:.
2308::
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2188:.
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2135:.
2121::
2100:.
2086::
2065:.
2053::
2032:.
2018::
1997:.
1977::
1971:5
1956:.
1942::
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1878:.
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1789:.
1767::
1761:6
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1655::
1628:.
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1568:.
1554::
1546::
1522:.
1504:.
1286:(
286:)
183:)
166::
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