83:
256:
129:
2389:
82:
433:
A majority of proteins contain multiple domains. Between 66-80% of eukaryotic proteins have multiple domains while about 40-60% of prokaryotic proteins have multiple domains. Over time, many of the superfamilies of domains have mixed together. In fact, it is very rare to find “consistently isolated
434:
superfamilies”. When domains do combine, the N- to C-terminal domain order (the "domain architecture") is typically well conserved. Additionally, the number of domain combinations seen in nature is small compared to the number of possibilities, suggesting that selection acts on all combinations.
219:
Using sequence similarity to infer homology has several limitations. There is no minimum level of sequence similarity guaranteed to produce identical structures. Over long periods of evolution, related proteins may show no detectable sequence similarity to one another. Sequences with many
318:
is much more evolutionarily conserved than sequence, such that proteins with highly similar structures can have entirely different sequences. Over very long evolutionary timescales, very few residues show detectable amino acid sequence conservation, however
266:(PA clan). The double β-barrel that characterises the superfamily is highlighted in red. Shown are representative structures from several families within the PA superfamily. Note that some proteins show partially modified structural.
369:
specificity may be significantly different. Catalytic residues also tend to occur in the same order in the protein sequence. For the families within the PA clan of proteases, although there has been divergent evolution of the
347:, use the 3D structure of a protein of interest to find proteins with similar folds. However, on rare occasions, related proteins may evolve to be structurally dissimilar and relatedness can only be inferred by other methods.
1026:"SUPFAM--a database of potential protein superfamily relationships derived by comparing sequence-based and structure-based families: implications for structural genomics and function annotation in genomes"
1160:
Silverman GA, Bird PI, Carrell RW, Church FC, Coughlin PB, Gettins PG, Irving JA, Lomas DA, Luke CJ, Moyer RW, Pemberton PA, Remold-O'Donnell E, Salvesen GS, Travis J, Whisstock JC (September 2001).
120:
Superfamilies of proteins are identified using a number of methods. Closely related members can be identified by different methods to those needed to group the most evolutionarily divergent members.
2323:
Nagano N, Orengo CA, Thornton JM (August 2002). "One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions".
1162:"The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature"
579:
1718:
Akiva, Eyal; Brown, Shoshana; Almonacid, Daniel E.; Barber, Alan E.; Custer, Ashley F.; Hicks, Michael A.; Huang, Conrad C.; Lauck, Florian; Mashiyama, Susan T. (2013-11-23).
240:. Conversely, the individual families that make up a superfamily are defined on the basis of their sequence alignment, for example the C04 protease family within the PA clan.
243:
Nevertheless, sequence similarity is the most commonly used form of evidence to infer relatedness, since the number of known sequences vastly outnumbers the number of known
382:
multiple times independently, and so form separate superfamilies, and in some superfamilies display a range of different (though often chemically similar) mechanisms.
1309:
Li D, Zhang L, Yin H, Xu H, Satkoski Trask J, Smith DG, Li Y, Yang M, Zhu Q (June 2014). "Evolution of primate α and θ defensins revealed by analysis of genomes".
398:
that is currently possible. They are therefore amongst the most ancient evolutionary events currently studied. Some superfamilies have members present in all
339:. Consequently, protein tertiary structure can be used to detect homology between proteins even when no evidence of relatedness remains in their sequences.
2049:
Bolognesi M, Onesti S, Gatti G, Coda A, Ascenzi P, Brunori M (February 1989). "Aplysia limacina myoglobin. Crystallographic analysis at 1.6 A resolution".
413:
Superfamily members may be in different species, with the ancestral protein being the form of the protein that existed in the ancestral species (
1252:"Cross-Over between Discrete and Continuous Protein Structure Space: Insights into Automatic Classification and Networks of Protein Structures"
89:
2258:"The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life"
1834:
Ranea JA, Sillero A, Thornton JM, Orengo CA (October 2006). "Protein superfamily evolution and the last universal common ancestor (LUCA)".
378:
on proteins, peptides or amino acids. However, mechanism alone is not sufficient to infer relatedness. Some catalytic mechanisms have been
204:), so it is a more sensitive detection method. Since some of the amino acids have similar properties (e.g., charge, hydrophobicity, size),
247:. In the absence of structural information, sequence similarity constrains the limits of which proteins can be assigned to a superfamily.
1963:
1445:
Dessailly, Benoit H.; Dawson, Natalie L.; Das, Sayoni; Orengo, Christine A. (2017), "Function
Diversity within Folds and Superfamilies",
1634:
Coutinho PM, Deleury E, Davies GJ, Henrissat B (April 2003). "An evolving hierarchical family classification for glycosyltransferases".
680:- Library of HMMs representing superfamilies and database of (superfamily and family) annotations for all completely sequenced organisms
1989:
Mohamed MF, Hollfelder F (January 2013). "Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer".
941:
344:
113:
2084:
Bork P, Holm L, Sander C (September 1994). "The immunoglobulin fold. Structural classification, sequence patterns and common core".
2148:"Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications"
2393:
683:
188:. Sequence similarity is considered a good predictor of relatedness, since similar sequences are more likely the result of
144:. Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting:
1669:
Zámocký M, Hofbauer S, Schaffner I, Gasselhuber B, Nicolussi A, Soudi M, Pirker KF, Furtmüller PG, Obinger C (May 2015).
2033:
978:
Han JH, Batey S, Nickson AA, Teichmann SA, Clarke J (April 2007). "The folding and evolution of multidomain proteins".
212:
to function. The most conserved sequence regions of a protein often correspond to functionally important regions like
2421:
1577:"Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad"
1462:
390:
Protein superfamilies represent the current limits of our ability to identify common ancestry. They are the largest
47:
can then be deduced even if not apparent (due to low sequence similarity). Superfamilies typically contain several
2715:
2720:
407:
2577:
184:
Historically, the similarity of different amino acid sequences has been the most common method of inferring
2700:
1024:
Pandit SB, Gosar D, Abhiman S, Sujatha S, Dixit SS, Mhatre NS, Sowdhamini R, Srinivasan N (January 2002).
417:). Conversely, the proteins may be in the same species, but evolved from a single protein whose gene was
271:
2205:
Vetter IR, Wittinghofer A (November 2001). "The guanine nucleotide-binding switch in three dimensions".
1928:
Nardini M, Dijkstra BW (December 1999). "Alpha/beta hydrolase fold enzymes: the family keeps growing".
515:
244:
2705:
2678:
2665:
2652:
2639:
2626:
2613:
2600:
2562:
283:
2572:
2526:
2469:
585:
366:
2474:
291:
1073:
Orengo CA, Thornton JM (2005). "Protein families and their evolution-a structural perspective".
702:
236:, for example, not a single residue is conserved through the superfamily, not even those in the
2710:
414:
302:
1967:
422:
2495:
2414:
1528:"Handicap-Recover Evolution Leads to a Chemically Versatile, Nucleophile-Permissive Protease"
1086:
756:
604:
332:
205:
156:
949:
2567:
2269:
2214:
2159:
2119:
Brümmendorf T, Rathjen FG (1995). "Cell adhesion molecules 1: immunoglobulin superfamily".
1843:
1588:
1263:
716:
649:
487:
379:
340:
320:
310:
197:
93:
40:
576:
Members share a common catalytic G domain of a 6-strand β sheet surrounded by 5 α-helices.
8:
529:
362:
324:
259:
193:
108:, L indicates loop. Below, sequence conservation for the same alignment. Arrows indicate
2273:
2218:
2163:
1847:
1592:
1267:
2464:
2300:
2257:
2238:
1875:
1788:
1752:
1719:
1695:
1670:
1611:
1576:
1552:
1527:
1503:
1478:
1419:
1394:
1334:
1286:
1251:
1227:
1202:
1134:
1109:
1003:
918:
893:
869:
844:
815:
790:
746:
612:
598:
592:
493:
443:
375:
336:
225:
149:
133:
60:
36:
2371:
2336:
2182:
2147:
1941:
1811:
1776:
1647:
2340:
2305:
2287:
2230:
2187:
2128:
2101:
2066:
2062:
2029:
2006:
1945:
1910:
1867:
1816:
1757:
1739:
1700:
1651:
1616:
1557:
1508:
1458:
1424:
1375:
1326:
1291:
1232:
1183:
1139:
1090:
1055:
1050:
1025:
995:
923:
874:
820:
741:
731:
695:
557:
477:
399:
315:
255:
185:
179:
44:
1879:
1370:
1353:
1338:
1007:
2510:
2505:
2479:
2407:
2367:
2332:
2295:
2277:
2242:
2222:
2177:
2167:
2093:
2058:
1998:
1937:
1902:
1859:
1851:
1806:
1798:
1747:
1731:
1690:
1682:
1643:
1606:
1596:
1547:
1539:
1498:
1490:
1450:
1414:
1406:
1365:
1318:
1281:
1271:
1222:
1214:
1173:
1129:
1121:
1082:
1045:
1037:
987:
913:
905:
864:
856:
810:
802:
561:
418:
374:
residues used to perform catalysis, all members use a similar mechanism to perform
356:
328:
209:
201:
189:
168:
141:
48:
2557:
2541:
2454:
2282:
2002:
1276:
736:
721:
608:
571:
457:
371:
279:
237:
109:
32:
1454:
690:- Classifications of protein structures into superfamilies, families and domains
200:. Amino acid sequence is typically more conserved than DNA sequence (due to the
2595:
2536:
2152:
Proceedings of the
National Academy of Sciences of the United States of America
1906:
1581:
Proceedings of the
National Academy of Sciences of the United States of America
726:
1855:
1777:"Protein structure and evolutionary history determine sequence space topology"
1686:
1410:
1322:
845:"MEROPS: the database of proteolytic enzymes, their substrates and inhibitors"
216:
and binding sites, since these regions are less tolerant to sequence changes.
2694:
2500:
2459:
2291:
1743:
533:
2226:
2172:
1601:
1125:
2449:
2344:
2309:
2234:
2097:
2010:
1949:
1914:
1871:
1820:
1761:
1704:
1655:
1620:
1561:
1543:
1512:
1428:
1379:
1330:
1295:
1236:
1187:
1178:
1161:
1143:
1094:
1059:
1041:
999:
878:
824:
632:
565:
545:
481:
391:
298:
287:
267:
213:
2191:
2132:
2105:
2070:
1735:
927:
698:
for proteins with structural homology to a target structure, for example:
406:, indicating that the last common ancestor of that superfamily was in the
2673:
2608:
2444:
1218:
860:
806:
761:
677:
553:
509:
505:
469:
295:
275:
1494:
549:
525:
1863:
1802:
1526:
Shafee T, Gatti-Lafranconi P, Minter R, Hollfelder F (September 2015).
618:
449:
140:
proteins. The similarity of the sequences implies that they evolved by
43:
and mechanistic similarity, even if no sequence similarity is evident.
1793:
1525:
909:
521:
453:
105:
101:
2647:
2621:
751:
636:
603:
Members share a high-energy, stressed fold which can undergo a large
492:
Members share an αβα sandwich structure as well as performing common
473:
461:
991:
556:
mechanisms but sequence identity of <10%. The clan contains both
128:
2256:
Atkinson, Gemma C.; Tenson, Tanel; Hauryliuk, Vasili (2011-08-09).
1668:
894:"Updating the sequence-based classification of glycosyl hydrolases"
668:
588:
395:
233:
56:
1893:
Carr PD, Ollis DL (2009). "Alpha/beta hydrolase fold: an update".
705:- Structural alignment based on a distance alignment matrix method
335:
of the protein structure may also be conserved, as is seen in the
1774:
662:
539:
465:
263:
229:
137:
97:
28:
365:
of enzymes within a superfamily is commonly conserved, although
2660:
2430:
2388:
2358:
Farber G (1993). "An α/β-barrel full of evolutionary trouble".
1775:
Shakhnovich BE, Deeds E, Delisi C, Shakhnovich E (March 2005).
1249:
652:
document protein superfamilies and protein folds, for example:
499:
64:
1633:
2634:
1991:
Biochimica et
Biophysica Acta (BBA) - Proteins and Proteomics
1671:"Independent evolution of four heme peroxidase superfamilies"
221:
165:
24:
665:- Database of protein domains, families and functional sites
51:
which show sequence similarity within each family. The term
1479:"Causes of evolutionary rate variation among protein sites"
766:
687:
656:
403:
68:
2399:
1833:
1354:"Structural drift: a possible path to protein fold change"
1159:
1717:
1023:
2048:
1444:
1110:"Sequence evolution correlates with structural dynamics"
977:
674:
PASS2 - Protein
Alignment as Structural Superfamilies v2
584:
Members share capability to hydrolyze and/or synthesize
228:
and so identify the homologous sequence regions. In the
2255:
1250:
Pascual-García A, Abia D, Ortiz ÁR, Bastolla U (2009).
1447:
From
Protein Structure to Function with Bioinformatics
842:
2322:
1476:
843:Rawlings ND, Barrett AJ, Bateman A (January 2012).
2204:
2118:
659:- Protein families database of alignments and HMMs
1988:
1477:Echave J, Spielman SJ, Wilke CO (February 2016).
532:), and are involved in recognition, binding, and
39:). Usually this common ancestry is inferred from
2692:
891:
643:
2145:
1927:
694:Similarly there are algorithms that search the
631:barrel structure. It is one of the most common
520:Members share a sandwich-like structure of two
460:residues in the same order, activities include
112:residues. Aligned on the basis of structure by
2083:
1574:
1351:
1072:
788:
2415:
885:
2198:
2023:
1921:
1308:
1155:
1153:
385:
2112:
2077:
2422:
2408:
1449:, Springer Netherlands, pp. 295–325,
1392:
1200:
2299:
2281:
2181:
2171:
2146:Bazan JF, Fletterick RJ (November 1988).
1892:
1810:
1792:
1751:
1720:"The Structure–Function Linkage Database"
1694:
1610:
1600:
1551:
1502:
1418:
1369:
1285:
1275:
1226:
1177:
1150:
1133:
1049:
1019:
1017:
917:
868:
814:
791:"Dali server: conservation mapping in 3D"
448:Members share an α/β sheet, containing 8
350:
1575:Buller AR, Townsend CA (February 2013).
1107:
1087:10.1146/annurev.biochem.74.082803.133029
838:
836:
834:
254:
250:
127:
2028:(2nd ed.). New York: Garland Pub.
1675:Archives of Biochemistry and Biophysics
639:of this superfamily is still contested.
2693:
2357:
1014:
973:
971:
969:
967:
123:
2403:
2360:Current Opinion in Structural Biology
1930:Current Opinion in Structural Biology
1440:
1438:
1399:Current Opinion in Structural Biology
1352:Krishna SS, Grishin NV (April 2005).
980:Nature Reviews Molecular Cell Biology
831:
607:, which is typically used to inhibit
892:Henrissat B, Bairoch A (June 1996).
784:
782:
1166:The Journal of Biological Chemistry
964:
671:- SuperFamily Classification System
224:can also sometimes be difficult to
13:
1435:
789:Holm L, Rosenström P (July 2010).
428:
327:motifs are highly conserved. Some
162:. semi-conservative mutations, and
96:conservation of 80 members of the
14:
2732:
2381:
2026:Introduction to protein structure
1393:Bryan PN, Orban J (August 2010).
1108:Liu Y, Bahar I (September 2012).
779:
292:snake venom plasminogen activator
74:
2387:
488:Alkaline phosphatase superfamily
376:covalent, nucleophilic catalysis
208:that interchange them are often
81:
2351:
2316:
2249:
2139:
2042:
2017:
1982:
1956:
1886:
1827:
1768:
1711:
1662:
1627:
1568:
1519:
1470:
1386:
1345:
1302:
1243:
1201:Holm L, Laakso LM (July 2016).
1194:
1114:Molecular Biology and Evolution
1836:Journal of Molecular Evolution
1101:
1066:
934:
615:by disrupting their structure.
408:last universal common ancestor
1:
2372:10.1016/S0959-440X(05)80114-9
2337:10.1016/s0022-2836(02)00649-6
1942:10.1016/S0959-440X(99)00037-8
1648:10.1016/S0022-2836(03)00307-3
1371:10.1093/bioinformatics/bti227
1075:Annual Review of Biochemistry
773:
644:Protein superfamily resources
2325:Journal of Molecular Biology
2283:10.1371/journal.pone.0023479
2086:Journal of Molecular Biology
2063:10.1016/0022-2836(89)90224-6
2051:Journal of Molecular Biology
2003:10.1016/j.bbapap.2012.07.015
1636:Journal of Molecular Biology
1395:"Proteins that switch folds"
1277:10.1371/journal.pcbi.1000331
801:(Web Server issue): W545–9.
196:, rather than the result of
7:
2429:
2024:Branden C, Tooze J (1999).
1895:Protein and Peptide Letters
1455:10.1007/978-94-024-1069-3_9
855:(Database issue): D343–50.
709:
437:
272:tobacco etch virus protease
100:(superfamily). H indicates
63:superfamilies based on the
10:
2737:
1907:10.2174/092986609789071298
1256:PLOS Computational Biology
516:Immunoglobulin superfamily
354:
308:
177:
169:non-conservative mutations
2586:
2578:Michaelis–Menten kinetics
2550:
2519:
2488:
2437:
1856:10.1007/s00239-005-0289-7
1687:10.1016/j.abb.2014.12.025
1411:10.1016/j.sbi.2010.06.002
1323:10.1007/s11033-014-3253-z
1311:Molecular Biology Reports
444:α/β hydrolase superfamily
394:grouping based on direct
386:Evolutionary significance
23:is the largest grouping (
2470:Diffusion-limited enzyme
1483:Nature Reviews. Genetics
222:insertions and deletions
71:classification systems.
2227:10.1126/science.1062023
2173:10.1073/pnas.85.21.7872
1602:10.1073/pnas.1221050110
898:The Biochemical Journal
623:Members share a large α
202:degenerate genetic code
2716:Protein classification
2098:10.1006/jmbi.1994.1582
1724:Nucleic Acids Research
1544:10.1002/cbic.201500295
1207:Nucleic Acids Research
1179:10.1074/jbc.R100016200
1030:Nucleic Acids Research
942:"Clustal FAQ #Symbols"
849:Nucleic Acids Research
795:Nucleic Acids Research
619:TIM barrel superfamily
496:by a common mechanism.
351:Mechanistic similarity
333:conformational changes
306:
303:equine arteritis virus
206:conservative mutations
175:
157:conservative mutations
2721:Protein superfamilies
2563:Eadie–Hofstee diagram
2496:Allosteric regulation
2394:Protein superfamilies
1126:10.1093/molbev/mss097
757:List of gene families
605:conformational change
494:promiscuous reactions
258:
251:Structural similarity
131:
55:is commonly used for
35:can be inferred (see
2573:Lineweaver–Burk plot
2396:at Wikimedia Commons
1203:"Dali server update"
1042:10.1093/nar/30.1.289
717:Structural alignment
650:biological databases
410:of all life (LUCA).
380:convergently evolved
341:Structural alignment
321:secondary structural
311:Structural alignment
198:convergent evolution
94:secondary structural
41:structural alignment
16:Grouping of proteins
2701:Molecular evolution
2274:2011PLoSO...623479A
2219:2001Sci...294.1299V
2164:1988PNAS...85.7872B
1848:2006JMolE..63..513R
1736:10.1093/nar/gkt1130
1593:2013PNAS..110E.653B
1495:10.1038/nrg.2015.18
1268:2009PLSCB...5E0331P
504:Members share an 8-
363:catalytic mechanism
325:tertiary structural
260:Structural homology
245:tertiary structures
194:divergent evolution
124:Sequence similarity
61:glycosyl hydrolases
21:protein superfamily
2532:Enzyme superfamily
2465:Enzyme promiscuity
2213:(5545): 1299–304.
1803:10.1101/gr.3133605
1219:10.1093/nar/gkw357
952:on 24 October 2016
861:10.1093/nar/gkr987
807:10.1093/nar/gkq366
747:Homology (biology)
613:cysteine proteases
599:Serpin superfamily
593:stringent response
500:Globin superfamily
478:epoxide hydrolases
343:programs, such as
337:serpin superfamily
307:
176:
150:conserved sequence
134:sequence alignment
2688:
2687:
2392:Media related to
1730:(D1): D521–D530.
1538:(13): 1866–1869.
910:10.1042/bj3160695
742:Protein structure
732:Protein subfamily
552:fold and similar
282:protease (1fp7),
180:Sequence homology
45:Sequence homology
2728:
2706:Protein families
2568:Hanes–Woolf plot
2511:Enzyme activator
2506:Enzyme inhibitor
2480:Enzyme catalysis
2424:
2417:
2410:
2401:
2400:
2391:
2376:
2375:
2355:
2349:
2348:
2320:
2314:
2313:
2303:
2285:
2253:
2247:
2246:
2202:
2196:
2195:
2185:
2175:
2143:
2137:
2136:
2116:
2110:
2109:
2081:
2075:
2074:
2046:
2040:
2039:
2021:
2015:
2014:
1986:
1980:
1979:
1977:
1975:
1966:. Archived from
1960:
1954:
1953:
1925:
1919:
1918:
1890:
1884:
1883:
1831:
1825:
1824:
1814:
1796:
1772:
1766:
1765:
1755:
1715:
1709:
1708:
1698:
1666:
1660:
1659:
1631:
1625:
1624:
1614:
1604:
1572:
1566:
1565:
1555:
1523:
1517:
1516:
1506:
1474:
1468:
1467:
1442:
1433:
1432:
1422:
1390:
1384:
1383:
1373:
1349:
1343:
1342:
1306:
1300:
1299:
1289:
1279:
1247:
1241:
1240:
1230:
1198:
1192:
1191:
1181:
1157:
1148:
1147:
1137:
1105:
1099:
1098:
1070:
1064:
1063:
1053:
1021:
1012:
1011:
975:
962:
961:
959:
957:
948:. Archived from
938:
932:
931:
921:
889:
883:
882:
872:
840:
829:
828:
818:
786:
562:serine proteases
544:Members share a
524:of antiparallel
357:Enzyme mechanism
329:protein dynamics
305:protease (1mbm).
284:exfoliatin toxin
190:gene duplication
142:gene duplication
98:PA protease clan
85:
49:protein families
2736:
2735:
2731:
2730:
2729:
2727:
2726:
2725:
2691:
2690:
2689:
2684:
2596:Oxidoreductases
2582:
2558:Enzyme kinetics
2546:
2542:List of enzymes
2515:
2484:
2455:Catalytic triad
2433:
2428:
2384:
2379:
2356:
2352:
2321:
2317:
2254:
2250:
2203:
2199:
2144:
2140:
2127:(9): 963–1108.
2121:Protein Profile
2117:
2113:
2082:
2078:
2047:
2043:
2036:
2022:
2018:
1987:
1983:
1973:
1971:
1970:on 29 July 2014
1962:
1961:
1957:
1926:
1922:
1901:(10): 1137–48.
1891:
1887:
1832:
1828:
1781:Genome Research
1773:
1769:
1716:
1712:
1667:
1663:
1632:
1628:
1573:
1569:
1524:
1520:
1475:
1471:
1465:
1443:
1436:
1391:
1387:
1350:
1346:
1307:
1303:
1262:(3): e1000331.
1248:
1244:
1199:
1195:
1172:(36): 33293–6.
1158:
1151:
1106:
1102:
1071:
1067:
1022:
1015:
992:10.1038/nrm2144
976:
965:
955:
953:
940:
939:
935:
904:(Pt 2): 695–6.
890:
886:
841:
832:
787:
780:
776:
771:
737:Protein mimetic
722:Protein domains
712:
646:
630:
626:
580:RSH superfamily
572:Ras superfamily
458:catalytic triad
440:
431:
429:Diversification
421:in the genome (
388:
372:catalytic triad
359:
353:
313:
280:west nile virus
253:
238:catalytic triad
214:catalytic sites
182:
174:
126:
118:
117:
116:
110:catalytic triad
91:
86:
77:
33:common ancestry
17:
12:
11:
5:
2734:
2724:
2723:
2718:
2713:
2708:
2703:
2686:
2685:
2683:
2682:
2669:
2656:
2643:
2630:
2617:
2604:
2590:
2588:
2584:
2583:
2581:
2580:
2575:
2570:
2565:
2560:
2554:
2552:
2548:
2547:
2545:
2544:
2539:
2534:
2529:
2523:
2521:
2520:Classification
2517:
2516:
2514:
2513:
2508:
2503:
2498:
2492:
2490:
2486:
2485:
2483:
2482:
2477:
2472:
2467:
2462:
2457:
2452:
2447:
2441:
2439:
2435:
2434:
2427:
2426:
2419:
2412:
2404:
2398:
2397:
2383:
2382:External links
2380:
2378:
2377:
2366:(3): 409–412.
2350:
2315:
2248:
2197:
2158:(21): 7872–6.
2138:
2111:
2076:
2041:
2035:978-0815323051
2034:
2016:
1981:
1955:
1920:
1885:
1826:
1767:
1710:
1661:
1626:
1587:(8): E653–61.
1567:
1518:
1469:
1463:
1434:
1385:
1364:(8): 1308–10.
1358:Bioinformatics
1344:
1317:(6): 3859–66.
1301:
1242:
1213:(W1): W351–5.
1193:
1149:
1120:(9): 2253–63.
1100:
1081:(1): 867–900.
1065:
1013:
963:
933:
884:
830:
777:
775:
772:
770:
769:
764:
759:
754:
749:
744:
739:
734:
729:
727:Protein family
724:
719:
713:
711:
708:
707:
706:
692:
691:
681:
675:
672:
666:
660:
645:
642:
641:
640:
628:
624:
621:
616:
601:
596:
582:
577:
574:
569:
542:
537:
518:
513:
502:
497:
490:
485:
446:
439:
436:
430:
427:
387:
384:
355:Main article:
352:
349:
309:Main article:
264:PA superfamily
252:
249:
178:Main article:
173:
172:
163:
160:
153:
145:
125:
122:
104:, E indicates
88:
87:
80:
79:
78:
76:
75:Identification
73:
15:
9:
6:
4:
3:
2:
2733:
2722:
2719:
2717:
2714:
2712:
2711:Protein folds
2709:
2707:
2704:
2702:
2699:
2698:
2696:
2680:
2676:
2675:
2670:
2667:
2663:
2662:
2657:
2654:
2650:
2649:
2644:
2641:
2637:
2636:
2631:
2628:
2624:
2623:
2618:
2615:
2611:
2610:
2605:
2602:
2598:
2597:
2592:
2591:
2589:
2585:
2579:
2576:
2574:
2571:
2569:
2566:
2564:
2561:
2559:
2556:
2555:
2553:
2549:
2543:
2540:
2538:
2537:Enzyme family
2535:
2533:
2530:
2528:
2525:
2524:
2522:
2518:
2512:
2509:
2507:
2504:
2502:
2501:Cooperativity
2499:
2497:
2494:
2493:
2491:
2487:
2481:
2478:
2476:
2473:
2471:
2468:
2466:
2463:
2461:
2460:Oxyanion hole
2458:
2456:
2453:
2451:
2448:
2446:
2443:
2442:
2440:
2436:
2432:
2425:
2420:
2418:
2413:
2411:
2406:
2405:
2402:
2395:
2390:
2386:
2385:
2373:
2369:
2365:
2361:
2354:
2346:
2342:
2338:
2334:
2331:(5): 741–65.
2330:
2326:
2319:
2311:
2307:
2302:
2297:
2293:
2289:
2284:
2279:
2275:
2271:
2268:(8): e23479.
2267:
2263:
2259:
2252:
2244:
2240:
2236:
2232:
2228:
2224:
2220:
2216:
2212:
2208:
2201:
2193:
2189:
2184:
2179:
2174:
2169:
2165:
2161:
2157:
2153:
2149:
2142:
2134:
2130:
2126:
2122:
2115:
2107:
2103:
2099:
2095:
2092:(4): 309–20.
2091:
2087:
2080:
2072:
2068:
2064:
2060:
2057:(3): 529–44.
2056:
2052:
2045:
2037:
2031:
2027:
2020:
2012:
2008:
2004:
2000:
1997:(1): 417–24.
1996:
1992:
1985:
1969:
1965:
1959:
1951:
1947:
1943:
1939:
1935:
1931:
1924:
1916:
1912:
1908:
1904:
1900:
1896:
1889:
1881:
1877:
1873:
1869:
1865:
1861:
1857:
1853:
1849:
1845:
1842:(4): 513–25.
1841:
1837:
1830:
1822:
1818:
1813:
1808:
1804:
1800:
1795:
1794:q-bio/0404040
1790:
1787:(3): 385–92.
1786:
1782:
1778:
1771:
1763:
1759:
1754:
1749:
1745:
1741:
1737:
1733:
1729:
1725:
1721:
1714:
1706:
1702:
1697:
1692:
1688:
1684:
1680:
1676:
1672:
1665:
1657:
1653:
1649:
1645:
1642:(2): 307–17.
1641:
1637:
1630:
1622:
1618:
1613:
1608:
1603:
1598:
1594:
1590:
1586:
1582:
1578:
1571:
1563:
1559:
1554:
1549:
1545:
1541:
1537:
1533:
1529:
1522:
1514:
1510:
1505:
1500:
1496:
1492:
1489:(2): 109–21.
1488:
1484:
1480:
1473:
1466:
1464:9789402410679
1460:
1456:
1452:
1448:
1441:
1439:
1430:
1426:
1421:
1416:
1412:
1408:
1404:
1400:
1396:
1389:
1381:
1377:
1372:
1367:
1363:
1359:
1355:
1348:
1340:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1305:
1297:
1293:
1288:
1283:
1278:
1273:
1269:
1265:
1261:
1257:
1253:
1246:
1238:
1234:
1229:
1224:
1220:
1216:
1212:
1208:
1204:
1197:
1189:
1185:
1180:
1175:
1171:
1167:
1163:
1156:
1154:
1145:
1141:
1136:
1131:
1127:
1123:
1119:
1115:
1111:
1104:
1096:
1092:
1088:
1084:
1080:
1076:
1069:
1061:
1057:
1052:
1047:
1043:
1039:
1036:(1): 289–93.
1035:
1031:
1027:
1020:
1018:
1009:
1005:
1001:
997:
993:
989:
986:(4): 319–30.
985:
981:
974:
972:
970:
968:
951:
947:
943:
937:
929:
925:
920:
915:
911:
907:
903:
899:
895:
888:
880:
876:
871:
866:
862:
858:
854:
850:
846:
839:
837:
835:
826:
822:
817:
812:
808:
804:
800:
796:
792:
785:
783:
778:
768:
765:
763:
760:
758:
755:
753:
750:
748:
745:
743:
740:
738:
735:
733:
730:
728:
725:
723:
720:
718:
715:
714:
704:
701:
700:
699:
697:
689:
685:
682:
679:
676:
673:
670:
667:
664:
661:
658:
655:
654:
653:
651:
638:
637:monophylicity
634:
633:protein folds
622:
620:
617:
614:
610:
606:
602:
600:
597:
594:
590:
587:
583:
581:
578:
575:
573:
570:
567:
563:
559:
555:
551:
548:-like double
547:
543:
541:
538:
535:
531:
527:
523:
519:
517:
514:
511:
507:
503:
501:
498:
495:
491:
489:
486:
483:
482:dehalogenases
479:
475:
471:
467:
463:
459:
455:
452:connected by
451:
447:
445:
442:
441:
435:
426:
424:
420:
416:
411:
409:
405:
401:
397:
393:
383:
381:
377:
373:
368:
364:
358:
348:
346:
342:
338:
334:
330:
326:
323:elements and
322:
317:
312:
304:
300:
297:
293:
289:
288:HtrA protease
285:
281:
277:
273:
269:
265:
261:
257:
248:
246:
241:
239:
235:
231:
227:
223:
217:
215:
211:
207:
203:
199:
195:
191:
187:
181:
170:
167:
164:
161:
158:
154:
151:
147:
146:
143:
139:
136:of mammalian
135:
130:
121:
115:
111:
107:
103:
99:
95:
90:
84:
72:
70:
66:
62:
58:
54:
50:
46:
42:
38:
34:
30:
26:
22:
2674:Translocases
2671:
2658:
2645:
2632:
2619:
2609:Transferases
2606:
2593:
2531:
2450:Binding site
2363:
2359:
2353:
2328:
2324:
2318:
2265:
2261:
2251:
2210:
2206:
2200:
2155:
2151:
2141:
2124:
2120:
2114:
2089:
2085:
2079:
2054:
2050:
2044:
2025:
2019:
1994:
1990:
1984:
1972:. Retrieved
1968:the original
1958:
1936:(6): 732–7.
1933:
1929:
1923:
1898:
1894:
1888:
1839:
1835:
1829:
1784:
1780:
1770:
1727:
1723:
1713:
1678:
1674:
1664:
1639:
1635:
1629:
1584:
1580:
1570:
1535:
1531:
1521:
1486:
1482:
1472:
1446:
1405:(4): 482–8.
1402:
1398:
1388:
1361:
1357:
1347:
1314:
1310:
1304:
1259:
1255:
1245:
1210:
1206:
1196:
1169:
1165:
1117:
1113:
1103:
1078:
1074:
1068:
1033:
1029:
983:
979:
954:. Retrieved
950:the original
945:
936:
901:
897:
887:
852:
848:
798:
794:
693:
647:
566:nucleophiles
546:chymotrypsin
432:
412:
392:evolutionary
389:
360:
314:
268:Chymotrypsin
242:
218:
183:
119:
53:protein clan
52:
20:
18:
2445:Active site
1864:10261/78338
1532:ChemBioChem
762:SUPERFAMILY
678:SUPERFAMILY
564:(different
554:proteolysis
510:globin fold
506:alpha helix
470:peroxidases
301:(4fln) and
296:chloroplast
276:calicivirin
2695:Categories
2648:Isomerases
2622:Hydrolases
2489:Regulation
1681:: 108–19.
956:8 December
774:References
419:duplicated
31:for which
2527:EC number
2292:1932-6203
1744:0305-1048
752:Interolog
589:alarmones
526:β strands
508:globular
474:esterases
462:proteases
415:orthology
367:substrate
316:Structure
234:proteases
2551:Kinetics
2475:Cofactor
2438:Activity
2345:12206759
2310:21858139
2262:PLOS ONE
2235:11701921
2011:22885024
1950:10607665
1915:19508187
1880:25258028
1872:17021929
1821:15741509
1762:24271399
1705:25575902
1656:12691742
1621:23382230
1562:26097079
1513:26781812
1429:20591649
1380:15604105
1339:14936647
1331:24557891
1296:19325884
1237:27131377
1188:11435447
1144:22427707
1095:15954844
1060:11752317
1008:13762291
1000:17356578
879:22086950
825:20457744
710:See also
648:Several
635:and the
558:cysteine
550:β-barrel
534:adhesion
438:Examples
423:paralogy
400:kingdoms
396:evidence
299:protease
294:(1bqy),
290:(1l1j),
286:(1exf),
278:(1wqs),
274:(1lvm),
270:(1gg6),
186:homology
155: :
57:protease
37:homology
29:proteins
2661:Ligases
2431:Enzymes
2301:3153485
2270:Bibcode
2243:6636339
2215:Bibcode
2207:Science
2192:3186696
2160:Bibcode
2133:8574878
2106:7932691
2071:2926816
1844:Bibcode
1753:3965090
1696:4420034
1612:3581919
1589:Bibcode
1553:4576821
1504:4724262
1420:2928869
1287:2654728
1264:Bibcode
1228:4987910
1135:3424413
946:Clustal
928:8687420
919:1217404
870:3245014
816:2896194
663:PROSITE
591:in the
540:PA clan
530:Ig-fold
466:lipases
456:, with
454:helices
450:strands
262:in the
230:PA clan
210:neutral
138:histone
106:β-sheet
102:α-helix
92:Above,
2635:Lyases
2343:
2308:
2298:
2290:
2241:
2233:
2190:
2183:282299
2180:
2131:
2104:
2069:
2032:
2009:
1974:28 May
1964:"SCOP"
1948:
1913:
1878:
1870:
1819:
1812:551565
1809:
1760:
1750:
1742:
1703:
1693:
1654:
1619:
1609:
1560:
1550:
1511:
1501:
1461:
1427:
1417:
1378:
1337:
1329:
1294:
1284:
1235:
1225:
1186:
1142:
1132:
1093:
1058:
1048:
1006:
998:
926:
916:
877:
867:
823:
813:
609:serine
522:sheets
65:MEROPS
2587:Types
2239:S2CID
1876:S2CID
1789:arXiv
1335:S2CID
1051:99061
1004:S2CID
669:PIRSF
586:ppGpp
226:align
27:) of
25:clade
2679:list
2672:EC7
2666:list
2659:EC6
2653:list
2646:EC5
2640:list
2633:EC4
2627:list
2620:EC3
2614:list
2607:EC2
2601:list
2594:EC1
2341:PMID
2306:PMID
2288:ISSN
2231:PMID
2188:PMID
2129:PMID
2102:PMID
2067:PMID
2030:ISBN
2007:PMID
1995:1834
1976:2014
1946:PMID
1911:PMID
1868:PMID
1817:PMID
1758:PMID
1740:ISSN
1701:PMID
1652:PMID
1617:PMID
1558:PMID
1509:PMID
1459:ISBN
1425:PMID
1376:PMID
1327:PMID
1292:PMID
1233:PMID
1184:PMID
1140:PMID
1091:PMID
1056:PMID
996:PMID
958:2014
924:PMID
875:PMID
821:PMID
767:CATH
703:DALI
688:CATH
686:and
684:SCOP
657:Pfam
611:and
560:and
480:and
404:life
361:The
345:DALI
331:and
192:and
114:DALI
69:CAZy
67:and
59:and
2368:doi
2333:doi
2329:321
2296:PMC
2278:doi
2223:doi
2211:294
2178:PMC
2168:doi
2094:doi
2090:242
2059:doi
2055:205
1999:doi
1938:doi
1903:doi
1860:hdl
1852:doi
1807:PMC
1799:doi
1748:PMC
1732:doi
1691:PMC
1683:doi
1679:574
1644:doi
1640:328
1607:PMC
1597:doi
1585:110
1548:PMC
1540:doi
1499:PMC
1491:doi
1451:doi
1415:PMC
1407:doi
1366:doi
1319:doi
1282:PMC
1272:doi
1223:PMC
1215:doi
1174:doi
1170:276
1130:PMC
1122:doi
1083:doi
1046:PMC
1038:doi
988:doi
914:PMC
906:doi
902:316
865:PMC
857:doi
811:PMC
803:doi
696:PDB
425:).
402:of
232:of
159:,
152:,
2697::
2362:.
2339:.
2327:.
2304:.
2294:.
2286:.
2276:.
2264:.
2260:.
2237:.
2229:.
2221:.
2209:.
2186:.
2176:.
2166:.
2156:85
2154:.
2150:.
2123:.
2100:.
2088:.
2065:.
2053:.
2005:.
1993:.
1944:.
1932:.
1909:.
1899:16
1897:.
1874:.
1866:.
1858:.
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