94:
267:
140:
2400:
93:
444:
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
445:
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.
230:
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
329:
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
277:(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.
380:
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
358:, 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.
1037:"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"
1171:
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).
131:
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.
2334:
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".
1173:"The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature"
590:
1729:
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).
251:. 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.
254:
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
393:
multiple times independently, and so form separate superfamilies, and in some superfamilies display a range of different (though often chemically similar) mechanisms.
1320:
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".
409:
that is currently possible. They are therefore amongst the most ancient evolutionary events currently studied. Some superfamilies have members present in all
350:. Consequently, protein tertiary structure can be used to detect homology between proteins even when no evidence of relatedness remains in their sequences.
2060:
Bolognesi M, Onesti S, Gatti G, Coda A, Ascenzi P, Brunori M (February 1989). "Aplysia limacina myoglobin. Crystallographic analysis at 1.6 A resolution".
424:
Superfamily members may be in different species, with the ancestral protein being the form of the protein that existed in the ancestral species (
1263:"Cross-Over between Discrete and Continuous Protein Structure Space: Insights into Automatic Classification and Networks of Protein Structures"
100:
2269:"The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life"
1845:
Ranea JA, Sillero A, Thornton JM, Orengo CA (October 2006). "Protein superfamily evolution and the last universal common ancestor (LUCA)".
389:
on proteins, peptides or amino acids. However, mechanism alone is not sufficient to infer relatedness. Some catalytic mechanisms have been
215:), so it is a more sensitive detection method. Since some of the amino acids have similar properties (e.g., charge, hydrophobicity, size),
258:. In the absence of structural information, sequence similarity constrains the limits of which proteins can be assigned to a superfamily.
1974:
1456:
Dessailly, Benoit H.; Dawson, Natalie L.; Das, Sayoni; Orengo, Christine A. (2017), "Function
Diversity within Folds and Superfamilies",
1645:
Coutinho PM, Deleury E, Davies GJ, Henrissat B (April 2003). "An evolving hierarchical family classification for glycosyltransferases".
691:- Library of HMMs representing superfamilies and database of (superfamily and family) annotations for all completely sequenced organisms
2000:
Mohamed MF, Hollfelder F (January 2013). "Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer".
952:
355:
124:
2095:
Bork P, Holm L, Sander C (September 1994). "The immunoglobulin fold. Structural classification, sequence patterns and common core".
2159:"Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications"
2404:
694:
17:
199:. Sequence similarity is considered a good predictor of relatedness, since similar sequences are more likely the result of
155:. Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting:
1680:
Zámocký M, Hofbauer S, Schaffner I, Gasselhuber B, Nicolussi A, Soudi M, Pirker KF, Furtmüller PG, Obinger C (May 2015).
2044:
989:
Han JH, Batey S, Nickson AA, Teichmann SA, Clarke J (April 2007). "The folding and evolution of multidomain proteins".
223:
to function. The most conserved sequence regions of a protein often correspond to functionally important regions like
2432:
1588:"Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad"
1473:
401:
Protein superfamilies represent the current limits of our ability to identify common ancestry. They are the largest
58:
can then be deduced even if not apparent (due to low sequence similarity). Superfamilies typically contain several
2726:
2731:
418:
2588:
195:
Historically, the similarity of different amino acid sequences has been the most common method of inferring
2711:
1035:
Pandit SB, Gosar D, Abhiman S, Sujatha S, Dixit SS, Mhatre NS, Sowdhamini R, Srinivasan N (January 2002).
428:). Conversely, the proteins may be in the same species, but evolved from a single protein whose gene was
282:
2216:
Vetter IR, Wittinghofer A (November 2001). "The guanine nucleotide-binding switch in three dimensions".
1939:
Nardini M, Dijkstra BW (December 1999). "Alpha/beta hydrolase fold enzymes: the family keeps growing".
526:
255:
2716:
2689:
2676:
2663:
2650:
2637:
2624:
2611:
2573:
294:
2583:
2537:
2480:
596:
377:
2485:
302:
1084:
Orengo CA, Thornton JM (2005). "Protein families and their evolution-a structural perspective".
713:
247:, for example, not a single residue is conserved through the superfamily, not even those in the
2721:
425:
313:
1978:
433:
2506:
2425:
1539:"Handicap-Recover Evolution Leads to a Chemically Versatile, Nucleophile-Permissive Protease"
1097:
767:
615:
343:
216:
167:
960:
2578:
2280:
2225:
2170:
2130:
Brümmendorf T, Rathjen FG (1995). "Cell adhesion molecules 1: immunoglobulin superfamily".
1854:
1599:
1274:
727:
660:
498:
390:
351:
331:
321:
208:
104:
51:
587:
Members share a common catalytic G domain of a 6-strand β sheet surrounded by 5 α-helices.
8:
540:
373:
335:
270:
204:
119:, L indicates loop. Below, sequence conservation for the same alignment. Arrows indicate
2284:
2229:
2174:
1858:
1603:
1278:
2475:
2311:
2268:
2249:
1886:
1799:
1763:
1730:
1706:
1681:
1622:
1587:
1563:
1538:
1514:
1489:
1430:
1405:
1345:
1297:
1262:
1238:
1213:
1145:
1120:
1014:
929:
904:
880:
855:
826:
801:
757:
623:
609:
603:
504:
454:
386:
347:
236:
160:
144:
71:
47:
2382:
2347:
2193:
2158:
1952:
1822:
1787:
1658:
2351:
2316:
2298:
2241:
2198:
2139:
2112:
2077:
2073:
2040:
2017:
1956:
1921:
1878:
1827:
1768:
1750:
1711:
1662:
1627:
1568:
1519:
1469:
1435:
1386:
1337:
1302:
1243:
1194:
1150:
1101:
1066:
1061:
1036:
1006:
934:
885:
831:
752:
742:
706:
568:
488:
410:
326:
266:
196:
190:
55:
1890:
1381:
1364:
1349:
1018:
2521:
2516:
2490:
2418:
2378:
2343:
2306:
2288:
2253:
2233:
2188:
2178:
2104:
2069:
2009:
1948:
1913:
1870:
1862:
1817:
1809:
1758:
1742:
1701:
1693:
1654:
1617:
1607:
1558:
1550:
1509:
1501:
1461:
1425:
1417:
1376:
1329:
1292:
1282:
1233:
1225:
1184:
1140:
1132:
1093:
1056:
1048:
998:
924:
916:
875:
867:
821:
813:
572:
429:
385:
residues used to perform catalysis, all members use a similar mechanism to perform
367:
339:
220:
212:
200:
179:
152:
59:
2568:
2552:
2465:
2293:
2013:
1287:
747:
732:
619:
582:
468:
382:
290:
248:
120:
43:
1465:
701:- Classifications of protein structures into superfamilies, families and domains
211:. Amino acid sequence is typically more conserved than DNA sequence (due to the
2606:
2547:
2163:
Proceedings of the
National Academy of Sciences of the United States of America
1917:
1592:
Proceedings of the
National Academy of Sciences of the United States of America
737:
1866:
1788:"Protein structure and evolutionary history determine sequence space topology"
1697:
1421:
1333:
856:"MEROPS: the database of proteolytic enzymes, their substrates and inhibitors"
227:
and binding sites, since these regions are less tolerant to sequence changes.
2705:
2511:
2470:
2302:
1754:
544:
2237:
2183:
1612:
1136:
2460:
2355:
2320:
2245:
2108:
2021:
1960:
1925:
1882:
1831:
1772:
1715:
1666:
1631:
1572:
1554:
1523:
1439:
1390:
1341:
1306:
1247:
1198:
1189:
1172:
1154:
1105:
1070:
1052:
1010:
889:
835:
643:
576:
556:
492:
402:
309:
298:
278:
224:
2202:
2143:
2116:
2081:
1746:
938:
709:
for proteins with structural homology to a target structure, for example:
417:, indicating that the last common ancestor of that superfamily was in the
2684:
2619:
2455:
1229:
871:
817:
772:
688:
564:
520:
516:
480:
306:
286:
1505:
560:
536:
1874:
1813:
1537:
Shafee T, Gatti-Lafranconi P, Minter R, Hollfelder F (September 2015).
629:
460:
151:
proteins. The similarity of the sequences implies that they evolved by
54:
and mechanistic similarity, even if no sequence similarity is evident.
1804:
1536:
920:
532:
464:
116:
112:
2658:
2632:
762:
647:
614:
Members share a high-energy, stressed fold which can undergo a large
503:
Members share an αβα sandwich structure as well as performing common
484:
472:
1002:
567:
mechanisms but sequence identity of <10%. The clan contains both
139:
2267:
Atkinson, Gemma C.; Tenson, Tanel; Hauryliuk, Vasili (2011-08-09).
1679:
905:"Updating the sequence-based classification of glycosyl hydrolases"
679:
599:
406:
244:
67:
1904:
Carr PD, Ollis DL (2009). "Alpha/beta hydrolase fold: an update".
716:- Structural alignment based on a distance alignment matrix method
346:
of the protein structure may also be conserved, as is seen in the
1785:
673:
550:
476:
274:
240:
148:
108:
39:
376:
of enzymes within a superfamily is commonly conserved, although
2671:
2441:
2399:
2369:
Farber G (1993). "An α/β-barrel full of evolutionary trouble".
1786:
Shakhnovich BE, Deeds E, Delisi C, Shakhnovich E (March 2005).
1260:
663:
document protein superfamilies and protein folds, for example:
510:
75:
1644:
2645:
2002:
Biochimica et
Biophysica Acta (BBA) - Proteins and Proteomics
1682:"Independent evolution of four heme peroxidase superfamilies"
232:
176:
35:
676:- Database of protein domains, families and functional sites
62:
which show sequence similarity within each family. The term
1490:"Causes of evolutionary rate variation among protein sites"
777:
698:
667:
414:
79:
2410:
1844:
1365:"Structural drift: a possible path to protein fold change"
1170:
1728:
1034:
2059:
1455:
1121:"Sequence evolution correlates with structural dynamics"
988:
685:
PASS2 - Protein
Alignment as Structural Superfamilies v2
595:
Members share capability to hydrolyze and/or synthesize
239:
and so identify the homologous sequence regions. In the
2266:
1261:
Pascual-García A, Abia D, Ortiz ÁR, Bastolla U (2009).
1458:
From
Protein Structure to Function with Bioinformatics
853:
2333:
1487:
854:Rawlings ND, Barrett AJ, Bateman A (January 2012).
2215:
2129:
670:- Protein families database of alignments and HMMs
1999:
1488:Echave J, Spielman SJ, Wilke CO (February 2016).
543:), and are involved in recognition, binding, and
50:). Usually this common ancestry is inferred from
2703:
902:
654:
2156:
1938:
705:Similarly there are algorithms that search the
642:barrel structure. It is one of the most common
531:Members share a sandwich-like structure of two
471:residues in the same order, activities include
123:residues. Aligned on the basis of structure by
2094:
1585:
1362:
1083:
799:
2426:
896:
2209:
2034:
1932:
1319:
1166:
1164:
396:
2123:
2088:
2433:
2419:
1460:, Springer Netherlands, pp. 295–325,
1403:
1211:
2310:
2292:
2192:
2182:
2157:Bazan JF, Fletterick RJ (November 1988).
1903:
1821:
1803:
1762:
1731:"The Structure–Function Linkage Database"
1705:
1621:
1611:
1562:
1513:
1429:
1380:
1296:
1286:
1237:
1188:
1161:
1144:
1060:
1030:
1028:
928:
879:
825:
802:"Dali server: conservation mapping in 3D"
459:Members share an α/β sheet, containing 8
361:
1586:Buller AR, Townsend CA (February 2013).
1118:
1098:10.1146/annurev.biochem.74.082803.133029
849:
847:
845:
265:
261:
138:
2039:(2nd ed.). New York: Garland Pub.
1686:Archives of Biochemistry and Biophysics
650:of this superfamily is still contested.
14:
2704:
2368:
1025:
984:
982:
980:
978:
134:
2414:
2371:Current Opinion in Structural Biology
1941:Current Opinion in Structural Biology
1451:
1449:
1410:Current Opinion in Structural Biology
1363:Krishna SS, Grishin NV (April 2005).
991:Nature Reviews Molecular Cell Biology
842:
618:, which is typically used to inhibit
903:Henrissat B, Bairoch A (June 1996).
795:
793:
1177:The Journal of Biological Chemistry
975:
682:- SuperFamily Classification System
235:can also sometimes be difficult to
24:
1446:
800:Holm L, Rosenström P (July 2010).
439:
338:motifs are highly conserved. Some
173:. semi-conservative mutations, and
107:conservation of 80 members of the
25:
2743:
2392:
2037:Introduction to protein structure
1404:Bryan PN, Orban J (August 2010).
1119:Liu Y, Bahar I (September 2012).
790:
303:snake venom plasminogen activator
85:
2398:
499:Alkaline phosphatase superfamily
387:covalent, nucleophilic catalysis
219:that interchange them are often
92:
2362:
2327:
2260:
2150:
2053:
2028:
1993:
1967:
1897:
1838:
1779:
1722:
1673:
1638:
1579:
1530:
1481:
1397:
1356:
1313:
1254:
1212:Holm L, Laakso LM (July 2016).
1205:
1125:Molecular Biology and Evolution
1847:Journal of Molecular Evolution
1112:
1077:
945:
626:by disrupting their structure.
419:last universal common ancestor
13:
1:
2383:10.1016/S0959-440X(05)80114-9
2348:10.1016/s0022-2836(02)00649-6
1953:10.1016/S0959-440X(99)00037-8
1659:10.1016/S0022-2836(03)00307-3
1382:10.1093/bioinformatics/bti227
1086:Annual Review of Biochemistry
784:
655:Protein superfamily resources
2336:Journal of Molecular Biology
2294:10.1371/journal.pone.0023479
2097:Journal of Molecular Biology
2074:10.1016/0022-2836(89)90224-6
2062:Journal of Molecular Biology
2014:10.1016/j.bbapap.2012.07.015
1647:Journal of Molecular Biology
1406:"Proteins that switch folds"
1288:10.1371/journal.pcbi.1000331
812:(Web Server issue): W545–9.
207:, rather than the result of
7:
2440:
2035:Branden C, Tooze J (1999).
1906:Protein and Peptide Letters
1466:10.1007/978-94-024-1069-3_9
866:(Database issue): D343–50.
720:
448:
283:tobacco etch virus protease
111:(superfamily). H indicates
74:superfamilies based on the
10:
2748:
1918:10.2174/092986609789071298
1267:PLOS Computational Biology
527:Immunoglobulin superfamily
365:
319:
188:
180:non-conservative mutations
2597:
2589:Michaelis–Menten kinetics
2561:
2530:
2499:
2448:
1867:10.1007/s00239-005-0289-7
1698:10.1016/j.abb.2014.12.025
1422:10.1016/j.sbi.2010.06.002
1334:10.1007/s11033-014-3253-z
1322:Molecular Biology Reports
455:α/β hydrolase superfamily
405:grouping based on direct
397:Evolutionary significance
34:is the largest grouping (
2481:Diffusion-limited enzyme
1494:Nature Reviews. Genetics
233:insertions and deletions
82:classification systems.
2238:10.1126/science.1062023
2184:10.1073/pnas.85.21.7872
1613:10.1073/pnas.1221050110
909:The Biochemical Journal
634:Members share a large α
213:degenerate genetic code
2727:Protein classification
2109:10.1006/jmbi.1994.1582
1735:Nucleic Acids Research
1555:10.1002/cbic.201500295
1218:Nucleic Acids Research
1190:10.1074/jbc.R100016200
1041:Nucleic Acids Research
953:"Clustal FAQ #Symbols"
860:Nucleic Acids Research
806:Nucleic Acids Research
630:TIM barrel superfamily
507:by a common mechanism.
362:Mechanistic similarity
344:conformational changes
317:
314:equine arteritis virus
217:conservative mutations
186:
168:conservative mutations
2732:Protein superfamilies
2574:Eadie–Hofstee diagram
2507:Allosteric regulation
2405:Protein superfamilies
1137:10.1093/molbev/mss097
768:List of gene families
616:conformational change
505:promiscuous reactions
269:
262:Structural similarity
142:
66:is commonly used for
46:can be inferred (see
18:Protein superfamilies
2584:Lineweaver–Burk plot
2407:at Wikimedia Commons
1214:"Dali server update"
1053:10.1093/nar/30.1.289
728:Structural alignment
661:biological databases
421:of all life (LUCA).
391:convergently evolved
352:Structural alignment
332:secondary structural
322:Structural alignment
209:convergent evolution
105:secondary structural
52:structural alignment
27:Grouping of proteins
2712:Molecular evolution
2285:2011PLoSO...623479A
2230:2001Sci...294.1299V
2175:1988PNAS...85.7872B
1859:2006JMolE..63..513R
1747:10.1093/nar/gkt1130
1604:2013PNAS..110E.653B
1506:10.1038/nrg.2015.18
1279:2009PLSCB...5E0331P
515:Members share an 8-
374:catalytic mechanism
336:tertiary structural
271:Structural homology
256:tertiary structures
205:divergent evolution
135:Sequence similarity
72:glycosyl hydrolases
32:protein superfamily
2543:Enzyme superfamily
2476:Enzyme promiscuity
2224:(5545): 1299–304.
1814:10.1101/gr.3133605
1230:10.1093/nar/gkw357
963:on 24 October 2016
872:10.1093/nar/gkr987
818:10.1093/nar/gkq366
758:Homology (biology)
624:cysteine proteases
610:Serpin superfamily
604:stringent response
511:Globin superfamily
489:epoxide hydrolases
354:programs, such as
348:serpin superfamily
318:
187:
161:conserved sequence
145:sequence alignment
2699:
2698:
2403:Media related to
1741:(D1): D521–D530.
1549:(13): 1866–1869.
921:10.1042/bj3160695
753:Protein structure
743:Protein subfamily
563:fold and similar
293:protease (1fp7),
191:Sequence homology
56:Sequence homology
16:(Redirected from
2739:
2717:Protein families
2579:Hanes–Woolf plot
2522:Enzyme activator
2517:Enzyme inhibitor
2491:Enzyme catalysis
2435:
2428:
2421:
2412:
2411:
2402:
2387:
2386:
2366:
2360:
2359:
2331:
2325:
2324:
2314:
2296:
2264:
2258:
2257:
2213:
2207:
2206:
2196:
2186:
2154:
2148:
2147:
2127:
2121:
2120:
2092:
2086:
2085:
2057:
2051:
2050:
2032:
2026:
2025:
1997:
1991:
1990:
1988:
1986:
1977:. Archived from
1971:
1965:
1964:
1936:
1930:
1929:
1901:
1895:
1894:
1842:
1836:
1835:
1825:
1807:
1783:
1777:
1776:
1766:
1726:
1720:
1719:
1709:
1677:
1671:
1670:
1642:
1636:
1635:
1625:
1615:
1583:
1577:
1576:
1566:
1534:
1528:
1527:
1517:
1485:
1479:
1478:
1453:
1444:
1443:
1433:
1401:
1395:
1394:
1384:
1360:
1354:
1353:
1317:
1311:
1310:
1300:
1290:
1258:
1252:
1251:
1241:
1209:
1203:
1202:
1192:
1168:
1159:
1158:
1148:
1116:
1110:
1109:
1081:
1075:
1074:
1064:
1032:
1023:
1022:
986:
973:
972:
970:
968:
959:. Archived from
949:
943:
942:
932:
900:
894:
893:
883:
851:
840:
839:
829:
797:
573:serine proteases
555:Members share a
535:of antiparallel
368:Enzyme mechanism
340:protein dynamics
316:protease (1mbm).
295:exfoliatin toxin
201:gene duplication
153:gene duplication
109:PA protease clan
96:
60:protein families
21:
2747:
2746:
2742:
2741:
2740:
2738:
2737:
2736:
2702:
2701:
2700:
2695:
2607:Oxidoreductases
2593:
2569:Enzyme kinetics
2557:
2553:List of enzymes
2526:
2495:
2466:Catalytic triad
2444:
2439:
2395:
2390:
2367:
2363:
2332:
2328:
2265:
2261:
2214:
2210:
2155:
2151:
2138:(9): 963–1108.
2132:Protein Profile
2128:
2124:
2093:
2089:
2058:
2054:
2047:
2033:
2029:
1998:
1994:
1984:
1982:
1981:on 29 July 2014
1973:
1972:
1968:
1937:
1933:
1912:(10): 1137–48.
1902:
1898:
1843:
1839:
1792:Genome Research
1784:
1780:
1727:
1723:
1678:
1674:
1643:
1639:
1584:
1580:
1535:
1531:
1486:
1482:
1476:
1454:
1447:
1402:
1398:
1361:
1357:
1318:
1314:
1273:(3): e1000331.
1259:
1255:
1210:
1206:
1183:(36): 33293–6.
1169:
1162:
1117:
1113:
1082:
1078:
1033:
1026:
1003:10.1038/nrm2144
987:
976:
966:
964:
951:
950:
946:
915:(Pt 2): 695–6.
901:
897:
852:
843:
798:
791:
787:
782:
748:Protein mimetic
733:Protein domains
723:
657:
641:
637:
591:RSH superfamily
583:Ras superfamily
469:catalytic triad
451:
442:
440:Diversification
432:in the genome (
399:
383:catalytic triad
370:
364:
324:
291:west nile virus
264:
249:catalytic triad
225:catalytic sites
193:
185:
137:
129:
128:
127:
121:catalytic triad
102:
97:
88:
44:common ancestry
28:
23:
22:
15:
12:
11:
5:
2745:
2735:
2734:
2729:
2724:
2719:
2714:
2697:
2696:
2694:
2693:
2680:
2667:
2654:
2641:
2628:
2615:
2601:
2599:
2595:
2594:
2592:
2591:
2586:
2581:
2576:
2571:
2565:
2563:
2559:
2558:
2556:
2555:
2550:
2545:
2540:
2534:
2532:
2531:Classification
2528:
2527:
2525:
2524:
2519:
2514:
2509:
2503:
2501:
2497:
2496:
2494:
2493:
2488:
2483:
2478:
2473:
2468:
2463:
2458:
2452:
2450:
2446:
2445:
2438:
2437:
2430:
2423:
2415:
2409:
2408:
2394:
2393:External links
2391:
2389:
2388:
2377:(3): 409–412.
2361:
2326:
2259:
2208:
2169:(21): 7872–6.
2149:
2122:
2087:
2052:
2046:978-0815323051
2045:
2027:
1992:
1966:
1931:
1896:
1837:
1778:
1721:
1672:
1637:
1598:(8): E653–61.
1578:
1529:
1480:
1474:
1445:
1396:
1375:(8): 1308–10.
1369:Bioinformatics
1355:
1328:(6): 3859–66.
1312:
1253:
1224:(W1): W351–5.
1204:
1160:
1131:(9): 2253–63.
1111:
1092:(1): 867–900.
1076:
1024:
974:
944:
895:
841:
788:
786:
783:
781:
780:
775:
770:
765:
760:
755:
750:
745:
740:
738:Protein family
735:
730:
724:
722:
719:
718:
717:
703:
702:
692:
686:
683:
677:
671:
656:
653:
652:
651:
639:
635:
632:
627:
612:
607:
593:
588:
585:
580:
553:
548:
529:
524:
513:
508:
501:
496:
457:
450:
447:
441:
438:
398:
395:
366:Main article:
363:
360:
320:Main article:
275:PA superfamily
263:
260:
189:Main article:
184:
183:
174:
171:
164:
156:
136:
133:
115:, E indicates
99:
98:
91:
90:
89:
87:
86:Identification
84:
26:
9:
6:
4:
3:
2:
2744:
2733:
2730:
2728:
2725:
2723:
2722:Protein folds
2720:
2718:
2715:
2713:
2710:
2709:
2707:
2691:
2687:
2686:
2681:
2678:
2674:
2673:
2668:
2665:
2661:
2660:
2655:
2652:
2648:
2647:
2642:
2639:
2635:
2634:
2629:
2626:
2622:
2621:
2616:
2613:
2609:
2608:
2603:
2602:
2600:
2596:
2590:
2587:
2585:
2582:
2580:
2577:
2575:
2572:
2570:
2567:
2566:
2564:
2560:
2554:
2551:
2549:
2548:Enzyme family
2546:
2544:
2541:
2539:
2536:
2535:
2533:
2529:
2523:
2520:
2518:
2515:
2513:
2512:Cooperativity
2510:
2508:
2505:
2504:
2502:
2498:
2492:
2489:
2487:
2484:
2482:
2479:
2477:
2474:
2472:
2471:Oxyanion hole
2469:
2467:
2464:
2462:
2459:
2457:
2454:
2453:
2451:
2447:
2443:
2436:
2431:
2429:
2424:
2422:
2417:
2416:
2413:
2406:
2401:
2397:
2396:
2384:
2380:
2376:
2372:
2365:
2357:
2353:
2349:
2345:
2342:(5): 741–65.
2341:
2337:
2330:
2322:
2318:
2313:
2308:
2304:
2300:
2295:
2290:
2286:
2282:
2279:(8): e23479.
2278:
2274:
2270:
2263:
2255:
2251:
2247:
2243:
2239:
2235:
2231:
2227:
2223:
2219:
2212:
2204:
2200:
2195:
2190:
2185:
2180:
2176:
2172:
2168:
2164:
2160:
2153:
2145:
2141:
2137:
2133:
2126:
2118:
2114:
2110:
2106:
2103:(4): 309–20.
2102:
2098:
2091:
2083:
2079:
2075:
2071:
2068:(3): 529–44.
2067:
2063:
2056:
2048:
2042:
2038:
2031:
2023:
2019:
2015:
2011:
2008:(1): 417–24.
2007:
2003:
1996:
1980:
1976:
1970:
1962:
1958:
1954:
1950:
1946:
1942:
1935:
1927:
1923:
1919:
1915:
1911:
1907:
1900:
1892:
1888:
1884:
1880:
1876:
1872:
1868:
1864:
1860:
1856:
1853:(4): 513–25.
1852:
1848:
1841:
1833:
1829:
1824:
1819:
1815:
1811:
1806:
1805:q-bio/0404040
1801:
1798:(3): 385–92.
1797:
1793:
1789:
1782:
1774:
1770:
1765:
1760:
1756:
1752:
1748:
1744:
1740:
1736:
1732:
1725:
1717:
1713:
1708:
1703:
1699:
1695:
1691:
1687:
1683:
1676:
1668:
1664:
1660:
1656:
1653:(2): 307–17.
1652:
1648:
1641:
1633:
1629:
1624:
1619:
1614:
1609:
1605:
1601:
1597:
1593:
1589:
1582:
1574:
1570:
1565:
1560:
1556:
1552:
1548:
1544:
1540:
1533:
1525:
1521:
1516:
1511:
1507:
1503:
1500:(2): 109–21.
1499:
1495:
1491:
1484:
1477:
1475:9789402410679
1471:
1467:
1463:
1459:
1452:
1450:
1441:
1437:
1432:
1427:
1423:
1419:
1415:
1411:
1407:
1400:
1392:
1388:
1383:
1378:
1374:
1370:
1366:
1359:
1351:
1347:
1343:
1339:
1335:
1331:
1327:
1323:
1316:
1308:
1304:
1299:
1294:
1289:
1284:
1280:
1276:
1272:
1268:
1264:
1257:
1249:
1245:
1240:
1235:
1231:
1227:
1223:
1219:
1215:
1208:
1200:
1196:
1191:
1186:
1182:
1178:
1174:
1167:
1165:
1156:
1152:
1147:
1142:
1138:
1134:
1130:
1126:
1122:
1115:
1107:
1103:
1099:
1095:
1091:
1087:
1080:
1072:
1068:
1063:
1058:
1054:
1050:
1047:(1): 289–93.
1046:
1042:
1038:
1031:
1029:
1020:
1016:
1012:
1008:
1004:
1000:
997:(4): 319–30.
996:
992:
985:
983:
981:
979:
962:
958:
954:
948:
940:
936:
931:
926:
922:
918:
914:
910:
906:
899:
891:
887:
882:
877:
873:
869:
865:
861:
857:
850:
848:
846:
837:
833:
828:
823:
819:
815:
811:
807:
803:
796:
794:
789:
779:
776:
774:
771:
769:
766:
764:
761:
759:
756:
754:
751:
749:
746:
744:
741:
739:
736:
734:
731:
729:
726:
725:
715:
712:
711:
710:
708:
700:
696:
693:
690:
687:
684:
681:
678:
675:
672:
669:
666:
665:
664:
662:
649:
648:monophylicity
645:
644:protein folds
633:
631:
628:
625:
621:
617:
613:
611:
608:
605:
601:
598:
594:
592:
589:
586:
584:
581:
578:
574:
570:
566:
562:
559:-like double
558:
554:
552:
549:
546:
542:
538:
534:
530:
528:
525:
522:
518:
514:
512:
509:
506:
502:
500:
497:
494:
493:dehalogenases
490:
486:
482:
478:
474:
470:
466:
463:connected by
462:
458:
456:
453:
452:
446:
437:
435:
431:
427:
422:
420:
416:
412:
408:
404:
394:
392:
388:
384:
379:
375:
369:
359:
357:
353:
349:
345:
341:
337:
334:elements and
333:
328:
323:
315:
311:
308:
304:
300:
299:HtrA protease
296:
292:
288:
284:
280:
276:
272:
268:
259:
257:
252:
250:
246:
242:
238:
234:
228:
226:
222:
218:
214:
210:
206:
202:
198:
192:
181:
178:
175:
172:
169:
165:
162:
158:
157:
154:
150:
147:of mammalian
146:
141:
132:
126:
122:
118:
114:
110:
106:
101:
95:
83:
81:
77:
73:
69:
65:
61:
57:
53:
49:
45:
41:
37:
33:
19:
2685:Translocases
2682:
2669:
2656:
2643:
2630:
2620:Transferases
2617:
2604:
2542:
2461:Binding site
2374:
2370:
2364:
2339:
2335:
2329:
2276:
2272:
2262:
2221:
2217:
2211:
2166:
2162:
2152:
2135:
2131:
2125:
2100:
2096:
2090:
2065:
2061:
2055:
2036:
2030:
2005:
2001:
1995:
1983:. Retrieved
1979:the original
1969:
1947:(6): 732–7.
1944:
1940:
1934:
1909:
1905:
1899:
1850:
1846:
1840:
1795:
1791:
1781:
1738:
1734:
1724:
1689:
1685:
1675:
1650:
1646:
1640:
1595:
1591:
1581:
1546:
1542:
1532:
1497:
1493:
1483:
1457:
1416:(4): 482–8.
1413:
1409:
1399:
1372:
1368:
1358:
1325:
1321:
1315:
1270:
1266:
1256:
1221:
1217:
1207:
1180:
1176:
1128:
1124:
1114:
1089:
1085:
1079:
1044:
1040:
994:
990:
965:. Retrieved
961:the original
956:
947:
912:
908:
898:
863:
859:
809:
805:
704:
658:
577:nucleophiles
557:chymotrypsin
443:
423:
403:evolutionary
400:
371:
325:
279:Chymotrypsin
253:
229:
194:
130:
64:protein clan
63:
31:
29:
2456:Active site
1875:10261/78338
1543:ChemBioChem
773:SUPERFAMILY
689:SUPERFAMILY
575:(different
565:proteolysis
521:globin fold
517:alpha helix
481:peroxidases
312:(4fln) and
307:chloroplast
287:calicivirin
2706:Categories
2659:Isomerases
2633:Hydrolases
2500:Regulation
1692:: 108–19.
967:8 December
785:References
430:duplicated
42:for which
2538:EC number
2303:1932-6203
1755:0305-1048
763:Interolog
600:alarmones
537:β strands
519:globular
485:esterases
473:proteases
426:orthology
378:substrate
327:Structure
245:proteases
2562:Kinetics
2486:Cofactor
2449:Activity
2356:12206759
2321:21858139
2273:PLOS ONE
2246:11701921
2022:22885024
1961:10607665
1926:19508187
1891:25258028
1883:17021929
1832:15741509
1773:24271399
1716:25575902
1667:12691742
1632:23382230
1573:26097079
1524:26781812
1440:20591649
1391:15604105
1350:14936647
1342:24557891
1307:19325884
1248:27131377
1199:11435447
1155:22427707
1106:15954844
1071:11752317
1019:13762291
1011:17356578
890:22086950
836:20457744
721:See also
659:Several
646:and the
569:cysteine
561:β-barrel
545:adhesion
449:Examples
434:paralogy
411:kingdoms
407:evidence
310:protease
305:(1bqy),
301:(1l1j),
297:(1exf),
289:(1wqs),
285:(1lvm),
281:(1gg6),
197:homology
166: :
68:protease
48:homology
40:proteins
2672:Ligases
2442:Enzymes
2312:3153485
2281:Bibcode
2254:6636339
2226:Bibcode
2218:Science
2203:3186696
2171:Bibcode
2144:8574878
2117:7932691
2082:2926816
1855:Bibcode
1764:3965090
1707:4420034
1623:3581919
1600:Bibcode
1564:4576821
1515:4724262
1431:2928869
1298:2654728
1275:Bibcode
1239:4987910
1146:3424413
957:Clustal
939:8687420
930:1217404
881:3245014
827:2896194
674:PROSITE
602:in the
551:PA clan
541:Ig-fold
477:lipases
467:, with
465:helices
461:strands
273:in the
241:PA clan
221:neutral
149:histone
117:β-sheet
113:α-helix
103:Above,
2646:Lyases
2354:
2319:
2309:
2301:
2252:
2244:
2201:
2194:282299
2191:
2142:
2115:
2080:
2043:
2020:
1985:28 May
1975:"SCOP"
1959:
1924:
1889:
1881:
1830:
1823:551565
1820:
1771:
1761:
1753:
1714:
1704:
1665:
1630:
1620:
1571:
1561:
1522:
1512:
1472:
1438:
1428:
1389:
1348:
1340:
1305:
1295:
1246:
1236:
1197:
1153:
1143:
1104:
1069:
1059:
1017:
1009:
937:
927:
888:
878:
834:
824:
620:serine
533:sheets
76:MEROPS
2598:Types
2250:S2CID
1887:S2CID
1800:arXiv
1346:S2CID
1062:99061
1015:S2CID
680:PIRSF
597:ppGpp
237:align
38:) of
36:clade
2690:list
2683:EC7
2677:list
2670:EC6
2664:list
2657:EC5
2651:list
2644:EC4
2638:list
2631:EC3
2625:list
2618:EC2
2612:list
2605:EC1
2352:PMID
2317:PMID
2299:ISSN
2242:PMID
2199:PMID
2140:PMID
2113:PMID
2078:PMID
2041:ISBN
2018:PMID
2006:1834
1987:2014
1957:PMID
1922:PMID
1879:PMID
1828:PMID
1769:PMID
1751:ISSN
1712:PMID
1663:PMID
1628:PMID
1569:PMID
1520:PMID
1470:ISBN
1436:PMID
1387:PMID
1338:PMID
1303:PMID
1244:PMID
1195:PMID
1151:PMID
1102:PMID
1067:PMID
1007:PMID
969:2014
935:PMID
886:PMID
832:PMID
778:CATH
714:DALI
699:CATH
697:and
695:SCOP
668:Pfam
622:and
571:and
491:and
415:life
372:The
356:DALI
342:and
203:and
125:DALI
80:CAZy
78:and
70:and
2379:doi
2344:doi
2340:321
2307:PMC
2289:doi
2234:doi
2222:294
2189:PMC
2179:doi
2105:doi
2101:242
2070:doi
2066:205
2010:doi
1949:doi
1914:doi
1871:hdl
1863:doi
1818:PMC
1810:doi
1759:PMC
1743:doi
1702:PMC
1694:doi
1690:574
1655:doi
1651:328
1618:PMC
1608:doi
1596:110
1559:PMC
1551:doi
1510:PMC
1502:doi
1462:doi
1426:PMC
1418:doi
1377:doi
1330:doi
1293:PMC
1283:doi
1234:PMC
1226:doi
1185:doi
1181:276
1141:PMC
1133:doi
1094:doi
1057:PMC
1049:doi
999:doi
925:PMC
917:doi
913:316
876:PMC
868:doi
822:PMC
814:doi
707:PDB
436:).
413:of
243:of
170:,
163:,
2708::
2373:.
2350:.
2338:.
2315:.
2305:.
2297:.
2287:.
2275:.
2271:.
2248:.
2240:.
2232:.
2220:.
2197:.
2187:.
2177:.
2167:85
2165:.
2161:.
2134:.
2111:.
2099:.
2076:.
2064:.
2016:.
2004:.
1955:.
1943:.
1920:.
1910:16
1908:.
1885:.
1877:.
1869:.
1861:.
1851:63
1849:.
1826:.
1816:.
1808:.
1796:15
1794:.
1790:.
1767:.
1757:.
1749:.
1739:42
1737:.
1733:.
1710:.
1700:.
1688:.
1684:.
1661:.
1649:.
1626:.
1616:.
1606:.
1594:.
1590:.
1567:.
1557:.
1547:16
1545:.
1541:.
1518:.
1508:.
1498:17
1496:.
1492:.
1468:,
1448:^
1434:.
1424:.
1414:20
1412:.
1408:.
1385:.
1373:21
1371:.
1367:.
1344:.
1336:.
1326:41
1324:.
1301:.
1291:.
1281:.
1269:.
1265:.
1242:.
1232:.
1222:44
1220:.
1216:.
1193:.
1179:.
1175:.
1163:^
1149:.
1139:.
1129:29
1127:.
1123:.
1100:.
1090:74
1088:.
1065:.
1055:.
1045:30
1043:.
1039:.
1027:^
1013:.
1005:.
993:.
977:^
955:.
933:.
923:.
911:.
907:.
884:.
874:.
864:40
862:.
858:.
844:^
830:.
820:.
810:38
808:.
804:.
792:^
606:.
579:).
487:,
483:,
479:,
475:,
159:*
143:A
30:A
2692:)
2688:(
2679:)
2675:(
2666:)
2662:(
2653:)
2649:(
2640:)
2636:(
2627:)
2623:(
2614:)
2610:(
2434:e
2427:t
2420:v
2385:.
2381::
2375:3
2358:.
2346::
2323:.
2291::
2283::
2277:6
2256:.
2236::
2228::
2205:.
2181::
2173::
2146:.
2136:2
2119:.
2107::
2084:.
2072::
2049:.
2024:.
2012::
1989:.
1963:.
1951::
1945:9
1928:.
1916::
1893:.
1873::
1865::
1857::
1834:.
1812::
1802::
1775:.
1745::
1718:.
1696::
1669:.
1657::
1634:.
1610::
1602::
1575:.
1553::
1526:.
1504::
1464::
1442:.
1420::
1393:.
1379::
1352:.
1332::
1309:.
1285::
1277::
1271:5
1250:.
1228::
1201:.
1187::
1157:.
1135::
1108:.
1096::
1073:.
1051::
1021:.
1001::
995:8
971:.
941:.
919::
892:.
870::
838:.
816::
640:8
638:β
636:8
547:.
539:(
523:.
495:.
182:.
177:␣
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
