{{Short description|Grouping of proteins}} A '''protein superfamily''' is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is inferred from structural alignment<ref name=":1">{{cite journal | vauthors = Holm L, Rosenström P | title = Dali server: conservation mapping in 3D | journal = Nucleic Acids Research | volume = 38 | issue = Web Server issue | pages = W545–9 | date = July 2010 | pmid = 20457744 | pmc = 2896194 | doi = 10.1093/nar/gkq366 }}</ref> and mechanistic similarity, even if no sequence similarity is evident.<ref name=merops>{{cite journal | vauthors = Rawlings ND, Barrett AJ, Bateman A | title = MEROPS: the database of proteolytic enzymes, their substrates and inhibitors | journal = Nucleic Acids Research | volume = 40 | issue = Database issue | pages = D343–50 | date = January 2012 | pmid = 22086950 | pmc = 3245014 | doi = 10.1093/nar/gkr987 }}</ref> Sequence homology can then be deduced even if not apparent (due to low sequence similarity). Superfamilies typically contain several protein families which show sequence similarity within each family. The term ''protein clan'' is commonly used for protease and glycosyl hydrolases superfamilies based on the MEROPS and CAZy classification systems.<ref name=merops/><ref name="Henrissat_1996">{{cite journal | vauthors = Henrissat B, Bairoch A | title = Updating the sequence-based classification of glycosyl hydrolases | journal = The Biochemical Journal | volume = 316 | issue = Pt 2 | pages = 695–6 | date = June 1996 | pmid = 8687420 | pmc = 1217404 | doi = 10.1042/bj3160695 }}</ref>
The term '''protein fold''' refers to a similar concept based on structual comparison. In some schemes such as SCOP and CATH it is treated as a level above the superfamily (with common ancestry at the fold level being not as strongly supported as the superfamily level), while other schemes treat them as synonymous. The level beyond the fold is the fold class, which describes a rough topology of the protein (e.g. all-α, all-β, α+β, α/β).<ref name=SCOPe>{{cite journal |last1=Fox |first1=NK |last2=Brenner |first2=SE |last3=Chandonia |first3=JM |title=SCOPe: Structural Classification of Proteins--extended, integrating SCOP and ASTRAL data and classification of new structures. |journal=Nucleic Acids Research |date=January 2014 |volume=42 |issue=Database issue |pages=D304-9 |doi=10.1093/nar/gkt1240 |pmid=24304899 |pmc=3965108 }}</ref>
== Identification == {{wide image|Structure vs sequence in the PA clan.png|1200px| Above, secondary structural conservation of 80 members of the PA protease clan (superfamily). H indicates α-helix, E indicates β-sheet, L indicates loop. Below, sequence conservation for the same alignment. Arrows indicate catalytic triad residues. Aligned on the basis of structure by DALI}}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.
===Sequence similarity=== [[File:Histone Alignment.png|thumb|500px|A sequence alignment of mammalian histone proteins. The similarity of the sequences implies that they evolved by gene duplication. Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting:<ref>{{cite web|url=http://www.ebi.ac.uk/Tools/msa/clustalw2/help/faq.html#23|website=Clustal|title=Clustal FAQ #Symbols|access-date=8 December 2014|archive-url=https://web.archive.org/web/20161024045656/http://www.ebi.ac.uk/Tools/msa/clustalw2/help/faq.html#23|archive-date=24 October 2016}}</ref> {{hlist | style=display:inline; | list_style=display:inline; | * conserved sequence, | : conservative mutations, | . semi-conservative mutations, and | ␣ non-conservative mutations. }}]] {{Main|Sequence homology}} Historically, the similarity of different amino acid sequences has been the most common method of inferring homology.<ref name="Han2">{{cite journal | vauthors = Han JH, Batey S, Nickson AA, Teichmann SA, Clarke J | title = The folding and evolution of multidomain proteins | journal = Nature Reviews Molecular Cell Biology | volume = 8 | issue = 4 | pages = 319–30 | date = April 2007 | pmid = 17356578 | doi = 10.1038/nrm2144 | s2cid = 13762291 }}</ref> Sequence similarity is considered a good predictor of relatedness, since similar sequences are more likely the result of gene duplication and divergent evolution, rather than the result of convergent evolution. Amino acid sequence is typically more conserved than DNA sequence (due to the degenerate genetic code), so it is a more sensitive detection method. Since some of the amino acids have similar properties (e.g., charge, hydrophobicity, size), conservative mutations that interchange them are often neutral to function. The most conserved sequence regions of a protein often correspond to functionally important regions like catalytic sites and binding sites, since these regions are less tolerant to sequence changes.
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 insertions and deletions can also sometimes be difficult to align and so identify the homologous sequence regions. In the PA clan of proteases, for example, not a single residue is conserved through the superfamily, not even those in the catalytic triad. 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.
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 tertiary structures.<ref name="Pandit2">{{cite journal | vauthors = Pandit SB, Gosar D, Abhiman S, Sujatha S, Dixit SS, Mhatre NS, Sowdhamini R, Srinivasan N | title = 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 | journal = Nucleic Acids Research | volume = 30 | issue = 1 | pages = 289–93 | date = January 2002 | pmid = 11752317 | pmc = 99061 | doi = 10.1093/nar/30.1.289 }}</ref> In the absence of structural information, sequence similarity constrains the limits of which proteins can be assigned to a superfamily.<ref name="Pandit2" />
===Structural similarity=== [[File:Structural homology of the PA clan.png|thumb|500px|Structural homology in the PA superfamily (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. Chymotrypsin (1gg6), tobacco etch virus protease (1lvm), calicivirin (1wqs), west nile virus protease (1fp7), exfoliatin toxin (1exf), HtrA protease (1l1j), snake venom plasminogen activator (1bqy), chloroplast protease (4fln) and equine arteritis virus protease (1mbm).]]{{Main|Structural alignment}} Structure is much more evolutionarily conserved than sequence, such that proteins with highly similar structures can have entirely different sequences.<ref>{{cite journal | vauthors = Orengo CA, Thornton JM | title = Protein families and their evolution-a structural perspective | journal = Annual Review of Biochemistry | volume = 74 | issue = 1 | pages = 867–900 | date = 2005 | pmid = 15954844 | doi = 10.1146/annurev.biochem.74.082803.133029 | bibcode = 2005ARBio..74..867O }}</ref> Over very long evolutionary timescales, very few residues show detectable amino acid sequence conservation, however secondary structural elements and tertiary structural motifs are highly conserved. Some protein dynamics<ref>{{cite journal | vauthors = Liu Y, Bahar I | title = Sequence evolution correlates with structural dynamics | journal = Molecular Biology and Evolution | volume = 29 | issue = 9 | pages = 2253–63 | date = September 2012 | pmid = 22427707 | pmc = 3424413 | doi = 10.1093/molbev/mss097 }}</ref> and conformational changes of the protein structure may also be conserved, as is seen in the serpin superfamily.<ref name="ReferenceA">{{cite journal | vauthors = 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 | title = The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature | journal = The Journal of Biological Chemistry | volume = 276 | issue = 36 | pages = 33293–6 | date = September 2001 | pmid = 11435447 | doi = 10.1074/jbc.R100016200 | doi-access = free }}</ref> Consequently, protein tertiary structure can be used to detect homology between proteins even when no evidence of relatedness remains in their sequences. Structural alignment programs, such as DALI, use the 3D structure of a protein of interest to find proteins with similar folds.<ref>{{cite journal | vauthors = Holm L, Laakso LM | title = Dali server update | journal = Nucleic Acids Research | volume = 44 | issue = W1 | pages = W351–5 | date = July 2016 | pmid = 27131377 | pmc = 4987910 | doi = 10.1093/nar/gkw357 }}</ref> However, on rare occasions, related proteins may evolve to be structurally dissimilar<ref>{{cite journal | vauthors = Pascual-García A, Abia D, Ortiz ÁR, Bastolla U | title = Cross-Over between Discrete and Continuous Protein Structure Space: Insights into Automatic Classification and Networks of Protein Structures | journal = PLOS Computational Biology | volume = 5 | issue = 3 | date = 2009 | article-number = e1000331 | doi = 10.1371/journal.pcbi.1000331 | pmid = 19325884 | pmc = 2654728 | bibcode = 2009PLSCB...5E0331P | doi-access = free }}</ref> and relatedness can only be inferred by other methods.<ref>{{cite journal | vauthors = Li D, Zhang L, Yin H, Xu H, Satkoski Trask J, Smith DG, Li Y, Yang M, Zhu Q | title = Evolution of primate α and θ defensins revealed by analysis of genomes | journal = Molecular Biology Reports | volume = 41 | issue = 6 | pages = 3859–66 | date = June 2014 | pmid = 24557891 | doi = 10.1007/s11033-014-3253-z | s2cid = 14936647 }}</ref><ref>{{cite journal | vauthors = Krishna SS, Grishin NV | title = Structural drift: a possible path to protein fold change | journal = Bioinformatics | volume = 21 | issue = 8 | pages = 1308–10 | date = April 2005 | pmid = 15604105 | doi = 10.1093/bioinformatics/bti227 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bryan PN, Orban J | title = Proteins that switch folds | journal = Current Opinion in Structural Biology | volume = 20 | issue = 4 | pages = 482–8 | date = August 2010 | pmid = 20591649 | pmc = 2928869 | doi = 10.1016/j.sbi.2010.06.002 }}</ref>
===Mechanistic similarity=== {{Main|Enzyme mechanism}}
The catalytic mechanism of enzymes within a superfamily is commonly conserved, although substrate specificity may be significantly different.<ref name=":0">{{Citation|last1=Dessailly|first1=Benoit H.|date=2017|work=From Protein Structure to Function with Bioinformatics|pages=295–325|publisher=Springer Netherlands|language=en|doi=10.1007/978-94-024-1069-3_9|isbn=978-94-024-1067-9|last2=Dawson|first2=Natalie L.|last3=Das|first3=Sayoni|last4=Orengo|first4=Christine A.|title=Function Diversity within Folds and Superfamilies }}</ref> Catalytic residues also tend to occur in the same order in the protein sequence.<ref>{{cite journal | vauthors = Echave J, Spielman SJ, Wilke CO | title = Causes of evolutionary rate variation among protein sites | language = En | journal = Nature Reviews. Genetics | volume = 17 | issue = 2 | pages = 109–21 | date = February 2016 | pmid = 26781812 | pmc = 4724262 | doi = 10.1038/nrg.2015.18 }}</ref> For the families within the PA clan of proteases, although there has been divergent evolution of the catalytic triad residues used to perform catalysis, all members use a similar mechanism to perform covalent, nucleophilic catalysis on proteins, peptides or amino acids.<ref>{{cite journal | vauthors = Shafee T, Gatti-Lafranconi P, Minter R, Hollfelder F | title = Handicap-Recover Evolution Leads to a Chemically Versatile, Nucleophile-Permissive Protease | journal = ChemBioChem | volume = 16 | issue = 13 | pages = 1866–1869 | date = September 2015 | pmid = 26097079 | pmc = 4576821 | doi = 10.1002/cbic.201500295 }}</ref> However, mechanism alone is not sufficient to infer relatedness. Some catalytic mechanisms have been convergently evolved multiple times independently, and so form separate superfamilies,<ref>{{cite journal | vauthors = Buller AR, Townsend CA | title = Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 8 | pages = E653–61 | date = February 2013 | pmid = 23382230 | pmc = 3581919 | doi = 10.1073/pnas.1221050110 | bibcode = 2013PNAS..110E.653B | doi-access = free }}</ref><ref>{{cite journal | vauthors = Coutinho PM, Deleury E, Davies GJ, Henrissat B | title = An evolving hierarchical family classification for glycosyltransferases | journal = Journal of Molecular Biology | volume = 328 | issue = 2 | pages = 307–17 | date = April 2003 | pmid = 12691742 | doi = 10.1016/S0022-2836(03)00307-3 }}</ref><ref>{{cite journal | vauthors = Zámocký M, Hofbauer S, Schaffner I, Gasselhuber B, Nicolussi A, Soudi M, Pirker KF, Furtmüller PG, Obinger C | title = Independent evolution of four heme peroxidase superfamilies | journal = Archives of Biochemistry and Biophysics | volume = 574 | pages = 108–19 | date = May 2015 | pmid = 25575902 | pmc = 4420034 | doi = 10.1016/j.abb.2014.12.025 | bibcode = 2015ArBB..574..108Z }}</ref> and in some superfamilies display a range of different (though often chemically similar) mechanisms.<ref name=":0" /><ref>{{Cite journal|last1=Akiva|first1=Eyal|last2=Brown|first2=Shoshana|last3=Almonacid|first3=Daniel E.|last4=Barber|first4=Alan E.|last5=Custer|first5=Ashley F.|last6=Hicks|first6=Michael A.|last7=Huang|first7=Conrad C.|last8=Lauck|first8=Florian|last9=Mashiyama|first9=Susan T.|date=2013-11-23|title=The Structure–Function Linkage Database|journal=Nucleic Acids Research|language=en|volume=42|issue=D1|pages=D521–D530|doi=10.1093/nar/gkt1130|pmid=24271399|pmc=3965090|issn=0305-1048}}</ref>
== Evolutionary significance == Protein superfamilies represent the current limits of our ability to identify common ancestry.<ref>{{cite journal | vauthors = Shakhnovich BE, Deeds E, Delisi C, Shakhnovich E | title = Protein structure and evolutionary history determine sequence space topology | journal = Genome Research | volume = 15 | issue = 3 | pages = 385–92 | date = March 2005 | pmid = 15741509 | pmc = 551565 | doi = 10.1101/gr.3133605 | arxiv = q-bio/0404040 }}</ref> They are the largest evolutionary grouping based on direct evidence that is currently possible. They are therefore amongst the most ancient evolutionary events currently studied. Some superfamilies have members present in all kingdoms of life, indicating that the last common ancestor of that superfamily was in the last universal common ancestor of all life (LUCA).<ref>{{cite journal | vauthors = Ranea JA, Sillero A, Thornton JM, Orengo CA | title = Protein superfamily evolution and the last universal common ancestor (LUCA) | journal = Journal of Molecular Evolution | volume = 63 | issue = 4 | pages = 513–25 | date = October 2006 | pmid = 17021929 | doi = 10.1007/s00239-005-0289-7 | bibcode = 2006JMolE..63..513R | hdl = 10261/78338 | s2cid = 25258028 }}</ref>
Superfamily members may be in different species, with the ancestral protein being the form of the protein that existed in the ancestral species (orthology). Conversely, the proteins may be in the same species, but evolved from a single protein whose gene was duplicated in the genome (paralogy).
===Diversification=== A majority of proteins contain multiple domains. Between 66 and 80% of eukaryotic proteins have multiple domains while about 40-60% of prokaryotic proteins have multiple domains.<ref name="Han2"/> Over time, many of the superfamilies of domains have mixed together. In fact, it is very rare to find "consistently isolated superfamilies".<ref name="Han2"/><ref name=":1" /> 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.<ref name="Han2"/>
== Examples == ; α/β hydrolase superfamily: Members share an α/β sheet, containing 8 strands connected by helices, with catalytic triad residues in the same order,<ref>{{cite journal | vauthors = Carr PD, Ollis DL | title = Alpha/beta hydrolase fold: an update | journal = Protein and Peptide Letters | volume = 16 | issue = 10 | pages = 1137–48 | year = 2009 | pmid = 19508187 | doi = 10.2174/092986609789071298}}</ref> activities include proteases, lipases, peroxidases, esterases, epoxide hydrolases and dehalogenases.<ref name="pmid10607665">{{cite journal | vauthors = Nardini M, Dijkstra BW | title = Alpha/beta hydrolase fold enzymes: the family keeps growing | journal = Current Opinion in Structural Biology | volume = 9 | issue = 6 | pages = 732–7 | date = December 1999 | pmid = 10607665 | doi = 10.1016/S0959-440X(99)00037-8 }}</ref> ; Alkaline phosphatase superfamily: Members share an αβα sandwich structure<ref>{{cite web|title=SCOP|url=http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.d.bah.A.html|access-date=28 May 2014|archive-url=https://web.archive.org/web/20140729042732/http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.d.bah.A.html|archive-date=29 July 2014}}</ref> as well as performing common promiscuous reactions by a common mechanism.<ref>{{cite journal | vauthors = Mohamed MF, Hollfelder F | title = Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1834 | issue = 1 | pages = 417–24 | date = January 2013 | pmid = 22885024 | doi = 10.1016/j.bbapap.2012.07.015 }}</ref> ; Globin superfamily: Members share an 8-alpha helix globular globin fold.<ref>{{cite book | last1 = Branden | first1 = Carl | last2 = Tooze | first2 = John | name-list-style = vanc | title = Introduction to protein structure|date=1999|publisher=Garland Pub.|location=New York|isbn=978-0-8153-2305-1|edition=2nd}}</ref><ref>{{cite journal | vauthors = Bolognesi M, Onesti S, Gatti G, Coda A, Ascenzi P, Brunori M | title = Aplysia limacina myoglobin. Crystallographic analysis at 1.6 A resolution | journal = Journal of Molecular Biology | volume = 205 | issue = 3 | pages = 529–44 | date = February 1989 | pmid = 2926816 | doi = 10.1016/0022-2836(89)90224-6 }}</ref> ; Immunoglobulin superfamily: Members share a sandwich-like structure of two sheets of antiparallel β strands (Ig-fold), and are involved in recognition, binding, and adhesion.<ref name="pmid7932691">{{cite journal | vauthors = Bork P, Holm L, Sander C | title = The immunoglobulin fold. Structural classification, sequence patterns and common core | journal = Journal of Molecular Biology | volume = 242 | issue = 4 | pages = 309–20 | date = September 1994 | pmid = 7932691 | doi = 10.1006/jmbi.1994.1582 }}</ref><ref name="pmid8574878">{{cite journal | vauthors = Brümmendorf T, Rathjen FG | title = Cell adhesion molecules 1: immunoglobulin superfamily | journal = Protein Profile | volume = 2 | issue = 9 | pages = 963–1108 | year = 1995 | pmid = 8574878 }}</ref> ; LYRM superfamily: Members share a conserved LYR motif (leucine–tyrosine–arginine) embedded within a three α‑helix structure and function as adaptor proteins essential for mitochondrial Fe–S cluster assembly and oxidative phosphorylation complex assembly.<ref>{{Cite journal |last1=Angerer |first1=Heike |date=2015-02-12 |title=Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes |journal=Biology |language=en |volume=4 |issue=1 |pages=133–150 |doi=10.3390/biology4010133 |issn=2079-7737 |pmc=4381221 |pmid=25686363 |doi-access=free}}</ref><ref>{{Cite journal |last1=Dohnálek |first1=Vít |last2=Doležal |first2=Pavel |date=May 2024 |title=Installation of LYRM proteins in early eukaryotes to regulate the metabolic capacity of the emerging mitochondrion |journal=Open Biology |language=en |volume=14 |issue=5 |article-number=240021 |doi=10.1098/rsob.240021 |issn=2046-2441 |pmc=11293456 |pmid=38772414 |doi-access=free}}</ref> ; PA clan: Members share a chymotrypsin-like double β-barrel fold and similar proteolysis mechanisms but sequence identity of <10%. The clan contains both cysteine and serine proteases (different nucleophiles).<ref name=merops/><ref>{{cite journal | vauthors = Bazan JF, Fletterick RJ | title = Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 85 | issue = 21 | pages = 7872–6 | date = November 1988 | pmid = 3186696 | pmc = 282299 | doi = 10.1073/pnas.85.21.7872 | bibcode = 1988PNAS...85.7872B | doi-access = free }}</ref> ; Ras superfamily: Members share a common catalytic G domain of a 6-strand β sheet surrounded by 5 α-helices.<ref name="pmid11701921">{{cite journal | vauthors = Vetter IR, Wittinghofer A | title = The guanine nucleotide-binding switch in three dimensions | journal = Science | volume = 294 | issue = 5545 | pages = 1299–304 | date = November 2001 | pmid = 11701921 | doi = 10.1126/science.1062023 | bibcode = 2001Sci...294.1299V | s2cid = 6636339 }}</ref> ; RSH superfamily: Members share capability to hydrolyze and/or synthesize ppGpp alarmones in the stringent response.<ref>{{Cite journal |last1=Atkinson |first1=Gemma C. |last2=Tenson |first2=Tanel |last3=Hauryliuk |first3=Vasili |date=2011-08-09 |title=The RelA/SpoT Homolog (RSH) Superfamily: Distribution and Functional Evolution of ppGpp Synthetases and Hydrolases across the Tree of Life |journal=PLOS ONE |volume=6 |issue=8 |article-number=e23479 |doi=10.1371/journal.pone.0023479 |issn=1932-6203 |pmc=3153485 |pmid=21858139|bibcode=2011PLoSO...623479A |doi-access=free }}</ref> ; Serpin superfamily: Members share a high-energy, stressed fold which can undergo a large conformational change, which is typically used to inhibit serine and cysteine proteases by disrupting their structure.<ref name="ReferenceA"/> ; TIM barrel superfamily: Members share a large α<sub>8</sub>β<sub>8</sub> barrel structure. It is one of the most common protein folds and the monophylicity of this superfamily is still contested.<ref>{{cite journal | vauthors = Nagano N, Orengo CA, Thornton JM | title = One fold with many functions: the evolutionary relationships between TIM barrel families based on their sequences, structures and functions | journal = Journal of Molecular Biology | volume = 321 | issue = 5 | pages = 741–65 | date = August 2002 | pmid = 12206759 | doi = 10.1016/s0022-2836(02)00649-6 | bibcode = 2002JMBio.321..741N }}</ref><ref>{{cite journal | vauthors = Farber G | title = An α/β-barrel full of evolutionary trouble | journal = Current Opinion in Structural Biology | year = 1993 | volume = 3 | issue = 3 | pages = 409–412 | doi = 10.1016/S0959-440X(05)80114-9}}</ref>
== Protein superfamily resources == Several biological databases document protein superfamilies and protein folds, for example: *Pfam - Protein families database of alignments and HMMs *PROSITE - Database of protein domains, families and functional sites *PIRSF - SuperFamily Classification System * PASS2 - Protein Alignment as Structural Superfamilies v2 *SUPERFAMILY - Library of HMMs representing superfamilies and database of (superfamily and family) annotations for all completely sequenced organisms * SCOP and CATH - Classifications of protein structures into superfamilies, families and domains
Similarly there are algorithms that search the PDB for proteins with structural homology to a target structure, for example: *DALI - Structural alignment based on a distance alignment matrix method
== See also == {{col div|colwidth=30em}} *Structural alignment *Protein domains *Protein family * Protein subfamily *Protein mimetic *Protein structure *Homology (biology) *Interolog *List of gene families *SUPERFAMILY *CATH {{colend}}
==References== {{reflist|35em}}
==External links== *{{Commonscatinline|Protein superfamilies}}
{{Enzymes}}
Category:Molecular evolution * * Category:Protein classification Category:Protein superfamilies