Summary: PA domain
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This is the Wikipedia entry entitled "PA clan of proteases". More...
PA clan of proteases Edit Wikipedia article
| PA protease clan | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | ? | ||||||||
| Pfam | CL0124 | ||||||||
| InterPro | IPR009003 | ||||||||
| SCOP2 | 50494 / SCOPe / SUPFAM | ||||||||
| |||||||||
The PA clan (proteases of mixed nucleophile, superfamily A) is the largest group of proteases with common ancestry. Members have a chymotrypsin-like fold and similar proteolysis mechanisms but sequence identity of <10%. The clan contains both cysteine and serine proteases (different nucleophiles)[1][2]. PA clan proteases can be found in plants[3] , animals[3], fungi[3], eubacteria[4], archaea[5][6] and viruses[7].
Structure
Despite retaining as little as 10% sequence identity, PA clan members isolated from viruses, prokaryotes and eukaryotes show structural homology and can be aligned by structural similarity (e.g. with DALI).
Double β-barrel
PA clan proteases all share a core motif of two β-barrels with covalent catalysis performed by an acid-histidine-nucleophile catalytic triad motif. The triad residues are split between the two barrels so that catalysis takes place at their interface[8].
Viral protease loop
In addition to the double β-barrel core, some viral proteases (such as TEV protease have a long, flexible C-terminal loop that forms a lid to which completely covers the substrate and create a binding tunnel. This tunnel contains a set of tight binding pockets such that each side chain of the substrate peptide (P6 to P1’) is bound in a complementary site (S6 to S1’)[9] and specificity is endowed by the large contact area between enzyme and substrate. Conversely, cellular proteases that lack this loop, such as trypsin have broader specificity.
Evolution and function
The PA clan contains a diverse array of proteases from eukaryotes, prokaryotes and viruses. It also encompasses varied functions including blood clotting (e.g. thrombin), digestion (e.g. trypsin), snake venoms (e.g. pit viper haemotoxin), bacterial toxins (e.g. exfoliative toxin) and viral polyprotein processing (e.g. polio, norovirus, and TEV proteases).
All cellular PA clan proteases are serine proteases, however there are both serine and cysteine protease families of viral proteases. This indicates that the nucleophile must have exchanged at some point by divergent evolution.
Families
| Family | Stereotype example | Known structure? |
|---|---|---|
| C03 | poliovirus-type picornain 3C (human poliovirus 1) | Yes |
| C04 | nuclear-inclusion-a peptidase (plum pox virus) (plum pox virus) | Yes |
| C24 | rabbit hemorrhagic disease virus 3C-like peptidase (rabbit hemorrhagic disease virus) | No |
| C30 | porcine transmissible gastroenteritis virus-type main peptidase (transmissible gastroenteritis virus) | Yes |
| C37 | calicivirin (Southampton virus) | Yes |
| C62 | gill-associated virus 3C-like peptidase (gill-associated virus) | No |
| C74 | pestivirus NS2 peptidase (bovine viral diarrhea virus 1) | No |
| C99 | iflavirus processing peptidase (Ectropis obliqua picorna-like virus) | No |
| S01 | chymotrypsin A (cattle-type) (Bos taurus) | Yes |
| S03 | togavirin (Sindbis virus) | Yes |
| S06 | IgA1-specific serine peptidase ({Neisseria}-type) (Neisseria gonorrhoeae) | Yes |
| S07 | flavivirin (yellow fever virus) | No |
| S29 | hepacivirin (hepatitis C virus) | Yes |
| S30 | potyvirus P1 peptidase (plum pox virus) | No |
| S31 | pestivirus NS3 polyprotein peptidase (bovine viral diarrhea virus 1) | No |
| S32 | equine arteritis virus serine peptidase (equine arteritis virus) | Yes |
| S39 | sobemovirus peptidase (cocksfoot mottle virus) | Yes |
| S46 | dipeptidyl-peptidase 7 ({Porphyromonas gingivalis}-type) (Porphyromonas gingivalis) | No |
| S55 | SpoIVB peptidase (Bacillus subtilis) | No |
| S64 | Ssy5 peptidase (Saccharomyces cerevisiae) | No |
| S65 | picornain-like cysteine peptidase (Breda-1 torovirus) (Breda virus) | No |
| S75 | White bream virus serine peptidase (White bream virus) | No |
See also
External resources
- MEROPS - Comprehensive protease database
- Superfamily -
References
- ^ Rawlings, ND (2012 Jan). "MEROPS: the database of proteolytic enzymes, their substrates and inhibitors". Nucleic acids research. 40 (Database issue): D343-50. PMIDÂ 22086950.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Bazan, JF (1988 Nov). "Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications". Proceedings of the National Academy of Sciences of the United States of America. 85 (21): 7872–6. PMID 3186696.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ a b c Laskar, A (2012 May 24). "Modeling and structural analysis of PA clan serine proteases". BMC research notes. 5: 256. PMIDÂ 22624962.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Barbosa, JA (1996 Jul). "Novel features of serine protease active sites and specificity pockets: sequence analysis and modelling studies of glutamate-specific endopeptidases and epidermolytic toxins". Protein engineering. 9 (7): 591–601. PMID 8844831.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ "MEROPS - Archeal S01 proteases". Retrieved 2013.
{{cite web}}: Check date values in:|accessdate=(help) - ^ Ruiz-Perez, F (2013 May 21). "Bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence". Cellular and molecular life sciences : CMLS. PMID 23689588.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Bazan, JF (1988 Nov). "Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications". Proceedings of the National Academy of Sciences of the United States of America. 85 (21): 7872–6. PMID 3186696.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Dougherty, WG (1989 Sep). "Characterization of the catalytic residues of the tobacco etch virus 49-kDa proteinase". Virology. 172 (1): 302–10. PMID 2475971.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Phan, J (2002 Dec 27). "Structural basis for the substrate specificity of tobacco etch virus protease". The Journal of biological chemistry. 277 (52): 50564–72. PMID 12377789.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help)
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
PA domain Provide feedback
The PA (Protease associated) domain is found as an insert domain in diverse proteases. The PA domain is also found in a plant vacuolar sorting receptor O22925 and members of the RZF family O43567. It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors [1].
Literature references
-
Luo X, Hofmann K; , Trends Biochem Sci 2001;26:147-148.: The protease-associated domain: a homology domain associated with multiple classes of proteases. PUBMED:11246007 EPMC:11246007
Internal database links
| SCOOP: | Peptidase_M36 Peptidase_M50 Peptidase_S8 |
External database links
| MEROPS: | S8 M28 A22 |
| SCOP: | 1cx8 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003137
The PA (Protease associated) domain is found as an insert domain in diverse proteases, which include the MEROPS peptidase families A22B, M28, and S8A [ PUBMED:7674922 ]. The PA domain is also found in a plant vacuolar sorting receptor SWISSPROT and members of the RZF family, e.g. SWISSPROT . It has been suggested that this domain forms a lid-like structure that covers the active site in active proteases, and is involved in protein recognition in vacuolar sorting receptors [ PUBMED:11246007 ].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Leu-IlvD (CL0364), which has the following description:
Superfamily includes LeuD-like, IlvD/EDD C-terminal domain-like, and AF0055-like families.
The clan contains the following 10 members:
AcnX_swivel_put Aconitase_2_N Aconitase_C CPSase_sm_chain Cyclase DUF2172 PA PEP-utilizers Peptidase_S66C RraA-likeAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (339) |
Full (25301) |
Representative proteomes | UniProt (59359) |
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| RP15 (3382) |
RP35 (10910) |
RP55 (21438) |
RP75 (31559) |
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| Jalview | |||||||
| HTML | |||||||
| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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not generated,
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
| Seed (339) |
Full (25301) |
Representative proteomes | UniProt (59359) |
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|---|---|---|---|---|---|---|---|
| RP15 (3382) |
RP35 (10910) |
RP55 (21438) |
RP75 (31559) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_259 (release 5.2) |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Bateman A  , Mahon P
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| Number in seed: | 339 |
| Number in full: | 25301 |
| Average length of the domain: | 96.6 aa |
| Average identity of full alignment: | 18 % |
| Average coverage of the sequence by the domain: | 14.22 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 92 | ||||||||||||
| Family (HMM) version: | 25 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
Archea
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Eukaryota
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Bacteria
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Other sequences
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Viruses
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Unclassified
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Viroids
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Unclassified sequence
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PA domain has been found. There are 167 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
