Summary: Astacin (Peptidase family M12A)
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Astacin Edit Wikipedia article
| Astacin | |||||||||
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 structure of astacin with a hydroxamic acid inhibitor | |||||||||
| Identifiers | |||||||||
| Symbol | Astacin | ||||||||
| Pfam | PF01400 | ||||||||
| Pfam clan | CL0126 | ||||||||
| InterPro | IPR001506 | ||||||||
| PROSITE | PDOC00129 | ||||||||
| MEROPS | M12 | ||||||||
| SCOPe | 1ast / SUPFAM | ||||||||
| CDD | cd04280 | ||||||||
| |||||||||
Astacins are a family of multidomain metalloendopeptidases which are either secreted or membrane-anchored.[1] These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH.[2]
The astacin family of metalloendopeptidases (EC 3.4.24.21) encompasses a range of proteins found in hydra to humans, in mature and developmental systems.[3] Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins.[3] The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease domain. They are either secreted from cells, or are associated with the plasma membrane.
The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains.[4] The zinc ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine residues, a tyrosine and a water molecule (which is also bound to the carboxylate side chain of Glu93).[4] The N-terminal domain comprises 2 alpha-helices and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity.[3]
History
Astacins are named after Astacus astacus, the European crayfish, a species of freshwater crustacean where they were discovered.[1] BMP1 was the first astacin described.[1]
Astacin family members
Proteins containing the astacin domain include:
- Astacin-like metallo-endopeptidase (ASTL)
- Bone morphogenetic protein 1 (BMP1)
- Meprin A subunit alpha (MEP1A)
- Meprin A subunit beta (MEP1B)
- Tolloid-like protein 1 (TLL1)
- Tolloid-like protein 2 (TLL2)
References
- ^ a b c Gomis-Rüth, FX; Trillo-Muyo, S; Stöcker, W (October 2012). "Functional and structural insights into astacin metallopeptidases". Biological Chemistry. 393 (10): 1027–41. doi:10.1515/hsz-2012-0149. PMID 23092796.
- ^ Rawlings ND, Barrett AJ (1995). "Evolutionary families of metallopeptidases". Meth. Enzymol. 248: 183–228. doi:10.1016/0076-6879(95)48015-3. PMID 7674922.
- ^ a b c Bond JS, Beynon RJ (July 1995). "The astacin family of metalloendopeptidases". Protein Sci. 4 (7): 1247–61. doi:10.1002/pro.5560040701. PMC 2143163. PMID 7670368.
- ^ a b Gomis-Ruth FX, Stocker W, Huber R, Zwilling R, Bode W (February 1993). "Refined 1.8 A X-ray crystal structure of astacin, a zinc-endopeptidase from the crayfish Astacus astacus L. Structure determination, refinement, molecular structure and comparison with thermolysin". J. Mol. Biol. 229 (4): 945–68. doi:10.1006/jmbi.1993.1098. PMID 8445658.
External links
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
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.
Astacin (Peptidase family M12A) Provide feedback
The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis. Members of this family contain two conserved disulphide bridges, these are joined 1-4 and 2-3. Members of this family have an amino terminal propeptide which is cleaved to give the active protease domain. All other linked domains are found to the carboxyl terminus of this domain. This family includes: Astacin P07584 a digestive enzyme from Crayfish. Meprin, Q16819 a multiple domain membrane component that is constructed from a homologous alpha and beta chain. Proteins involved in morphogenesis such as P13497 and Tolloid from drosophila P25723.
Literature references
-
Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922 EPMC:7674922
Internal database links
| SCOOP: | Metallopep Peptidase_M10 Peptidase_M43 Peptidase_M57 Peptidase_M66 Reprolysin_3 Reprolysin_4 Reprolysin_5 |
| Similarity to PfamA using HHSearch: | Peptidase_M10 |
External database links
| HOMSTRAD: | Astacin |
| MEROPS: | M12 |
| PROSITE: | PDOC00129 |
| SCOP: | 1ast |
This tab holds annotation information from the InterPro database.
InterPro entry IPR001506
This group of metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH [PUBMED:7674922].
The astacin (EC) family of metalloendopeptidases encompasses a range of proteins found in hydra to humans, in mature and developmental systems [PUBMED:7670368]. Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins [PUBMED:7670368]. The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease domain. They are either secreted from cells, or are associated with the plasma membrane.
The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains [PUBMED:8445658]. The zinc ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine residues, a tyrosine and a water molecule (which is also bound to the carboxylate side chain of Glu93) [PUBMED:8445658]. The N-terminal domain comprises 2 alpha-helices and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity [PUBMED:7670368].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | metalloendopeptidase activity (GO:0004222) |
| Biological process | proteolysis (GO:0006508) |
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 Peptidase_MA (CL0126), which has the following description:
Clan MA is one of two zinc-dependent metallopeptidases that contain the HEXXH motif. The two histidines are zinc ligands. The structures of this clan show the active site is between its two sub-domains.
The clan contains the following 72 members:
Aminopep Aspzincin_M35 Astacin ATLF BSP DA1-like DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3810 DUF3920 DUF4157 DUF4344 DUF45 DUF4953 DUF885 HRXXH Metallopep MPTase-PolyVal Peptidase_M1 Peptidase_M10 Peptidase_M11 Peptidase_M13 Peptidase_M2 Peptidase_M27 Peptidase_M3 Peptidase_M30 Peptidase_M32 Peptidase_M35 Peptidase_M36 Peptidase_M4 Peptidase_M41 Peptidase_M43 Peptidase_M48 Peptidase_M49 Peptidase_M4_C Peptidase_M50 Peptidase_M50B Peptidase_M54 Peptidase_M56 Peptidase_M57 Peptidase_M6 Peptidase_M60 Peptidase_M61 Peptidase_M64 Peptidase_M66 Peptidase_M7 Peptidase_M76 Peptidase_M78 Peptidase_M8 Peptidase_M85 Peptidase_M9 Peptidase_M90 Peptidase_M91 Peptidase_MA_2 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like UPF0054 WLM Zincin_1 Zincin_2 Zn_peptidase Zn_peptidase_2Alignments
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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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 (22) |
Full (8275) |
Representative proteomes | UniProt (12307) |
NCBI (13710) |
Meta (22) |
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| RP15 (3281) |
RP35 (4668) |
RP55 (6625) |
RP75 (7898) |
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| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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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 (22) |
Full (8275) |
Representative proteomes | UniProt (12307) |
NCBI (13710) |
Meta (22) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (3281) |
RP35 (4668) |
RP55 (6625) |
RP75 (7898) |
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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: | Swissprot |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Bateman A 
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| Number in seed: | 22 |
| Number in full: | 8275 |
| Average length of the domain: | 165.30 aa |
| Average identity of full alignment: | 27 % |
| Average coverage of the sequence by the domain: | 37.76 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 191 | ||||||||||||
| Family (HMM) version: | 24 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
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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 Astacin domain has been found. There are 20 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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