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17  structures 615  species 2  interactions 3536  sequences 229  architectures

Family: Astacin (PF01400)

Summary: Astacin (Peptidase family M12A)

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Astacin". More...

Astacin Edit Wikipedia article

Astacin
PDB 1qjj EBI.jpg
structure of astacin with a hydroxamic acid inhibitor
Identifiers
Symbol Astacin
Pfam PF01400
Pfam clan CL0126
InterPro IPR001506
PROSITE PDOC00129
MEROPS M12
SCOP 1ast
SUPERFAMILY 1ast
CDD cd04280
astacin
Identifiers
EC number 3.4.24.21
CAS number 143179-21-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In molecular biology, astacin is a family of metallopeptidases. 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.[1]

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.[2] Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins.[2] 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.[3] 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).[3] 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.[2]

Examples

Human genes encoding proteins containing the astacin domain include:

References

  1. ^ Rawlings ND, Barrett AJ (1995). "Evolutionary families of metallopeptidases". Meth. Enzymol. 248: 183–228. doi:10.1016/0076-6879(95)48015-3. PMID 7674922. 
  2. ^ 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. 
  3. ^ 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 article incorporates text from the public domain Pfam and InterPro IPR001506

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

  1. Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922 EPMC:7674922


Internal database links

External database links

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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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
(3536)
Representative proteomes NCBI
(4239)
Meta
(24)
RP15
(705)
RP35
(1005)
RP55
(1482)
RP75
(1721)
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Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(22)
Full
(3536)
Representative proteomes NCBI
(4239)
Meta
(24)
RP15
(705)
RP35
(1005)
RP55
(1482)
RP75
(1721)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(3536)
Representative proteomes NCBI
(4239)
Meta
(24)
RP15
(705)
RP35
(1005)
RP55
(1482)
RP75
(1721)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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 View help on the curation process

Seed source: Swissprot
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 22
Number in full: 3536
Average length of the domain: 167.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 38.08 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 191
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

MATH MAM

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 17 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 seqence.

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