Summary: Signal peptide peptidase
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Signal peptide peptidase Provide feedback
The members of this family are membrane proteins. In some proteins this region is found associated with PF02225. This family corresponds with Merops subfamily A22B, the type example of which is signal peptide peptidase. There is a sequence-similarity relationship with PF01080.
McLauchlan J, Lemberg MK, Hope G, Martoglio B; , EMBO J 2002;21:3980-3988.: Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. PUBMED:12145199 EPMC:12145199
Lemberg MK, Bland FA, Weihofen A, Braud VM, Martoglio B; , J Immunol 2001;167:6441-6446.: Intramembrane proteolysis of signal peptides: an essential step in the generation of HLA-E epitopes. PUBMED:11714810 EPMC:11714810
Internal database links
|Similarity to PfamA using HHSearch:||DUF1119|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007369
In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:
- Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
- Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.
In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.
Aspartic endopeptidases EC of vertebrate, fungal and retroviral origin have been characterised [PUBMED:1455179]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [PUBMED:10625704] and archaean preflagellin have been described [PUBMED:16983194, PUBMED:14622420].
Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.
This group of sequences contain aspartic endopeptidases belong to MEROPS peptidase family A22 (presenilin family, clan AD): subfamily A22B.
The peptidases were originally classified by hierarchical homology to the most conserved member - IMPAS 1. They are also known as signal peptide peptidase (SPP) [PUBMED:14741365]. They belong to the I-CliP family of peptidases. SPP cleaves cleaves remnant signal peptides left behind in the membrane by the action of signal peptidase and also plays key roles in immune surveillance and the maturation of certain viral proteins [PUBMED:12966028]. SPPs do not require cofactors as demonstrated by expression in bacteria and purification of a proteolytically active form. The C-terminal region defines the functional domain, which is in itself sufficient for proteolytic activity [PUBMED:17517891].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral to membrane (GO:0016021)|
|Molecular function||aspartic-type endopeptidase activity (GO:0004190)|
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Members of this clan are peptidases that are integral membrane proteins. The catalytic aspartate is in the conserved GXGD motif.
The clan contains the following 4 members:DUF1119 Peptidase_A22B Peptidase_A24 Presenilin
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
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Curation and family details
|Seed source:||Bateman A|
|Author:||Bateman A, Studholme DJ|
|Number in seed:||14|
|Number in full:||885|
|Average length of the domain:||274.40 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||63.39 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||8|
|Download:||download the raw HMM for this family|
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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 Peptidase_A22B domain has been found. There are 2 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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