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2  structures 383  species 1  interaction 1249  sequences 14  architectures

Family: Peptidase_A22B (PF04258)

Summary: Signal peptide peptidase

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

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.

Literature references

  1. Lemberg MK, Martoglio B; , Mol Cell 2002;10:735-744.: Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis. PUBMED:12419218 EPMC:12419218

  2. 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

  3. Weihofen A, Binns K, Lemberg MK, Ashman K, Martoglio B; , Science 2002;296:2215-2218.: Identification of signal peptide peptidase, a presenilin-type aspartic protease. PUBMED:12077416 EPMC:12077416

  4. 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

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007369

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].

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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Pfam Clan

This family is a member of clan Peptidase_AD (CL0130), which has the following description:

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:

Peptidase_A22B Peptidase_A24 Presenilin SPP

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 (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...

View options

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
(14)
Full
(1249)
Representative proteomes UniProt
(2608)
NCBI
(3350)
Meta
(49)
RP15
(323)
RP35
(664)
RP55
(979)
RP75
(1158)
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HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(14)
Full
(1249)
Representative proteomes UniProt
(2608)
NCBI
(3350)
Meta
(49)
RP15
(323)
RP35
(664)
RP55
(979)
RP75
(1158)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(14)
Full
(1249)
Representative proteomes UniProt
(2608)
NCBI
(3350)
Meta
(49)
RP15
(323)
RP35
(664)
RP55
(979)
RP75
(1158)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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: Bateman A
Previous IDs: DUF435;
Type: Family
Author: Bateman A, Studholme DJ
Number in seed: 14
Number in full: 1249
Average length of the domain: 259.10 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 64.21 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.3 23.3
Trusted cut-off 23.6 23.3
Noise cut-off 22.5 23.2
Model length: 284
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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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Interactions

There is 1 interaction for this family. More...

MHC_I

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 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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