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13  structures 174  species 0  interactions 2372  sequences 44  architectures

Family: SQAPI (PF16845)

Summary: Aspartic acid proteinase inhibitor

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 "Cystatin". More...

Cystatin Edit Wikipedia article

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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.

Aspartic acid proteinase inhibitor Provide feedback

SQAPI, aspartic acid inhibitor first isolated from squash, inhibits a wide range of aspartic proteinases. This particular family of PAAPIs (proteinaceous aspartic acid inhibitors) seems to have evolved quite recently from an ancestral cystatin. Structurally it consists of a four-stranded anti-parallel beta-sheet gripping an alpha-helix in much the same manner that a hand grips a tennis racket. The unstructured N-terminus and the loop connecting beta-strands 1 and 2 are important for pepsin inhibition, but the loop connecting strands 3 and 4 is not [1].

Literature references

  1. Headey SJ, Macaskill UK, Wright MA, Claridge JK, Edwards PJ, Farley PC, Christeller JT, Laing WA, Pascal SM;, J Biol Chem. 2010;285:27019-27025.: Solution structure of the squash aspartic acid proteinase inhibitor (SQAPI) and mutational analysis of pepsin inhibition. PUBMED:20538608 EPMC:20538608

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000010

Cystatins are a family of cysteine protease inhibitors belonging to MEROPS inhibitor family I25, clan IH [ PUBMED:2107324 , PUBMED:14587292 , PUBMED:1855589 ]. They mainly inhibit peptidases belonging to peptidase families C1 (papain family) and C13 (legumain family). They occur mainly as single domain proteins. However, some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.

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 Cystatin (CL0121), which has the following description:

This superfamily includes cystatins and cathelicidins [1]. The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. Stefins - included in Pfam:PF00031 - remain encoded by a single or a small number of genes throughout the eukaryotes, whereas the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications [2].

The clan contains the following 13 members:

Cathelicidins Cystatin DUF3889 DUF5590 FTP Latexin Monellin PP1 Spp-24 SQAPI Staphopain_pro YebF YPEB


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.

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

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

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Representative proteomes UniProt

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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.

Representative proteomes UniProt
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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...


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: pdb_2kxg
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 13
Number in full: 2372
Average length of the domain: 81.6 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 53.79 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 31.0 31.0
Trusted cut-off 31.0 31.0
Noise cut-off 30.9 30.9
Model length: 83
Family (HMM) version: 8
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


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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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The tree shows the occurrence of this domain across different species. More...


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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 SQAPI domain has been found. There are 13 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.

Protein Predicted structure External Information
A0A0P0VTN6 View 3D Structure Click here
A0A0R0G8Z2 View 3D Structure Click here
A0A0R0J8T0 View 3D Structure Click here
A0A0R4J4X3 View 3D Structure Click here
A0A0R4J598 View 3D Structure Click here
A0A1D6JQ67 View 3D Structure Click here
A0A1D6JQ68 View 3D Structure Click here
A2XS65 View 3D Structure Click here
B4FTY6 View 3D Structure Click here
B4FV48 View 3D Structure Click here
B6TMF0 View 3D Structure Click here
B6UGN8 View 3D Structure Click here
C6SV68 View 3D Structure Click here
C6SYG7 View 3D Structure Click here
C6TCH0 View 3D Structure Click here
I1K3Q1 View 3D Structure Click here
I1L003 View 3D Structure Click here
I1L2L4 View 3D Structure Click here
I1LHN1 View 3D Structure Click here
I1LN44 View 3D Structure Click here
I1M0K3 View 3D Structure Click here
I1M152 View 3D Structure Click here
I1MYC1 View 3D Structure Click here
I1N0U3 View 3D Structure Click here
I1NB12 View 3D Structure Click here
K7M4T1 View 3D Structure Click here
K7TVP8 View 3D Structure Click here
K7VLF2 View 3D Structure Click here
K7VPW5 View 3D Structure Click here
K7W249 View 3D Structure Click here
K7WGR9 View 3D Structure Click here
O04720 View 3D Structure Click here
P0C579 View 3D Structure Click here
P20907 View 3D Structure Click here
P86472 View 3D Structure Click here
P93627 View 3D Structure Click here
Q0JGM8 View 3D Structure Click here
Q0JNR2 View 3D Structure Click here
Q10J94 View 3D Structure Click here
Q10Q46 View 3D Structure Click here