Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
13  structures 150  species 3  interactions 270  sequences 1  architecture

Family: SSI (PF00720)

Summary: Subtilisin inhibitor-like

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 "SSI protease inhibitor". More...

SSI protease inhibitor Edit Wikipedia article

PDB 5sic EBI.jpg
Molecular recognition at the active site of subtilisin BPN': crystallographic studies using genetically engineered protease inhibitor SSI (Streptomyces subtilisin inhibitor)
Symbol SSI
Pfam PF00720
InterPro IPR000691
SCOP 2sic

In molecular biology the protein SSI is a Subtilisin inhibitor-like which stands for Streptomyces subtilisin inhibitor. This is a protease inhibitor. These are often synthesised as part of a larger precursor protein, either as a prepropeptide. The function of this protein domain is to prevent access of the substrate to the active site. It is found only in bacteria.


SSI is a protease inhibitor, it prevents enzymes from acting on a substrate. Some SSI's also inhibit trypsin, chymotrypsin and griselysin.[1][2] Commercially, SSI's have huge potential in the commercial market, they help stabilise proteases in products such as laundry detergents to prevent autolysis of biological washing powders.[3] This means that the enzymes in the washing powder are kept in optimum performance.


SSI is a homodimer, in other words, it is made of two subunits which are exactly the same as each other. Each monomer contains 2 antiparallel beta-sheets and 2 short alpha-helices. Protease binding induces the widening of a channel-like structure, in which hydrophobic side-chains are sandwiched between 2 lobes.[4]

Studies have shown that the loss of the C-terminal domain reduces the inhibitory effect of the proteins. This implies that the C-terminal domain is responsible for maintaining the correct 3D fold.[5]

Structural similarities between the primary and secondary contact loops of SSI, and the ovomucoid and pancreatic secretory trypsin inhibitor family suggest evolution of the 2 families from a common ancestor.[4]


  1. ^ Rawlings ND, Tolle DP, Barrett AJ (March 2004). "Evolutionary families of peptidase inhibitors". Biochem. J. 378 (Pt 3): 705–16. doi:10.1042/BJ20031825. PMC 1224039. PMID 14705960. 
  2. ^ Kojima S, Nishiyama Y, Kumagai I, Miura K (March 1991). "Inhibition of subtilisin BPN' by reaction site P1 mutants of Streptomyces subtilisin inhibitor". J. Biochem. 109 (3): 377–82. PMID 1908859. 
  3. ^ Ganz PJ, Bauer MD, Sun Y, Fieno AM, Grant RA, Correa PE; et al. (2004). "Stabilized variant of Streptomyces subtilisin inhibitor and its use in stabilizing subtilisin BPN'.". Protein Eng Des Sel 17 (4): 333–9. doi:10.1093/protein/gzh045. PMID 15187224. 
  4. ^ a b Hirono S, Akagawa H, Mitsui Y, Iitaka Y (September 1984). "Crystal structure at 2.6 A resolution of the complex of subtilisin BPN' with streptomyces subtilisin inhibitor". J. Mol. Biol. 178 (2): 389–414. doi:10.1016/0022-2836(84)90150-5. PMID 6387152. 
  5. ^ Sakai M, Odani S, Ikenaka T (March 1980). "Importance of the carboxyl-terminal four amino acid residues in the inhibitory activity of Streptomyces subtilisin inhibitor (with a revision of its carboxyl-terminal sequence)". J. Biochem. 87 (3): 891–8. PMID 6993452. 

This article incorporates text from the public domain Pfam and InterPro IPR000691

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.

Subtilisin inhibitor-like Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR023549

The Streptomyces family of bacteria produce a number of proteinase inhibitors, which belong to MEROPS inhibitor family I16, clan IY. They are characterised by their strong activity towards subtilisin (MEROPS peptidase family S8, INTERPRO) and are collectively known as Streptomyces subtilisin inhibitors (SSI). Some SSI also inhibit trypsin, chymotrypsin (MEROPS peptidase family S1, INTERPRO) and griselysin (MEROPS peptidase family M4, INTERPRO) [PUBMED:14705960]. Mutation of the active site residue can influence inhibition specificity [PUBMED:1908859].

SSI is a homodimer, each monomer containing 2 anti-parallel beta-sheets and 2 short alpha-helices. Protease binding induces the widening of a channel-like structure, in which hydrophobic side-chains are sandwiched between 2 lobes [PUBMED:6387152]. Loss of the C-terminal tetrapeptide VFAF drastically reduces the inhibitory effect of the proteins when there is less than one molecule of inhibitor present per molecule of enzyme. This implies that the tetrapeptide is neccessary to maintain the correct 3D fold [PUBMED:6993452]. Structural similarities between the primary and secondary contact loops of SSI, and the ovomucoid and pancreatic secretory trypsin inhibitor family suggest evolution of the 2 families from a common ancestor [PUBMED:6387152].

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...

Loading domain graphics...


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...

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.

Representative proteomes NCBI
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

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

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

Format an alignment

Representative proteomes NCBI

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.

Representative proteomes NCBI
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...


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: Pfam-B_679 (release 2.1)
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 25
Number in full: 270
Average length of the domain: 88.90 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 61.55 %

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 21.8 21.8
Trusted cut-off 21.8 23.4
Noise cut-off 21.1 20.6
Model length: 92
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

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...

Loading sunburst data...

Tree controls


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


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


There are 3 interactions for this family. More...

Peptidase_S8 Peptidase_M7 Trypsin


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 SSI 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 seqence.

Loading structure mapping...