Proteinase inhibitor I25A, stefin (IPR001713)

Short name: Prot_inh_stefin

Overlapping homologous superfamilies


Family relationships



The cystatins are a superfamily of similar proteins present in mammals, birds, fish, insects, plants and protozoa. In general they are potent peptidase inhibitors [PMID: 3555466, PMID: 2107324, PMID: 1855589, PMID: 14587292] belonging to MEROPS inhibitor family I25, clan IH.

The type 1 cystatins or stefins (A and B) are mainly intracellular, the type 2 cystatins (C, D, E/M, F, G, S, SN and SA) are extracellular, and the type 3 cystatins (L- and H-kininogens) are intravascular proteins. All true cystatins inhibit cysteine peptidases of the papain family (MEROPS peptidase family C1), and some also inhibit legumain family enzymes (MEROPS peptidase family C13). These peptidases play key roles in physiological processes, such as intracellular protein degradation (cathepsins B, H and L), are pivotal in the remodelling of bone (cathepsin K), and may be important in the control of antigen presentation (cathepsin S, mammalian legumain). Moreover, the activities of such peptidases are increased in pathophysiological conditions, such as cancer metastasis and inflammation. Additionally, such peptidases are essential for several pathogenic parasites and bacteria. Thus in animals cystatins not only have capacity to regulate normal body processes and perhaps cause disease when down-regulated, but in other organisms may also participate in defence against biotic and abiotic stress.

The stefin family (MEROPS inhibitor family I25 clan IH, subfamily I25A) includes proteins that lack disulphide bonds and carbohydrates. The most abundant source of stefin A is poly-morphonuclear leucocytes from the liver, but it is also found in extracts of squamous epithelia from the mouth and oesophagus, and has been localised to the cytoplasm of the strata corneum and granulosum of the epidermis. The selective distribution of the inhibitor correlates with tissues that constitute a 'first line of defence' against pathogenic organisms. Stefin A may thus provide a protective function as an inhibitor of cysteine proteases utilised as invasive tools by many infectious agents [PMID: 7869384].

The structure of stefin A contains a 5-stranded anti-parallel beta-sheet, wrapped around a central helix. The loops formed between the strands are involved in inhibitor binding, one of these containing a QVVAG sequence, which is highly conserved in most members of the cystatin superfamily [PMID: 1855589].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004866 endopeptidase inhibitor activity

Cellular Component

GO:0005622 intracellular

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.