Fetuin-A-type cystatin domain (IPR025760)

Short name: Cystatin_Fetuin_A

Overlapping homologous superfamilies


Domain relationships


The cystatin superfamily consists of a large group of cystatin domain- containing proteins, most of which are reversible and tight-binding inhibitors of the papain (C1) and legumain (C13) families of cysteine proteases. Fetuins have been identified as main members of the cystatin superfamily and are composed of fetuin-A and fetuin-B. Fetuins are characterised by the presence of 2 N-terminally located cystatin-like repeats and a unique C-terminal domain which is not present in other proteins of the cystatin family [PMID: 19919722, PMID: 1372866, PMID: 1373325].

Fetuin-A [PMID: 1372866, PMID: 1373325, PMID: 1707273, PMID: 9133634, PMID: 12556469] also called alpha-2-HS-glycoprotein, bone sialic acid- containing protein (BSP), countertrypin or PP63, is expressed in a tissue- and development-specific pattern which seems to be significantly different between species. A wide functional diversity of fetuin-A has been observed. It has been shown to function in many physiological aspects, such as fatty acid transport, regulation of insulin activity and hepatocyte-growth-factor activity, response to systemic inflammation, and inhibition of unwanted mineralization. It has been demonstrated that fetuin-A plays important roles during developmental processes, including osteogenesis, myotubule, fetal brain and nervous system development. Human fetuin is a heterodimer of chain A and B, which are derived by cleavage of a connecting peptide from a common precursor. Snake fetuin family proteins (antihemorrhagic proteins HSF, BJ46a and MSF and HLP-A and HLP-B) show a significant degree of sequence homology to fetuin-A [PMID: 19481564].

The cystatin fold is formed by a five stranded anti-parallel beta-sheet wrapped around a five-turn alpha-helix [PMID: 19919722]. Fetuin contains twelve conserved cysteines involved in six disulphide bonds. Eleven of the twelve invariant cysteines are located within the cystatin-like repeats. The 12th cysteine is located near the C terminus of the protein, separated by a region of variable length.

Contributing signatures

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