CY Cystatin-like domain
SMART ACC:	SM000043
Description:	Cystatins are a family of cysteine protease inhibitors that occur mainly as single domain proteins. However some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains.
InterPro ACC:	IPR000010
InterPro abstract:	This entry represents the cystatin domain. Cystatins occur mainly as single-domain proteins. However, some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains. Cystatins are cysteine proteinase inhibitors belonging to MEROPS inhibitor family I25, clan IH [ PUBMED:2107324 … expand This entry represents the cystatin domain. Cystatins occur mainly as single-domain proteins. However, some extracellular proteins such as kininogen, His-rich glycoprotein and fetuin also contain these domains. Cystatins are cysteine proteinase 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). The cystatin family includes: The Type 1 cystatins, which are intracellular cystatins that are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither disulphide bonds nor carbohydrate side chains. The Type 2 cystatins, which are mainly extracellular secreted polypeptides synthesised with a 19-28 residue signal peptide. They are broadly distributed and found in most body fluids. The Type 3 cystatins, which are multidomain proteins. The mammalian representatives of this group are the kininogens. There are three different kininogens in mammals: H- (high molecular mass, IPR002395 ) and L- (low molecular mass) kininogen which are found in a number of species, and T-kininogen that is found only in rat. Unclassified cystatins. These are cystatin-like proteins found in a range of organisms: plant phytocystatins, fetuin in mammals, insect cystatins and a puff adder venom cystatin which inhibits metalloproteases of the MEROPS peptidase family M12 (astacin/adamalysin). Also a number of the cystatins-like proteins have been shown to be devoid of inhibitory activity. 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. collapse
GO function:	cysteine-type endopeptidase inhibitor activity (GO:0004869)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 9 885 CY domains in 7 379 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing CY domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing CY domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Relevant references for this domain

Primary literature for the CY domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the CY domain.

Protein	Description	Disease / phenotype
CYTC_HUMAN		OMIM:105150 : Cerebral amyloid angiopathy
		OMIM:604312 : Cerebral amyloid angiopathy
		OMIM:105150 : no description
CYTB_HUMAN		OMIM:601145 : Epilepsy, progressive myoclonic 1
CYTB_HUMAN		OMIM:254800 : no description
FETUA_HUMAN		OMIM:138680 : ALPHA-2-HS-GLYCOPROTEIN; AHSG

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a CY domain which could be assigned to a KEGG orthologous group, and not all proteins containing CY domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

Pfam	cystatin
PROSITE	CY_DOMAIN
InterPro	IPR000010