The domain within your query sequence starts at position 1 and ends at position 96; the E-value for the CY domain shown below is 3.09e-16.

MYGGVSEAKPATPEIQKIADKVRSQLEAKTNKKYEKFEAVEYKTQAVAGENIFIKMDVGH
GCFIHIKVFSGPTGKDNYELHGYQTDKAKDDELTYF

CY

Cystatin-like domain

• SMART accession number: SM00043
• 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 abstract (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.

• GO function: cysteine-type endopeptidase inhibitor activity (GO:0004869)

There are 9885 CY domains in 7379 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Brown WM, Dziegielewska KM
• Friends and relations of the cystatin superfamily--new members and their evolution.
• Protein Sci. 1997; 6: 5-12

The cystatin "superfamily" encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. In recent years, several new members of the superfamily have characterized, including proteins from insects and plants. Based on partial amino acid homology, new members, such as the invariant chain (Ii), and the transforming growth factor-beta receptor type II (TGF-beta receptor II) may, in fact, represent members of an emerging family within the superfamily that may have used some common building blocks to form functionally diverse proteins. Cystatin super-family members have been found throughout evolution and members of each family of the superfamily are present in mammals today. In this review, the new and older, established members of the family are arranged into a possible evolutionary order, based on sequence homology and functional similarities.

• Turk V, Bode W
• The cystatins: protein inhibitors of cysteine proteinases.
• FEBS Lett. 1991; 285: 213-9

The last decade has witnessed enormous progress of protein inhibitors of cysteine proteinases concerning their structures, functions and evolutionary relationships. Although they differ in their molecular properties and biological distribution, they are structurally related proteins. All three inhibitory families, the stefins, the cystatins and the kininogens, are members of the same superfamily. Recently determined crystal structures of chicken cystatin and human stefin B established a new mechanism of interaction between cysteine proteinases and their inhibitors which is fundamentally different from the standard mechanism for serine proteinases and their inhibitors.

Disease (disease genes where sequence variants are found in this domain)

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

Protein	Disease
Cystatin-C (P01034) (SMART)	OMIM:105150: Cerebral amyloid angiopathy OMIM:604312: Cerebral amyloid angiopathy OMIM:105150:
Alpha-2-HS-glycoprotein (P02765) (SMART)	OMIM:138680: ALPHA-2-HS-GLYCOPROTEIN; AHSG
Cystatin-B (P04080) (SMART)	OMIM:601145: Epilepsy, progressive myoclonic 1 OMIM:254800:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
100.00	map04610	Complement and coagulation cascades

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

Structure (3D structures containing this domain)

3D Structures of CY domains in PDB

PDB code	Title
1a67	CHICKEN EGG WHITE CYSTATIN WILDTYPE, NMR, 16 STRUCTURES
1a90	RECOMBINANT MUTANT CHICKEN EGG WHITE CYSTATIN, NMR, 31 STRUCTURES
1cew	THE 2.0 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF CHICKEN EGG WHITE CYSTATIN AND ITS POSSIBLE MODE OF INTERACTION WITH CYSTEINE PROTEINASES
1cyu	SOLUTION NMR STRUCTURE OF RECOMBINANT HUMAN CYSTATIN A UNDER THE CONDITION OF PH 3.8 AND 310K
1cyv	SOLUTION NMR STRUCTURE OF RECOMBINANT HUMAN CYSTATIN A UNDER THE CONDITION OF PH 3.8 AND 310K
1dvc	SOLUTION NMR STRUCTURE OF HUMAN STEFIN A AT PH 5.5 AND 308K, NMR, MINIMIZED AVERAGE STRUCTURE
1dvd	SOLUTION NMR STRUCTURE OF HUMAN STEFIN A AT PH 5.5 AND 308K, NMR, 17 STRUCTURES
1eqk	SOLUTION STRUCTURE OF ORYZACYSTATIN-I, A CYSTEINE PROTEINASE INHIBITOR OF THE RICE, ORYZA SATIVA L. JAPONICA
1g96	HUMAN CYSTATIN C; DIMERIC FORM WITH 3D DOMAIN SWAPPING
1gd3	refined solution structure of human cystatin A
1gd4	SOLUTION STRUCTURE OF P25S CYSTATIN A
1n9j	Solution Structure of the 3D domain swapped dimer of Stefin A
1nb3	Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo-and exopeptidases
1nb5	Crystal structure of stefin A in complex with cathepsin H
1r4c	N-Truncated Human Cystatin C; Dimeric Form With 3D Domain Swapping
1rn7	Structure of human cystatin D
1roa	Structure of human cystatin D
1stf	THE REFINED 2.4 ANGSTROMS X-RAY CRYSTAL STRUCTURE OF RECOMBINANT HUMAN STEFIN B IN COMPLEX WITH THE CYSTEINE PROTEINASE PAPAIN: A NOVEL TYPE OF PROTEINASE INHIBITOR INTERACTION
1tij	3D Domain-swapped human cystatin C with amyloid-like intermolecular beta-sheets
1yvb	the Plasmodium falciparum Cysteine Protease Falcipain-2
2ch9	Crystal structure of dimeric human cystatin F
2l4v	Three Dimensional Structure of Pineapple Cystatin
2mzv	2MZV
2oct	Stefin B (Cystatin B) tetramer
2w9p	Crystal Structure of Potato Multicystatin
2w9q	Crystal Structure of Potato Multicystatin-P212121
3gax	Crystal structure of monomeric human cystatin C stabilized against aggregation
3ima	Complex strcuture of tarocystatin and papain
3k9m	Cathepsin B in complex with stefin A
3kfq	Unreduced cathepsin V in complex with stefin A
3kse	Unreduced cathepsin L in complex with stefin A
3l0r	Crystal Structure of Salivary Cystatin from the Soft Tick Ornithodoros moubata
3lh4	Crystal Structure of Sialostatin L2
3mwz	Crystal structure of the selenomethionine derivative of the L 22,47,100 M mutant of sialostatin L2
3nx0	Hinge-loop mutation can be used to control 3D domain swapping and amyloidogenesis of human cystatin C
3ps8	Crystal structure of L68V mutant of human cystatin C
3qrd	Crystal structure of L68V mutant of human cystatin C
3s67	Crystal structure of V57P mutant of human cystatin C
3sva	Crystal structure of V57D mutant of human cystatin C
3ul5	Saccharum officinarum canecystatin-1 in space group C2221
3ul6	Saccharum officinarum canecystatin-1 in space group P6422
4ccv	Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: Implications for the regulation of angiogenesis
4it7	Crystal structure of Al-CPI
4lzi	Characterization of Solanum tuberosum Multicystatin and Significance of Core Domains
4n6l	4N6L
4n6m	4N6M
4n6n	4N6N
4n6o	4N6O
4n6t	Adhiron: a stable and versatile peptide display scaffold - full length adhiron
4n6u	Adhiron: a stable and versatile peptide display scaffold - truncated adhiron
4n6v	Partial rotational order disorder structure of human stefin B
4tx4	4TX4
4zm8	4ZM8
5a0o	5A0O
5elj	5ELJ
5elu	5ELU
5eql	5EQL

Links (links to other resources describing this domain)

• PROSITE: CY_DOMAIN
• INTERPRO: IPR000010
• PFAM: cystatin