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101  structures 319  species 3  interactions 2145  sequences 30  architectures

Family: Cystatin (PF00031)

Summary: Cystatin domain

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Cystatin Edit Wikipedia article

Proteinase inhibitor I25, cystatin
Salivary Cystatin from Ornithodoros moubata.png
Crystal structure of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata from PDB entry 3L0R.[1]
Identifiers
Symbol Prot_inh_cystat
Pfam PF00031
Pfam clan CL0121
InterPro IPR000010
SMART SM00043
PROSITE PDOC00259

The cystatins are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below.

Cystatins show similarity to fetuins, kininogens, histidine-rich glycoproteins and cystatin-related proteins.[2][3][4] Cystatins mainly inhibit peptidase enzymes (another term for proteases) belonging to peptidase families C1 (papain family) and C13 (legumain family). They are known to mis-fold to form amyloid deposits and are implicated in several diseases.[citation needed]

Types

The cystatin family includes:

  • The Type 1 cystatins, which are intracellular and 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 disulfide bonds nor carbohydrate side-chains. Type 1 cystatins are also known as Stefins (after the Stefan Institute where they were first discovered [5])
  • The Type 2 cystatins, which are mainly extracellular secreted polypeptides are largely acidic, contain four conserved cysteine residues known to form two disulfide bonds, may be glycosylated and/or phosphorylated. They are synthesised with a 19- to 28-residue signal peptide. They are broadly distributed and found in most body fluids.[citation needed]
  • 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, InterPro: IPR002395) and L- (low-molecular-mass) kininogen, which are found in a number of species, and T-kininogen, which is found only in rats.[citation needed]
  • 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 cystatin-like proteins have been shown to be devoid of inhibitory activity.[citation needed]

Human cystatins

Plant cystatins

Plant cystatins have special characteristics which permit them to be classified in a special class called Phytocystatin. One is the presence of a N-terminal alpha-helix, present only in plant cystatins. Phytocystatins are involved in several process, including plant germination and defense. van Wyk et al. found some 19 different cystatins similar to oryzacystatin-I in the soybean along with related cysteine proteases.[6]

Membrane permeability

Chicken cystatin quickly passed the membrane of MCF-10A neo T cells and inhibited cathepsin B when it was acylated with fatty acyl residues of 6-18 carbon atoms.[7][relevant? ]

See also

  • Affimer, a type of engineered protein that is based on the cystatin scaffold

References

  1. ^ Salát J, Paesen GC, Rezácová P, Kotsyfakis M, Kovárová Z, Sanda M, Majtán J, Grunclová L, Horká H, Andersen JF, Brynda J, Horn M, Nunn MA, Kopácek P, Kopecký J, Mares M (July 2010). "Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata". The Biochemical Journal. 429 (1): 103–12. PMC 3523712Freely accessible. PMID 20545626. doi:10.1042/BJ20100280. ; rendered with PyMOL
  2. ^ Rawlings ND, Barrett AJ (January 1990). "Evolution of proteins of the cystatin superfamily". Journal of Molecular Evolution. 30 (1): 60–71. PMID 2107324. doi:10.1007/BF02102453. 
  3. ^ Abrahamson M, Alvarez-Fernandez M, Nathanson CM (2003). "Cystatins". Biochemical Society Symposium. 70 (70): 179–99. PMID 14587292. doi:10.1042/bss0700179. 
  4. ^ Turk V, Bode W (July 1991). "The cystatins: protein inhibitors of cysteine proteinases". FEBS Letters. 285 (2): 213–9. PMID 1855589. doi:10.1016/0014-5793(91)80804-C. 
  5. ^ Machleidt W, Borchart U, Fritz H, Brzin J, Ritonja A, Turk V (November 1983). "Protein inhibitors of cysteine proteinases. II. Primary structure of stefin, a cytosolic protein inhibitor of cysteine proteinases from human polymorphonuclear granulocytes". Hoppe-Seyler's Zeitschrift Fur Physiologische Chemie. 364 (11): 1481–6. PMID 6689312. doi:10.1515/bchm2.1983.364.2.1481. 
  6. ^ van Wyk SG, Du Plessis M, Cullis CA, Kunert KJ, Vorster BJ (November 2014). "cysteine protease and cystatin expression and activity during soybean nodule development and senescence". BMC Plant Biology. 14: 294. PMC 4243279Freely accessible. PMID 25404209. doi:10.1186/s12870-014-0294-3. 
  7. ^ Kocevar N, Obermajer N, Kreft S (September 2008). "Membrane permeability of acylated cystatin depends on the fatty acyl chain length". Chemical Biology & Drug Design. 72 (3): 217–24. PMID 18702630. doi:10.1111/j.1747-0285.2008.00693.x. 

Further reading

  • Lee C, Bongcam-Rudloff E, Sollner C, Jahnen-Dechent W, Claesson-Welsh L (January 2009). "Type 3 cystatins; fetuins, kininogen and histidine-rich glycoprotein". Frontiers in Bioscience. 14 (14): 2911–22. PMID 19273244. doi:10.2741/3422. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR000010


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.

Cystatin domain Provide feedback

Very diverse family. Attempts to define separate sub-families failed. Typically, either the N-terminal or C-terminal end is very divergent. But splitting into two domains would make very short families. All members except Q03196 and Q10993 are found. PF00666 are related to this family but have not been included.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry 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.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Cystatin (CL0121), which has the following description:

This superfamily includes cystatins and cathelicidins [1]. The cystatin superfamily comprises cysteine protease inhibitors that play key regulatory roles in protein degradation processes. The progenitor of this superfamily was most probably intracellular and lacked a signal peptide and disulfide bridges, much like the extant Giardia cystatin. A primordial gene duplication produced two ancestral eukaryotic lineages, cystatins and stefins. Stefins - included in Pfam:PF00031 - remain encoded by a single or a small number of genes throughout the eukaryotes, whereas the cystatins have undergone a more complex and dynamic evolution through numerous gene and domain duplications [2].

The clan contains the following 12 members:

Cathelicidins Cystatin DUF3889 FTP Latexin Monellin PP1 Spp-24 SQAPI Staphopain_pro YebF YPEB

Alignments

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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.

  Seed
(35)
Full
(2145)
Representative proteomes UniProt
(3874)
NCBI
(8477)
Meta
(4)
RP15
(510)
RP35
(878)
RP55
(1527)
RP75
(1994)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(35)
Full
(2145)
Representative proteomes UniProt
(3874)
NCBI
(8477)
Meta
(4)
RP15
(510)
RP35
(878)
RP55
(1527)
RP75
(1994)
Alignment:
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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.

  Seed
(35)
Full
(2145)
Representative proteomes UniProt
(3874)
NCBI
(8477)
Meta
(4)
RP15
(510)
RP35
(878)
RP55
(1527)
RP75
(1994)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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Trees

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.

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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: Prosite
Previous IDs: cystatin;
Type: Domain
Author: Bateman A, Sonnhammer ELL
Number in seed: 35
Number in full: 2145
Average length of the domain: 89.70 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 48.59 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.2 22.2
Trusted cut-off 22.2 22.2
Noise cut-off 22.1 22.1
Model length: 92
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Interactions

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

Cystatin Peptidase_C1 Peptidase_C1

Structures

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 Cystatin domain has been found. There are 101 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 sequence.

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