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128  structures 575  species 0  interactions 5280  sequences 74  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
SymbolProt_inh_cystat
PfamPF00031
Pfam clanCL0121
InterProIPR000010
SMARTSM00043
PROSITEPDOC00259

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, InterProIPR002395) 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. doi:10.1042/BJ20100280. PMC 3523712. PMID 20545626.; 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. doi:10.1007/BF02102453. PMID 2107324.
  3. ^ Abrahamson M, Alvarez-Fernandez M, Nathanson CM (2003). "Cystatins". Biochemical Society Symposium. 70 (70): 179–99. doi:10.1042/bss0700179. PMID 14587292.
  4. ^ Turk V, Bode W (July 1991). "The cystatins: protein inhibitors of cysteine proteinases". FEBS Letters. 285 (2): 213–9. doi:10.1016/0014-5793(91)80804-C. PMID 1855589.
  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 für Physiologische Chemie. 364 (11): 1481–6. doi:10.1515/bchm2.1983.364.2.1481. PMID 6689312.
  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. doi:10.1186/s12870-014-0294-3. PMC 4243279. PMID 25404209.
  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. doi:10.1111/j.1747-0285.2008.00693.x. PMID 18702630.

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. doi:10.2741/3422. PMID 19273244.

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 and the UniProtKB 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
(34)
Full
(5280)
Representative proteomes UniProt
(9601)
RP15
(764)
RP35
(1884)
RP55
(4460)
RP75
(5972)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(34)
Full
(5280)
Representative proteomes UniProt
(9601)
RP15
(764)
RP35
(1884)
RP55
(4460)
RP75
(5972)
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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
(34)
Full
(5280)
Representative proteomes UniProt
(9601)
RP15
(764)
RP35
(1884)
RP55
(4460)
RP75
(5972)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

Note: You can also download the data file for the tree.

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
Sequence Ontology: SO:0000417
Author: Bateman A , Sonnhammer ELL
Number in seed: 34
Number in full: 5280
Average length of the domain: 89.90 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 45.44 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 23
Download: download the raw HMM for this family

Species distribution

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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 128 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2KNW8 View 3D Structure Click here
A0A2R8QAT4 View 3D Structure Click here
A0A2R8QDV2 View 3D Structure Click here
A5WWI5 View 3D Structure Click here
A7MCL7 View 3D Structure Click here
B2RV77 View 3D Structure Click here
B3DJF1 View 3D Structure Click here
B8A4D0 View 3D Structure Click here
B8A4D2 View 3D Structure Click here
D3ZC49 View 3D Structure Click here
D3ZCV2 View 3D Structure Click here
D3ZF44 View 3D Structure Click here
D3ZMP7 View 3D Structure Click here
D3ZMS9 View 3D Structure Click here
D3ZNB1 View 3D Structure Click here
D3ZP68 View 3D Structure Click here
D3ZVG0 View 3D Structure Click here
D3ZZA3 View 3D Structure Click here
D4AAU9 View 3D Structure Click here
E7EYW5 View 3D Structure Click here
E7FE90 View 3D Structure Click here
E7FF41 View 3D Structure Click here
F1M861 View 3D Structure Click here
F1QLQ5 View 3D Structure Click here
F1R4C2 View 3D Structure Click here
F1RE14 View 3D Structure Click here
G3V9M0 View 3D Structure Click here
G5ECM9 View 3D Structure Click here
G5EDZ9 View 3D Structure Click here
L7N257 View 3D Structure Click here
O08677 View 3D Structure Click here
O08677 View 3D Structure Click here
O08677 View 3D Structure Click here
O16454 View 3D Structure Click here
O60676 View 3D Structure Click here
O76096 View 3D Structure Click here
O88969 View 3D Structure Click here
O89098 View 3D Structure Click here
P01034 View 3D Structure Click here
P01036 View 3D Structure Click here
P01037 View 3D Structure Click here
P01039 View 3D Structure Click here
P01040 View 3D Structure Click here
P01041 View 3D Structure Click here
P01042 View 3D Structure Click here
P01042 View 3D Structure Click here
P01042 View 3D Structure Click here
P01048 View 3D Structure Click here
P01048 View 3D Structure Click here
P01048 View 3D Structure Click here
P02765 View 3D Structure Click here
P04080 View 3D Structure Click here
P04196 View 3D Structure Click here
P08932 View 3D Structure Click here
P08932 View 3D Structure Click here
P08932 View 3D Structure Click here
P08934 View 3D Structure Click here
P08934 View 3D Structure Click here
P08934 View 3D Structure Click here
P09228 View 3D Structure Click here
P09229 View 3D Structure Click here
P14841 View 3D Structure Click here
P19313 View 3D Structure Click here
P21460 View 3D Structure Click here
P23779 View 3D Structure Click here
P24090 View 3D Structure Click here
P25973 View 3D Structure Click here
P28325 View 3D Structure Click here
P29699 View 3D Structure Click here
P31726 View 3D Structure Click here
P32766 View 3D Structure Click here
P35173 View 3D Structure Click here
P35174 View 3D Structure Click here
P35175 View 3D Structure Click here
P56567 View 3D Structure Click here
Q15828 View 3D Structure Click here
Q1LUV0 View 3D Structure Click here
Q1LYJ7 View 3D Structure Click here
Q1LYJ7 View 3D Structure Click here
Q497J0 View 3D Structure Click here
Q58FY9 View 3D Structure Click here
Q58G57 View 3D Structure Click here
Q5R1U3 View 3D Structure Click here
Q5W188 View 3D Structure Click here
Q62426 View 3D Structure Click here
Q65YR7 View 3D Structure Click here
Q65YR8 View 3D Structure Click here
Q6IE17 View 3D Structure Click here
Q6IE18 View 3D Structure Click here
Q6IE28 View 3D Structure Click here
Q6S9I3 View 3D Structure Click here
Q6S9I3 View 3D Structure Click here
Q6S9I3 View 3D Structure Click here
Q7TP75 View 3D Structure Click here
Q80Y72 View 3D Structure Click here
Q80ZN5 View 3D Structure Click here
Q8BWM3 View 3D Structure Click here
Q8K5A3 View 3D Structure Click here
Q8LC76 View 3D Structure Click here
Q8SZN1 View 3D Structure Click here
Q8VHC1 View 3D Structure Click here
Q8VIH8 View 3D Structure Click here
Q8VII2 View 3D Structure Click here
Q8VII3 View 3D Structure Click here
Q9D1B1 View 3D Structure Click here
Q9D264 View 3D Structure Click here
Q9D269 View 3D Structure Click here
Q9D8D6 View 3D Structure Click here
Q9DAN8 View 3D Structure Click here
Q9FF70 View 3D Structure Click here
Q9H112 View 3D Structure Click here
Q9H114 View 3D Structure Click here
Q9H4G1 View 3D Structure Click here
Q9JM84 View 3D Structure Click here
Q9QX79 View 3D Structure Click here
Q9QX79 View 3D Structure Click here
Q9QXC1 View 3D Structure Click here
Q9QXC1 View 3D Structure Click here
Q9UGM5 View 3D Structure Click here
Q9UGM5 View 3D Structure Click here
Q9VFI3 View 3D Structure Click here
Q9W370 View 3D Structure Click here
Q9Z0H6 View 3D Structure Click here