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30  structures 332  species 2  interactions 2514  sequences 97  architectures

Family: Peptidase_C2 (PF00648)

Summary: Calpain family cysteine protease

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Calpain". More...

Calpain Edit Wikipedia article

Calpain
PDB 1mdw EBI.jpg
Crystal structure of the peptidase core of Calpain II.
Identifiers
Symbol Calpain
Pfam PF00648
Pfam clan CL0125
InterPro IPR001300
SMART CysPc
PROSITE PDOC50203
MEROPS C2
SCOP 1mdw
SUPERFAMILY 1mdw
calpain-1
Identifiers
EC number 3.4.22.52
CAS number 689772-75-6
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
calpain-2
Identifiers
EC number 3.4.22.53
CAS number 702693-80-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

A calpain (pronounced /ˈkælpeɪn/;[1] EC 3.4.22.52, EC 3.4.22.53) is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases (proteolytic enzymes) expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small regulatory subunit CAPNS1, also known as CAPN4, and the endogenous calpain-specific inhibitor, calpastatin.

Contents

[edit] Discovery

The history of calpain originates in 1964, when calcium-dependent proteolytic activities caused by a “calcium-activated neutral protease” (CANP) were detected in brain, lens of the eye and other tissues. In the late 1960s the enzymes were isolated and characterised independently in both rat brain and skeletal muscle. These activities were caused by an intracellular cysteine protease not associated with the lysosome and having an optimum activity at neutral pH, which clearly distinguished it from the cathepsin family of proteases. The calcium-dependent activity, intracellular localization, along with the limited, specific proteolysis on its substrates, highlighted calpain’s role as a regulatory, rather than a digestive protease. When the sequence of this enzyme became known,[2] it was given the name “calpain”, to recognize it as a hybrid of two well-known proteins at the time, the calcium-regulated signalling protein, calmodulin, and the cysteine protease of papaya, papain. Shortly thereafter, the activity was found to be attributable to two main isoforms, dubbed μ("mu")-calpain and m-calpain (a.k.a. calpain I and II), that differed primarily in their calcium requirements in vitro. Their names reflect the fact that they are activated by micro- and nearly millimolar concentrations of Ca2+ within the cell, respectively.[3]

To date, these two isoforms remain the best characterised members of the calpain family. Structurally, these two heterodimeric isoforms share an identical small (28k) subunit (CAPNS1 (formerly CAPN4)), but have distinct large (80k) subunits, known as calpain 1 and calpain 2 (each encoded by the CAPN1 and CAPN2 genes, respectively).

[edit] Cleavage specificity

No specific amino acid sequence is uniquely recognized by calpains. Amongst protein substrates, tertiary structure elements rather than primary amino acid sequences are likely responsible for directing cleavage to a specific substrate. Amongst peptide and small-molecule substrates, the most consistently reported specificity is for small, hydrophobic amino acids (e.g. leucine, valine and isoleucine) at the P2 position, and large hydrophobic amino acids (e.g. phenylalanine and tyrosine) at the P1 position.[4] Arguably, the best currently available fluorogenic calpain substrate is (EDANS)-Glu-Pro-Leu-Phe=Ala-Glu-Arg-Lys-(DABCYL), with cleavage occurring at the Phe=Ala bond.

[edit] Extended family

The Human Genome Project has revealed that there are more than a dozen other calpain isoforms, some with multiple splice variants.[5][6][7] As the first calpain whose three-dimensional structure was determined, m-calpain is the type-protease for the C2 (calpain) family in the MEROPS database.

Gene Protein Aliases Tissue expression Disease linkage
CAPN1 Calpain 1 Calpain-1 large subunit, Calpain mu-type Central Nervous System
CAPN2 Calpain 2 Calpain-2 large subunit Central Nervous System
CAPN3 Calpain 3 skeletal muscle retina and lens specific Limb Girdle muscular dystrophy 2A
CAPN5 Calpain 5 ubiquitous (high in colon, small intestine and testis) might be linked to necrosis,
as it is an ortholog of the C. elegans necrosis gene tra-3
CAPN6 Calpain 6 CAPNX, Calpamodulin
CAPN7 Calpain 7 palBH ubiquitous
CAPN8 Calpain 8 exclusive to stomach mucosa and the GI track might be linked to colon polyp formation
CAPN9 Calpain 9 exclusive to stomach mucosa and the GI track might be linked to colon polyp formation
CAPN10 Calpain 10 susceptibility gene for type II diabetes
CAPN11 Calpain 11 testis
CAPN12 Calpain 12 ubiquitous but high in hair follicle
CAPN13 Calpain 13 testis and lung
CAPN14 Calpain 14 ubiquitous
SOLH Calpain 15 Sol H (homolog of the drosophila gene sol)
CAPNS1 Calpain small subunit 1 Calpain 4
CAPNS2 Calpain small subunit 2

[edit] Function

Although the physiological role of calpains is still poorly understood, they have been shown to be active participants in processes such as cell mobility and cell cycle progression, as well as cell-type specific functions such as long-term potentiation in neurons and cell fusion in myoblasts. Under these physiological conditions, a transient and localized influx of calcium into the cell activates a small local population of calpains (for example, those close to Ca2+ channels), which then advance the signal transduction pathway by catalyzing the controlled proteolysis of its target proteins. Other reported roles of calpains are in cell function, helping to regulate clotting and the diameter of blood vessels, and playing a role in memory. Calpains have been implicated in apoptotic cell death, and appear to be an essential component of necrosis.

In the brain, while μ-calpain is mainly located in the cell body and dendrites of neurons and to a lesser extent in axons and glial cells, m-calpain is found in glia and a small amount in axons.[8] Calpain is also involved in skeletal muscle protein breakdown due to exercise and altered nutritional states.[9]

[edit] Clinical significance

[edit] Pathology

The structural and functional diversity of calpains in the cell is reflected in their involvement in the pathogenesis of a wide range of disorders. At least two well known genetic disorders and one form of cancer have been linked to tissue-specific calpains. When defective, the mammalian calpain 3 (also known as p94) is the gene product responsible for limb-girdle muscular dystrophy type 2A,[10][11] calpain 10 has been identified as a susceptibility gene for type II diabetes mellitus, and calpain 9 has been identified as a tumour suppressor for gastric cancer. Moreover, the hyperactivation of calpains is implicated in a number of pathologies associated with altered calcium homeostasis such as Alzheimer’s disease, and cataract formation, as well as secondary degeneration resulting from acute cellular stress following myocardial ischemia, cerebral (neuronal) ischemia, traumatic brain injury and spinal cord injury. Excessive amounts of calpain can be activated due to Ca2+ influx after cerebrovascular accident (during the ischemic cascade) or some types of traumatic brain injury such as diffuse axonal injury. Increase in concentration of calcium in the cell results in calpain activation, which leads to unregulated proteolysis of both target and non-target proteins and consequent irreversible tissue damage. Excessively active calpain breaks down molecules in the cytoskeleton such as spectrin, microtubule subunits, microtubule-associated proteins, and neurofilaments.[12][13] It may also damage ion channels, other enzymes, cell adhesion molecules, and cell surface receptors.[8] This can lead to degradation of the cytoskeleton and plasma membrane. Calpain may also break down sodium channels that have been damaged due to axonal stretch injury,[14] leading to an influx of sodium into the cell. This, in turn, leads to the neuron's depolarization and the influx of more Ca2+. A significant consequence of calpain activation is the development of cardiac contractile dysfunction that follows ischemic insult to the heart. Upon reperfusion of the ischemic myocardium, there is development of calcium overload or excess in the heart cell (cardiomyocytes). This increase in calcium leads to activation of calpain.[15]

[edit] Therapeutic inhibitors

The exogenous regulation of calpain activity is therefore of interest for the development of therapeutics in a wide array of pathological states. As a few of the many examples supporting the therapeutic potential of calpain inhibition in ischemia, calpain inhibitor AK275 protected against focal ischemic brain damage in rats when administered after ischemia, and MDL28170 significantly reduced the size of damaged infarct tissue in a rat focal ischemia model. There are also known calpain inhibitors with neuroprotective effects: PD150606,[16] SJA6017,[17] ABT-705253,[18][19] and SNJ-1945.[20]

Calpain may be released in the brain for up to a month after a head injury, and may be responsible for a shrinkage of the brain sometimes found after such injuries.[21] However, calpain may also be involved in a "resculpting" process that helps repair damage after injury.[21]

[edit] See also

[edit] References

  1. ^ http://dictionary.reference.com/browse/calpain?r=75&src=ref&ch=dic
  2. ^ Ohno S, Emori Y, Imajoh S, Kawasaki H, Kisaragi M, Suzuki K (1984). "Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein?". Nature 312 (5994): 566–70. doi:10.1038/312566a0. PMID 6095110.
  3. ^ Glass JD, Culver DG, Levey AI, Nash NR (April 2002). "Very early activation of m-calpain in peripheral nerve during Wallerian degeneration". J. Neurol. Sci. 196 (1-2): 9–20. doi:10.1016/S0022-510X(02)00013-8. PMID 11959150.
  4. ^ Cuerrier D, Moldoveanu T, Davies PL (December 2005). "Determination of peptide substrate specificity for mu-calpain by a peptide library-based approach: the importance of primed side interactions". J. Biol. Chem. 280 (49): 40632–41. doi:10.1074/jbc.M506870200. PMID 16216885.
  5. ^ Thompson V (2002-02-12). "Calpain Nomenclature". College of Agriculture and Life Sciences at the University of Arizona. http://ag.arizona.edu/calpains/nomenclature.html. Retrieved 2010-08-06.
  6. ^ Huang Y, Wang KK (August 2001). "The calpain family and human disease". Trends Mol Med 7 (8): 355–62. doi:10.1016/S1471-4914(01)02049-4. PMID 11516996.
  7. ^ Suzuki K, Hata S, Kawabata Y, Sorimachi H (February 2004). "Structure, activation, and biology of calpain". Diabetes. 53 Suppl 1: S12–8. PMID 14749260.
  8. ^ a b Lenzlinger PM, Saatman KE, Raghupathi R, Mcintosh TK (2000). "Chapter 1: Overview of basic mechanisms underlying neuropathological consequences of head trauma". In Newcomb JK, Miller LS, Hayes RL. Head trauma: basic, preclinical, and clinical directions. New York: Wiley-Liss. ISBN 0-471-36015-5.
  9. ^ Belcastro AN, Albisser TA, Littlejohn B (October 1996). "Role of calcium-activated neutral protease (calpain) with diet and exercise". Can J Appl Physiol 21 (5): 328–46. PMID 8905185.
  10. ^ Richard I, Broux O, Allamand V, et al. (April 1995). "Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A". Cell 81 (1): 27–40. doi:10.1016/0092-8674(95)90368-2. PMID 7720071.
  11. ^ Ono Y, Shimada H, Sorimachi H, et al. (July 1998). "Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A". J. Biol. Chem. 273 (27): 17073–8. doi:10.1074/jbc.273.27.17073. PMID 9642272.
  12. ^ Liu J, Liu MC, Wang KK (April 2008). "Calpain in the CNS: from synaptic function to neurotoxicity". Sci Signal. 1 (14): re 1. doi:10.1126/stke.114re1. PMID 18398107.
  13. ^ Castillo MR, Babson JR (October 1998). "Ca2+-dependent mechanisms of cell injury in cultured cortical neurons". Neuroscience 86 (4): 1133–44. doi:10.1016/S0306-4522(98)00070-0. PMID 9697120.
  14. ^ Iwata A, Stys PK, Wolf JA, et al. (May 2004). "Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors". J. Neurosci. 24 (19): 4605–13. doi:10.1523/JNEUROSCI.0515-03.2004. PMID 15140932.
  15. ^ Wang KK, Larner SF, Robinson G, Hayes RL (December 2006). "Neuroprotection targets after traumatic brain injury". Curr. Opin. Neurol. 19 (6): 514–9. doi:10.1097/WCO.0b013e3280102b10. PMID 17102687.
  16. ^ Wang KK, Nath R, Posner A, Raser KJ, Buroker-Kilgore M, Hajimohammadreza I, Probert A W, Marcoux FW, Ye Q, Takano E, Hatanaka M, Maki M, Caner H, Collins JL, Fergus A, Lee KS, Lunney EA, Hays SJ, Yuen P (June 1996). "An alpha-mercaptoacrylic acid derivative is a selective nonpeptide cell-permeable calpain inhibitor and is neuroprotective". Proc. Natl. Acad. Sci. U.S.A. 93 (13): 6687–92. doi:10.1073/pnas.93.13.6687. PMC 39087. PMID 8692879. //www.ncbi.nlm.nih.gov/pmc/articles/PMC39087/.
  17. ^ Kupina NC, Nath R, Bernath EE, Inoue J, Mitsuyoshi A, Yuen PW, Wang KK, Hall ED (November 2001). "The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury". J. Neurotrauma 18 (11): 1229–40. doi:10.1089/089771501317095269. PMID 11721741.
  18. ^ Lubisch W, Beckenbach E, Bopp S, Hofmann HP, Kartal A, Kästel C, Lindner T, Metz-Garrecht M, Reeb J, Regner F, Vierling M, Möller A (June 2003). "Benzoylalanine-derived ketoamides carrying vinylbenzyl amino residues: discovery of potent water-soluble calpain inhibitors with oral bioavailability". J. Med. Chem. 46 (12): 2404–12. doi:10.1021/jm0210717. PMID 12773044.
  19. ^ Nimmrich V, Reymann KG, Strassburger M, Schöder UH, Gross G, Hahn A, Schoemaker H, Wicke K, Möller A (April 2010). "Inhibition of calpain prevents NMDA-induced cell death and beta-amyloid-induced synaptic dysfunction in hippocampal slice cultures". Br. J. Pharmacol. 159 (7): 1523–31. doi:10.1111/j.1476-5381.2010.00652.x. PMC 2850408. PMID 20233208. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2850408/.
  20. ^ Koumura A, Nonaka Y, Hyakkoku K, Oka T, Shimazawa M, Hozumi I, Inuzuka T, Hara H (November 2008). "A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice". Neuroscience 157 (2): 309–18. doi:10.1016/j.neuroscience.2008.09.007. PMID 18835333.
  21. ^ a b White V (1999-10-21). "– ‘Biochemical Storm’ Following Brain Trauma An Important Factor In Treatment, University of Florida Researcher Finds". University of Florida News. http://news.ufl.edu/1999/10/21/braintra/. Retrieved 2010-08-07.

[edit] Further reading

  • Liu J, Liu MC, Wang KK (2008). "Calpain in the CNS: from synaptic function to neurotoxicity". Sci Signal 1 (14): re1. doi:10.1126/stke.114re1. PMID 18398107.
  • Suzuki K, Hata S, Kawabata Y, Sorimachi H (February 2004). "Structure, activation, and biology of calpain". Diabetes. 53 Suppl 1: S12–8. PMID 14749260.
  • Yuen P-W, Wang KW (1999). Calpains : Pharmacology and Toxicology of a Cellular Protease. Boca Raton: CRC Press. ISBN 1-56032-713-8.

[edit] External links
Caspase
Fruit-derived
Calpain
Cathepsin
Other
Cell membrane
Other
Intracellular signaling
& calc. regulation
  • Calpain
Cytoskeleton remodeling proteins
Other
Calcium-binding
protein domains
Extracellular ligands
Calcium-binding proteins

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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.

Calpain family cysteine protease Provide feedback

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External database links

MEROPS: C2
PANDIT: PF00648
PROSITE: PDOC00126
PROSITE profile: PS50203
Pseudofam: PF00648
SCOP: 1dkv
SYSTERS: Peptidase_C2

This tab holds annotation information from the InterPro database.

InterPro entry IPR001300

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad [PUBMED:11517925].

This group of cysteine peptidases belong to the MEROPS peptidase family C2 (calpain family, clan CA). A type example is calpain, which is an intracellular protease involved in many important cellular functions that are regulated by calcium [PUBMED:2539381]. The protein is a complex of 2 polypeptide chains (light and heavy), with three known forms in mammals [PUBMED:7845226, PUBMED:2555341]: a highly calcium-sensitive (i.e., micro-molar range) form known as mu-calpain, mu-CANP or calpain I; a form sensitive to calcium in the milli-molar range, known as m-calpain, m-CANP or calpain II; and a third form, known as p94, which is found in skeletal muscle only [PUBMED:2555341].

All forms have identical light but different heavy chains. Both mu- and m-calpain are heterodimers containing an identical 28kDa subunit and an 80kDa subunit that shares 55-65% sequence homology between the two proteases [PUBMED:7845226, PUBMED:2539381]. The crystallographic structure of m-calpain reveals six "domains" in the 80kDa subunit:

  1. A 19-amino acid NH2-terminal sequence;
  2. Active site domain IIa;
  3. Active site domain IIb.

    Domain 2 shows low levels of sequence similarity to papain; although the catalytic His has not been located by biochemical means, it is likely that calpain and papain are related [PUBMED:7845226].

  4. Domain III;
  5. An 18-amino acid extended sequence linking domain III to domain IV;
  6. Domain IV, which resembles the penta EF-hand family of polypeptides, binds calcium and regulates activity [PUBMED:7845226]. />]. Ca2+-binding causes a rearrangement of the protein backbone, the net effect of which is that a Trp side chain, which acts as a wedge between catalytic domains IIa and IIb in the apo state, moves away from the active site cleft allowing for the proper formation of the catalytic triad [PUBMED:11914728].

Calpain-like mRNAs have been identified in other organisms including bacteria, but the molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in these organisms cells is still unclear In metazoans, the activity of calpain is controlled by a single proteinase inhibitor, calpastatin (INTERPRO). The calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. The calpains ostensibly participate in a variety of cellular processes including remodelling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma [PUBMED:12843408].

Calpains are a family of cytosolic cysteine proteinases (see PROSITEDOC). Members of the calpain family are believed to function in various biological processes, including integrin-mediated cell migration, cytoskeletal remodeling, cell differentiation and apoptosis [PUBMED:11854009, PUBMED:11950589].

The calpain family includes numerous members from C. elegans to mammals and with homologues in yeast and bacteria. The best characterised members are the m- and mu-calpains, both proteins are heterodimer composed of a large catalytic subunit and a small regulatory subunit. The large subunit comprises four domains (dI-dIV) while the small subunit has two domains (dV-dVI). Domain dI is a short region cleaved by autolysis, dII is the catalytic core, dIII is a C2-like domain, dIV consists of five calcium binding EF-hand motifs [PUBMED:11950589].

The crystal structure of calpain has been solved [PUBMED:10601010, PUBMED:11893336]. The catalytic region consists of two distinct structural domains (dIIa and dIIb). dIIa contains a central helix flanked on three faces by a cluster of alpha-helices and is entirely unrelated to the corresponding domain in the typical thiol proteinases. The fold of dIIb is similar to the corresponding domain in other cysteine proteinases and contains two three-stranded anti-parallel beta-sheets. The catalytic triad residues (C,H,N) are located in dIIa and dIIb. The activation of the domain is dependent on the binding of two calcium atoms in two non EF-hand calcium binding sites located in the catalytic core, one close to the Cys active site in dIIa and one at the end of dIIb. Calcium-binding induced conformational changes in the catalytic domain which align the active site [PUBMED:11893336][PUBMED:11914728].

The profile covers the whole catalytic domain.

Gene Ontology

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

Cellular component intracellular (GO:0005622)
Molecular function calcium-dependent cysteine-type endopeptidase activity (GO:0004198)
Biological process proteolysis (GO:0006508)

Domain organisation

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Alignments

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  Seed
(9)		 Full
(2514)		 Representative proteomes NCBI
(2331)		 Meta
(90)
RP15
(477)		 RP35
(681)		 RP55
(1105)		 RP75
(1434)
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  Seed
(9)		 Full
(2514)		 Representative proteomes NCBI
(2331)		 Meta
(90)
RP15
(477)		 RP35
(681)		 RP55
(1105)		 RP75
(1434)
Alignment:
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Sequence:
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  Seed
(9)		 Full
(2514)		 Representative proteomes NCBI
(2331)		 Meta
(90)
RP15
(477)		 RP35
(681)		 RP55
(1105)		 RP75
(1434)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

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Pfam alignments:

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: Cys_protease_2;
Type: Family
Author: Bateman A
Number in seed: 9
Number in full: 2514
Average length of the domain: 246.30 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 35.47 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.1 20.1
Trusted cut-off 20.3 20.3
Noise cut-off 20.0 20.0
Model length: 298
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Peptidase_C2 Calpain_III

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 Peptidase_C2 domain has been found. There are 30 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 seqence.

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