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Calpain large subunit, middle domain (domain III) superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All beta proteins [ 48724] (174)
Fold:   Calpain large subunit, middle domain (domain III) [ 49757]
Superfamily:   Calpain large subunit, middle domain (domain III) [ 49758]
Families:   Calpain large subunit, middle domain (domain III) [ 49759]


Superfamily statistics
Genomes (437) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 2,711 0 4
Proteins 2,124 0 4


Functional annotation
General category Processes_IC
Detailed category Proteases

Document:
Function annotation of SCOP domain superfamilies

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Acting on peptide bonds (peptide hydrolases)0Least InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0Moderately InformativeDirect

Document: EC annotation of SCOP domains

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)disease of metabolism0Moderately InformativeDirect
Disease Ontology (DO)muscle tissue disease0.0001424InformativeDirect
Disease Ontology (DO)overnutrition0.0003995InformativeDirect

Document: DO annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)cell physiology variant0.0008653Least InformativeDirect
Worm Phenotype (WP)cell morphology variant0.001644Least InformativeInherited
Worm Phenotype (WP)organ system morphology variant0.002271Least InformativeInherited
Worm Phenotype (WP)organism metabolism processing variant0.007479Least InformativeInherited
Worm Phenotype (WP)metabolic pathway variant0.00001126Moderately InformativeDirect
Worm Phenotype (WP)cell component morphology variant0.0002419Moderately InformativeDirect
Worm Phenotype (WP)cell homeostasis metabolism variant0.01081Moderately InformativeInherited
Worm Phenotype (WP)protein degradation variant0.000000005008InformativeDirect
Worm Phenotype (WP)mitochondria morphology variant0.00000007549InformativeDirect
Worm Phenotype (WP)body wall muscle sarcomere morphology variant0.0000001905InformativeDirect

Document: WP annotation of SCOP domains

Xenopus Anatomy (XA)

(show details) Document: XA annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0Least InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Cysteine endopeptidases0InformativeDirect

Document: EC annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Cellular componentCytoplasm0.00004107Least InformativeDirect
Cellular componentMembrane0.002494Least InformativeInherited
Cellular componentCell membrane0.000002178Moderately InformativeDirect
DomainRepeat0Least InformativeDirect
Molecular functionMetal-binding0.0000000004034Least InformativeDirect
Molecular functionCalcium0Moderately InformativeDirect
Post-translational modificationHydrolase0Least InformativeDirect
Post-translational modificationProtease0Moderately InformativeDirect
Post-translational modificationThiol protease0InformativeDirect
Post-translational modificationAutocatalytic cleavage0InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR001300 SSF49758 Protein matches
Abstract

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 [PubMed2539381]. The protein is a complex of 2 polypeptide chains (light and heavy), with three known forms in mammals [PubMed7845226, PubMed2555341]: 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 [PubMed2555341].

All forms have identical light but different heavy chains. Both mu- and m-calpain are heterodimers containing an identical 28-kDa subunit and an 80-kDa subunit that shares 55-65% sequence homology between the two proteases [PubMed7845226, PubMed2539381]. The crystallographic structure of m-calpain reveals six "domains" in the 80-kDa 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 [PubMed7845226].

  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 [PubMed7845226]. />]. 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 [PubMed11914728].

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 . 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 [PubMed12843408].


InterPro database


PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Disease Ontology (DO) · Worm Phenotype (WP) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.


Alignments of sequences to 3 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.


Browse and view proteins in genomes which have different domain combinations including a Calpain large subunit, middle domain (domain III) domain.


Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.


Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 3 hidden Markov models representing the Calpain large subunit, middle domain (domain III) superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.


Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Disease Ontology (DO) · Worm Phenotype (WP) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]