SUPERFAMILY 1.75 HMM library and genome assignments server


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 (419) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 2,540 3,167 4
Proteins 1,971 2,404 4


Functional annotation
General category Processes_IC
Detailed category Proteases

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) protein metabolic process 0 Least Informative Direct
Biological Process (BP) developmental process 7.853e-11 Least Informative Direct
Biological Process (BP) cellular component organization or biogenesis 1.294e-10 Least Informative Direct
Biological Process (BP) regulation of cellular process 2.103e-07 Least Informative Direct
Biological Process (BP) single-organism cellular process 1.813e-06 Least Informative Direct
Biological Process (BP) response to stimulus 6.958e-06 Least Informative Direct
Biological Process (BP) localization 0.7854 Least Informative Inherited
Biological Process (BP) cellular macromolecule metabolic process 1 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.2146 Least Informative Inherited
Biological Process (BP) cell differentiation 0 Moderately Informative Direct
Biological Process (BP) positive regulation of molecular function 0 Moderately Informative Direct
Biological Process (BP) regulation of protein metabolic process 2.974e-11 Moderately Informative Direct
Biological Process (BP) negative regulation of metabolic process 5.037e-11 Moderately Informative Direct
Biological Process (BP) regulation of catalytic activity 5.449e-11 Moderately Informative Direct
Biological Process (BP) organelle organization 1.064e-10 Moderately Informative Direct
Biological Process (BP) regulation of developmental process 7.882e-10 Moderately Informative Direct
Biological Process (BP) regulation of multicellular organismal process 8.757e-09 Moderately Informative Direct
Biological Process (BP) regulation of biosynthetic process 1.146e-08 Moderately Informative Direct
Biological Process (BP) cellular component biogenesis 1.255e-08 Moderately Informative Direct
Biological Process (BP) single-organism developmental process 6.618e-07 Moderately Informative Direct
Biological Process (BP) positive regulation of metabolic process 1.245e-06 Moderately Informative Direct
Biological Process (BP) positive regulation of cellular process 2.137e-06 Moderately Informative Direct
Biological Process (BP) anatomical structure morphogenesis 4.249e-06 Moderately Informative Direct
Biological Process (BP) cellular response to chemical stimulus 1.157e-05 Moderately Informative Direct
Biological Process (BP) macromolecular complex subunit organization 1.349e-05 Moderately Informative Direct
Biological Process (BP) regulation of signal transduction 5.851e-05 Moderately Informative Direct
Biological Process (BP) response to endogenous stimulus 0.04653 Moderately Informative Inherited
Biological Process (BP) cellular response to stress 0.2026 Moderately Informative Inherited
Biological Process (BP) response to oxygen-containing compound 0.04492 Moderately Informative Inherited
Biological Process (BP) macromolecule localization 0.00574 Moderately Informative Inherited
Biological Process (BP) cellular localization 0.6595 Moderately Informative Inherited
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 0.00107 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 0.009347 Moderately Informative Inherited
Biological Process (BP) regulation of localization 0.02364 Moderately Informative Inherited
Biological Process (BP) cellular catabolic process 0.03372 Moderately Informative Inherited
Biological Process (BP) organic substance catabolic process 1 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.006283 Moderately Informative Inherited
Biological Process (BP) gene expression 1 Moderately Informative Inherited
Biological Process (BP) response to organic substance 0.6513 Moderately Informative Inherited
Biological Process (BP) response to abiotic stimulus 0.08558 Moderately Informative Inherited
Biological Process (BP) organelle assembly 0 Informative Direct
Biological Process (BP) proteolysis 0 Informative Direct
Biological Process (BP) muscle structure development 0 Informative Direct
Biological Process (BP) protein complex assembly 0 Informative Direct
Biological Process (BP) actin filament-based process 0 Informative Direct
Biological Process (BP) regulation of apoptotic process 0 Informative Direct
Biological Process (BP) negative regulation of protein metabolic process 0 Informative Direct
Biological Process (BP) anatomical structure formation involved in morphogenesis 0 Informative Direct
Biological Process (BP) regulation of growth 0 Informative Direct
Biological Process (BP) regulation of response to external stimulus 0 Informative Direct
Biological Process (BP) cytoskeleton organization 0 Informative Direct
Biological Process (BP) negative regulation of cell death 4.724e-14 Informative Direct
Biological Process (BP) cellular component morphogenesis 1.136e-13 Informative Direct
Biological Process (BP) regulation of response to stress 2.467e-11 Informative Direct
Biological Process (BP) positive regulation of developmental process 3.554e-11 Informative Direct
Biological Process (BP) regulation of intracellular transport 7.464e-11 Informative Direct
Biological Process (BP) positive regulation of nitrogen compound metabolic process 9.054e-11 Informative Direct
Biological Process (BP) negative regulation of nitrogen compound metabolic process 2.364e-10 Informative Direct
Biological Process (BP) regulation of intracellular protein kinase cascade 2.86e-10 Informative Direct
Biological Process (BP) positive regulation of cellular biosynthetic process 1.584e-09 Informative Direct
Biological Process (BP) regulation of anatomical structure morphogenesis 1.869e-09 Informative Direct
Biological Process (BP) positive regulation of gene expression 4.094e-09 Informative Direct
Biological Process (BP) negative regulation of biosynthetic process 4.71e-09 Informative Direct
Biological Process (BP) positive regulation of macromolecule biosynthetic process 1.156e-08 Informative Direct
Biological Process (BP) response to organonitrogen compound 2.028e-06 Informative Direct
Biological Process (BP) cellular response to endogenous stimulus 2.101e-06 Informative Direct
Biological Process (BP) cellular response to nitrogen compound 0.0001186 Informative Direct
Biological Process (BP) regulation of ion transport 0.0004694 Informative Direct
Biological Process (BP) positive regulation of transport 0.0004864 Informative Direct
Biological Process (BP) cellular membrane organization 0.0005945 Informative Direct
Biological Process (BP) response to inorganic substance 0.00577 Informative Inherited
Biological Process (BP) cellular response to oxygen-containing compound 0.01569 Informative Inherited
Biological Process (BP) regulation of proteolysis 0 Highly Informative Direct
Biological Process (BP) positive regulation of growth 0 Highly Informative Direct
Biological Process (BP) regulation of wound healing 0 Highly Informative Direct
Biological Process (BP) positive regulation of cell activation 0 Highly Informative Direct
Biological Process (BP) positive regulation of sequence-specific DNA binding transcription factor activity 0 Highly Informative Direct
Biological Process (BP) regulation of developmental growth 0 Highly Informative Direct
Biological Process (BP) actomyosin structure organization 0 Highly Informative Direct
Biological Process (BP) cellular component assembly involved in morphogenesis 0 Highly Informative Direct
Biological Process (BP) negative regulation of protein modification process 0 Highly Informative Direct
Biological Process (BP) positive regulation of intracellular transport 1.422e-14 Highly Informative Direct
Biological Process (BP) response to calcium ion 2.766e-13 Highly Informative Direct
Biological Process (BP) regulation of calcium ion transport 1.316e-11 Highly Informative Direct
Biological Process (BP) cellular response to metal ion 2.527e-11 Highly Informative Direct
Biological Process (BP) negative regulation of transcription, DNA-dependent 7.871e-11 Highly Informative Direct
Biological Process (BP) regulation of ion homeostasis 9.225e-11 Highly Informative Direct
Biological Process (BP) response to acid 9.616e-10 Highly Informative Direct
Biological Process (BP) positive regulation of homeostatic process 1.435e-09 Highly Informative Direct
Biological Process (BP) response to salt stress 3.552e-09 Highly Informative Direct
Biological Process (BP) protein processing 4.335e-07 Highly Informative Direct
Biological Process (BP) positive regulation of transcription, DNA-dependent 1.194e-06 Highly Informative Direct
Biological Process (BP) positive regulation of ion transport 1.946e-06 Highly Informative Direct
Biological Process (BP) negative regulation of apoptotic process 2.366e-05 Highly Informative Direct
Molecular Function (MF) hydrolase activity 0 Least Informative Direct
Molecular Function (MF) binding 9.929e-07 Least Informative Direct
Molecular Function (MF) cation binding 0 Moderately Informative Direct
Molecular Function (MF) enzyme regulator activity 0 Moderately Informative Direct
Molecular Function (MF) structural molecule activity 0 Moderately Informative Direct
Molecular Function (MF) cytoskeletal protein binding 0 Informative Direct
Molecular Function (MF) peptidase activity 0 Informative Direct
Molecular Function (MF) calcium ion binding 0 Highly Informative Direct
Molecular Function (MF) endopeptidase activity 1.489e-09 Highly Informative Direct
Cellular Component (CC) intracellular non-membrane-bounded organelle 1.842e-13 Least Informative Direct
Cellular Component (CC) membrane 3.79e-09 Least Informative Direct
Cellular Component (CC) protein complex 5.356e-08 Least Informative Direct
Cellular Component (CC) cytoplasmic part 0.05373 Least Informative Inherited
Cellular Component (CC) intracellular membrane-bounded organelle 0.6398 Least Informative Inherited
Cellular Component (CC) cytosol 3.126e-09 Moderately Informative Direct
Cellular Component (CC) plasma membrane 9.172e-09 Moderately Informative Direct
Cellular Component (CC) cell projection 0.1069 Moderately Informative Inherited
Cellular Component (CC) contractile fiber part 0 Informative Direct
Cellular Component (CC) neuron projection 0.008648 Informative Inherited
Cellular Component (CC) sarcomere 0 Highly Informative Direct
Cellular Component (CC) sarcolemma 0 Highly Informative Direct
Cellular Component (CC) dendrite 7.201e-07 Highly Informative Direct

Document: GO annotation of SCOP domains

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)nervous system disease0.2702Least InformativeInherited
Disease Ontology (DO)disease of metabolism0Moderately InformativeDirect
Disease Ontology (DO)neuromuscular disease2.243e-05InformativeDirect
Disease Ontology (DO)overnutrition0.0003843InformativeDirect

Document: DO annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)growth variant0Least InformativeDirect
Worm Phenotype (WP)developmental timing variant0Least InformativeDirect
Worm Phenotype (WP)larval development variant0Least InformativeDirect
Worm Phenotype (WP)cell physiology variant0.001274Least InformativeInherited
Worm Phenotype (WP)larval lethal0Moderately InformativeDirect
Worm Phenotype (WP)sterile progeny0Moderately InformativeDirect
Worm Phenotype (WP)cell death variant1.066e-06Moderately InformativeDirect

Document: WP annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)head0Least InformativeDirect

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 (peptide hydrolases)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 componentCytoplasm3.946e-05Least InformativeDirect
Cellular componentMembrane0.001643Least InformativeInherited
Cellular componentCell membrane1.146e-06Moderately InformativeDirect
DomainRepeat0Least InformativeDirect
Molecular functionMetal-binding4.37e-11Least 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 · Gene Ontology (high-coverage) · 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 · Gene Ontology (high-coverage) · Enzyme Commission (EC) · Disease Ontology (DO) · Worm Phenotype (WP) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · UniProtKB KeyWords (KW) · Internal database links ]