Calpain Family

Aliases: calpain 1, large subunit, Calpain mu-type, Micromolar-calpain, calpain, large polypeptide L1, Calcium-activated neutral proteinase 1, calcium-activated neutral proteinase, cell proliferation-inducing protein 30, CANP 1, CANP, CAPN1, CANP1, CANPL1, muCANP, muCL

Processes & Diseases

Processes involved: retraction

Pfam Domain Structure

From CAPN2 (human) - phosphorylation sites added via direct mapping

Members of the Calpain Family
1: CAPN1 » Human Mouse Rat Chicken Fly Worm
CMKB CAPN1 Capn1 Capn1 CAPN1 - -
Entrez Gene 823 12333 29153 396240 - -
Uniprot CAN1_HUMAN CAN1_MOUSE CAN1_RAT CANX_CHICK - -
OMIM 114220 - - - - -
Reagents - 1 available - - - -
Results 3 available - - - - -
2: CAPN2 » Human Mouse Rat Chicken Fly Worm
CMKB CAPN2 Capn2 Capn2 CAPN2 CalpB -
Entrez Gene 824 12334 29154 395963 39165 -
Uniprot CAN2_HUMAN CAN2_MOUSE CAN2_RAT CAN2_CHICK CANB_DROME -
OMIM 114230 - - - - -
Reagents - 1 available - - - -
Results 3 available - - - 2 available -
3: CAPN3 » Human Mouse Rat Chicken Fly Worm
CMKB CAPN3 Capn3 Capn3 CAPN3 - -
Entrez Gene 825 12335 29155 423233 - -
Uniprot CAN3_HUMAN CAN3_MOUSE CAN3_RAT CAN3_CHICK - -
OMIM 114240 - - - - -
Reagents - - - - - -
Results 2 available - - - - -
4: CAPN7 » Human Mouse Rat Chicken Fly Worm
CMKB CAPN7 Capn7 Capn7 CAPN7 - clp-2
Entrez Gene 23473 12339 306260 420683 - 175618
Uniprot CAN7_HUMAN CAN7_MOUSE - - - -
OMIM 606400 - - - - -
Reagents - - - - - -
Results 4 available - - - - -
5: CAPN8 » Human Mouse Rat Chicken Fly Worm
CMKB CAPN8 Capn8 Capn8 CAPN8 - clp-4
Entrez Gene 388743 170725 170808 428561 - 175326
Uniprot CAN8_HUMAN CAN8_MOUSE CAN8_RAT - - -
OMIM - - - - - -
Reagents - - - - - -
Results - - - - - -
6: CAPNS1 » Human Mouse Rat Chicken Fly Worm
CMKB CAPNS1 Capns1 Capns1 - - -
Entrez Gene 826 12336 29156 - - -
Uniprot CPNS1_HUMAN CPNS1_MOUSE CPNS1_RAT - - -
OMIM 114170 - - - - -
Reagents - 2 available - - - -
Results 3 available - - - - -
Family Summary

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. The muscle-specific member of the calpain large subunit family specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.

References
  1. Carragher NO, Walker SM, Scott Carragher LA, Harris F, Sawyer TK, Brunton VG, Ozanne BW, Frame MC. Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. Oncogene 2006; 25:5726-40 (PubMed)
  2. Chan KT, Bennin DA, Huttenlocher A. Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J. Biol. Chem. 2010; 285:11418-26 (Full Text)
  3. Fernández-Montalván A, Assfalg-Machleidt I, Pfeiler D, Fritz H, Jochum M, Machleidt W. Mu-calpain binds to lipid bilayers via the exposed hydrophobic surface of its Ca2+-activated conformation. Biol. Chem. 2006; 387:617-27 (PubMed)
  4. Franco SJ, Rodgers MA, Perrin BJ, Han J, Bennin DA, Critchley DR, Huttenlocher A. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat. Cell Biol. 2004; 6:977-83 (PubMed)
  5. Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol. Rev. 2003; 83:731-801 (PubMed)
  6. Huttenlocher A, Palecek SP, Lu Q, Zhang W, Mellgren RL, Lauffenburger DA, Ginsberg MH, Horwitz AF. Regulation of cell migration by the calcium-dependent protease calpain. J. Biol. Chem. 1997; 272:32719-22 (PubMed)
  7. Su LT, Agapito MA, Li M, Simonson WT, Huttenlocher A, Habas R, Yue L, Runnels LW. TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain. J. Biol. Chem. 2006; 281:11260-70 (PubMed)
  8. Wu M, Yu Z, Fan J, Caron A, Whiteway M, Shen SH. Functional dissection of human protease mu-calpain in cell migration using RNAi. FEBS Lett. 2006; 580:3246-56 (PubMed)
Consortium Results & Data
Results & Data
Ortholog Species Type Description Method Status Source Publications
CAPN2 none binding partner Calpain 2 Ectopic expression in HEK cells Proteins co-purifying with expressed FLAG-tagged calpain Horwitz
-
CAPN2 none phosphorylation site Calpain 2 Ectopic expression in HEK cells 4 phospho-sites in 88.1% coverage of 708 aa Parsons
-
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
CAPN3
Aliases: p94, CANP3, LGMD2, nCL-1, CANPL3, LGMD2A
Entrez Gene: 825
siRNA catalog
calpain 3, (p94)
mRNA: NM_000070
Library: MAR
Classification: protease
Final bin: Discordant
SMARTpool bin: Low Alamar
Avg area: 1.78
Avg Alamar: 0.76
Knockdown %: not done
ERBB2: No Change
BCL2: Low Alamar
CAPN3
Link
CAPN3
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
CAPN3
Aliases: p94, CANP3, LGMD2, nCL-1, CANPL3, LGMD2A
Entrez Gene: 825
siRNA catalog
calpain 3, (p94)
mRNA: NM_000070
Library: MAR
CAPN3
Link
CAPN3
Link
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
CAPNS1
Aliases: 30K, CANP, CDPS, CANPS, CAPN4, CALPAIN4
Entrez Gene: 826
siRNA catalog
calpain, small subunit 1
mRNA: NM_001749
Library: MAR
Classification: protease
Final bin: Discordant
SMARTpool bin: Low Alamar
Avg area: 2.02
Avg Alamar: 0.76
Knockdown %: not done
ERBB2: Impaired
BCL2: Low Alamar
CAPNS1
Link
CAPNS1
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
CAPNS1
Aliases: 30K, CANP, CDPS, CANPS, CAPN4, CALPAIN4
Entrez Gene: 826
siRNA catalog
calpain, small subunit 1
mRNA: NM_001749
Library: MAR
CAPNS1
Link
CAPNS1
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00025084 CAPNS1 SIMILAR TO CALCIUM-DEPENDENT PROTEASE, SMALL SUBUNIT. 35 9 63 13 1.80
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
CAPN2
Aliases: mCANP, CANPL2, CANPml
Entrez Gene: 824
siRNA catalog
calpain 2, (m/II) large subunit
mRNA: NM_001748
Library: MAR
Classification: protease
Final bin: Discordant
SMARTpool bin: Low Alamar
Avg area: 2.94
Avg Alamar: 0.68
Knockdown %: not done
ERBB2: Impaired
BCL2: Low Alamar
CAPN2
Link
CAPN2
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
CAPN2
Aliases: mCANP, CANPL2, CANPml
Entrez Gene: 824
siRNA catalog
calpain 2, (m/II) large subunit
mRNA: NM_001748
Library: MAR
CAPN2
Link
CAPN2
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00289758 CAPN2 CALPAIN 2, LARGE [CATALYTIC] SUBUNIT PRECURSOR. 41 15 41 20 1.00
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
CAPN7
Aliases: PALBH, CALPAIN7
Entrez Gene: 23473
siRNA catalog
calpain 7
mRNA: NM_014296
Library: MAR
Classification: protease
Final bin: Discordant
SMARTpool bin: No change
Avg area: 0.94
Avg Alamar: 1.06
Knockdown %: not done
  CAPN7
Link
CAPN7
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
CAPN7
Aliases: PALBH, CALPAIN7
Entrez Gene: 23473
siRNA catalog
calpain 7
mRNA: NM_014296
Library: MAR
CAPN7
Link
CAPN7
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00003765 CAPN7 CALPAIN 7. 1 1 3 3 3.00
Proteomics» Table 2. Proteins in major organelles and subcellular compartments
IPI Locus Description CB Spectra PD Spectra ratio Location
IPI00003765 CAPN7 CALPAIN 7. 1 3 3 nucleus
Discovery» wt-migratory_cells vs wt-non-migratory_cells
Symbol Description Median Values Fold Change Probe ID
CalpB
Flybase
Entrez
CMCKB
Calpain-B Mig: 307.8
Non-Mig: 448.9
0.68568 151648_at
Discovery» Drosophila Morphology Genes
Gene Name Cell Count/
Normalization
Stellate11
NumCorners
Stellate22
Binsum6
Non-Spreading3
CG8107
Entrez Gene: 39165
Calpain-B
Aliases: Calpain B; calpain B
11.875
1.558
1.028 1.024 Actin: 1.097
Area: 0.846
Ratio: 1.297
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
CAPN1
Aliases: CANP, muCL, CANPL1, muCANP
Entrez Gene: 823
siRNA catalog
calpain 1, (mu/I) large subunit
mRNA: NM_005186
Library: MAR
Classification: protease
Focal Adhesion Related: Yes
Final bin: No Phenotype
SMARTpool bin: No change
Avg area: 1.18
Avg Alamar: 0.98
Knockdown %: not done
  CAPN1
Link
CAPN1
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
CAPN1
Aliases: CANP, muCL, CANPL1, muCANP
Entrez Gene: 823
siRNA catalog
calpain 1, (mu/I) large subunit
mRNA: NM_005186
Library: MAR
CAPN1
Link
CAPN1
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00011285 CAPN1 CALPAIN 1, LARGE [CATALYTIC] SUBUNIT. 14 12 26 14 1.86
Consortium Related Products*
Mice » activity page
Ortholog Species Name Method Phenotype Status Jax Availability Source Publications
CAPN1 mouse Calpain I (μ-calpain) (Capn1)
-
Viable and fertile. Reduced platelet aggregation and reduced tyrosine phosphorylation of the beta3 subunit of alphaIIbbeta3 integrin. completed
-
-
Azam et al.
CAPN2 mouse Calpain II (m-calpain) (Capn2)
-
None, though elimination of the Capn4 gene (see below) destroys the CalpainII complex. completed
-
-
Arthur et al.
CAPNS1 mouse Calpain IV (Capn4) - fibroblasts
-
Decreased migration rates, abnormal organization of actin cytoskeleton, loss of central stress fibers, and decreased numbers of focal adhesions. No proteolysis of talin. completed
-
-
Dourdin et al.
CAPNS1 mouse Calpain IV (Capn4)
-
Embryonic lethality at mid-gestation with defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors. completed
-
-
Arthur et al.
Biosensors » activity page
Ortholog Species Name Type Source Publications
CAPN1 none Calpain Intramolecular FRET between FPs - YFP-Calpain cleavage site (alpha-spectrin)-CFP
-
Vanderklish et al.

* The resources presented here are largely those generated by the Consortium. The sidebar provides public databases that complement Consortium activities. For mice and biosensors, a public database is not available and therefore we have attempted to generate a migration related list for your convenience.

The primary classification of CMKB families is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture).