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
- 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)
- 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 (PubMed)
- 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)
- 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)
- Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol. Rev. 2003; 83:731-801 (PubMed)
- 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)
- 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)
- 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 |
&lib=MAR&fbin=Discordant) Link |
&lib=MAR&fbin=Discordant) 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 |
&lib=MAR) Link |
&lib=MAR) Link |
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 |
%20large%20subunit&lib=MAR&fbin=Discordant) Link |
%20large%20subunit&lib=MAR&fbin=Discordant) 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 |
%20large%20subunit&lib=MAR) Link |
%20large%20subunit&lib=MAR) 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 |
|
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 |
 Link |
 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 |
 Link |
 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 |
|
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 |
 Link |
 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 |
 Link |
 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 |
%20large%20subunit&lib=MAR&fbin=No%20Phenotype) Link |
%20large%20subunit&lib=MAR&fbin=No%20Phenotype) 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 |
%20large%20subunit&lib=MAR) Link |
%20large%20subunit&lib=MAR) 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).