Calpains are a ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. Calpain families have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. Calpain I and II are heterodimeric with distinct large subunits associated with common small subunits, all of which are encoded by different genes. The small regulatory subunit consists of an N-terminal domain, containing about 30% glycine residues and a C-terminal Ca-binding domain.[8] Two transcript variants encoding the same protein have been identified for this gene.[7]
Functions[]
Myotonic dystrophy[]
This gene encodes a small subunit common to both calpain I and II and is associated with myotonic dystrophy.[7]
Biomarker[]
Elevated expression of Capn4 has been found to be associated with progression of various cancers such as hepatocellular and renal carcinoma.
[9]
^Lin GD, Chattopadhyay D, Maki M, Wang KK, Carson M, Jin L, Yuen PW, Takano E, Hatanaka M, DeLucas LJ, Narayana SV (July 1997). "Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding". Nature Structural Biology. 4 (7): 539–47. doi:10.1038/nsb0797-539. PMID9228946. S2CID31913560.
Suzuki K, Sorimachi H, Yoshizawa T, Kinbara K, Ishiura S (September 1995). "Calpain: novel family members, activation, and physiologic function". Biological Chemistry Hoppe-Seyler. 376 (9): 523–9. doi:10.1515/bchm3.1995.376.9.523. PMID8561910.
Tidball JG, Spencer MJ (January 2000). "Calpains and muscular dystrophies". The International Journal of Biochemistry & Cell Biology. 32 (1): 1–5. doi:10.1016/S1357-2725(99)00095-3. PMID10661889.
Huang Y, Wang KK (August 2001). "The calpain family and human disease". Trends in Molecular Medicine. 7 (8): 355–62. doi:10.1016/S1471-4914(01)02049-4. PMID11516996.
Reverter D, Sorimachi H, Bode W (August 2001). "The structure of calcium-free human m-calpain: implications for calcium activation and function". Trends in Cardiovascular Medicine. 11 (6): 222–9. doi:10.1016/S1050-1738(01)00112-8. PMID11673052.
Banik NL, DeVries GH, Neuberger T, Russell T, Chakrabarti AK, Hogan EL (July 1991). "Calcium-activated neutral proteinase (CANP; calpain) activity in Schwann cells: immunofluorescence localization and compartmentation of mu- and mCANP". Journal of Neuroscience Research. 29 (3): 346–54. doi:10.1002/jnr.490290310. PMID1656060. S2CID40120102.
Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K (1990). "Four genes for the calpain family locate on four distinct human chromosomes". Cytogenetics and Cell Genetics. 53 (4): 225–9. doi:10.1159/000132937. PMID2209092.
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID8619474.
Masumoto H, Nakagawa K, Irie S, Sorimachi H, Suzuki K, Bourenkov GP, Bartunik H, Fernandez-Catalan C, Bode W, Strobl S (January 2000). "Crystallization and preliminary X-ray analysis of recombinant full-length human m-calpain". Acta Crystallographica Section D. 56 (Pt 1): 73–5. doi:10.1107/S0907444999013748. PMID10666632.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC16267. PMID10737800.
Reverter D, Strobl S, Fernandez-Catalan C, Sorimachi H, Suzuki K, Bode W (May 2001). "Structural basis for possible calcium-induced activation mechanisms of calpains". Biological Chemistry. 382 (5): 753–66. doi:10.1515/BC.2001.091. PMID11517928. S2CID23221865.
v
t
PDB gallery
1aj5: CALPAIN DOMAIN VI APO
1alv: CALCIUM BOUND DOMAIN VI OF PORCINE CALPAIN
1alw: INHIBITOR AND CALCIUM BOUND DOMAIN VI OF PORCINE CALPAIN
1df0: CRYSTAL STRUCTURE OF M-CALPAIN
1dvi: CALPAIN DOMAIN VI WITH CALCIUM BOUND
1kfu: Crystal Structure of Human m-Calpain Form II
1kfx: Crystal Structure of Human m-Calpain Form I
1np8: 18-k C-terminally trunucated small subunit of calpain
1nx0: Structure of Calpain Domain 6 in Complex with Calpastatin DIC
1nx1: Calpain Domain VI Complexed with Calpastatin Inhibitory Domain C (DIC)
1nx2: Calpain Domain VI
1nx3: Calpain Domain VI in Complex with the Inhibitor PD150606
1u5i: Crystal Structure analysis of rat m-calpain mutant Lys10 Thr