Calpain small subunit 1 explained

Calpain small subunit 1 (CSS1) is a protein that in humans is encoded by the CAPNS1 gene.^{[1] [2] [3]}

Function

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.^[4] Two transcript variants encoding the same protein have been identified for this gene.

Functions

Myotonic dystrophy

This gene encodes a small subunit common to both calpain I and II and is associated with myotonic dystrophy.

Biomarker

'Elevated expression of CAPNS1 has been found to be associated with progression of various cancers such as hepatocellular and renal carcinoma. ^[5]

Further reading

• Suzuki K, Sorimachi H, Yoshizawa T, Kinbara K, Ishiura S . Calpain: novel family members, activation, and physiologic function . Biological Chemistry Hoppe-Seyler . 376 . 9 . 523–9 . September 1995 . 8561910 . 10.1515/bchm3.1995.376.9.523.
• Tidball JG, Spencer MJ . Calpains and muscular dystrophies . The International Journal of Biochemistry & Cell Biology . 32 . 1 . 1–5 . January 2000 . 10661889 . 10.1016/S1357-2725(99)00095-3 .
• Huang Y, Wang KK . The calpain family and human disease . Trends in Molecular Medicine . 7 . 8 . 355–62 . August 2001 . 11516996 . 10.1016/S1471-4914(01)02049-4 .
• Reverter D, Sorimachi H, Bode W . The structure of calcium-free human m-calpain: implications for calcium activation and function . Trends in Cardiovascular Medicine . 11 . 6 . 222–9 . August 2001 . 11673052 . 10.1016/S1050-1738(01)00112-8 .
• Banik NL, DeVries GH, Neuberger T, Russell T, Chakrabarti AK, Hogan EL . 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 . July 1991 . 1656060 . 10.1002/jnr.490290310 . 40120102 .
• Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K . Four genes for the calpain family locate on four distinct human chromosomes . Cytogenetics and Cell Genetics . 53 . 4 . 225–9 . 1990 . 2209092 . 10.1159/000132937 .
• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–13 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Zhang W, Lane RD, Mellgren RL . The major calpain isozymes are long-lived proteins. Design of an antisense strategy for calpain depletion in cultured cells . The Journal of Biological Chemistry . 271 . 31 . 18825–30 . August 1996 . 8702541 . 10.1074/jbc.271.31.18825 . free .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–8 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Noguchi M, Sarin A, Aman MJ, Nakajima H, Shores EW, Henkart PA, Leonard WJ . Functional cleavage of the common cytokine receptor gamma chain (gammac) by calpain . Proceedings of the National Academy of Sciences of the United States of America . 94 . 21 . 11534–9 . October 1997 . 9326644 . 23528 . 10.1073/pnas.94.21.11534 . 1997PNAS...9411534N . free .
• Strobl S, Fernandez-Catalan C, Braun M, Huber R, Masumoto H, Nakagawa K, Irie A, Sorimachi H, Bourenkow G, Bartunik H, Suzuki K, Bode W . The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium . Proceedings of the National Academy of Sciences of the United States of America . 97 . 2 . 588–92 . January 2000 . 10639123 . 15374 . 10.1073/pnas.97.2.588 . 2000PNAS...97..588S . free .
• Masumoto H, Nakagawa K, Irie S, Sorimachi H, Suzuki K, Bourenkov GP, Bartunik H, Fernandez-Catalan C, Bode W, Strobl S . Crystallization and preliminary X-ray analysis of recombinant full-length human m-calpain . Acta Crystallographica Section D . 56 . Pt 1 . 73–5 . January 2000 . 10666632 . 10.1107/S0907444999013748 . 2000AcCrD..56...73M .
• 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 . 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 . March 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
• Reverter D, Strobl S, Fernandez-Catalan C, Sorimachi H, Suzuki K, Bode W . Structural basis for possible calcium-induced activation mechanisms of calpains . Biological Chemistry . 382 . 5 . 753–66 . May 2001 . 11517928 . 10.1515/BC.2001.091 . 23221865 .

Notes and References

1. Miyake S, Emori Y, Suzuki K . Gene organization of the small subunit of human calcium-activated neutral protease . Nucleic Acids Research . 14 . 22 . 8805–17 . November 1986 . 3024120 . 311912 . 10.1093/nar/14.22.8805 .
2. Ohno S, Emori Y, Suzuki K . Nucleotide sequence of a cDNA coding for the small subunit of human calcium-dependent protease . Nucleic Acids Research . 14 . 13 . 5559 . July 1986 . 3016651 . 311560 .
3. Web site: Entrez Gene: CAPNS1 calpain, small subunit 1.
4. Lin GD, Chattopadhyay D, Maki M, Wang KK, Carson M, Jin L, Yuen PW, Takano E, Hatanaka M, DeLucas LJ, Narayana SV . 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 . July 1997 . 9228946 . 10.1038/nsb0797-539. 31913560 .
5. Zhuang Q, Qian X, Cao Y, Fan M, Xu X, He X . Capn4 mRNA level is correlated with tumour progression and clinical outcome in clear cell renal cell carcinoma . The Journal of International Medical Research . 42 . 2 . 282–91 . April 2014 . 24514433 . 10.1177/0300060513505524 . free .