Biology:CKMT1A
| creatine kinase, mitochondrial 1A | |
|---|---|
| Identifiers | |
| Symbol | CKMT1A |
| Alt. symbols | CKMT1 |
| NCBI gene | 548596 |
| HGNC | 31736 |
| RefSeq | NM_001015001 |
| UniProt | P12532 |
| Other data | |
| EC number | 2.7.3.2 |
| Locus | Chr. 15 q15 |
Creatine kinase U-type, mitochondrial, also called ubiquitous mitochondrial creatine kinase (uMtCK), is in humans encoded by CKMT1A gene. CKMT1A catalyzes the reversible transfer of the γ-phosphate group of ATP to the guanidino group of Cr to yield ADP and PCr. The impairment of CKMT1A has been reported in ischaemia, cardiomyopathy, and neurodegenerative disorders. Overexpression of CKMT1A has been reported related with several tumors.[1][2][3]
Structure
Gene
The CKMT1A gene lies on the chromosome location of 15q15.3 and consists of 11 exons.
Protein
CKMT1A consists of 417 amino acids and weighs 47037Da. CKMT1A is rich in amino acids with hydroxyl-containing and basic side chains.[4]
Function
There are four distinct types of CK subunits in the tissue of mammals, which are expressed species specifically, developmental stage specifically, and tissue specifically. Ubiquitously expressed, CKMT1A is located in the mitochondrial intermembrane space and form both homodimeric and homooctameric molecules that are readily interconvertible.[5] Like all the other CK isoenzymes, CKMT1A catalyzes the reversible transfer of the γ-phosphate group of ATP to the guanidino group of Cr to yield ADP and PCr.[6] According to the “transport” (“shuttle”) hypothesis for the CK system, after synthesis within the mitochondrial matrix, the γ-phosphate group of ATP is transferred by CKMT1A in the mitochondrial intermembrane space to Cr to yield ADP plus PCr.
Clinical significance
As an enzyme central to cell energetics, CKMT1A is often impaired in pathological situations. CKMT1A is known as a primary target of oxidative and radical-induced molecular damage; and the impairment of CKMT1A has been reported in ischaemia, cardiomyopathy, and neurodegenerative disorders due to the failure in maintaining metabolic homeostasis.[7][8] Overexpression of uMtCK has been reported for several tumors with poor prognosis and this may be the adaption of cancer cells to maintain the high growth rate.[9][10][11][12]
Interactions
References
- ↑ "Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase". The Journal of Biological Chemistry 264 (5): 2890–7. February 1989. doi:10.1016/S0021-9258(19)81696-4. PMID 2914937.
- ↑ "Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: implications for cellular function and mitochondrial structure". Molecular and Cellular Biochemistry 184 (1–2): 141–51. July 1998. doi:10.1023/A:1006803431821. PMID 9746318.
- ↑ "Mitochondrial creatine kinase: properties and function". Biochemistry. Biokhimiia 66 (10): 1098–111. October 2001. doi:10.1023/A:1012428812780. PMID 11736631.
- ↑ "Cophylogeny of the anther smut fungi and their caryophyllaceous hosts: prevalence of host shifts and importance of delimiting parasite species for inferring cospeciation". BMC Evolutionary Biology 8 (1). March 2008. doi:10.1186/1471-2148-8-100. PMID 18371215. Bibcode: 2008BMCEE...8..100R.
- ↑ "Poly[bis-(μ(2)-formato-κO:O')(quinoxaline-κN)copper(II)"]. Acta Crystallographica Section E 64 (Pt 1): m53. December 2007. doi:10.1107/S1600536807063015. PMID 21200625.
- ↑ "Creatine and creatinine metabolism". Physiological Reviews 80 (3): 1107–213. July 2000. doi:10.1152/physrev.2000.80.3.1107. PMID 10893433.
- ↑ "Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent". Journal of Neuroscience Research 66 (5): 866–72. December 2001. doi:10.1002/jnr.10060. PMID 11746413.
- ↑ "Mitochondrial creatine kinase in human health and disease". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1762 (2): 164–80. February 2006. doi:10.1016/j.bbadis.2005.09.004. PMID 16236486.
- ↑ "Non-gonococcal urethritis: epidemiological and etiological study in Italy". Bollettino dell'Istituto Sieroterapico Milanese 59 (6): 599–603. 1980-01-01. PMID 7236360.
- ↑ "Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients". International Journal of Cancer 135 (4): 871–9. August 2014. doi:10.1002/ijc.28720. PMID 24420733.
- ↑ "High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential". International Journal of Cancer 134 (9): 2189–98. May 2014. doi:10.1002/ijc.28547. PMID 24174293.
- ↑ "Hodgkin disease-derived cell lines expressing ubiquitous mitochondrial creatine kinase show growth inhibition by cyclocreatine treatment independent of apoptosis". International Journal of Cancer 94 (4): 513–9. November 2001. doi:10.1002/ijc.1502. PMID 11745437.
- ↑ "Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system". Bioscience Reports 31 (5): 429–37. October 2011. doi:10.1042/BSR20100127. PMID 21370995.
- ↑ "ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function". BMC Biology 8. March 2010. doi:10.1186/1741-7007-8-23. PMID 20302626.
External links
- Creatine+Kinase,+Mitochondrial+Form at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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