CKMT1A explained

creatine kinase, mitochondrial 1A
Hgncid:31736
Symbol:CKMT1A
Altsymbols:CKMT1
Entrezgene:548596
Refseq:NM_001015001
Uniprot:P12532
Ecnumber:2.7.3.2
Chromosome:15
Arm:q
Band:15

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

Notes and References

  1. Haas RC, Korenfeld C, Zhang ZF, Perryman B, Roman D, Strauss AW . Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase . The Journal of Biological Chemistry . 264 . 5 . 2890–7 . February 1989 . 10.1016/S0021-9258(19)81696-4 . 2914937 . free .
  2. Stachowiak O, Schlattner U, Dolder M, Wallimann T . 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 . 9746318 . 10.1023/A:1006803431821 . 22668868 .
  3. Lipskaya TY . Mitochondrial creatine kinase: properties and function . Biochemistry. Biokhimiia . 66 . 10 . 1098–111 . October 2001 . 11736631 . 10.1023/A:1012428812780 . 32593074 .
  4. Refrégier G, Le Gac M, Jabbour F, Widmer A, Shykoff JA, Yockteng R, Hood ME, Giraud T . 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 . 100 . March 2008 . 1 . 18371215 . 2324105 . 10.1186/1471-2148-8-100 . 2008BMCEE...8..100R . free .
  5. Sieroń L . Poly[bis-(μ(2)-formato-κO:O')(quinoxaline-κN)copper(II)] . Acta Crystallographica Section E . 64 . Pt 1 . m53 . December 2007 . 21200625 . 2914937 . 10.1107/S1600536807063015 .
  6. Wyss M, Kaddurah-Daouk R . Creatine and creatinine metabolism . Physiological Reviews . 80 . 3 . 1107–213 . July 2000 . 10893433 . 10.1152/physrev.2000.80.3.1107.
  7. Kekelidze T, Khait I, Togliatti A, Benzecry JM, Wieringa B, Holtzman D . Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent . Journal of Neuroscience Research . 66 . 5 . 866–72 . December 2001 . 11746413 . 10.1002/jnr.10060 . 20976134 . free .
  8. Schlattner U, Tokarska-Schlattner M, Wallimann T . Mitochondrial creatine kinase in human health and disease . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1762 . 2 . 164–80 . February 2006 . 16236486 . 10.1016/j.bbadis.2005.09.004 . free .
  9. Cevenini R, Varotti C, Rumpianesi F, Donati M, Tosti A, Negosanti M . Non-gonococcal urethritis: epidemiological and etiological study in Italy . Bollettino dell'Istituto Sieroterapico Milanese . 59 . 6 . 599–603 . 1980-01-01 . 7236360 .
  10. Enooku K, Nakagawa H, Soroida Y, Ohkawa R, Kageyama Y, Uranbileg B, Watanabe N, Tateishi R, Yoshida H, Koike K, Yatomi Y, Ikeda H . 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 . 24420733 . 10.1002/ijc.28720 . free .
  11. Uranbileg B, Enooku K, Soroida Y, Ohkawa R, Kudo Y, Nakagawa H, Tateishi R, Yoshida H, Shinzawa S, Moriya K, Ohtomo N, Nishikawa T, Inoue Y, Tomiya T, Kojima S, Matsuura T, Koike K, Yatomi Y, Ikeda H . 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 . 24174293 . 10.1002/ijc.28547 . 24244814 . free .
  12. Kornacker M, Schlattner U, Wallimann T, Verneris MR, Negrin RS, Kornacker B, Staratschek-Jox A, Diehl V, Wolf J . 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 . 11745437 . 10.1002/ijc.1502. 5612884 . free .
  13. Cui J, Yu M, Niu J, Yue Z, Xu Z . 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 . 21370995 . 3971885 . 10.1042/BSR20100127 .
  14. Kwon S, Kim D, Rhee JW, Park JA, Kim DW, Kim DS, Lee Y, Kwon HJ . ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function . BMC Biology . 8 . 23 . March 2010 . 20302626 . 2852384 . 10.1186/1741-7007-8-23 . free .

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