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'''Creatine kinase, mitochondrial 1A''' also known as '''CKMT1A''' is one of two [[gene]]s which encode the ubiquitous mitochondrial [[creatine kinase]] ('''ubiquitous mtCK''' or '''CKMT1''').<ref name="pmid2914937">{{cite journal | vauthors = Haas RC, Korenfeld C, Zhang ZF, Perryman B, Roman D, Strauss AW | title = Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase | journal = J. Biol. Chem. | volume = 264 | issue = 5 | pages = 2890–7 |date=February 1989 | pmid = 2914937 | doi = | url = http://www.jbc.org/cgi/content/abstract/264/5/2890 | issn = }}</ref><ref name="pmid9746318">{{cite journal | vauthors = Stachowiak O, Schlattner U, Dolder M, Wallimann T | title = Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: implications for cellular function and mitochondrial structure | journal = Mol. Cell. Biochem. | volume = 184 | issue = 1-2 | pages = 141–51 |date=July 1998 | pmid = 9746318 | doi = 10.1023/A:1006803431821 | url = | issn = }}</ref><ref name="pmid11736631">{{cite journal | author = Lipskaya TY | title = Mitochondrial creatine kinase: properties and function | journal = Biochemistry Mosc. | volume = 66 | issue = 10 | pages = 1098–111 |date=October 2001 | pmid = 11736631 | doi = 10.1023/A:1012428812780| url = http://protein.bio.msu.ru/biokhimiya/contents/v66/full/66101361.html | issn = }}</ref>
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.<ref name="pmid2914937">{{cite journal | vauthors = Haas RC, Korenfeld C, Zhang ZF, Perryman B, Roman D, Strauss AW | title = Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase | journal = J. Biol. Chem. | volume = 264 | issue = 5 | pages = 2890–7 |date=February 1989 | pmid = 2914937 | doi = | url = http://www.jbc.org/cgi/content/abstract/264/5/2890 | issn = }}</ref><ref name="pmid9746318">{{cite journal | vauthors = Stachowiak O, Schlattner U, Dolder M, Wallimann T | title = Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: implications for cellular function and mitochondrial structure | journal = Mol. Cell. Biochem. | volume = 184 | issue = 1-2 | pages = 141–51 |date=July 1998 | pmid = 9746318 | doi = 10.1023/A:1006803431821 | url = | issn = }}</ref><ref name="pmid11736631">{{cite journal | author = Lipskaya TY | title = Mitochondrial creatine kinase: properties and function | journal = Biochemistry Mosc. | volume = 66 | issue = 10 | pages = 1098–111 |date=October 2001 | pmid = 11736631 | doi = 10.1023/A:1012428812780| url = http://protein.bio.msu.ru/biokhimiya/contents/v66/full/66101361.html | issn = }}</ref>

== 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.<ref>{{Cite journal|last=Refrégier|first=Guislaine|last2=Le Gac|first2=Mickaël|last3=Jabbour|first3=Florian|last4=Widmer|first4=Alex|last5=Shykoff|first5=Jacqui A|last6=Yockteng|first6=Roxana|last7=Hood|first7=Michael E|last8=Giraud|first8=Tatiana|date=2008-03-27|title=Cophylogeny of the anther smut fungi and their caryophyllaceous hosts: Prevalence of host shifts and importance of delimiting parasite species for inferring cospeciation|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2324105/|journal=BMC Evolutionary Biology|volume=8|pages=100|doi=10.1186/1471-2148-8-100|issn=1471-2148|pmc=2324105|pmid=18371215}}</ref>    


== Function ==
== 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.<ref>{{Cite journal|last=Sieroń|first=Lesław|date=2007-12-06|title=Poly[bis­(μ2-formato-κ2 O:O′)(quinoxaline-κN)copper(II)]|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914937/|journal=Acta Crystallographica Section E: Structure Reports Online|volume=64|issue=Pt 1|pages=m53|doi=10.1107/S1600536807063015|issn=1600-5368|pmc=2914937|pmid=21200625}}</ref> 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. <ref>{{Cite journal|last=Wyss|first=M.|last2=Kaddurah-Daouk|first2=R.|date=2000-07-01|title=Creatine and creatinine metabolism|url=https://www.ncbi.nlm.nih.gov/pubmed/10893433|journal=Physiological Reviews|volume=80|issue=3|pages=1107–1213|issn=0031-9333|pmid=10893433}}</ref> 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.<ref>{{Cite journal|last=Kekelidze|first=T.|last2=Khait|first2=I.|last3=Togliatti|first3=A.|last4=Benzecry|first4=J. M.|last5=Wieringa|first5=B.|last6=Holtzman|first6=D.|date=2001-12-01|title=Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent|url=https://www.ncbi.nlm.nih.gov/pubmed/11746413|journal=Journal of Neuroscience Research|volume=66|issue=5|pages=866–872|doi=10.1002/jnr.10060|issn=0360-4012|pmid=11746413}}</ref><ref>{{Cite journal|last=Schlattner|first=Uwe|last2=Tokarska-Schlattner|first2=Malgorzata|last3=Wallimann|first3=Theo|date=2006-02-01|title=Mitochondrial creatine kinase in human health and disease|url=https://www.ncbi.nlm.nih.gov/pubmed/16236486|journal=Biochimica Et Biophysica Acta|volume=1762|issue=2|pages=164–180|doi=10.1016/j.bbadis.2005.09.004|issn=0006-3002|pmid=16236486}}</ref>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.<ref>{{Cite journal|last=Cevenini|first=R.|last2=Varotti|first2=C.|last3=Rumpianesi|first3=F.|last4=Donati|first4=M.|last5=Tosti|first5=A.|last6=Negosanti|first6=M.|date=1980-01-01|title=Non-gonococcal urethritis: epidemiological and etiological study in Italy|url=https://www.ncbi.nlm.nih.gov/pubmed/?term=7236360|journal=Bollettino dell'Istituto Sieroterapico Milanese|volume=59|issue=6|pages=599–603|issn=0021-2547|pmid=7236360}}</ref><ref>{{Cite journal|last=Enooku|first=Kenichiro|last2=Nakagawa|first2=Hayato|last3=Soroida|first3=Yoko|last4=Ohkawa|first4=Ryunosuke|last5=Kageyama|first5=Yuko|last6=Uranbileg|first6=Baasanjav|last7=Watanabe|first7=Naoko|last8=Tateishi|first8=Ryosuke|last9=Yoshida|first9=Haruhiko|date=2014-08-15|title=Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients|url=https://www.ncbi.nlm.nih.gov/pubmed/24420733|journal=International Journal of Cancer|volume=135|issue=4|pages=871–879|doi=10.1002/ijc.28720|issn=1097-0215|pmid=24420733}}</ref><ref>{{Cite journal|last=Uranbileg|first=Baasanjav|last2=Enooku|first2=Kenichiro|last3=Soroida|first3=Yoko|last4=Ohkawa|first4=Ryunosuke|last5=Kudo|first5=Yotaro|last6=Nakagawa|first6=Hayato|last7=Tateishi|first7=Ryosuke|last8=Yoshida|first8=Haruhiko|last9=Shinzawa|first9=Seiko|date=2014-05-01|title=High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential|url=https://www.ncbi.nlm.nih.gov/pubmed/24174293|journal=International Journal of Cancer|volume=134|issue=9|pages=2189–2198|doi=10.1002/ijc.28547|issn=1097-0215|pmid=24174293}}</ref><ref>{{Cite journal|last=Kornacker|first=M.|last2=Schlattner|first2=U.|last3=Wallimann|first3=T.|last4=Verneris|first4=M. R.|last5=Negrin|first5=R. S.|last6=Kornacker|first6=B.|last7=Staratschek-Jox|first7=A.|last8=Diehl|first8=V.|last9=Wolf|first9=J.|date=2001-11-01|title=Hodgkin disease-derived cell lines expressing ubiquitous mitochondrial creatine kinase show growth inhibition by cyclocreatine treatment independent of apoptosis|url=https://www.ncbi.nlm.nih.gov/pubmed/11745437|journal=International Journal of Cancer|volume=94|issue=4|pages=513–519|issn=0020-7136|pmid=11745437}}</ref>

== Interactions ==
Leucine-rich repeat kinase <ref>{{Cite journal|last=Cui|first=Jie|last2=Yu|first2=Mei|last3=Niu|first3=Jingwen|last4=Yue|first4=Zhenyu|last5=Xu|first5=Zhiheng|date=2011-10-01|title=Expression of leucine-rich repeat kinase 2 (LRRK2) inhibits the processing of uMtCK to induce cell death in a cell culture model system|url=https://www.ncbi.nlm.nih.gov/pubmed/21370995|journal=Bioscience Reports|volume=31|issue=5|pages=429–437|doi=10.1042/BSR20100127|issn=1573-4935|pmc=3971885|pmid=21370995}}</ref>


ASB9 <ref>{{Cite journal|last=Kwon|first=Sanghoon|last2=Kim|first2=Dongbum|last3=Rhee|first3=Jae Won|last4=Park|first4=Jeong-A.|last5=Kim|first5=Dae-Won|last6=Kim|first6=Doo-Sik|last7=Lee|first7=Younghee|last8=Kwon|first8=Hyung-Joo|date=2010-03-19|title=ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function|url=https://www.ncbi.nlm.nih.gov/pubmed/20302626|journal=BMC biology|volume=8|pages=23|doi=10.1186/1741-7007-8-23|issn=1741-7007|pmc=2852384|pmid=20302626}}</ref>
Mitochondrial creatine (MtCK) kinase is responsible for the transfer of high energy phosphate from [[mitochondria]] to the cytosolic carrier, [[creatine]]. It belongs to the [[creatine kinase]] isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK ([[CKMT2]]) and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 (CKMT1A (this gene) and [[CKMT1B]]) have been identified which encode identical mitochondrial creatine kinase proteins.<ref name="entrez">{{cite web | title = Entrez Gene: CKMT1B creatine kinase, mitochondrial 1A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=548596| accessdate = }}</ref>


== References ==
== References ==

Revision as of 19:01, 12 January 2017

creatine kinase, mitochondrial 1A
Identifiers
SymbolCKMT1A
Alt. symbolsCKMT1
NCBI gene548596
HGNC31736
RefSeqNM_001015001
UniProtP12532
Other data
EC number2.7.3.2
LocusChr. 15 q15
Search for
StructuresSwiss-model
DomainsInterPro

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

Leucine-rich repeat kinase [13]

ASB9 [14]

References

  1. ^ Haas RC, Korenfeld C, Zhang ZF, Perryman B, Roman D, Strauss AW (February 1989). "Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase". J. Biol. Chem. 264 (5): 2890–7. PMID 2914937.
  2. ^ Stachowiak O, Schlattner U, Dolder M, Wallimann T (July 1998). "Oligomeric state and membrane binding behaviour of creatine kinase isoenzymes: implications for cellular function and mitochondrial structure". Mol. Cell. Biochem. 184 (1–2): 141–51. doi:10.1023/A:1006803431821. PMID 9746318.
  3. ^ Lipskaya TY (October 2001). "Mitochondrial creatine kinase: properties and function". Biochemistry Mosc. 66 (10): 1098–111. doi:10.1023/A:1012428812780. PMID 11736631.
  4. ^ Refrégier, Guislaine; Le Gac, Mickaël; Jabbour, Florian; Widmer, Alex; Shykoff, Jacqui A; Yockteng, Roxana; Hood, Michael E; Giraud, Tatiana (2008-03-27). "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. doi:10.1186/1471-2148-8-100. ISSN 1471-2148. PMC 2324105. PMID 18371215.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Sieroń, Lesław (2007-12-06). "Poly[bis­(μ2-formato-κ2 O:O′)(quinoxaline-κN)copper(II)]". Acta Crystallographica Section E: Structure Reports Online. 64 (Pt 1): m53. doi:10.1107/S1600536807063015. ISSN 1600-5368. PMC 2914937. PMID 21200625. {{cite journal}}: soft hyphen character in |title= at position 9 (help)
  6. ^ Wyss, M.; Kaddurah-Daouk, R. (2000-07-01). "Creatine and creatinine metabolism". Physiological Reviews. 80 (3): 1107–1213. ISSN 0031-9333. PMID 10893433.
  7. ^ Kekelidze, T.; Khait, I.; Togliatti, A.; Benzecry, J. M.; Wieringa, B.; Holtzman, D. (2001-12-01). "Altered brain phosphocreatine and ATP regulation when mitochondrial creatine kinase is absent". Journal of Neuroscience Research. 66 (5): 866–872. doi:10.1002/jnr.10060. ISSN 0360-4012. PMID 11746413.
  8. ^ Schlattner, Uwe; Tokarska-Schlattner, Malgorzata; Wallimann, Theo (2006-02-01). "Mitochondrial creatine kinase in human health and disease". Biochimica Et Biophysica Acta. 1762 (2): 164–180. doi:10.1016/j.bbadis.2005.09.004. ISSN 0006-3002. PMID 16236486.
  9. ^ Cevenini, R.; Varotti, C.; Rumpianesi, F.; Donati, M.; Tosti, A.; Negosanti, M. (1980-01-01). "Non-gonococcal urethritis: epidemiological and etiological study in Italy". Bollettino dell'Istituto Sieroterapico Milanese. 59 (6): 599–603. ISSN 0021-2547. PMID 7236360.
  10. ^ Enooku, Kenichiro; Nakagawa, Hayato; Soroida, Yoko; Ohkawa, Ryunosuke; Kageyama, Yuko; Uranbileg, Baasanjav; Watanabe, Naoko; Tateishi, Ryosuke; Yoshida, Haruhiko (2014-08-15). "Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients". International Journal of Cancer. 135 (4): 871–879. doi:10.1002/ijc.28720. ISSN 1097-0215. PMID 24420733.
  11. ^ Uranbileg, Baasanjav; Enooku, Kenichiro; Soroida, Yoko; Ohkawa, Ryunosuke; Kudo, Yotaro; Nakagawa, Hayato; Tateishi, Ryosuke; Yoshida, Haruhiko; Shinzawa, Seiko (2014-05-01). "High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential". International Journal of Cancer. 134 (9): 2189–2198. doi:10.1002/ijc.28547. ISSN 1097-0215. PMID 24174293.
  12. ^ Kornacker, M.; Schlattner, U.; Wallimann, T.; Verneris, M. R.; Negrin, R. S.; Kornacker, B.; Staratschek-Jox, A.; Diehl, V.; Wolf, J. (2001-11-01). "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): 513–519. ISSN 0020-7136. PMID 11745437.
  13. ^ Cui, Jie; Yu, Mei; Niu, Jingwen; Yue, Zhenyu; Xu, Zhiheng (2011-10-01). "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): 429–437. doi:10.1042/BSR20100127. ISSN 1573-4935. PMC 3971885. PMID 21370995.
  14. ^ Kwon, Sanghoon; Kim, Dongbum; Rhee, Jae Won; Park, Jeong-A.; Kim, Dae-Won; Kim, Doo-Sik; Lee, Younghee; Kwon, Hyung-Joo (2010-03-19). "ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function". BMC biology. 8: 23. doi:10.1186/1741-7007-8-23. ISSN 1741-7007. PMC 2852384. PMID 20302626.{{cite journal}}: CS1 maint: unflagged free DOI (link)

External links

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