Alternative titles; symbols
HGNC Approved Gene Symbol: CKMT1B
Cytogenetic location: 15q15.3 Genomic coordinates (GRCh38): 15:43,592,857-43,599,406 (from NCBI)
Creatine kinases (CKs; EC 2.7.3.2) catalyze the reversible transfer of high energy phosphate from ATP to creatine, generating ADP and phosphocreatine. CK isoenzymes are crucial to energy metabolism, particularly in tissues with high energy requirements. Nuclear genes encode 4 CK subunits: cytoplasmic muscle (CKM; 123310), cytoplasmic brain (CKB; 123280), ubiquitous mitochondrial (CKMT1B), and sarcomeric mitochondrial (CKMTS; 123295) (Klein et al., 1991). A nearly identical copy of CKMT1B, designated CKMT1A (613415), is telomeric to CKMT1B on chromosome 15 (Zhang et al., 2007).
Haas et al. (1989) cloned CKMT1B, which they called placental MTCK, from a human placenta cDNA library. The deduced 416-amino acid protein contains a 38-amino acid N-terminal mitochondrial targeting and import signal and an active site, cys278. In vitro-translated placental MTCK was translocated into rat liver mitochondria and proteolytically processed into smaller intermediate and mature forms. Northern blot analysis using a placental MTCK-specific probe detected expression in small intestine and placenta, but not in skeletal muscle, ventricle, and liver.
Bark (1980) observed appearance of mitochondrial creatine kinase in the serum of patients with profound shock, which in most of the patients was fatal.
Human NDPKD (NME4; 601818) and MTCK are basic peripheral membrane proteins with symmetrical homooligomeric structures. Using lipid dilution assays, Epand et al. (2007) showed that NDPKD and ubiquitous MTCK facilitated lipid transfer from one bilayer to another. Lipid transfer occurred between liposomes mimicking the lipid composition of mitochondrial contact sites, containing 30 mol % cardiolipin, but transfer did not occur when cardiolipin was replaced by phosphatidylglycerol. Ubiquitous MTCK, but not NDPKD, showed some specificity in lipids transferred, and it was not active with phosphatidylcholine alone. Ubiquitous MTCK underwent reversible oligomerization between dimeric and octameric forms, but only the octamer bridged membranes and promoted lipid transfer. Lipid transfer did not involve vesicle fusion or loss of internal contents of the liposomes.
Using Western blot analysis and confocal immunohistochemistry, Schlattner et al. (2002) investigated the localization of creatine kinases in mouse and human skin under healthy and pathologic conditions. In mouse skin, they found high amounts of Ckb coexpressed with lower amounts of Ckmt1b, both mainly localized in suprabasal layers of the dermis, different cell types of hair follicles, sebaceous glands, and the subcutaneous panniculus carnosus muscle. Except for sebaceous glands, these cells also expressed creatine transporter (CRT, or SLC6A8; 300036). Ckm and Ckmts were restricted to panniculus carnosus. Western blot analysis showed that Ckb and Crt were upregulated about 3-fold immediately after wounding of mouse skin, whereas the amount of Ckmt1b increased 10 to 15 days after wounding. Healthy and psoriatic human skin showed a similar coexpression pattern of CKB, CKMT1B, and CRT, with CRT upregulated in psoriasis.
Haas et al. (1989) determined that the CKMT1B gene contains 9 exons and spans 5.5 kb. The 5-prime flanking region lacks CAAT and TATA motifs, but it has a high GC content and 2 putative SP1 (189906)-binding sites.
By means of a clone from the human CKMT1B gene in Southern analysis of somatic cell hybrid DNA, Stallings et al. (1988) assigned the CKMT1B gene to chromosome 15. Steeghs et al. (1994) mapped the CKMT1B gene to human chromosome 15q15 and to mouse chromosome 2 bands F1-F3 by fluorescence in situ hybridization.
Zhang et al. (2007) stated that a nearly identical copy of CKMT1B, designated CKMT1A, is telomeric to the CKMT1B gene on chromosome 15q15.
Bark, C. J. Mitochondrial creatine kinase: a poor prognostic sign. JAMA 243: 2058-2060, 1980. [PubMed: 7373746]
Epand, R. F., Schlattner, U., Wallimann, T., Lacombe, M.-L., Epand, R. M. Novel lipid transfer property of two mitochondrial proteins that bridge the inner and outer membranes. Biophys. J. 92: 126-137, 2007. [PubMed: 17028143] [Full Text: https://doi.org/10.1529/biophysj.106.092353]
Haas, R. C., Korenfeld, C., Zhang, Z., Perryman, B., Roman, D., Strauss, A. W. Isolation and characterization of the gene and cDNA encoding human mitochondrial creatine kinase. J. Biol. Chem. 264: 2890-2897, 1989. Note: Erratum: J. Biol. Chem. 264: 16332 only, 1989. [PubMed: 2914937]
Klein, S. C., Haas, R. C., Perryman, M. B., Billadello, J. J., Strauss, A. W. Regulatory element analysis and structural characterization of the human sarcomeric mitochondrial creatine kinase gene. J. Biol. Chem. 266: 18058-18065, 1991. [PubMed: 1917943] [Full Text: https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)55236-4]
Schlattner, U., Mockli, N., Speer, O., Werner, S., Wallimann, T. Creatine kinase and creatine transporter in normal, wounded, and diseased skin. J. Invest. Derm. 118: 416-423, 2002. [PubMed: 11874479] [Full Text: https://doi.org/10.1046/j.0022-202x.2001.01697.x]
Stallings, R. L., Olson, E., Strauss, A. W., Thompson, L. H., Bachinski, L. L., Siciliano, M. J. Human creatine kinase genes on chromosomes 15 and 19, and proximity of the gene for the muscle form to the genes for apolipoprotein C2 and excision repair. Am. J. Hum. Genet. 43: 144-151, 1988. [PubMed: 3400641]
Steeghs, K., Merkx, G., Wieringa, B. The ubiquitous mitochondrial creatine kinase gene maps to a conserved region on human chromosome 15q15 and mouse chromosome 2 bands F1-F3. Genomics 24: 193-195, 1994. [PubMed: 7896282] [Full Text: https://doi.org/10.1006/geno.1994.1604]
Zhang, Y., Malekpour, M., Al-Madani, N., Kahrizi, K., Zanganeh, M., Lohr, N. J., Mohseni, M., Mojahedi, F., Daneshi, A., Najmabadi, H., Smith, R. J. H. Sensorineural deafness and male infertility: a contiguous gene deletion syndrome. J. Med. Genet. 44: 233-240, 2007. Note: Erratum: J. Med. Genet. 44: 544 only, 2007. [PubMed: 17098888] [Full Text: https://doi.org/10.1136/jmg.2006.045765]