MetaCyc Enzyme: creatine kinase MB isoform

Synonyms: MB, M-B, MB-CK

Species: Homo sapiens

Subunit composition of creatine kinase MB isoform = [CKM][CKB]
         creatine kinase M-type subunit = CKM
         creatine kinase B-type subunit = CKB

Creatine kinase is found in vertebrate tissues with high and fluctuating energy demand including muscle (skeletal and cardiac), brain, retina and spermatozoa. It appears to be absent in liver. Reviewed in [Wyss00].

In mammals and birds, four types of subunits are expressed in a species-specific, tissue-specific, and developmental stage-specific manner. Cytosolic muscle (M) and brain (B) subunits form MM, BB and MB isozymes. Two mitochondrial isoforms are found, the ubiquitous form expressed in brain, kidney and other tissues and the sarcomeric form expressed in skeletal and heart muscle cells [Payne]. Both of these forms form interconvertible homodimers and homooctamers. Evidence suggests that the homooctameric form is the predominant form in vivo and is important for its function (in [Schlattner00]). In addition to vertebrate cytosolic and mitochondrial isoforms, a flagellar isoform is found in the spermatozoa of protochordates and some invertebrates (in [Bertin07]). Reviewed in [Wyss00].

Creatine kinase is a member of the highly conserved phosphagen (guanidino) kinases that also include arginine, glycoyamine, hypotaurocyamine, lombricine, opheline and thalassemine kinases. Creatine kinase is the only phosphagen kinase used by lower chordates and vertebrates. (in [Bertin07, Tanaka07]).

A variety of creatine kinase assays exist, due to their use as clinical indicators of myocardial and skeletal muscle disorders and as a marker for myocardial infarction (reviewed in [McLeish05]).

The muscle and brain isoforms show approximately 81% amino acid sequence identity. However, the two isoforms showed differences in isoelectric heterogeneity and were immunologically distinct [Chen00].

This enzyme is a heterodimer of the M and B subunits and is found in skeletal and heart muscle (in [MouradTerzian00]).

See also ubiquitous mitochondrial creatine kinase, sarcomeric mitochondrial creatine kinase, creatine kinase MM isoform and creatine kinase BB isoform.

Gene-Reaction Schematic

Gene-Reaction Schematic

Created 12-Mar-2009 by Fulcher CA, SRI International

Enzymatic reaction of: creatine kinase

Inferred from experiment

EC Number:

creatine + ATP ⇄ creatine-phosphate + ADP + H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Wyss00]

In Pathways: creatine-phosphate biosynthesis

This enzyme catalyzes the reversible transfer of the γ-phosphoryl group of ATP to creatine to produce ADP and creatine-phosphate.

Normal, enzymatically active heterodimeric MB isozyme was prepared from purified muscle and brain component polypeptide chains and analyzed using steady state kinetics [Jacobs80].

Partially purified MM, BB and MB isoforms were anlayzed kinetically. The MB isoform showed intermediate values between the MM and BB isoforms in velocity versus substrate response using a luciferase-based assay system [Witteveen74].

Cofactors or Prosthetic Groups: Mg2+ [Jacobs80]

Subunit of creatine kinase MB isoform: creatine kinase M-type subunit

Synonyms: creatine kinase M-type

Gene: CKM Accession Number: G-11143 (MetaCyc)

Sequence Length: 5487 AAs

Molecular Weight: 43.101 kD (from nucleotide sequence)

Unification Links: PhosphoSite:P06732, PhylomeDB:P06732, Pride:P06732, Protein Model Portal:P06732, SMR:P06732, UniProt:P06732

Relationship Links: InterPro:IN-FAMILY:IPR000749, InterPro:IN-FAMILY:IPR014746, InterPro:IN-FAMILY:IPR022413, InterPro:IN-FAMILY:IPR022414, InterPro:IN-FAMILY:IPR022415, Panther:IN-FAMILY:PTHR11547, PDB:Structure:1I0E, Pfam:IN-FAMILY:PF00217, Pfam:IN-FAMILY:PF02807, Prosite:IN-FAMILY:PS00112, Prosite:IN-FAMILY:PS51509, Prosite:IN-FAMILY:PS51510

Subunit of creatine kinase MB isoform: creatine kinase B-type subunit

Synonyms: creatine kinase B-type

Gene: CKB Accession Number: G-11144 (MetaCyc)

Sequence Length: 3172/3 AAs

Molecular Weight: 42.644 kD (from nucleotide sequence)

Unification Links: Mint:MINT-1484821, PhosphoSite:P12277, PhylomeDB:P12277, Pride:P12277, Protein Model Portal:P12277, SMR:P12277, UniProt:P12277

Relationship Links: InterPro:IN-FAMILY:IPR000749, InterPro:IN-FAMILY:IPR014746, InterPro:IN-FAMILY:IPR022413, InterPro:IN-FAMILY:IPR022414, InterPro:IN-FAMILY:IPR022415, Panther:IN-FAMILY:PTHR11547, PDB:Structure:3B6R, PDB:Structure:3DRB, PDB:Structure:3DRE, Pfam:IN-FAMILY:PF00217, Pfam:IN-FAMILY:PF02807, Prosite:IN-FAMILY:PS00112, Prosite:IN-FAMILY:PS51509, Prosite:IN-FAMILY:PS51510


Bertin07: Bertin M, Pomponi SM, Kokuhuta C, Iwasaki N, Suzuki T, Ellington WR (2007). "Origin of the genes for the isoforms of creatine kinase." Gene 392(1-2);273-82. PMID: 17329042

Chen00: Chen LH, White CB, Babbitt PC, McLeish MJ, Kenyon GL (2000). "A comparative study of human muscle and brain creatine kinases expressed in Escherichia coli." J Protein Chem 19(1);59-66. PMID: 10882173

Jacobs80: Jacobs HK, Kuby SA (1980). "Studies on muscular dystrophy. A comparison of the steady kinetics of the normal human ATP-creatine transphosphorylase isoenzymes (creatine kinases) with those from tissues of Duchenne muscular dystrophy." J Biol Chem 255(18);8477-82. PMID: 7410371

McLeish05: McLeish MJ, Kenyon GL (2005). "Relating structure to mechanism in creatine kinase." Crit Rev Biochem Mol Biol 40(1);1-20. PMID: 15804623

MouradTerzian00: Mourad-Terzian T, Steghens JP, Min KL, Collombel C, Bozon D (2000). "Creatine kinase isoenzymes specificities: histidine 65 in human CK-BB, a role in protein stability, not in catalysis." FEBS Lett 475(1);22-6. PMID: 10854850

Payne: Payne RM, Strauss AW (1994). "Expression of the mitochondrial creatine kinase genes." Mol Cell Biochem 133-134;235-43. PMID: 7808456

Schlattner00: Schlattner U, Eder M, Dolder M, Khuchua ZA, Strauss AW, Wallimann T (2000). "Divergent enzyme kinetics and structural properties of the two human mitochondrial creatine kinase isoenzymes." Biol Chem 381(11);1063-70. PMID: 11154064

Tanaka07: Tanaka K, Uda K, Shimada M, Takahashi K, Gamou S, Ellington WR, Suzuki T (2007). "Evolution of the cytoplasmic and mitochondrial phosphagen kinases unique to annelid groups." J Mol Evol 65(5);616-25. PMID: 17932618

Witteveen74: Witteveen SA, Sobel BE, DeLuca M (1974). "Kinetic properties of the isoenzymes of human creatine phosphokinase." Proc Natl Acad Sci U S A 71(4);1384-7. PMID: 4524644

Wyss00: Wyss M, Kaddurah-Daouk R (2000). "Creatine and creatinine metabolism." Physiol Rev 80(3);1107-213. PMID: 10893433

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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