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MetaCyc Enzyme: creatine kinase BB isoform

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

Synonyms: CKBB, creatine kinase B-type, creatine kinase B chain, B-CK, brain creatine kinase, CK-BB, BB, BB-CK, B-B

Species: Homo sapiens

Component of: creatine kinase MB isoform (extended summary available)

Subunit composition of creatine kinase BB isoform = [CKB]2
         creatine kinase B-type subunit = CKB

Summary:
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 [Payne94]. 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 brain isoform shows approximately 81% amino acid sequence identity with the muscle isoform. However, the two isoforms showed differences in isoelectric heterogeneity and were immunologically distinct [Chen00].

Recombinant, His-tagged enzyme has been overexpressed in COS-7 cells and purified. Its structure-function relationships were investigated by site-directed mutagenesis [MouradTerzian00].

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

Gene Citations: [VillarrealLevy87, Mariman87, Mariman89, Daouk88]

Locations: cytosol

Map Position: [103,055,749 <- 103,058,923]

Molecular Weight of Polypeptide: 42.644 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P12277 , Entrez-gene:1152 , Mint:MINT-1484821 , PhosphoSite:P12277 , PhylomeDB:P12277 , Pride:P12277 , Protein Model Portal:P12277 , SMR:P12277 , String:9606.ENSP00000299198 , UniProt:P12277

Relationship Links: 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

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005829 - cytosol [Burklen07]

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


Enzymatic reaction of: creatine kinase

EC Number: 2.7.3.2

creatine + ATP <=> creatine-phosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Wyss00]

In Pathways: creatine-phosphate biosynthesis

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

Purified, recombinant, His-tagged enzyme overexpressed in COS-7 cells was assayed for activity in the reverse direction (ATP synthesis) [MouradTerzian00].

Purified, recombinant enzyme expressed in Escherichia coli was assayed in the forward direction [Chen00].

Cofactors or Prosthetic Groups: Mg2+ [Chen00]

Inhibitors (Unknown Mechanism): 4-hydroxy-2-nonenal [Eliuk07]

Kinetic Parameters:

Substrate
Km (μM)
Citations
creatine-phosphate
650.0
[MouradTerzian00]
ADP
280.0
[MouradTerzian00]
creatine
4900.0
[Chen00]


Subunit of: 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

Summary:
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 [Payne94]. 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.

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


Enzymatic reaction of: creatine kinase

EC Number: 2.7.3.2

creatine + ATP <=> creatine-phosphate + ADP + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible. [Wyss00]

In Pathways: creatine-phosphate biosynthesis

Summary:
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]


References

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

Burklen07: Burklen TS, Hirschy A, Wallimann T (2007). "Brain-type creatine kinase BB-CK interacts with the Golgi Matrix Protein GM130 in early prophase." Mol Cell Biochem 297(1-2);53-64. PMID: 17036164

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

Daouk88: Daouk GH, Kaddurah-Daouk R, Putney S, Kingston R, Schimmel P (1988). "Isolation of a functional human gene for brain creatine kinase." J Biol Chem 263(5);2442-6. PMID: 2828370

Eliuk07: Eliuk SM, Renfrow MB, Shonsey EM, Barnes S, Kim H (2007). "active site modifications of the brain isoform of creatine kinase by 4-hydroxy-2-nonenal correlate with reduced enzyme activity: mapping of modified sites by Fourier transform-ion cyclotron resonance mass spectrometry." Chem Res Toxicol 20(9);1260-8. PMID: 17696488

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

Mariman87: Mariman EC, Broers CA, Claesen CA, Tesser GI, Wieringa B (1987). "Structure and expression of the human creatine kinase B gene." Genomics 1(2);126-37. PMID: 3692484

Mariman89: Mariman EC, Schepens JT, Wieringa B (1989). "Complete nucleotide sequence of the human creatine kinase B gene." Nucleic Acids Res 17(15);6385. PMID: 2771648

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

Payne94: 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

VillarrealLevy87: Villarreal-Levy G, Ma TS, Kerner SA, Roberts R, Perryman MB (1987). "Human creatine kinase: isolation and sequence analysis of cDNA clones for the B subunit, development of subunit specific probes and determination of gene copy number." Biochem Biophys Res Commun 144(3);1116-27. PMID: 3034271

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


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Fri Nov 28, 2014, biocyc12.