CBR1

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Carbonyl reductase 1
Protein CBR1 PDB 1wma.png
PDB rendering based on 1wma.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CBR1 ; CBR; SDR21C1; hCBR1
External IDs OMIM114830 MGI88284 HomoloGene37524 ChEMBL: 5586 GeneCards: CBR1 Gene
EC number 1.1.1.184, 1.1.1.189, 1.1.1.197
RNA expression pattern
PBB GE CBR1 209213 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 873 12408
Ensembl ENSG00000159228 ENSMUSG00000051483
UniProt P16152 P48758
RefSeq (mRNA) NM_001286789 NM_007620
RefSeq (protein) NP_001273718 NP_031646
Location (UCSC) Chr 21:
37.44 – 37.45 Mb
Chr 16:
93.61 – 93.61 Mb
PubMed search [1] [2]

Carbonyl reductase 1, also known as CBR1, is an enzyme which in humans is encoded by the CBR1 gene.[1][2][3]

Function[edit]

Carbonyl reductase is one of several monomeric, NADPH-dependent oxidoreductases having wide specificity for carbonyl compounds. This enzyme is widely distributed in human tissues. Another carbonyl reductase gene, CRB3, lies close to this gene on chromosome 21q.[1] CBR1 metabolizes many toxic environmental quinones and pharmacological relevant substrates such as the anticancer doxorubicin.[4]

Polymorphisms[edit]

Up-to-date two non-synonymous polymorphisms on CBR1 have been identified. The CBR1 V88I polymorphism encodes for a valine-to-isoleucin substitution at position 88 of the aminoacid chain. In vitro studies with recombinant proteins indicate that the CBR1 V88 isoform has a higher Vmax towards the substrates menadione (vitamin K3) and daunorubicin.[5] Recent studies in human liver cytosols show that an untranslated polymorphism on the 3'UTR region of the CBR1 gene (rs9024)[6] is associated with higher levels of the cardiotoxic metabolite doxorubicinol.[7]

References[edit]

  1. ^ a b "Entrez Gene: CBR1 carbonyl reductase 1". 
  2. ^ Lemieux N, Malfoy B, Forrest GL (January 1993). "Human carbonyl reductase (CBR) localized to band 21q22.1 by high-resolution fluorescence in situ hybridization displays gene dosage effects in trisomy 21 cells". Genomics 15 (1): 169–172. doi:10.1006/geno.1993.1024. PMID 8432528. 
  3. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (March 2009). "The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative". Chem. Biol. Interact. 178 (1–3): 94–98. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726. 
  4. ^ Wermuth B, Platts KL, Seidel A, Oesch F (April 1986). "Carbonyl reductase provides the enzymatic basis of quinone detoxication in man". Biochem. Pharmacol. 35 (8): 1277–1282. doi:10.1016/0006-2952(86)90271-6. PMID 3083821. 
  5. ^ Gonzalez-Covarrubias V, Ghosh D, Lakhman SS, Pendyala L, Blanco JG (June 2007). "A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity". Drug Metab. Dispos. 35 (6): 973–980. doi:10.1124/dmd.107.014779. PMC 2442771. PMID 17344335. 
  6. ^ "Reference SNP Cluster Report: rs9024". Entrez SNP. National Center for Biotechnology Information/National Institutes of Health. 
  7. ^ Gonzalez-Covarrubias V, Zhang J, Kalabus JL, Relling MV, Blanco JG (February 2009). "Pharmacogenetics of human carbonyl reductase 1 (CBR1) in livers from black and white donors". Drug Metab. Dispos. 37 (2): 400–407. doi:10.1124/dmd.108.024547. PMC 2680526. PMID 19022938. 

Further reading[edit]