Carboxymethylenebutenolidase homolog (CMBL)
The protein contains 245 amino acids for an estimated molecular weight of 28048 Da.
Cysteine hydrolase. Can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. May also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs35489000 |
No binding partner found
The reference OMIM entry for this protein is 613379
Carboxymethylenebutenolidase-like protein; cmbl
Carboxymethylenebutenolidase, pseudomonas, homolog of
DESCRIPTION
CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase family that is highly expressed in liver cytosol. CMBL preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al., 2010).CLONING
By mass spectrometry of purified cytosolic human liver CMBL, followed by database analysis and PCR of a human liver and skeletal muscle cDNA library, Ishizuka et al. (2010) cloned CMBL. The deduced 245-amino acid protein has a calculated molecular mass of 28 kD. CMBL has a C-terminal dienelactone hydrolase domain containing a catalytic triad of cys132, asp179, and his212. Quantitative RT-PCR detected variable CMBL expression in all tissues examined, with highest expression in liver, followed by kidney, small intestine, and colon. Lowest expression was in brain, thymus, bone marrow, and placenta. Fetal liver and brain also showed relatively low expression. Western blot analysis confirmed expression of CMBL in cytosolic fractions of human liver and intestine. The endogenous protein had an apparent molecular mass of 30 kD.GENE FUNCTION
Using transfected HEK293 cells, Ishizuka et al. (2010) showed that CMBL hydrolyzed the angiotensin receptor (AGTR1; 106165) blocker olmesartan medoxomil to the bioavailable molecule olmesartan with simple Michaelis-Menten kinetics. It also catalyzed the hydrolytic activation of other medoxomil-ester prodrugs with the medoxomil moiety linked to an oxygen atom, but not those with medoxomil linked to a nitrogen atom. CMBL appeared to prefer cyclic esters over simple esters and amides, and it did not hydrolyze typical esterase substrates. Inhibitor studies showed that CMBL was sensitive to a carboxylesterase inhibitor and a free thiol modifier, indicating that CMBL is a cysteine hydrolase. Site-directed mutagenesis confirmed that cys132 is the catalytic cysteine in CMBL.GENE STRUCTURE
Ishizuka et al. (2010) determined that the CMBL gene contains 5 exons.MAPPING
By genomic sequence analysis, Ishizuka et al. (2010) mapped the CMBL gene to chromosome 5p15.2. They mapped the mouse Cmbl gene to chromosome 15B2. ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 613379 was added.