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 [PubMed 20177059]).[supplied by OMIM, Apr 2010] See more...

Aliases for CMBL Gene

Aliases for CMBL Gene

  • Carboxymethylenebutenolidase Homolog 2 3 4 5
  • Carboxymethylenebutenolidase Homolog (Pseudomonas) 2 3
  • Carboxymethylenebutenolidase-Like (Pseudomonas) 2 3
  • EC 3.1.-.- 4
  • JS-1 3

External Ids for CMBL Gene

Previous GeneCards Identifiers for CMBL Gene

  • GC05M010330

Summaries for CMBL Gene

Entrez Gene Summary for CMBL Gene

  • 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 [PubMed 20177059]).[supplied by OMIM, Apr 2010]

GeneCards Summary for CMBL Gene

CMBL (Carboxymethylenebutenolidase Homolog) is a Protein Coding gene. Diseases associated with CMBL include Waardenburg Syndrome, Type 3 and Waardenburg Syndrome, Type 1. Among its related pathways are Cytochrome P450 - arranged by substrate type and Metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity.

UniProtKB/Swiss-Prot Summary for CMBL Gene

  • 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.

Additional gene information for CMBL Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CMBL Gene

Genomics for CMBL Gene

GeneHancer (GH) Regulatory Elements for CMBL Gene

Promoters and enhancers for CMBL Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CMBL on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CMBL

Top Transcription factor binding sites by QIAGEN in the CMBL gene promoter:
  • Evi-1
  • HNF-4alpha1
  • HNF-4alpha2
  • ITF-2
  • Nkx2-5
  • POU2F1
  • POU2F1a
  • STAT5A
  • Tal-1beta
  • TBP

Genomic Locations for CMBL Gene

Genomic Locations for CMBL Gene
chr5:10,275,875-10,308,056
(GRCh38/hg38)
Size:
32,182 bases
Orientation:
Minus strand
chr5:10,275,987-10,308,168
(GRCh37/hg19)
Size:
32,182 bases
Orientation:
Minus strand

Genomic View for CMBL Gene

Genes around CMBL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CMBL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CMBL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CMBL Gene

Proteins for CMBL Gene

  • Protein details for CMBL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96DG6-CMBL_HUMAN
    Recommended name:
    Carboxymethylenebutenolidase homolog
    Protein Accession:
    Q96DG6
    Secondary Accessions:
    • D3DTC7
    • Q8TED6

    Protein attributes for CMBL Gene

    Size:
    245 amino acids
    Molecular mass:
    28048 Da
    Quaternary structure:
    No Data Available

neXtProt entry for CMBL Gene

Post-translational modifications for CMBL Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CMBL Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CMBL Gene

Domains & Families for CMBL Gene

Gene Families for CMBL Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for CMBL Gene

Blocks:
  • Dienelactone hydrolase
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CMBL Gene

GenScript: Design optimal peptide antigens:
  • Carboxymethylenebutenolidase homolog (CMBL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96DG6

UniProtKB/Swiss-Prot:

CMBL_HUMAN :
  • Belongs to the dienelactone hydrolase family.
Family:
  • Belongs to the dienelactone hydrolase family.
genes like me logo Genes that share domains with CMBL: view

Function for CMBL Gene

Molecular function for CMBL Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot EnzymeRegulation:
Strongly inhibited by p-chloromercuribenzoate (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP). Not inhibited by DFP, PMSF, eserine or EDTA.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=170 uM for olmesartan medoxomil {ECO:0000269 PubMed:20177059}; KM=283 uM for faropenem medoxomil {ECO:0000269 PubMed:20177059}; KM=63.4 uM for lenampicillin {ECO:0000269 PubMed:20177059}; Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil {ECO:0000269 PubMed:20177059}; Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil {ECO:0000269 PubMed:20177059}; Vmax=4 nmol/min/mg enzyme toward lenampicillin {ECO:0000269 PubMed:20177059};

Enzyme Numbers (IUBMB) for CMBL Gene

Phenotypes From GWAS Catalog for CMBL Gene

Gene Ontology (GO) - Molecular Function for CMBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016787 hydrolase activity TAS --
genes like me logo Genes that share ontologies with CMBL: view
genes like me logo Genes that share phenotypes with CMBL: view

Animal Models for CMBL Gene

MGI Knock Outs for CMBL:
  • Cmbl Cmbl<tm1b(KOMP)Wtsi>

Animal Model Products

CRISPR Products

miRNA for CMBL Gene

miRTarBase miRNAs that target CMBL

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CMBL Gene

Localization for CMBL Gene

Subcellular locations from UniProtKB/Swiss-Prot for CMBL Gene

Cytoplasm, cytosol.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CMBL gene
Compartment Confidence
cytosol 5
extracellular 2
nucleus 2
plasma membrane 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for CMBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 19056867
genes like me logo Genes that share ontologies with CMBL: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CMBL Gene

Pathways & Interactions for CMBL Gene

genes like me logo Genes that share pathways with CMBL: view

Pathways by source for CMBL Gene

1 KEGG pathway for CMBL Gene

Interacting Proteins for CMBL Gene

STRING Interaction Network Preview (showing top 5 STRING interactants - click image to see top 6)
STRING Interaction Network
Selected Interacting proteins: ENSP00000296658 Q96DG6-CMBL_HUMAN for CMBL Gene via STRING IID

;

Gene Ontology (GO) - Biological Process for CMBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006805 xenobiotic metabolic process TAS --
genes like me logo Genes that share ontologies with CMBL: view

No data available for SIGNOR curated interactions for CMBL Gene

Drugs & Compounds for CMBL Gene

(1) Drugs for CMBL Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0

(18) Additional Compounds for CMBL Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
2,3,5-Trichlorodienelactone
2,3,5-Trichloromaleylacetate
2,5-Dichloro-4-oxohex-2-enedioate
2,5-Dichloro-carboxymethylenebut-2-en-4-olide
2-Chloro-5-methyl-cis-dienelactone
genes like me logo Genes that share compounds with CMBL: view

Transcripts for CMBL Gene

mRNA/cDNA for CMBL Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
7 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CMBL Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b
SP1: - - -
SP2: - - -
SP3: - -
SP4: -

Relevant External Links for CMBL Gene

GeneLoc Exon Structure for
CMBL

Expression for CMBL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CMBL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CMBL Gene

This gene is overexpressed in Kidney - Cortex (x7.4), Muscle - Skeletal (x5.7), and Liver (x4.7).

Protein differential expression in normal tissues from HIPED for CMBL Gene

This gene is overexpressed in Liver, secretome (16.9), Kidney (14.4), and Liver (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CMBL Gene



Protein tissue co-expression partners for CMBL Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CMBL

SOURCE GeneReport for Unigene cluster for CMBL Gene:

Hs.192586

mRNA Expression by UniProt/SwissProt for CMBL Gene:

Q96DG6-CMBL_HUMAN
Tissue specificity: Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level).

Evidence on tissue expression from TISSUES for CMBL Gene

  • Liver(4.6)
  • Muscle(4.4)
  • Kidney(2.6)
genes like me logo Genes that share expression patterns with CMBL: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for CMBL Gene

Orthologs for CMBL Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CMBL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CMBL 31 30
  • 97.78 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CMBL 31 30
  • 87.35 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CMBL 31 30
  • 86.8 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cmbl 30
  • 82.59 (n)
mouse
(Mus musculus)
Mammalia Cmbl 17 31 30
  • 81.9 (n)
oppossum
(Monodelphis domestica)
Mammalia CMBL 31
  • 72 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CMBL 31
  • 71 (a)
OneToOne
chicken
(Gallus gallus)
Aves CMBL 30
  • 68.71 (n)
-- 31
  • 54 (a)
OneToMany
-- 31
  • 54 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia CMBL 31
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cmbl 30
  • 68.3 (n)
MGC76315 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.26292 30
zebrafish
(Danio rerio)
Actinopterygii cmbl 31 30
  • 65.44 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes AIM2 33 31
  • 25 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT1G35420 30
  • 44.6 (n)
Species where no ortholog for CMBL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CMBL Gene

ENSEMBL:
Gene Tree for CMBL (if available)
TreeFam:
Gene Tree for CMBL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CMBL: view image

Paralogs for CMBL Gene

Pseudogenes.org Pseudogenes for CMBL Gene

genes like me logo Genes that share paralogs with CMBL: view

No data available for Paralogs for CMBL Gene

Variants for CMBL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CMBL Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
726244 Likely Benign: not provided 10,282,266(-) G/A SYNONYMOUS_VARIANT
775222 Benign: not provided 10,282,221(-) A/G SYNONYMOUS_VARIANT
780516 Benign: not provided 10,280,617(-) G/A NONSENSE
rs35489000 - p.Tyr155Cys

Additional dbSNP identifiers (rs#s) for CMBL Gene

Structural Variations from Database of Genomic Variants (DGV) for CMBL Gene

Variant ID Type Subtype PubMed ID
esv32585 CNV loss 17666407
esv3603997 CNV loss 21293372
nsv1029129 CNV gain 25217958
nsv597118 CNV loss 21841781
nsv823000 CNV gain 20364138

Variation tolerance for CMBL Gene

Residual Variation Intolerance Score: 58% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.01; 37.00% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CMBL Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CMBL

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CMBL Gene

Disorders for CMBL Gene

MalaCards: The human disease database

(3) MalaCards diseases for CMBL Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search CMBL in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CMBL

genes like me logo Genes that share disorders with CMBL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CMBL Gene

Publications for CMBL Gene

  1. Human carboxymethylenebutenolidase as a bioactivating hydrolase of olmesartan medoxomil in liver and intestine. (PMID: 20177059) Ishizuka T … Okazaki O (The Journal of biological chemistry 2010) 2 3 4 54
  2. Nucleotide sequence and expression of clcD, a plasmid-borne dienelactone hydrolase gene from Pseudomonas sp. strain B13. (PMID: 3804974) Frantz B … Chakrabarty AM (Journal of bacteriology 1987) 2 3 54
  3. Loss of ER retention motif of AGR2 can impact mTORC signaling and promote cancer metastasis. (PMID: 30575818) Tiemann K … Kani K (Oncogene 2019) 3 54
  4. VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. (PMID: 29507755) Yue Y … Liu J (Cell discovery 2018) 3 54
  5. The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation. (PMID: 29845934) Faust TB … Frankel AD (eLife 2018) 3 54

Products for CMBL Gene

Sources for CMBL Gene