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Protein

Carboxymethylenebutenolidase homolog

Gene

CMBL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Enzyme regulationi

Strongly inhibited by p-chloromercuribenzoate (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP). Not inhibited by DFP, PMSF, eserine or EDTA.

Kineticsi

  1. KM=170 µM for olmesartan medoxomil1 Publication
  2. KM=283 µM for faropenem medoxomil1 Publication
  3. KM=63.4 µM for lenampicillin1 Publication
  1. Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil1 Publication
  2. Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil1 Publication
  3. Vmax=4 nmol/min/mg enzyme toward lenampicillin1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1321
Active sitei179By similarity1
Active sitei212By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase

Enzyme and pathway databases

ReactomeiR-HSA-211945 Phase I - Functionalization of compounds

Protein family/group databases

ESTHERihuman-CMBL Dienelactone_hydrolase

Names & Taxonomyi

Protein namesi
Recommended name:
Carboxymethylenebutenolidase homolog (EC:3.1.-.-)
Gene namesi
Name:CMBL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164237.8
HGNCiHGNC:25090 CMBL
MIMi613379 gene
neXtProtiNX_Q96DG6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132C → A: 97% inhibition of enzymatic activity. 1 Publication1
Mutagenesisi132C → S: 70% inhibition of enzymatic activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000164237
PharmGKBiPA162382521

Polymorphism and mutation databases

BioMutaiCMBL
DMDMi74731452

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00003081882 – 245Carboxymethylenebutenolidase homologAdd BLAST244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei36N6-acetyllysineCombined sources1
Modified residuei223PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96DG6
MaxQBiQ96DG6
PaxDbiQ96DG6
PeptideAtlasiQ96DG6
PRIDEiQ96DG6

PTM databases

CarbonylDBiQ96DG6
iPTMnetiQ96DG6
PhosphoSitePlusiQ96DG6

Expressioni

Tissue specificityi

Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000164237
CleanExiHS_CMBL
GenevisibleiQ96DG6 HS

Organism-specific databases

HPAiHPA036571

Interactioni

Protein-protein interaction databases

BioGridi126387, 16 interactors
IntActiQ96DG6, 15 interactors
STRINGi9606.ENSP00000296658

Structurei

3D structure databases

ProteinModelPortaliQ96DG6
SMRiQ96DG6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the dienelactone hydrolase family.Curated

Phylogenomic databases

eggNOGiKOG3043 Eukaryota
COG0412 LUCA
GeneTreeiENSGT00390000000183
HOGENOMiHOG000241423
HOVERGENiHBG057427
InParanoidiQ96DG6
KOiK01061
OMAiVHEHIAD
OrthoDBiEOG091G0F2J
PhylomeDBiQ96DG6
TreeFamiTF331795

Family and domain databases

Gene3Di3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002925 Dienelactn_hydro
PfamiView protein in Pfam
PF01738 DLH, 1 hit
SUPFAMiSSF53474 SSF53474, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96DG6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANEAYPCPC DIGHRLEYGG LGREVQVEHI KAYVTKSPVD AGKAVIVIQD
60 70 80 90 100
IFGWQLPNTR YIADMISGNG YTTIVPDFFV GQEPWDPSGD WSIFPEWLKT
110 120 130 140 150
RNAQKIDREI SAILKYLKQQ CHAQKIGIVG FCWGGTAVHH LMMKYSEFRA
160 170 180 190 200
GVSVYGIVKD SEDIYNLKNP TLFIFAENDV VIPLKDVSLL TQKLKEHCKV
210 220 230 240
EYQIKTFSGQ THGFVHRKRE DCSPADKPYI DEARRNLIEW LNKYM
Length:245
Mass (Da):28,048
Last modified:December 1, 2001 - v1
Checksum:i222A22E3AD859495
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99K → N in BAB85014 (PubMed:14702039).Curated1
Sequence conflicti104Q → H in BAB85014 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036751155Y → C. Corresponds to variant dbSNP:rs35489000Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ278125 mRNA Translation: CAC81950.1
AK074197 mRNA Translation: BAB85014.1
CH471102 Genomic DNA Translation: EAX08070.1
CH471102 Genomic DNA Translation: EAX08071.1
BC001573 mRNA Translation: AAH01573.1
CCDSiCCDS3878.1
RefSeqiNP_620164.1, NM_138809.3
XP_016864523.1, XM_017009034.1
XP_016864524.1, XM_017009035.1
UniGeneiHs.192586

Genome annotation databases

EnsembliENST00000296658; ENSP00000296658; ENSG00000164237
GeneIDi134147
KEGGihsa:134147
UCSCiuc003jes.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCMBL_HUMAN
AccessioniPrimary (citable) accession number: Q96DG6
Secondary accession number(s): D3DTC7, Q8TED6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: December 1, 2001
Last modified: April 25, 2018
This is version 134 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health