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Protein

Carboxymethylenebutenolidase homolog

Gene

CMBL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciZFISH:HS09043-MONOMER.
ReactomeiR-HSA-211945. Phase 1 - 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

HGNCiHGNC:25090. CMBL.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

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

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. 15 interactors.
IntActiQ96DG6. 7 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.
OMAiGGLECYA.
OrthoDBiEOG091G0F2J.
PhylomeDBiQ96DG6.
TreeFamiTF331795.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002925. Dienelactn_hydro.
[Graphical view]
PfamiPF01738. DLH. 1 hit.
[Graphical view]
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 rs35489000dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ96DG6.
SMRiQ96DG6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi126387. 15 interactors.
IntActiQ96DG6. 7 interactors.
STRINGi9606.ENSP00000296658.

Protein family/group databases

ESTHERihuman-CMBL. Dienelactone_hydrolase.

PTM databases

iPTMnetiQ96DG6.
PhosphoSitePlusiQ96DG6.

Polymorphism and mutation databases

BioMutaiCMBL.
DMDMi74731452.

Proteomic databases

EPDiQ96DG6.
MaxQBiQ96DG6.
PaxDbiQ96DG6.
PeptideAtlasiQ96DG6.
PRIDEiQ96DG6.

Protocols and materials databases

DNASUi134147.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi134147.
GeneCardsiCMBL.
HGNCiHGNC:25090. CMBL.
HPAiHPA036571.
MIMi613379. gene.
neXtProtiNX_Q96DG6.
OpenTargetsiENSG00000164237.
PharmGKBiPA162382521.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS09043-MONOMER.
ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.

Miscellaneous databases

ChiTaRSiCMBL. human.
GenomeRNAii134147.
PROiQ96DG6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164237.
CleanExiHS_CMBL.
GenevisibleiQ96DG6. HS.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002925. Dienelactn_hydro.
[Graphical view]
PfamiPF01738. DLH. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCMBL_HUMAN
AccessioniPrimary (citable) accession number: Q96DG6
Secondary accession number(s): D3DTC7, Q8TED6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: December 1, 2001
Last modified: November 2, 2016
This is version 126 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.