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Q96DG6 (CMBL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxymethylenebutenolidase homolog

EC=3.1.-.-
Gene names
Name:CMBL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length245 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7

Enzyme regulation

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

Subcellular location

Cytoplasmcytosol Ref.7.

Tissue specificity

Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level). Ref.7

Sequence similarities

Belongs to the dienelactone hydrolase family.

Biophysicochemical properties

Kinetic parameters:

KM=170 µM for olmesartan medoxomil Ref.7

KM=283 µM for faropenem medoxomil

KM=63.4 µM for lenampicillin

Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil

Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil

Vmax=4 nmol/min/mg enzyme toward lenampicillin

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   Molecular functionHydrolase
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

   Molecular_functionhydrolase activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 245244Carboxymethylenebutenolidase homolog
PRO_0000308188

Sites

Active site1321
Active site1791 By similarity
Active site2121 By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.5
Modified residue361N6-acetyllysine Ref.6

Natural variations

Natural variant1551Y → C.
Corresponds to variant rs35489000 [ dbSNP | Ensembl ].
VAR_036751

Experimental info

Mutagenesis1321C → A: 97% inhibition of enzymatic activity. Ref.7
Mutagenesis1321C → S: 70% inhibition of enzymatic activity. Ref.7
Sequence conflict991K → N in BAB85014. Ref.2
Sequence conflict1041Q → H in BAB85014. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q96DG6 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 222A22E3AD859495

FASTA24528,048
        10         20         30         40         50         60 
MANEAYPCPC DIGHRLEYGG LGREVQVEHI KAYVTKSPVD AGKAVIVIQD IFGWQLPNTR 

        70         80         90        100        110        120 
YIADMISGNG YTTIVPDFFV GQEPWDPSGD WSIFPEWLKT RNAQKIDREI SAILKYLKQQ 

       130        140        150        160        170        180 
CHAQKIGIVG FCWGGTAVHH LMMKYSEFRA GVSVYGIVKD SEDIYNLKNP TLFIFAENDV 

       190        200        210        220        230        240 
VIPLKDVSLL TQKLKEHCKV EYQIKTFSGQ THGFVHRKRE DCSPADKPYI DEARRNLIEW 


LNKYM 

« Hide

References

« Hide 'large scale' references
[1]"Full length sequencing of some human and murine muscular transcripts (Telethon Italy project B41)."
Ievolella C., Zara I., Millino C., Faulkner G., Lanfranchi G.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skeletal muscle.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Adipose tissue.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]Bienvenut W.V., Calvo F., Kolch W.
Submitted (MAR-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-31; 150-168; 206-217 AND 236-245, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[6]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Human carboxymethylenebutenolidase as a bioactivating hydrolase of olmesartan medoxomil in liver and intestine."
Ishizuka T., Fujimori I., Kato M., Noji-Sakikawa C., Saito M., Yoshigae Y., Kubota K., Kurihara A., Izumi T., Ikeda T., Okazaki O.
J. Biol. Chem. 285:11892-11902(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-132, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_620164.1. NM_138809.3.
UniGeneHs.192586.

3D structure databases

ProteinModelPortalQ96DG6.
SMRQ96DG6. Positions 29-192.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid126387. 10 interactions.
IntActQ96DG6. 1 interaction.
STRING9606.ENSP00000296658.

PTM databases

PhosphoSiteQ96DG6.

Polymorphism databases

DMDM74731452.

Proteomic databases

PaxDbQ96DG6.
PeptideAtlasQ96DG6.
PRIDEQ96DG6.

Protocols and materials databases

DNASU134147.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296658; ENSP00000296658; ENSG00000164237.
GeneID134147.
KEGGhsa:134147.
UCSCuc003jes.3. human.

Organism-specific databases

CTD134147.
GeneCardsGC05M010275.
HGNCHGNC:25090. CMBL.
HPAHPA036571.
MIM613379. gene.
neXtProtNX_Q96DG6.
PharmGKBPA162382521.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0412.
HOGENOMHOG000241423.
HOVERGENHBG057427.
InParanoidQ96DG6.
KOK01061.
OMAFRAGVSI.
OrthoDBEOG7F24TH.
PhylomeDBQ96DG6.
TreeFamTF331795.

Gene expression databases

BgeeQ96DG6.
CleanExHS_CMBL.
GenevestigatorQ96DG6.

Family and domain databases

InterProIPR002925. Dienelactn_hydro.
[Graphical view]
PfamPF01738. DLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCMBL. human.
GenomeRNAi134147.
NextBio83328.
PROQ96DG6.
SOURCESearch...

Entry information

Entry nameCMBL_HUMAN
AccessionPrimary (citable) accession number: Q96DG6
Secondary accession number(s): D3DTC7, Q8TED6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM