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Q96DG6

- CMBL_HUMAN

UniProt

Q96DG6 - CMBL_HUMAN

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Protein

Carboxymethylenebutenolidase homolog

Gene

CMBL

Organism
Homo sapiens (Human)
Status
Reviewed - 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

Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil1 Publication

Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil1 Publication

Vmax=4 nmol/min/mg enzyme toward lenampicillin1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei132 – 1321
Active sitei179 – 1791By similarity
Active sitei212 – 2121By similarity

GO - Molecular functioni

  1. hydrolase activity Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Names & Taxonomyi

Protein namesi
Recommended name:
Carboxymethylenebutenolidase homolog (EC:3.1.-.-)
Gene namesi
Name:CMBL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:25090. CMBL.

Subcellular locationi

Cytoplasmcytosol 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi132 – 1321C → A: 97% inhibition of enzymatic activity. 1 Publication
Mutagenesisi132 – 1321C → S: 70% inhibition of enzymatic activity. 1 Publication

Organism-specific databases

PharmGKBiPA162382521.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 245244Carboxymethylenebutenolidase homologPRO_0000308188Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei36 – 361N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ96DG6.
PaxDbiQ96DG6.
PeptideAtlasiQ96DG6.
PRIDEiQ96DG6.

PTM databases

PhosphoSiteiQ96DG6.

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

BgeeiQ96DG6.
CleanExiHS_CMBL.
GenevestigatoriQ96DG6.

Organism-specific databases

HPAiHPA036571.

Interactioni

Protein-protein interaction databases

BioGridi126387. 10 interactions.
IntActiQ96DG6. 1 interaction.
STRINGi9606.ENSP00000296658.

Structurei

3D structure databases

ProteinModelPortaliQ96DG6.
SMRiQ96DG6. Positions 29-192.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the dienelactone hydrolase family.Curated

Phylogenomic databases

eggNOGiCOG0412.
GeneTreeiENSGT00390000000183.
HOGENOMiHOG000241423.
HOVERGENiHBG057427.
InParanoidiQ96DG6.
KOiK01061.
OMAiFRAGVSI.
OrthoDBiEOG7F24TH.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti99 – 991K → N in BAB85014. (PubMed:14702039)Curated
Sequence conflicti104 – 1041Q → H in BAB85014. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti155 – 1551Y → C.
Corresponds to variant rs35489000 [ dbSNP | Ensembl ].
VAR_036751

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGeneiHs.192586.

Genome annotation databases

EnsembliENST00000296658; ENSP00000296658; ENSG00000164237.
GeneIDi134147.
KEGGihsa:134147.
UCSCiuc003jes.3. human.

Polymorphism databases

DMDMi74731452.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS3878.1.
RefSeqi NP_620164.1. NM_138809.3.
UniGenei Hs.192586.

3D structure databases

ProteinModelPortali Q96DG6.
SMRi Q96DG6. Positions 29-192.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 126387. 10 interactions.
IntActi Q96DG6. 1 interaction.
STRINGi 9606.ENSP00000296658.

PTM databases

PhosphoSitei Q96DG6.

Polymorphism databases

DMDMi 74731452.

Proteomic databases

MaxQBi Q96DG6.
PaxDbi Q96DG6.
PeptideAtlasi Q96DG6.
PRIDEi Q96DG6.

Protocols and materials databases

DNASUi 134147.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296658 ; ENSP00000296658 ; ENSG00000164237 .
GeneIDi 134147.
KEGGi hsa:134147.
UCSCi uc003jes.3. human.

Organism-specific databases

CTDi 134147.
GeneCardsi GC05M010275.
HGNCi HGNC:25090. CMBL.
HPAi HPA036571.
MIMi 613379. gene.
neXtProti NX_Q96DG6.
PharmGKBi PA162382521.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0412.
GeneTreei ENSGT00390000000183.
HOGENOMi HOG000241423.
HOVERGENi HBG057427.
InParanoidi Q96DG6.
KOi K01061.
OMAi FRAGVSI.
OrthoDBi EOG7F24TH.
PhylomeDBi Q96DG6.
TreeFami TF331795.

Miscellaneous databases

ChiTaRSi CMBL. human.
GenomeRNAii 134147.
NextBioi 83328.
PROi Q96DG6.
SOURCEi Search...

Gene expression databases

Bgeei Q96DG6.
CleanExi HS_CMBL.
Genevestigatori Q96DG6.

Family and domain databases

Gene3Di 3.40.50.1820. 1 hit.
InterProi IPR029058. AB_hydrolase.
IPR002925. Dienelactn_hydro.
[Graphical view ]
Pfami PF01738. DLH. 1 hit.
[Graphical view ]
SUPFAMi SSF53474. SSF53474. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: October 29, 2014
This is version 106 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

External Data

Dasty 3