Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q96DG6

- CMBL_HUMAN

UniProt

Q96DG6 - CMBL_HUMAN

Protein

Carboxymethylenebutenolidase homolog

Gene

CMBL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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. cytosol Source: UniProtKB-SubCell
    2. extracellular vesicular exosome Source: UniProt

    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.
    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

    MANEAYPCPC DIGHRLEYGG LGREVQVEHI KAYVTKSPVD AGKAVIVIQD    50
    IFGWQLPNTR YIADMISGNG YTTIVPDFFV GQEPWDPSGD WSIFPEWLKT 100
    RNAQKIDREI SAILKYLKQQ CHAQKIGIVG FCWGGTAVHH LMMKYSEFRA 150
    GVSVYGIVKD SEDIYNLKNP TLFIFAENDV VIPLKDVSLL TQKLKEHCKV 200
    EYQIKTFSGQ THGFVHRKRE DCSPADKPYI DEARRNLIEW LNKYM 245
    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.
    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

    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 1, 2014
    This is version 105 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