Full text data of CMBL
CMBL
[Confidence: low (only semi-automatic identification from reviews)]
Carboxymethylenebutenolidase homolog; 3.1.-.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Carboxymethylenebutenolidase homolog; 3.1.-.-
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96DG6
ID CMBL_HUMAN Reviewed; 245 AA.
AC Q96DG6; D3DTC7; Q8TED6;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Carboxymethylenebutenolidase homolog;
DE EC=3.1.-.-;
GN Name=CMBL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RA Ievolella C., Zara I., Millino C., Faulkner G., Lanfranchi G.;
RT "Full length sequencing of some human and murine muscular transcripts
RT (Telethon Italy project B41).";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-31; 150-168; 206-217 AND 236-245, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-132.
RX PubMed=20177059; DOI=10.1074/jbc.M109.072629;
RA Ishizuka T., Fujimori I., Kato M., Noji-Sakikawa C., Saito M.,
RA Yoshigae Y., Kubota K., Kurihara A., Izumi T., Ikeda T., Okazaki O.;
RT "Human carboxymethylenebutenolidase as a bioactivating hydrolase of
RT olmesartan medoxomil in liver and intestine.";
RL J. Biol. Chem. 285:11892-11902(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Cysteine hydrolase. Can convert the prodrug olmesartan
CC medoxomil into its pharmacologically active metabolite
CC olmerstatan, an angiotensin receptor blocker, in liver and
CC intestine. May also activate beta-lactam antibiotics faropenem
CC medoxomil and lenampicillin.
CC -!- ENZYME REGULATION: Strongly inhibited by p-chloromercuribenzoate
CC (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP).
CC Not inhibited by DFP, PMSF, eserine or EDTA.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=170 uM for olmesartan medoxomil;
CC KM=283 uM for faropenem medoxomil;
CC KM=63.4 uM for lenampicillin;
CC Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil;
CC Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil;
CC Vmax=4 nmol/min/mg enzyme toward lenampicillin;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in
CC liver, followed by kidney, small intestine and colon. Present in
CC liver and intestine (at protein level).
CC -!- SIMILARITY: Belongs to the dienelactone hydrolase family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AJ278125; CAC81950.1; -; mRNA.
DR EMBL; AK074197; BAB85014.1; -; mRNA.
DR EMBL; CH471102; EAX08070.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08071.1; -; Genomic_DNA.
DR EMBL; BC001573; AAH01573.1; -; mRNA.
DR RefSeq; NP_620164.1; NM_138809.3.
DR UniGene; Hs.192586; -.
DR ProteinModelPortal; Q96DG6; -.
DR SMR; Q96DG6; 29-192.
DR IntAct; Q96DG6; 1.
DR STRING; 9606.ENSP00000296658; -.
DR PhosphoSite; Q96DG6; -.
DR DMDM; 74731452; -.
DR PaxDb; Q96DG6; -.
DR PeptideAtlas; Q96DG6; -.
DR PRIDE; Q96DG6; -.
DR DNASU; 134147; -.
DR Ensembl; ENST00000296658; ENSP00000296658; ENSG00000164237.
DR GeneID; 134147; -.
DR KEGG; hsa:134147; -.
DR UCSC; uc003jes.3; human.
DR CTD; 134147; -.
DR GeneCards; GC05M010275; -.
DR HGNC; HGNC:25090; CMBL.
DR HPA; HPA036571; -.
DR MIM; 613379; gene.
DR neXtProt; NX_Q96DG6; -.
DR PharmGKB; PA162382521; -.
DR eggNOG; COG0412; -.
DR HOGENOM; HOG000241423; -.
DR HOVERGEN; HBG057427; -.
DR InParanoid; Q96DG6; -.
DR KO; K01061; -.
DR OMA; FRAGVSI; -.
DR OrthoDB; EOG7F24TH; -.
DR PhylomeDB; Q96DG6; -.
DR ChiTaRS; CMBL; human.
DR GenomeRNAi; 134147; -.
DR NextBio; 83328; -.
DR PRO; PR:Q96DG6; -.
DR Bgee; Q96DG6; -.
DR CleanEx; HS_CMBL; -.
DR Genevestigator; Q96DG6; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR InterPro; IPR002925; Dienelactn_hydro.
DR Pfam; PF01738; DLH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 245 Carboxymethylenebutenolidase homolog.
FT /FTId=PRO_0000308188.
FT ACT_SITE 132 132
FT ACT_SITE 179 179 By similarity.
FT ACT_SITE 212 212 By similarity.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 36 36 N6-acetyllysine.
FT VARIANT 155 155 Y -> C (in dbSNP:rs35489000).
FT /FTId=VAR_036751.
FT MUTAGEN 132 132 C->A: 97% inhibition of enzymatic
FT activity.
FT MUTAGEN 132 132 C->S: 70% inhibition of enzymatic
FT activity.
FT CONFLICT 99 99 K -> N (in Ref. 2; BAB85014).
FT CONFLICT 104 104 Q -> H (in Ref. 2; BAB85014).
SQ SEQUENCE 245 AA; 28048 MW; 222A22E3AD859495 CRC64;
MANEAYPCPC DIGHRLEYGG LGREVQVEHI KAYVTKSPVD AGKAVIVIQD IFGWQLPNTR
YIADMISGNG YTTIVPDFFV GQEPWDPSGD WSIFPEWLKT RNAQKIDREI SAILKYLKQQ
CHAQKIGIVG FCWGGTAVHH LMMKYSEFRA GVSVYGIVKD SEDIYNLKNP TLFIFAENDV
VIPLKDVSLL TQKLKEHCKV EYQIKTFSGQ THGFVHRKRE DCSPADKPYI DEARRNLIEW
LNKYM
//
ID CMBL_HUMAN Reviewed; 245 AA.
AC Q96DG6; D3DTC7; Q8TED6;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-DEC-2001, sequence version 1.
DT 22-JAN-2014, entry version 98.
DE RecName: Full=Carboxymethylenebutenolidase homolog;
DE EC=3.1.-.-;
GN Name=CMBL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skeletal muscle;
RA Ievolella C., Zara I., Millino C., Faulkner G., Lanfranchi G.;
RT "Full length sequencing of some human and murine muscular transcripts
RT (Telethon Italy project B41).";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adipose tissue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-31; 150-168; 206-217 AND 236-245, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Calvo F., Kolch W.;
RL Submitted (MAR-2008) to UniProtKB.
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-36, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [7]
RP MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-132.
RX PubMed=20177059; DOI=10.1074/jbc.M109.072629;
RA Ishizuka T., Fujimori I., Kato M., Noji-Sakikawa C., Saito M.,
RA Yoshigae Y., Kubota K., Kurihara A., Izumi T., Ikeda T., Okazaki O.;
RT "Human carboxymethylenebutenolidase as a bioactivating hydrolase of
RT olmesartan medoxomil in liver and intestine.";
RL J. Biol. Chem. 285:11892-11902(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Cysteine hydrolase. Can convert the prodrug olmesartan
CC medoxomil into its pharmacologically active metabolite
CC olmerstatan, an angiotensin receptor blocker, in liver and
CC intestine. May also activate beta-lactam antibiotics faropenem
CC medoxomil and lenampicillin.
CC -!- ENZYME REGULATION: Strongly inhibited by p-chloromercuribenzoate
CC (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP).
CC Not inhibited by DFP, PMSF, eserine or EDTA.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=170 uM for olmesartan medoxomil;
CC KM=283 uM for faropenem medoxomil;
CC KM=63.4 uM for lenampicillin;
CC Vmax=24.6 nmol/min/mg enzyme toward olmesartan medoxomil;
CC Vmax=16.4 nmol/min/mg enzyme toward faropenem medoxomil;
CC Vmax=4 nmol/min/mg enzyme toward lenampicillin;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in
CC liver, followed by kidney, small intestine and colon. Present in
CC liver and intestine (at protein level).
CC -!- SIMILARITY: Belongs to the dienelactone hydrolase family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AJ278125; CAC81950.1; -; mRNA.
DR EMBL; AK074197; BAB85014.1; -; mRNA.
DR EMBL; CH471102; EAX08070.1; -; Genomic_DNA.
DR EMBL; CH471102; EAX08071.1; -; Genomic_DNA.
DR EMBL; BC001573; AAH01573.1; -; mRNA.
DR RefSeq; NP_620164.1; NM_138809.3.
DR UniGene; Hs.192586; -.
DR ProteinModelPortal; Q96DG6; -.
DR SMR; Q96DG6; 29-192.
DR IntAct; Q96DG6; 1.
DR STRING; 9606.ENSP00000296658; -.
DR PhosphoSite; Q96DG6; -.
DR DMDM; 74731452; -.
DR PaxDb; Q96DG6; -.
DR PeptideAtlas; Q96DG6; -.
DR PRIDE; Q96DG6; -.
DR DNASU; 134147; -.
DR Ensembl; ENST00000296658; ENSP00000296658; ENSG00000164237.
DR GeneID; 134147; -.
DR KEGG; hsa:134147; -.
DR UCSC; uc003jes.3; human.
DR CTD; 134147; -.
DR GeneCards; GC05M010275; -.
DR HGNC; HGNC:25090; CMBL.
DR HPA; HPA036571; -.
DR MIM; 613379; gene.
DR neXtProt; NX_Q96DG6; -.
DR PharmGKB; PA162382521; -.
DR eggNOG; COG0412; -.
DR HOGENOM; HOG000241423; -.
DR HOVERGEN; HBG057427; -.
DR InParanoid; Q96DG6; -.
DR KO; K01061; -.
DR OMA; FRAGVSI; -.
DR OrthoDB; EOG7F24TH; -.
DR PhylomeDB; Q96DG6; -.
DR ChiTaRS; CMBL; human.
DR GenomeRNAi; 134147; -.
DR NextBio; 83328; -.
DR PRO; PR:Q96DG6; -.
DR Bgee; Q96DG6; -.
DR CleanEx; HS_CMBL; -.
DR Genevestigator; Q96DG6; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR InterPro; IPR002925; Dienelactn_hydro.
DR Pfam; PF01738; DLH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 245 Carboxymethylenebutenolidase homolog.
FT /FTId=PRO_0000308188.
FT ACT_SITE 132 132
FT ACT_SITE 179 179 By similarity.
FT ACT_SITE 212 212 By similarity.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 36 36 N6-acetyllysine.
FT VARIANT 155 155 Y -> C (in dbSNP:rs35489000).
FT /FTId=VAR_036751.
FT MUTAGEN 132 132 C->A: 97% inhibition of enzymatic
FT activity.
FT MUTAGEN 132 132 C->S: 70% inhibition of enzymatic
FT activity.
FT CONFLICT 99 99 K -> N (in Ref. 2; BAB85014).
FT CONFLICT 104 104 Q -> H (in Ref. 2; BAB85014).
SQ SEQUENCE 245 AA; 28048 MW; 222A22E3AD859495 CRC64;
MANEAYPCPC DIGHRLEYGG LGREVQVEHI KAYVTKSPVD AGKAVIVIQD IFGWQLPNTR
YIADMISGNG YTTIVPDFFV GQEPWDPSGD WSIFPEWLKT RNAQKIDREI SAILKYLKQQ
CHAQKIGIVG FCWGGTAVHH LMMKYSEFRA GVSVYGIVKD SEDIYNLKNP TLFIFAENDV
VIPLKDVSLL TQKLKEHCKV EYQIKTFSGQ THGFVHRKRE DCSPADKPYI DEARRNLIEW
LNKYM
//
MIM
613379
*RECORD*
*FIELD* NO
613379
*FIELD* TI
*613379 CARBOXYMETHYLENEBUTENOLIDASE-LIKE PROTEIN; CMBL
;;CARBOXYMETHYLENEBUTENOLIDASE, PSEUDOMONAS, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase
family that is highly expressed in liver cytosol. CMBL preferentially
cleaves cyclic esters, and it activates medoxomil-ester prodrugs in
which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al.,
2010).
CLONING
By mass spectrometry of purified cytosolic human liver CMBL, followed by
database analysis and PCR of a human liver and skeletal muscle cDNA
library, Ishizuka et al. (2010) cloned CMBL. The deduced 245-amino acid
protein has a calculated molecular mass of 28 kD. CMBL has a C-terminal
dienelactone hydrolase domain containing a catalytic triad of cys132,
asp179, and his212. Quantitative RT-PCR detected variable CMBL
expression in all tissues examined, with highest expression in liver,
followed by kidney, small intestine, and colon. Lowest expression was in
brain, thymus, bone marrow, and placenta. Fetal liver and brain also
showed relatively low expression. Western blot analysis confirmed
expression of CMBL in cytosolic fractions of human liver and intestine.
The endogenous protein had an apparent molecular mass of 30 kD.
GENE FUNCTION
Using transfected HEK293 cells, Ishizuka et al. (2010) showed that CMBL
hydrolyzed the angiotensin receptor (AGTR1; 106165) blocker olmesartan
medoxomil to the bioavailable molecule olmesartan with simple
Michaelis-Menten kinetics. It also catalyzed the hydrolytic activation
of other medoxomil-ester prodrugs with the medoxomil moiety linked to an
oxygen atom, but not those with medoxomil linked to a nitrogen atom.
CMBL appeared to prefer cyclic esters over simple esters and amides, and
it did not hydrolyze typical esterase substrates. Inhibitor studies
showed that CMBL was sensitive to a carboxylesterase inhibitor and a
free thiol modifier, indicating that CMBL is a cysteine hydrolase.
Site-directed mutagenesis confirmed that cys132 is the catalytic
cysteine in CMBL.
GENE STRUCTURE
Ishizuka et al. (2010) determined that the CMBL gene contains 5 exons.
MAPPING
By genomic sequence analysis, Ishizuka et al. (2010) mapped the CMBL
gene to chromosome 5p15.2. They mapped the mouse Cmbl gene to chromosome
15B2.
*FIELD* RF
1. Ishizuka, T.; Fujimori, I.; Kato, M.; Noji-Sakikawa, C.; Saito,
M.; Yoshigae, Y.; Kubota, K.; Kurihara, A.; Izumi, T.; Ikeda, T.;
Okazaki, O.: Human carboxymethylenebutenolidase as a bioactivating
hydrolase of olmesartan medoxomil in liver and intestine. J. Biol.
Chem. 285: 11892-11902, 2010.
*FIELD* CD
Patricia A. Hartz: 4/23/2010
*FIELD* ED
mgross: 04/23/2010
*RECORD*
*FIELD* NO
613379
*FIELD* TI
*613379 CARBOXYMETHYLENEBUTENOLIDASE-LIKE PROTEIN; CMBL
;;CARBOXYMETHYLENEBUTENOLIDASE, PSEUDOMONAS, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase
family that is highly expressed in liver cytosol. CMBL preferentially
cleaves cyclic esters, and it activates medoxomil-ester prodrugs in
which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al.,
2010).
CLONING
By mass spectrometry of purified cytosolic human liver CMBL, followed by
database analysis and PCR of a human liver and skeletal muscle cDNA
library, Ishizuka et al. (2010) cloned CMBL. The deduced 245-amino acid
protein has a calculated molecular mass of 28 kD. CMBL has a C-terminal
dienelactone hydrolase domain containing a catalytic triad of cys132,
asp179, and his212. Quantitative RT-PCR detected variable CMBL
expression in all tissues examined, with highest expression in liver,
followed by kidney, small intestine, and colon. Lowest expression was in
brain, thymus, bone marrow, and placenta. Fetal liver and brain also
showed relatively low expression. Western blot analysis confirmed
expression of CMBL in cytosolic fractions of human liver and intestine.
The endogenous protein had an apparent molecular mass of 30 kD.
GENE FUNCTION
Using transfected HEK293 cells, Ishizuka et al. (2010) showed that CMBL
hydrolyzed the angiotensin receptor (AGTR1; 106165) blocker olmesartan
medoxomil to the bioavailable molecule olmesartan with simple
Michaelis-Menten kinetics. It also catalyzed the hydrolytic activation
of other medoxomil-ester prodrugs with the medoxomil moiety linked to an
oxygen atom, but not those with medoxomil linked to a nitrogen atom.
CMBL appeared to prefer cyclic esters over simple esters and amides, and
it did not hydrolyze typical esterase substrates. Inhibitor studies
showed that CMBL was sensitive to a carboxylesterase inhibitor and a
free thiol modifier, indicating that CMBL is a cysteine hydrolase.
Site-directed mutagenesis confirmed that cys132 is the catalytic
cysteine in CMBL.
GENE STRUCTURE
Ishizuka et al. (2010) determined that the CMBL gene contains 5 exons.
MAPPING
By genomic sequence analysis, Ishizuka et al. (2010) mapped the CMBL
gene to chromosome 5p15.2. They mapped the mouse Cmbl gene to chromosome
15B2.
*FIELD* RF
1. Ishizuka, T.; Fujimori, I.; Kato, M.; Noji-Sakikawa, C.; Saito,
M.; Yoshigae, Y.; Kubota, K.; Kurihara, A.; Izumi, T.; Ikeda, T.;
Okazaki, O.: Human carboxymethylenebutenolidase as a bioactivating
hydrolase of olmesartan medoxomil in liver and intestine. J. Biol.
Chem. 285: 11892-11902, 2010.
*FIELD* CD
Patricia A. Hartz: 4/23/2010
*FIELD* ED
mgross: 04/23/2010