Q96DG6 (CMBL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxymethylenebutenolidase homolog
EC=3.1.-.-

Gene names

Name:

CMBL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Cytoplasm › cytosol 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 component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.5
	Chain	2 – 245	244	Carboxymethylenebutenolidase homolog		PRO_0000308188
Sites
	Active site	132	1
	Active site	179	1	By similarity
	Active site	212	1	By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.5
	Modified residue	36	1	N6-acetyllysine Ref.6
Natural variations
	Natural variant	155	1	Y → C. Corresponds to variant rs35489000 [ dbSNP | Ensembl ].		VAR_036751
Experimental info
	Mutagenesis	132	1	C → A: 97% inhibition of enzymatic activity. Ref.7
	Mutagenesis	132	1	C → S: 70% inhibition of enzymatic activity. Ref.7
	Sequence conflict	99	1	K → N in BAB85014. Ref.2
	Sequence conflict	104	1	Q → H in BAB85014. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q96DG6 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 222A22E3AD859495	FASTA	245	28,048
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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, MASS SPECTROMETRY.
[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: MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-132.
[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.
IPI	IPI00383046.
RefSeq	NP_620164.1. NM_138809.3.
UniGene	Hs.192586.
3D structure databases
ProteinModelPortal	Q96DG6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96DG6. 1 interaction.
STRING	9606.ENSP00000296658.
PTM databases
PhosphoSite	Q96DG6.
Polymorphism databases
DMDM	74731452.
Proteomic databases
PaxDb	Q96DG6.
PeptideAtlas	Q96DG6.
PRIDE	Q96DG6.
Protocols and materials databases
DNASU	134147.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296658; ENSP00000296658; ENSG00000164237.
GeneID	134147.
KEGG	hsa:134147.
UCSC	uc003jes.3. human.
Organism-specific databases
CTD	134147.
GeneCards	GC05M010275.
HGNC	HGNC:25090. CMBL.
HPA	HPA036571.
MIM	613379. gene.
neXtProt	NX_Q96DG6.
PharmGKB	PA162382521.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0412.
HOGENOM	HOG000241423.
HOVERGEN	HBG057427.
InParanoid	Q96DG6.
KO	K01061.
OMA	CFGGGRV.
OrthoDB	EOG4W3SNQ.
PhylomeDB	Q96DG6.
Gene expression databases
Bgee	Q96DG6.
CleanEx	HS_CMBL.
Genevestigator	Q96DG6.
Family and domain databases
InterPro	IPR002925. Dienelactn_hydro. [Graphical view]
Pfam	PF01738. DLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CMBL. human.
GenomeRNAi	134147.
NextBio	83328.
SOURCE	Search...

Entry information

Entry name

CMBL_HUMAN

Accession

Primary (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 3, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.