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Reviewed, UniProtKB/Swiss-Prot P22760 (AAAD_HUMAN)

Last modified July 13, 2010. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
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Names and originHide

Protein namesRecommended name:
Arylacetamide deacetylase

EC=3.1.1.3
Gene names
Name:AADAC
Synonyms:DAC
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
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Protein attributesHide

Sequence length399 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.
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General annotation (Comments)Hide

Function

Arylacetamide deacetylation is an important enzyme activity in the metabolic activation of arylamine substrates to ultimate carcinogens. Displays major serine hydrolase activity in liver microsomes. Hydrolyzes also flutamide, which is an antiandrogen drug used for the treatment of prostate cancer that occasionnaly causes severe hepatotoxicity. Displays cellular triglyceride lipase activity in liver. Increases intracellular fatty acids derived from hydrolysis of newly formed triglyceride stores. Ref.6 Ref.7

Catalytic activity

Triacylglycerol + H2O = diacylglycerol + a carboxylate.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein. Microsome membrane; Single-pass type II membrane protein Ref.7.

Tissue specificity

Mainly expressed in liver, small intestine, colon and adrenal gland. Ref.7

Sequence similarities

Belongs to the 'GDXG' lipolytic enzyme family.

Biophysicochemical properties

Kinetic parameters:

KM=0.8 mM for flutamide

Vmax=1.1 nmol/min/mg enzyme toward flutamide

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Sequence annotation (Features)Hide

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 399398Arylacetamide deacetylase
PRO_0000071542

Regions

Topological domain2 – 54Cytoplasmic Potential
Transmembrane6 – 2318Helical; Signal-anchor for type II membrane protein; Potential
Topological domain24 – 399376Lumenal Potential

Sites

Active site1111 Potential
Active site1891 Potential

Amino acid modifications

Glycosylation781N-linked (GlcNAc...) Ref.8
Glycosylation2821N-linked (GlcNAc...) Ref.8
Disulfide bond116 ↔ 340 By similarity

Natural variations

Natural variant2811I → V. [dbSNP:rs1803155] Ref.4 Ref.9
VAR_014798

Experimental info

Sequence conflict31R → M AA sequence Ref.5
Sequence conflict53 – 575LGLHH → HGSSI in AAA35551. Ref.1
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SequencesHide

Sequence LengthMass (Da)Tools
P22760-1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 6BF9CB7162D74966

FASTA39945,748
        10         20         30         40         50         60 
MGRKSLYLLI VGILIAYYIY TPLPDNVEEP WRMMWINAHL KTIQNLATFV ELLGLHHFMD 

        70         80         90        100        110        120 
SFKVVGSFDE VPPTSDENVT VTETKFNNIL VRVYVPKRKS EALRRGLFYI HGGGWCVGSA 

       130        140        150        160        170        180 
ALSGYDLLSR WTADRLDAVV VSTNYRLAPK YHFPIQFEDV YNALRWFLRK KVLAKYGVNP 

       190        200        210        220        230        240 
ERIGISGDSA GGNLAAAVTQ QLLDDPDVKI KLKIQSLIYP ALQPLDVDLP SYQENSNFLF 

       250        260        270        280        290        300 
LSKSLMVRFW SEYFTTDRSL EKAMLSRQHV PVESSHLFKF INWSSLLPER FIKGHVYNNP 

       310        320        330        340        350        360 
NYGSSELAKK YPGFLDVRAA PLLADDNKLR GLPLTYVITC QYDLLRDDGL MYVTRLRNTG 

       370        380        390 
VQVTHNHVED GFHGAFSFLG LKISHRLINQ YIEWLKENL 

« Hide

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ReferencesHide

« Hide 'large scale' references
[1]"Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase."
Probst M.R., Beer M., Beer D., Jenoe P., Meyer U.A., Gasser R.
J. Biol. Chem. 269:21650-21656(1994) [PubMed: 8063807] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Heart.
[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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-281.
Tissue: Colon.
[5]"Purification and characterization of a human liver arylacetamide deacetylase."
Probst M.R., Jenoe P., Meyer U.A.
Biochem. Biophys. Res. Commun. 177:453-459(1991) [PubMed: 2043131] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION.
Tissue: Liver.
[6]"Human carboxylesterases and their role in xenobiotic and endobiotic metabolism."
Ross M.K., Crow J.A.
J. Biochem. Mol. Toxicol. 21:187-196(2007) [PubMed: 17936933] [Abstract]
Cited for: FUNCTION.
[7]"Human arylacetamide deacetylase is a principal enzyme in flutamide hydrolysis."
Watanabe A., Fukami T., Nakajima M., Takamiya M., Aoki Y., Yokoi T.
Drug Metab. Dispos. 37:1513-1520(2009) [PubMed: 19339378] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
[8]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78 AND ASN-282, MASS SPECTROMETRY.
Tissue: Liver.
[9]"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population."
Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y.
J. Hum. Genet. 48:249-270(2003) [PubMed: 12721789] [Abstract]
Cited for: VARIANT VAL-281.
+Additional computationally mapped references.
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Cross-referencesHide

Sequence databases

EMBL
GenBank
DDBJ
L32179 mRNA. Translation: AAA35551.1.
AK290628 mRNA. Translation: BAF83317.1.
CH471052 Genomic DNA. Translation: EAW78791.1.
BC032309 mRNA. Translation: AAH32309.1.
IPIIPI00383879.
PIRA53856.
RefSeqNP_001077.2.
UniGeneHs.506908

3D structure databases

SMRP22760. Positions 87-397.
ModBaseSearch...

Protein-protein interaction databases

STRINGP22760.

Protein family/group databases

MEROPSS09.991.

Proteomic databases

PRIDEP22760.

Genome annotation databases

EnsemblENST00000232892; ENSP00000232892; ENSG00000114771; Homo sapiens. [Genome view]
GeneID13.
KEGGhsa:13.

Organism-specific databases

CTD13.
GeneCardsGC03P153014.
HGNCHGNC:17. AADAC.
HPAHPA002911.
MIM600338. gene.
PharmGKBPA24363.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11671.
HOGENOMHBG757640.
HOVERGENHBG058974.
InParanoidP22760.

Gene expression databases

ArrayExpressP22760.
BgeeP22760.
CleanExHS_AADAC.
GenevestigatorP22760.
GermOnlineENSG00000114771. Homo sapiens.

Family and domain databases

InterProIPR013094. AB_hydrolase_3.
IPR017157. Arylacetamide_deacetylase.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamPF07859. Abhydrolase_3. 2 hits.
[Graphical view]
PIRSFPIRSF037251. Arylacetamide_deacetylase. 1 hit.
PROSITEPS01173. LIPASE_GDXG_HIS. False negative.
PS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio27.
SOURCESearch...
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Entry informationHide

Entry nameAAAD_HUMAN
AccessionPrimary (citable) accession number: P22760
Secondary accession number(s): A8K3L3, Q8N1A9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2007
Last modified: July 13, 2010
This is version 101 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.
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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents