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P22760 (AAAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Arylacetamide deacetylase

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

Protein attributes

Sequence length399 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly. Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity. Ref.7 Ref.8 Ref.10 Ref.11 Ref.13

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.8 Ref.11.

Tissue specificity

Detected in liver (at protein level). Mainly expressed in liver, small intestine, colon, adrenal gland and bladder. Ref.8 Ref.10 Ref.11

Induction

Down-regulated following infection with hepatis C virus which results in impaired triacylglycerol lipolysis and impaired assembly of very low density lipoproteins. This may represent a cellular adaptation to infection that is aimed at limiting viral production. Ref.13

Post-translational modification

Glycosylation is required for enzyme activity.

Polymorphism

Three alleles are known: AADAC*1, AADAC*2 and AADAC*3. The sequence shown is that of AADAC*1 which is found in European American, African American, Japanese and Korean populations at allelic frequencies of 39.3 to 47.4%. The AADAC*2 allele is found in European American, African American, Korean, and Japanese populations at allelic frequencies of 52.6 to 63.5% whereas the AADAC*3 allele is found in European American (1.3%) and African American (2.0%) samples but not in Japanese or Korean samples.

Miscellaneous

Can hydrolyze a number of clinical drugs such as flutamide, an antiandrogen drug used for the treatment of prostate cancer; phenacetin, an analgesic antipyretic which has been withdrawn from the market due to its links with renal failure; and rifamycins which have been used as antituberculosis drugs.

Sequence similarities

Belongs to the 'GDXG' lipolytic enzyme family.

Biophysicochemical properties

Kinetic parameters:

KM=0.8 mM for flutamide (Ref.8) Ref.8 Ref.10 Ref.11 Ref.12

KM=0.6 mM for flutamide (Ref.10)

KM=0.472 mM for flutamide (Ref.11)

KM=3.05 mM for phenacetin (Ref.12)

KM=1.8 mM for phenacetin (Ref.10)

KM=1.42 mM for phenacetin (Ref.11)

KM=0.2 mM for rifampicin (Ref.10)

KM=0.154 mM for rifampicin (Ref.11)

Vmax=1.1 nmol/min/mg enzyme toward flutamide (Ref.8)

Vmax=1.1 nmol/min/mg enzyme toward flutamide (Ref.10)

Vmax=0.617 nmol/min/mg enzyme toward flutamide (Ref.11)

Vmax=1.34 nmol/min/mg enzyme toward phenacetin (Ref.12)

Vmax=6.4 nmol/min/mg enzyme toward phenacetin (Ref.10)

Vmax=1.42 nmol/min/mg enzyme toward phenacetin (Ref.11)

Vmax=0.149 nmol/min/mg enzyme toward rifampicin (Ref.10)

Vmax=0.060 nmol/min/mg enzyme toward rifampicin (Ref.11)

Sequence caution

The sequence AAA35551.1 differs from that shown. Reason: Frameshift at positions 53 and 56.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 399399Arylacetamide deacetylase
PRO_0000071542

Regions

Topological domain1 – 55Cytoplasmic Potential
Transmembrane6 – 2318Helical; Signal-anchor for type II membrane protein; Potential
Topological domain24 – 399376Lumenal Potential
Motif111 – 1133Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole By similarity

Sites

Active site1111 Potential
Active site1891 Potential

Amino acid modifications

Glycosylation781N-linked (GlcNAc...) Ref.9 Ref.12
Glycosylation2821N-linked (GlcNAc...) Ref.9 Ref.12
Disulfide bond116 ↔ 340 By similarity

Natural variations

Natural variant2811V → I in alleles AADAC*2 and AADAC*3; mildly decreased enzyme activity. Ref.1 Ref.2 Ref.4 Ref.11 Ref.14
Corresponds to variant rs1803155 [ dbSNP | Ensembl ].
VAR_014798
Natural variant3991L → LQ in allele AADAC*3; decreased enzyme activity.
VAR_070543

Experimental info

Mutagenesis781N → Q: Abolishes glycosylation at this site and causes moderate decrease in activity. Ref.12
Mutagenesis2821N → Q: Abolishes glycosylation at this site and causes substantial decrease in activity and reduced substrate affinity. Ref.12
Sequence conflict31R → M AA sequence Ref.6
Sequence conflict55 – 573LHH → VHI in AAA35551. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P22760 [UniParc].

Last modified January 11, 2011. Version 5.
Checksum: 34F9CB717DD7417A

FASTA39945,734
        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 VNWSSLLPER FIKGHVYNNP 

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

       370        380        390 
VQVTHNHVED GFHGAFSFLG LKISHRLINQ YIEWLKENL 

« Hide

References

« 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT ILE-281.
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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-281.
Tissue: Heart.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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], VARIANT ILE-281.
[5]"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: Colon.
[6]"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] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION.
Tissue: Liver.
[7]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-78 AND ASN-282.
Tissue: Liver.
[10]"Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse."
Kobayashi Y., Fukami T., Nakajima A., Watanabe A., Nakajima M., Yokoi T.
Drug Metab. Dispos. 40:671-679(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, TISSUE SPECIFICITY.
[11]"A novel polymorphic allele of human arylacetamide deacetylase leads to decreased enzyme activity."
Shimizu M., Fukami T., Kobayashi Y., Takamiya M., Aoki Y., Nakajima M., Yokoi T.
Drug Metab. Dispos. 40:1183-1190(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ILE-281 AND GLN-399 EXT, CHARACTERIZATION OF VARIANTS ILE-281 AND GLN-399 EXT.
[12]"N-Glycosylation during translation is essential for human arylacetamide deacetylase enzyme activity."
Muta K., Fukami T., Nakajima M., Yokoi T.
Biochem. Pharmacol. 87:352-359(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION AT ASN-78 AND ASN-282, MUTAGENESIS OF ASN-78 AND ASN-282.
[13]"Arylacetamide deacetylase: a novel host factor with important roles in the lipolysis of cellular triacylglycerol stores, VLDL assembly and HCV production."
Nourbakhsh M., Douglas D.N., Pu C.H., Lewis J.T., Kawahara T., Lisboa L.F., Wei E., Asthana S., Quiroga A.D., Law L.M., Chen C., Addison W.R., Nelson R., Houghton M., Lehner R., Kneteman N.M.
J. Hepatol. 59:336-343(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[14]"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] [Europe PMC] [Abstract]
Cited for: VARIANT ILE-281.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L32179 mRNA. Translation: AAA35551.1. Frameshift.
AK290628 mRNA. Translation: BAF83317.1.
AC068647 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78791.1.
CH471052 Genomic DNA. Translation: EAW78792.1.
BC032309 mRNA. Translation: AAH32309.1.
CCDSCCDS33877.1.
PIRA53856.
RefSeqNP_001077.2. NM_001086.2.
XP_005247160.1. XM_005247103.2.
UniGeneHs.506908.

3D structure databases

ProteinModelPortalP22760.
SMRP22760. Positions 69-379.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106531. 1 interaction.
STRING9606.ENSP00000232892.

Protein family/group databases

MEROPSS09.991.

PTM databases

PhosphoSiteP22760.

Polymorphism databases

DMDM317373587.

Proteomic databases

PaxDbP22760.
PRIDEP22760.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000232892; ENSP00000232892; ENSG00000114771.
GeneID13.
KEGGhsa:13.
UCSCuc003eze.3. human.

Organism-specific databases

CTD13.
GeneCardsGC03P151531.
HGNCHGNC:17. AADAC.
HPAHPA002911.
MIM600338. gene.
neXtProtNX_P22760.
PharmGKBPA24363.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0657.
HOGENOMHOG000033738.
HOVERGENHBG058974.
InParanoidP22760.
KOK13616.
OMAYVYEPIP.
OrthoDBEOG7HB599.
PhylomeDBP22760.
TreeFamTF314978.

Enzyme and pathway databases

SABIO-RKP22760.

Gene expression databases

ArrayExpressP22760.
BgeeP22760.
CleanExHS_AADAC.
GenevestigatorP22760.

Family and domain databases

Gene3D3.40.50.1820. 2 hits.
InterProIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR017157. Arylacetamide_deacetylase.
IPR002168. Lipase_GDXG_AS.
[Graphical view]
PfamPF07859. Abhydrolase_3. 2 hits.
[Graphical view]
PIRSFPIRSF037251. Arylacetamide_deacetylase. 1 hit.
SUPFAMSSF53474. SSF53474. 1 hit.
PROSITEPS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAADAC.
GenomeRNAi13.
NextBio27.
PROP22760.
SOURCESearch...

Entry information

Entry nameAAAD_HUMAN
AccessionPrimary (citable) accession number: P22760
Secondary accession number(s): A8K3L3, D3DNJ6, Q8N1A9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 133 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM