P22760 (AAAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Arylacetamide deacetylase
EC=3.1.1.3

Gene names

Name:	AADAC
Synonyms:	DAC

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	399 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	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 occasionally causes severe hepatotoxicity. Displays cellular triglyceride lipase activity in liver. Increases intracellular fatty acids derived from hydrolysis of newly formed triglyceride stores. Ref.7 Ref.8
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.
Tissue specificity	Mainly expressed in liver, small intestine, colon and adrenal gland. Ref.8
Sequence similarities	Belongs to the 'GDXG' lipolytic enzyme family.
Biophysicochemical properties	Kinetic parameters: KM=0.8 mM for flutamide Ref.8 Vmax=1.1 nmol/min/mg enzyme toward flutamide
Sequence caution	The sequence AAA35551.1 differs from that shown. Reason: Frameshift at positions 53 and 56.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of triglyceride catabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Inferred from direct assay PubMed 10318829PubMed 15152005Ref.8. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	carboxylesterase activity Inferred from electronic annotation. Source: InterPro deacetylase activity Inferred from direct assay PubMed 9665742. Source: UniProtKB retinyl-palmitate esterase activity Inferred from electronic annotation. Source: EC serine hydrolase activity Inferred from direct assay Ref.7. Source: UniProtKB triglyceride lipase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 399	398	Arylacetamide deacetylase		PRO_0000071542
Regions
	Topological domain	2 – 5	4	Cytoplasmic Potential
	Transmembrane	6 – 23	18	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	24 – 399	376	Lumenal Potential
Sites
	Active site	111	1	Potential
	Active site	189	1	Potential
Amino acid modifications
	Glycosylation	78	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	282	1	N-linked (GlcNAc...) Ref.9
	Disulfide bond	116 ↔ 340		By similarity
Natural variations
	Natural variant	281	1	V → I. Ref.1 Ref.2 Ref.4 Ref.10 Corresponds to variant rs1803155 [ dbSNP | Ensembl ].		VAR_014798
Experimental info
	Sequence conflict	3	1	R → M AA sequence Ref.6
	Sequence conflict	55 – 57	3	LHH → VHI in AAA35551. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P22760 [UniParc]. Last modified January 11, 2011. Version 5. Checksum: 34F9CB717DD7417A	FASTA	399	45,734
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. Tissue: Liver.
[10]	"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.
IPI	IPI00383879.
PIR	A53856.
RefSeq	NP_001077.2. NM_001086.2.
UniGene	Hs.506908.
3D structure databases
ProteinModelPortal	P22760.
SMR	P22760. Positions 69-379.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000232892.
Protein family/group databases
MEROPS	S09.991.
PTM databases
PhosphoSite	P22760.
Polymorphism databases
DMDM	57015294.
Proteomic databases
PaxDb	P22760.
PRIDE	P22760.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000232892; ENSP00000232892; ENSG00000114771.
GeneID	13.
KEGG	hsa:13.
UCSC	uc003eze.3. human.
Organism-specific databases
CTD	13.
GeneCards	GC03P151531.
HGNC	HGNC:17. AADAC.
HPA	HPA002911.
MIM	600338. gene.
neXtProt	NX_P22760.
PharmGKB	PA24363.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0657.
HOGENOM	HOG000033738.
HOVERGEN	HBG058974.
InParanoid	P22760.
KO	K13616.
OMA	SGYEMYL.
OrthoDB	EOG41NTM4.
PhylomeDB	P22760.
Enzyme and pathway databases
SABIO-RK	P22760.
Gene expression databases
ArrayExpress	P22760.
Bgee	P22760.
CleanEx	HS_AADAC.
Genevestigator	P22760.
GermOnline	ENSG00000114771. Homo sapiens.
Family and domain databases
InterPro	IPR013094. AB_hydrolase_3. IPR017157. Arylacetamide_deacetylase. IPR002168. Lipase_GDXG_AS. [Graphical view]
Pfam	PF07859. Abhydrolase_3. 2 hits. [Graphical view]
PIRSF	PIRSF037251. Arylacetamide_deacetylase. 1 hit.
PROSITE	PS01173. LIPASE_GDXG_HIS. False negative. PS01174. LIPASE_GDXG_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	13.
NextBio	27.
SOURCE	Search...

Entry information

Entry name

AAAD_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 123 of the entry and version 5 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.