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Protein

Arylacetamide deacetylase

Gene

AADAC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.5 Publications

Catalytic activityi

Triacylglycerol + H2O = diacylglycerol + a carboxylate.

Kineticsi

  1. KM=0.8 mM for flutamide4 Publications
  2. KM=0.6 mM for flutamide4 Publications
  3. KM=0.472 mM for flutamide4 Publications
  4. KM=3.05 mM for phenacetin4 Publications
  5. KM=1.8 mM for phenacetin4 Publications
  6. KM=1.42 mM for phenacetin4 Publications
  7. KM=0.2 mM for rifampicin4 Publications
  8. KM=0.154 mM for rifampicin4 Publications
  1. Vmax=1.1 nmol/min/mg enzyme toward flutamide4 Publications
  2. Vmax=1.1 nmol/min/mg enzyme toward flutamide4 Publications
  3. Vmax=0.617 nmol/min/mg enzyme toward flutamide4 Publications
  4. Vmax=1.34 nmol/min/mg enzyme toward phenacetin4 Publications
  5. Vmax=6.4 nmol/min/mg enzyme toward phenacetin4 Publications
  6. Vmax=1.42 nmol/min/mg enzyme toward phenacetin4 Publications
  7. Vmax=0.149 nmol/min/mg enzyme toward rifampicin4 Publications
  8. Vmax=0.060 nmol/min/mg enzyme toward rifampicin4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei189PROSITE-ProRule annotationBy similarity1
Active sitei343By similarity1
Active sitei373By similarity1

GO - Molecular functioni

  • catalytic activity Source: ProtInc
  • deacetylase activity Source: UniProtKB
  • lipase activity Source: UniProtKB
  • serine hydrolase activity Source: UniProtKB
  • triglyceride lipase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114771-MONOMER.
ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
SABIO-RKP22760.

Protein family/group databases

ESTHERihuman-AADAC. Hormone-sensitive_lipase_like_1.
MEROPSiS09.991.

Names & Taxonomyi

Protein namesi
Recommended name:
Arylacetamide deacetylase (EC:3.1.1.3)
Gene namesi
Name:AADAC
Synonyms:DAC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17. AADAC.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 5CytoplasmicSequence analysis5
Transmembranei6 – 23Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST18
Topological domaini24 – 399LumenalSequence analysisAdd BLAST376

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi78N → Q: Abolishes glycosylation at this site and causes moderate decrease in activity. 1 Publication1
Mutagenesisi282N → Q: Abolishes glycosylation at this site and causes substantial decrease in activity and reduced substrate affinity. 1 Publication1

Organism-specific databases

DisGeNETi13.
OpenTargetsiENSG00000114771.
PharmGKBiPA24363.

Chemistry databases

ChEMBLiCHEMBL3509584.

Polymorphism and mutation databases

BioMutaiAADAC.
DMDMi317373587.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000715421 – 399Arylacetamide deacetylaseAdd BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi78N-linked (GlcNAc...)2 Publications1
Disulfide bondi116 ↔ 340By similarity
Glycosylationi282N-linked (GlcNAc...)2 Publications1

Post-translational modificationi

Glycosylation is required for enzyme activity.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP22760.
PeptideAtlasiP22760.
PRIDEiP22760.

PTM databases

iPTMnetiP22760.
PhosphoSitePlusiP22760.

Expressioni

Tissue specificityi

Detected in liver (at protein level). Mainly expressed in liver, small intestine, colon, adrenal gland and bladder.3 Publications

Inductioni

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.1 Publication

Gene expression databases

BgeeiENSG00000114771.
CleanExiHS_AADAC.
ExpressionAtlasiP22760. baseline and differential.
GenevisibleiP22760. HS.

Organism-specific databases

HPAiHPA002911.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000232892.

Chemistry databases

BindingDBiP22760.

Structurei

3D structure databases

ProteinModelPortaliP22760.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi111 – 113Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion holeBy similarity3

Sequence similaritiesi

Belongs to the 'GDXG' lipolytic enzyme family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1515. Eukaryota.
COG0657. LUCA.
GeneTreeiENSGT00550000074556.
HOGENOMiHOG000033738.
HOVERGENiHBG058974.
InParanoidiP22760.
KOiK13616.
OMAiRENAHYP.
OrthoDBiEOG091G082E.
PhylomeDBiP22760.
TreeFamiTF314978.

Family and domain databases

Gene3Di3.40.50.1820. 2 hits.
InterProiIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR017157. Arylacetamide_deacetylase.
IPR033140. Lipase_GDXG_put_SER_AS.
[Graphical view]
PfamiPF07859. Abhydrolase_3. 2 hits.
[Graphical view]
PIRSFiPIRSF037251. Arylacetamide_deacetylase. 1 hit.
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P22760-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRKSLYLLI VGILIAYYIY TPLPDNVEEP WRMMWINAHL KTIQNLATFV
60 70 80 90 100
ELLGLHHFMD SFKVVGSFDE VPPTSDENVT VTETKFNNIL VRVYVPKRKS
110 120 130 140 150
EALRRGLFYI HGGGWCVGSA ALSGYDLLSR WTADRLDAVV VSTNYRLAPK
160 170 180 190 200
YHFPIQFEDV YNALRWFLRK KVLAKYGVNP ERIGISGDSA GGNLAAAVTQ
210 220 230 240 250
QLLDDPDVKI KLKIQSLIYP ALQPLDVDLP SYQENSNFLF LSKSLMVRFW
260 270 280 290 300
SEYFTTDRSL EKAMLSRQHV PVESSHLFKF VNWSSLLPER FIKGHVYNNP
310 320 330 340 350
NYGSSELAKK YPGFLDVRAA PLLADDNKLR GLPLTYVITC QYDLLRDDGL
360 370 380 390
MYVTRLRNTG VQVTHNHVED GFHGAFSFLG LKISHRLINQ YIEWLKENL
Length:399
Mass (Da):45,734
Last modified:January 11, 2011 - v5
Checksum:i34F9CB717DD7417A
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3R → M AA sequence (PubMed:2043131).Curated1
Sequence conflicti55 – 57LHH → VHI in AAA35551 (PubMed:8063807).Curated3

Polymorphismi

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.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_014798281V → I in alleles AADAC*2 and AADAC*3; mildly decreased enzyme activity. 5 PublicationsCorresponds to variant rs1803155dbSNPEnsembl.1
Natural variantiVAR_070543399L → LQ in allele AADAC*3; decreased enzyme activity. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS33877.1.
PIRiA53856.
RefSeqiNP_001077.2. NM_001086.2.
UniGeneiHs.506908.

Genome annotation databases

EnsembliENST00000232892; ENSP00000232892; ENSG00000114771.
GeneIDi13.
KEGGihsa:13.
UCSCiuc003eze.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS33877.1.
PIRiA53856.
RefSeqiNP_001077.2. NM_001086.2.
UniGeneiHs.506908.

3D structure databases

ProteinModelPortaliP22760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000232892.

Chemistry databases

BindingDBiP22760.
ChEMBLiCHEMBL3509584.

Protein family/group databases

ESTHERihuman-AADAC. Hormone-sensitive_lipase_like_1.
MEROPSiS09.991.

PTM databases

iPTMnetiP22760.
PhosphoSitePlusiP22760.

Polymorphism and mutation databases

BioMutaiAADAC.
DMDMi317373587.

Proteomic databases

PaxDbiP22760.
PeptideAtlasiP22760.
PRIDEiP22760.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000232892; ENSP00000232892; ENSG00000114771.
GeneIDi13.
KEGGihsa:13.
UCSCiuc003eze.4. human.

Organism-specific databases

CTDi13.
DisGeNETi13.
GeneCardsiAADAC.
HGNCiHGNC:17. AADAC.
HPAiHPA002911.
MIMi600338. gene.
neXtProtiNX_P22760.
OpenTargetsiENSG00000114771.
PharmGKBiPA24363.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1515. Eukaryota.
COG0657. LUCA.
GeneTreeiENSGT00550000074556.
HOGENOMiHOG000033738.
HOVERGENiHBG058974.
InParanoidiP22760.
KOiK13616.
OMAiRENAHYP.
OrthoDBiEOG091G082E.
PhylomeDBiP22760.
TreeFamiTF314978.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114771-MONOMER.
ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
SABIO-RKP22760.

Miscellaneous databases

GeneWikiiAADAC.
GenomeRNAii13.
PROiP22760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114771.
CleanExiHS_AADAC.
ExpressionAtlasiP22760. baseline and differential.
GenevisibleiP22760. HS.

Family and domain databases

Gene3Di3.40.50.1820. 2 hits.
InterProiIPR029058. AB_hydrolase.
IPR013094. AB_hydrolase_3.
IPR017157. Arylacetamide_deacetylase.
IPR033140. Lipase_GDXG_put_SER_AS.
[Graphical view]
PfamiPF07859. Abhydrolase_3. 2 hits.
[Graphical view]
PIRSFiPIRSF037251. Arylacetamide_deacetylase. 1 hit.
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS01174. LIPASE_GDXG_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAAAD_HUMAN
AccessioniPrimary (citable) accession number: P22760
Secondary accession number(s): A8K3L3, D3DNJ6, Q8N1A9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 11, 2011
Last modified: November 2, 2016
This is version 154 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.