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Protein

Aminoacylase-1

Gene

ACY1

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

Functioni

Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate).1 Publication

Catalytic activityi

An N-acyl-aliphatic-L-amino acid + H2O = an aliphatic L-amino acid + a carboxylate.1 Publication
An N-acetyl-L-cysteine-S-conjugate + H2O = an L-cysteine-S-conjugate + acetate.1 Publication

Cofactori

Zn2+1 PublicationNote: Binds 2 Zn2+ ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi80Zinc 11
Active sitei82By similarity1
Metal bindingi113Zinc 11
Metal bindingi113Zinc 21
Active sitei147Proton acceptor1 Publication1
Metal bindingi148Zinc 21
Metal bindingi175Zinc 11
Metal bindingi373Zinc 21

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS03800-MONOMER.
ZFISH:HS03800-MONOMER.
BRENDAi3.5.1.14. 2681.
ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
SABIO-RKQ03154.

Protein family/group databases

MEROPSiM20.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Aminoacylase-1 (EC:3.5.1.14)
Short name:
ACY-1
Alternative name(s):
N-acyl-L-amino-acid amidohydrolase
Gene namesi
Name:ACY1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:177. ACY1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Aminoacylase-1 deficiency (ACY1D)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn enzymatic deficiency resulting in encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.
See also OMIM:609924
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043113197R → W in ACY1D; loss of activity. 2 PublicationsCorresponds to variant rs121912700dbSNPEnsembl.1
Natural variantiVAR_026104233E → D in ACY1D; loss of activity. 2 PublicationsCorresponds to variant rs121912699dbSNPEnsembl.1
Natural variantiVAR_026105353R → C in ACY1D; loss of activity. 4 PublicationsCorresponds to variant rs121912698dbSNPEnsembl.1
Natural variantiVAR_065562378R → Q in ACY1D. 1 PublicationCorresponds to variant rs150480963dbSNPEnsembl.1
Natural variantiVAR_065563378R → W in ACY1D; slightly reduced activity. 1 PublicationCorresponds to variant rs148346337dbSNPEnsembl.1
Natural variantiVAR_020452386R → C in ACY1D; loss of activity. 1 PublicationCorresponds to variant rs2229152dbSNPEnsembl.1
Natural variantiVAR_043114393R → H in ACY1D. 1 PublicationCorresponds to variant rs121912701dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi80H → A: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi113D → A: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi147E → A or Q: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi147E → D: Decreased protein stability. Loss of enzyme activity. 1 Publication1
Mutagenesisi148E → A: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi175E → A: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi206H → N: Almost abolishes enzyme activity. 1 Publication1
Mutagenesisi373H → A: Almost abolishes enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi95.
MalaCardsiACY1.
MIMi609924. phenotype.
OpenTargetsiENSG00000243989.
Orphaneti137754. Neurological conditions associated with aminoacylase 1 deficiency.
PharmGKBiPA24497.

Chemistry databases

DrugBankiDB06151. Acetylcysteine.
DB00128. L-Aspartic Acid.

Polymorphism and mutation databases

BioMutaiACY1.
DMDMi461466.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001852362 – 408Aminoacylase-1Add BLAST407

Proteomic databases

EPDiQ03154.
PaxDbiQ03154.
PeptideAtlasiQ03154.
PRIDEiQ03154.

2D gel databases

REPRODUCTION-2DPAGEIPI00009268.

PTM databases

iPTMnetiQ03154.
PhosphoSitePlusiQ03154.

Expressioni

Tissue specificityi

Expression is highest in kidney, strong in brain and weaker in placenta and spleen.1 Publication

Gene expression databases

BgeeiENSG00000243989.
CleanExiHS_ACY1.
ExpressionAtlasiQ03154. baseline and differential.
GenevisibleiQ03154. HS.

Organism-specific databases

HPAiCAB003695.
HPA036174.
HPA036175.

Interactioni

Subunit structurei

Homodimer. Interacts with SPHK1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-742064,EBI-742064
TERF1P542742EBI-742064,EBI-710997

Protein-protein interaction databases

BioGridi106610. 23 interactors.
IntActiQ03154. 11 interactors.
MINTiMINT-4999851.
STRINGi9606.ENSP00000384296.

Structurei

Secondary structure

1408
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 20Combined sources10
Helixi31 – 45Combined sources15
Beta strandi48 – 55Combined sources8
Beta strandi58 – 65Combined sources8
Beta strandi74 – 80Combined sources7
Helixi88 – 90Combined sources3
Turni95 – 97Combined sources3
Beta strandi104 – 107Combined sources4
Turni109 – 114Combined sources6
Helixi115 – 130Combined sources16
Beta strandi139 – 145Combined sources7
Helixi147 – 149Combined sources3
Turni152 – 154Combined sources3
Helixi155 – 158Combined sources4
Helixi162 – 165Combined sources4
Beta strandi169 – 174Combined sources6
Beta strandi180 – 188Combined sources9
Helixi194 – 196Combined sources3
Helixi322 – 333Combined sources12
Beta strandi338 – 342Combined sources5
Helixi348 – 354Combined sources7
Beta strandi359 – 362Combined sources4
Beta strandi378 – 380Combined sources3
Helixi381 – 399Combined sources19
Helixi405 – 407Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Q7LX-ray1.40A/C1-198[»]
B/D321-408[»]
ProteinModelPortaliQ03154.
SMRiQ03154.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ03154.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M20A family.Curated

Phylogenomic databases

eggNOGiKOG2275. Eukaryota.
COG0624. LUCA.
GeneTreeiENSGT00840000129850.
HOGENOMiHOG000021196.
HOVERGENiHBG000982.
InParanoidiQ03154.
KOiK14677.
OrthoDBiEOG091G0A7U.
PhylomeDBiQ03154.
TreeFamiTF313693.

Family and domain databases

CDDicd05646. M20_AcylaseI_like. 1 hit.
Gene3Di3.30.70.360. 1 hit.
InterProiIPR001261. ArgE/DapE_CS.
IPR010159. N-acyl_aa_amidohydrolase.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamiPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFiPIRSF036696. ACY-1. 1 hit.
SUPFAMiSSF55031. SSF55031. 1 hit.
TIGRFAMsiTIGR01880. Ac-peptdase-euk. 1 hit.
PROSITEiPS00758. ARGE_DAPE_CPG2_1. 1 hit.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q03154-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTSKGPEEEH PSVTLFRQYL RIRTVQPKPD YGAAVAFFEE TARQLGLGCQ
60 70 80 90 100
KVEVAPGYVV TVLTWPGTNP TLSSILLNSH TDVVPVFKEH WSHDPFEAFK
110 120 130 140 150
DSEGYIYARG AQDMKCVSIQ YLEAVRRLKV EGHRFPRTIH MTFVPDEEVG
160 170 180 190 200
GHQGMELFVQ RPEFHALRAG FALDEGIANP TDAFTVFYSE RSPWWVRVTS
210 220 230 240 250
TGRPGHASRF MEDTAAEKLH KVVNSILAFR EKEWQRLQSN PHLKEGSVTS
260 270 280 290 300
VNLTKLEGGV AYNVIPATMS ASFDFRVAPD VDFKAFEEQL QSWCQAAGEG
310 320 330 340 350
VTLEFAQKWM HPQVTPTDDS NPWWAAFSRV CKDMNLTLEP EIMPAATDNR
360 370 380 390 400
YIRAVGVPAL GFSPMNRTPV LLHDHDERLH EAVFLRGVDI YTRLLPALAS

VPALPSDS
Length:408
Mass (Da):45,885
Last modified:February 1, 1994 - v1
Checksum:i293350CD7759826C
GO
Isoform 2 (identifier: Q03154-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     103-174: Missing.

Note: Gene prediction based on EST data.
Show »
Length:336
Mass (Da):37,597
Checksum:i68C1E4266A8CBE70
GO
Isoform 3 (identifier: Q03154-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     220-284: Missing.

Note: Gene prediction based on EST data.
Show »
Length:343
Mass (Da):38,629
Checksum:i75F9FBDC8348189E
GO
Isoform 4 (identifier: Q03154-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-66: Missing.

Note: Gene prediction based on EST data.
Show »
Length:373
Mass (Da):42,195
Checksum:i343DC089BDBDC22F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051805179N → S.Corresponds to variant rs887540dbSNPEnsembl.1
Natural variantiVAR_043113197R → W in ACY1D; loss of activity. 2 PublicationsCorresponds to variant rs121912700dbSNPEnsembl.1
Natural variantiVAR_026104233E → D in ACY1D; loss of activity. 2 PublicationsCorresponds to variant rs121912699dbSNPEnsembl.1
Natural variantiVAR_026105353R → C in ACY1D; loss of activity. 4 PublicationsCorresponds to variant rs121912698dbSNPEnsembl.1
Natural variantiVAR_065562378R → Q in ACY1D. 1 PublicationCorresponds to variant rs150480963dbSNPEnsembl.1
Natural variantiVAR_065563378R → W in ACY1D; slightly reduced activity. 1 PublicationCorresponds to variant rs148346337dbSNPEnsembl.1
Natural variantiVAR_036076381E → D in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_020452386R → C in ACY1D; loss of activity. 1 PublicationCorresponds to variant rs2229152dbSNPEnsembl.1
Natural variantiVAR_043114393R → H in ACY1D. 1 PublicationCorresponds to variant rs121912701dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04687632 – 66Missing in isoform 4. CuratedAdd BLAST35
Alternative sequenceiVSP_046877103 – 174Missing in isoform 2. CuratedAdd BLAST72
Alternative sequenceiVSP_046878220 – 284Missing in isoform 3. CuratedAdd BLAST65

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07548 mRNA. Translation: AAA02852.1.
D14524 mRNA. Translation: BAA03397.1.
D16307 mRNA. Translation: BAA03814.1.
AC115284 Genomic DNA. No translation available.
BC000545 mRNA. Translation: AAH00545.1.
BC003023 mRNA. Translation: AAH03023.1.
BC014112 mRNA. Translation: AAH14112.1.
CCDSiCCDS2844.1. [Q03154-1]
CCDS56261.1. [Q03154-2]
CCDS56262.1. [Q03154-3]
CCDS56263.1. [Q03154-4]
PIRiA47488.
RefSeqiNP_000657.1. NM_000666.2. [Q03154-1]
NP_001185824.1. NM_001198895.1. [Q03154-1]
NP_001185825.1. NM_001198896.1. [Q03154-2]
NP_001185826.1. NM_001198897.1. [Q03154-3]
NP_001185827.1. NM_001198898.1. [Q03154-4]
UniGeneiHs.334707.

Genome annotation databases

EnsembliENST00000404366; ENSP00000384296; ENSG00000243989. [Q03154-1]
ENST00000476351; ENSP00000417056; ENSG00000243989. [Q03154-4]
ENST00000476854; ENSP00000419262; ENSG00000243989. [Q03154-3]
ENST00000494103; ENSP00000417618; ENSG00000243989. [Q03154-2]
ENST00000636358; ENSP00000490149; ENSG00000243989. [Q03154-1]
GeneIDi95.
KEGGihsa:95.
UCSCiuc021wzb.2. human. [Q03154-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L07548 mRNA. Translation: AAA02852.1.
D14524 mRNA. Translation: BAA03397.1.
D16307 mRNA. Translation: BAA03814.1.
AC115284 Genomic DNA. No translation available.
BC000545 mRNA. Translation: AAH00545.1.
BC003023 mRNA. Translation: AAH03023.1.
BC014112 mRNA. Translation: AAH14112.1.
CCDSiCCDS2844.1. [Q03154-1]
CCDS56261.1. [Q03154-2]
CCDS56262.1. [Q03154-3]
CCDS56263.1. [Q03154-4]
PIRiA47488.
RefSeqiNP_000657.1. NM_000666.2. [Q03154-1]
NP_001185824.1. NM_001198895.1. [Q03154-1]
NP_001185825.1. NM_001198896.1. [Q03154-2]
NP_001185826.1. NM_001198897.1. [Q03154-3]
NP_001185827.1. NM_001198898.1. [Q03154-4]
UniGeneiHs.334707.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Q7LX-ray1.40A/C1-198[»]
B/D321-408[»]
ProteinModelPortaliQ03154.
SMRiQ03154.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106610. 23 interactors.
IntActiQ03154. 11 interactors.
MINTiMINT-4999851.
STRINGi9606.ENSP00000384296.

Chemistry databases

DrugBankiDB06151. Acetylcysteine.
DB00128. L-Aspartic Acid.

Protein family/group databases

MEROPSiM20.973.

PTM databases

iPTMnetiQ03154.
PhosphoSitePlusiQ03154.

Polymorphism and mutation databases

BioMutaiACY1.
DMDMi461466.

2D gel databases

REPRODUCTION-2DPAGEIPI00009268.

Proteomic databases

EPDiQ03154.
PaxDbiQ03154.
PeptideAtlasiQ03154.
PRIDEiQ03154.

Protocols and materials databases

DNASUi95.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000404366; ENSP00000384296; ENSG00000243989. [Q03154-1]
ENST00000476351; ENSP00000417056; ENSG00000243989. [Q03154-4]
ENST00000476854; ENSP00000419262; ENSG00000243989. [Q03154-3]
ENST00000494103; ENSP00000417618; ENSG00000243989. [Q03154-2]
ENST00000636358; ENSP00000490149; ENSG00000243989. [Q03154-1]
GeneIDi95.
KEGGihsa:95.
UCSCiuc021wzb.2. human. [Q03154-1]

Organism-specific databases

CTDi95.
DisGeNETi95.
GeneCardsiACY1.
HGNCiHGNC:177. ACY1.
HPAiCAB003695.
HPA036174.
HPA036175.
MalaCardsiACY1.
MIMi104620. gene.
609924. phenotype.
neXtProtiNX_Q03154.
OpenTargetsiENSG00000243989.
Orphaneti137754. Neurological conditions associated with aminoacylase 1 deficiency.
PharmGKBiPA24497.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2275. Eukaryota.
COG0624. LUCA.
GeneTreeiENSGT00840000129850.
HOGENOMiHOG000021196.
HOVERGENiHBG000982.
InParanoidiQ03154.
KOiK14677.
OrthoDBiEOG091G0A7U.
PhylomeDBiQ03154.
TreeFamiTF313693.

Enzyme and pathway databases

BioCyciMetaCyc:HS03800-MONOMER.
ZFISH:HS03800-MONOMER.
BRENDAi3.5.1.14. 2681.
ReactomeiR-HSA-5423646. Aflatoxin activation and detoxification.
SABIO-RKQ03154.

Miscellaneous databases

ChiTaRSiACY1. human.
EvolutionaryTraceiQ03154.
GeneWikiiACY1.
GenomeRNAii95.
PROiQ03154.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000243989.
CleanExiHS_ACY1.
ExpressionAtlasiQ03154. baseline and differential.
GenevisibleiQ03154. HS.

Family and domain databases

CDDicd05646. M20_AcylaseI_like. 1 hit.
Gene3Di3.30.70.360. 1 hit.
InterProiIPR001261. ArgE/DapE_CS.
IPR010159. N-acyl_aa_amidohydrolase.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamiPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFiPIRSF036696. ACY-1. 1 hit.
SUPFAMiSSF55031. SSF55031. 1 hit.
TIGRFAMsiTIGR01880. Ac-peptdase-euk. 1 hit.
PROSITEiPS00758. ARGE_DAPE_CPG2_1. 1 hit.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiACY1_HUMAN
AccessioniPrimary (citable) accession number: Q03154
Secondary accession number(s): C9J6I6, C9J9D8, C9JWD4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 170 of the entry and version 1 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

Keywords - Technical termi

3D-structure, Complete proteome, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.