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Q03154 (ACY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Aminoacylase-1

Short name=ACY-1
EC=3.5.1.14
Alternative name(s):
N-acyl-L-amino-acid amidohydrolase
Gene names
Name:ACY1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length408 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate). Ref.7

Catalytic activity

An N-acyl-aliphatic-L-amino acid + H2O = an aliphatic L-amino acid + a carboxylate. Ref.7

An N-acetyl-L-cysteine-S-conjugate + H2O = an L-cysteine-S-conjugate + acetate. Ref.7

Cofactor

Binds 2 zinc ions per subunit. Ref.7

Subunit structure

Homodimer. Interacts with SPHK1 By similarity. Ref.7

Subcellular location

Cytoplasm.

Tissue specificity

Expression is highest in kidney, strong in brain and weaker in placenta and spleen. Ref.9

Involvement in disease

Aminoacylase-1 deficiency (ACY1D) [MIM:609924]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11 Ref.12

Sequence similarities

Belongs to the peptidase M20A family.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q03154-1)

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.
Isoform 2 (identifier: Q03154-2)

The sequence of this isoform differs from the canonical sequence as follows:
     103-174: Missing.
Note: Gene prediction based on EST data.
Isoform 3 (identifier: Q03154-3)

The sequence of this isoform differs from the canonical sequence as follows:
     220-284: Missing.
Note: Gene prediction based on EST data.
Isoform 4 (identifier: Q03154-4)

The sequence of this isoform differs from the canonical sequence as follows:
     32-66: Missing.
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 408407Aminoacylase-1
PRO_0000185236

Sites

Active site821 By similarity
Active site1471Proton acceptor Ref.7
Metal binding801Zinc 1
Metal binding1131Zinc 1
Metal binding1131Zinc 2
Metal binding1481Zinc 2
Metal binding1751Zinc 1
Metal binding3731Zinc 2

Natural variations

Alternative sequence32 – 6635Missing in isoform 4.
VSP_046876
Alternative sequence103 – 17472Missing in isoform 2.
VSP_046877
Alternative sequence220 – 28465Missing in isoform 3.
VSP_046878
Natural variant1791N → S.
Corresponds to variant rs887540 [ dbSNP | Ensembl ].
VAR_051805
Natural variant1971R → W in ACY1D; loss of activity. Ref.11 Ref.12
VAR_043113
Natural variant2331E → D in ACY1D; loss of activity. Ref.9 Ref.12
VAR_026104
Natural variant3531R → C in ACY1D; loss of activity. Ref.8 Ref.9 Ref.11 Ref.12
Corresponds to variant rs121912698 [ dbSNP | Ensembl ].
VAR_026105
Natural variant3781R → Q in ACY1D. Ref.12
VAR_065562
Natural variant3781R → W in ACY1D; slightly reduced activity. Ref.12
VAR_065563
Natural variant3811E → D in a breast cancer sample; somatic mutation. Ref.10
VAR_036076
Natural variant3861R → C in ACY1D; loss of activity. Ref.12
Corresponds to variant rs2229152 [ dbSNP | Ensembl ].
VAR_020452
Natural variant3931R → H in ACY1D. Ref.11
Corresponds to variant rs121912701 [ dbSNP | Ensembl ].
VAR_043114

Experimental info

Mutagenesis801H → A: Almost abolishes enzyme activity. Ref.7
Mutagenesis1131D → A: Almost abolishes enzyme activity. Ref.7
Mutagenesis1471E → A or Q: Almost abolishes enzyme activity. Ref.7
Mutagenesis1471E → D: Decreased protein stability. Loss of enzyme activity. Ref.7
Mutagenesis1481E → A: Almost abolishes enzyme activity. Ref.7
Mutagenesis1751E → A: Almost abolishes enzyme activity. Ref.7
Mutagenesis2061H → N: Almost abolishes enzyme activity. Ref.7
Mutagenesis3731H → A: Almost abolishes enzyme activity. Ref.7

Secondary structure

................................................ 408
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 293350CD7759826C

FASTA40845,885
        10         20         30         40         50         60 
MTSKGPEEEH PSVTLFRQYL RIRTVQPKPD YGAAVAFFEE TARQLGLGCQ KVEVAPGYVV 

        70         80         90        100        110        120 
TVLTWPGTNP TLSSILLNSH TDVVPVFKEH WSHDPFEAFK DSEGYIYARG AQDMKCVSIQ 

       130        140        150        160        170        180 
YLEAVRRLKV EGHRFPRTIH MTFVPDEEVG GHQGMELFVQ RPEFHALRAG FALDEGIANP 

       190        200        210        220        230        240 
TDAFTVFYSE RSPWWVRVTS TGRPGHASRF MEDTAAEKLH KVVNSILAFR EKEWQRLQSN 

       250        260        270        280        290        300 
PHLKEGSVTS VNLTKLEGGV AYNVIPATMS ASFDFRVAPD VDFKAFEEQL QSWCQAAGEG 

       310        320        330        340        350        360 
VTLEFAQKWM HPQVTPTDDS NPWWAAFSRV CKDMNLTLEP EIMPAATDNR YIRAVGVPAL 

       370        380        390        400 
GFSPMNRTPV LLHDHDERLH EAVFLRGVDI YTRLLPALAS VPALPSDS 

« Hide

Isoform 2 [UniParc].

Checksum: 68C1E4266A8CBE70
Show »

FASTA33637,597
Isoform 3 [UniParc].

Checksum: 75F9FBDC8348189E
Show »

FASTA34338,629
Isoform 4 [UniParc].

Checksum: 343DC089BDBDC22F
Show »

FASTA37342,195

References

« Hide 'large scale' references
[1]"The nucleotide sequence of human aminoacylase-1."
Mitta M., Kato I., Tsunasawa S.
Biochim. Biophys. Acta 1174:201-203(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Human aminoacylase-1. Cloning, sequence, and expression analysis of a chromosome 3p21 gene inactivated in small cell lung cancer."
Cook R.M., Burke B.J., Buchhagen D.L., Minna J.D., Miller Y.E.
J. Biol. Chem. 268:17010-17017(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]Iwaki K., Tanaka Y., Ohta T., Fukuda S., Kurimoto M.
Submitted (JUN-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"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].
[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] (ISOFORM 1).
Tissue: Brain, Lung and Skin.
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family."
Lindner H.A., Lunin V.V., Alary A., Hecker R., Cygler M., Menard R.
J. Biol. Chem. 278:44496-44504(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF HIS-80; ASP-113; GLU-147; GLU-148; GLU-175; HIS-206 AND HIS-373.
[8]"Aminoacylase I deficiency: a novel inborn error of metabolism."
Van Coster R.N., Gerlo E.A., Giardina T.G., Engelke U.F., Smet J.E., De Praeter C.M., Meersschaut V.A., De Meirleir L.J., Seneca S.H., Devreese B., Leroy J.G., Herga S., Perrier J.P., Wevers R.A., Lissens W.
Biochem. Biophys. Res. Commun. 338:1322-1326(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ACY1D CYS-353.
[9]"Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism."
Sass J.O., Mohr V., Olbrich H., Engelke U., Horvath J., Fliegauf M., Loges N.T., Schweitzer-Krantz S., Moebus R., Weiler P., Kispert A., Superti-Furga A., Wevers R.A., Omran H.
Am. J. Hum. Genet. 78:401-409(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACY1D ASP-233 AND CYS-353, TISSUE SPECIFICITY.
[10]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-381.
[11]"Neurological findings in aminoacylase 1 deficiency."
Sass J.O., Olbrich H., Mohr V., Hart C., Woldseth B., Krywawych S., Bjurulf B., Lakhani P.K., Buchdahl R.M., Omran H.
Neurology 68:2151-2153(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACY1D TRP-197; CYS-353 AND HIS-393.
[12]"The molecular basis of aminoacylase 1 deficiency."
Sommer A., Christensen E., Schwenger S., Seul R., Haas D., Olbrich H., Omran H., Sass J.O.
Biochim. Biophys. Acta 1812:685-690(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ACY1D GLN-378; TRP-378 AND CYS-386, CHARACTERIZATION OF VARIANTS ACY1D TRP-197; ASP-233; CYS-353; TRP-378 AND CYS-386.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA47488.
RefSeqNP_000657.1. NM_000666.2.
NP_001185824.1. NM_001198895.1.
NP_001185825.1. NM_001198896.1.
NP_001185826.1. NM_001198897.1.
NP_001185827.1. NM_001198898.1.
UniGeneHs.334707.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q7LX-ray1.40A/C1-198[»]
B/D321-408[»]
ProteinModelPortalQ03154.
SMRQ03154. Positions 7-408.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106610. 7 interactions.
IntActQ03154. 5 interactions.
MINTMINT-4999851.
STRING9606.ENSP00000232907.

Chemistry

DrugBankDB00128. L-Aspartic Acid.

Protein family/group databases

MEROPSM20.973.

PTM databases

PhosphoSiteQ03154.

Polymorphism databases

DMDM461466.

2D gel databases

REPRODUCTION-2DPAGEIPI00009268.

Proteomic databases

PaxDbQ03154.
PeptideAtlasQ03154.
PRIDEQ03154.

Protocols and materials databases

DNASU95.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000404366; ENSP00000384296; ENSG00000243989. [Q03154-1]
ENST00000476351; ENSP00000417056; ENSG00000243989. [Q03154-4]
ENST00000476854; ENSP00000419262; ENSG00000243989. [Q03154-3]
ENST00000494103; ENSP00000417618; ENSG00000243989. [Q03154-2]
GeneID95.
KEGGhsa:95.
UCSCuc003dcp.3. human. [Q03154-1]

Organism-specific databases

CTD95.
GeneCardsGC03P052017.
HGNCHGNC:177. ACY1.
HPACAB003695.
HPA036174.
HPA036175.
MIM104620. gene.
609924. phenotype.
neXtProtNX_Q03154.
Orphanet137754. Neurological conditions associated with aminoacylase 1 deficiency.
PharmGKBPA24497.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0624.
HOGENOMHOG000021196.
HOVERGENHBG000982.
InParanoidQ03154.
KOK14677.
PhylomeDBQ03154.
TreeFamTF313693.

Enzyme and pathway databases

BioCycMetaCyc:HS03800-MONOMER.
BRENDA3.5.1.14. 2681.
SABIO-RKQ03154.

Gene expression databases

BgeeQ03154.
CleanExHS_ACY1.
GenevestigatorQ03154.

Family and domain databases

Gene3D3.30.70.360. 1 hit.
InterProIPR001261. ArgE/DapE_CS.
IPR010159. N-acyl_aa_amidohydrolase.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]
PfamPF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]
PIRSFPIRSF036696. ACY-1. 1 hit.
SUPFAMSSF55031. SSF55031. 1 hit.
TIGRFAMsTIGR01880. Ac-peptdase-euk. 1 hit.
PROSITEPS00758. ARGE_DAPE_CPG2_1. 1 hit.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSACY1. human.
EvolutionaryTraceQ03154.
GeneWikiACY1.
GenomeRNAi95.
NextBio361.
PROQ03154.
SOURCESearch...

Entry information

Entry nameACY1_HUMAN
AccessionPrimary (citable) accession number: Q03154
Secondary accession number(s): C9J6I6, C9J9D8, C9JWD4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: April 16, 2014
This is version 142 of the entry and version 1 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

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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