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Reviewed, UniProtKB/Swiss-Prot Q03154 (ACY1_HUMAN)

Last modified February 9, 2010. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

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

Protein attributes

Sequence length408 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Binds 2 zinc ions per subunit.

Subunit structure

Homodimer. Interacts with SPHK1 By similarity.

Subcellular location

Cytoplasm.

Tissue specificity

Expression is highest in kidney, strong in brain and weaker in placenta and spleen. Ref.7

Involvement in disease

Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:609924]. ACY1D results in a metabolic disorder manifesting with 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. Ref.7 Ref.6 Ref.9

Sequence similarities

Belongs to the peptidase M20A family.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processcellular amino acid metabolic process

Inferred from electronic annotation. Source: InterPro

proteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentcytosol Ref.2

Traceable author statement. Source: ProtInc

   Molecular functionaminoacylase activity

Traceable author statement. Source: ProtInc

metallopeptidase activity

Inferred from electronic annotation. Source: InterPro

protein dimerization activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 408408Aminoacylase-1
PRO_0000185236

Sites

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

Natural variations

Natural variant1791N → S: dbSNP rs887540.
VAR_051805
Natural variant1971R → W in ACY1D. Ref.9
VAR_043113
Natural variant2331E → D in ACY1D. Ref.7
VAR_026104
Natural variant3531R → C in ACY1D. Ref.7 Ref.6 Ref.9
VAR_026105
Natural variant3811E → D in a breast cancer sample; somatic mutation. Ref.8
VAR_036076
Natural variant3861R → C: dbSNP rs2229152.
VAR_020452
Natural variant3931R → H in ACY1D. Ref.9
VAR_043114

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q03154-1 [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

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: 8357837] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 8394326] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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].
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Lung and Skin.
[5]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]"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: 16274666] [Abstract]
Cited for: VARIANT ACY1D CYS-353.
[7]"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: 16465618] [Abstract]
Cited for: VARIANTS ACY1D ASP-233 AND CYS-353, TISSUE SPECIFICITY.
[8]"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: 16959974] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-381.
[9]"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: 17562838] [Abstract]
Cited for: VARIANTS ACY1D TRP-197; CYS-353 AND HIS-393.
+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.
BC000545 mRNA. Translation: AAH00545.1.
BC003023 mRNA. Translation: AAH03023.1.
BC014112 mRNA. Translation: AAH14112.1.
IPIIPI00940464.
PIRA47488.
RefSeqNP_000657.1.
UniGeneHs.334707

3D structure databases

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

Protein-protein interaction databases

IntActQ03154. 5 interactions.
STRINGQ03154.

Protein family/group databases

MEROPSM20.973.

2-D gel databases

REPRODUCTION-2DPAGEIPI00009268.

Proteomic databases

PeptideAtlasQ03154.
PRIDEQ03154.

Genome annotation databases

EnsemblENST00000232907; ENSP00000232907; ENSG00000243989; Homo sapiens. [Genome view]
ENST00000404366; ENSP00000384296; ENSG00000243989; Homo sapiens. [Genome view]
ENST00000458031; ENSP00000390557; ENSG00000243989; Homo sapiens. [Genome view]
GeneID95.
KEGGhsa:95.
UCSCuc003dcp.1. human.

Organism-specific databases

CTD95.
GeneCardsGC03P051992.
H-InvDBHIX0003341.
HGNCHGNC:177. ACY1.
HPACAB003695.
MIM104620. gene.
609924. phenotype.
Orphanet137754. Neurological conditions associated with aminoacylase 1 deficiency.
PharmGKBPA24497.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16910.
HOVERGENQ03154.
InParanoidQ03154.
PhylomeDBQ03154.

Enzyme and pathway databases

BRENDA3.5.1.14. 247.

Gene expression databases

ArrayExpressQ03154.
BgeeQ03154.
CleanExHS_ACY1.
GenevestigatorQ03154.
GermOnlineENSG00000114786. Homo sapiens.

Family and domain databases

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.
TIGRFAMsTIGR01880. Ac-peptdase-euk. 1 hit.
PROSITEPS00758. ARGE_DAPE_CPG2_1. 1 hit.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00128. L-Aspartic Acid.
NextBio361.
SOURCESearch...

Entry information

Entry nameACY1_HUMAN
AccessionPrimary (citable) accession number: Q03154
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: February 9, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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

Human chromosome 3

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents