Q03154 (ACY1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	408 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	Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate). Ref.6
Catalytic activity	An N-acyl-L-amino acid + H2O = a carboxylate + an L-amino acid. Ref.6
Cofactor	Binds 2 zinc ions per subunit. Ref.6
Subunit structure	Homodimer. Interacts with SPHK1 By similarity. Ref.6
Subcellular location	Cytoplasm.
Tissue specificity	Expression is highest in kidney, strong in brain and weaker in placenta and spleen. Ref.8
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.7 Ref.8 Ref.10 Ref.11
Sequence similarities	Belongs to the peptidase M20A family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular amino acid metabolic process Inferred from electronic annotation. Source: InterPro proteolysis Inferred from electronic annotation. Source: InterPro
Cellular_component	cytosol Traceable author statement Ref.2. Source: ProtInc
Molecular_function	aminoacylase activity Traceable author statement PubMed 1707030. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 408

407

Aminoacylase-1

PRO_0000185236

Sites

Active site

82

1

By similarity

Active site

147

1

Proton acceptor Ref.6

Metal binding

80

1

Zinc 1

Metal binding

113

1

Zinc 1

Metal binding

113

1

Zinc 2

Metal binding

148

1

Zinc 2

Metal binding

175

1

Zinc 1

Metal binding

373

1

Zinc 2

Natural variations

Natural variant

179

1

N → S.
Corresponds to variant rs887540 [ dbSNP | Ensembl ].

VAR_051805

Natural variant

197

1

R → W in ACY1D; loss of activity. Ref.10 Ref.11

VAR_043113

Natural variant

233

1

E → D in ACY1D; loss of activity. Ref.8 Ref.11

VAR_026104

Natural variant

353

1

R → C in ACY1D; loss of activity. Ref.7 Ref.8 Ref.10 Ref.11

VAR_026105

Natural variant

378

1

R → Q in ACY1D. Ref.11

VAR_065562

Natural variant

378

1

R → W in ACY1D; slightly reduced activity. Ref.11

VAR_065563

Natural variant

381

1

E → D in a breast cancer sample; somatic mutation. Ref.9

VAR_036076

Natural variant

386

1

R → C in ACY1D; loss of activity. Ref.11
Corresponds to variant rs2229152 [ dbSNP | Ensembl ].

VAR_020452

Natural variant

393

1

R → H in ACY1D. Ref.10

VAR_043114

Experimental info

Mutagenesis

80

1

H → A: Almost abolishes enzyme activity. Ref.6

Mutagenesis

113

1

D → A: Almost abolishes enzyme activity. Ref.6

Mutagenesis

147

1

E → A or Q: Almost abolishes enzyme activity. Ref.6

Mutagenesis

147

1

E → D: Decreased protein stability. Loss of enzyme activity. Ref.6

Mutagenesis

148

1

E → A: Almost abolishes enzyme activity. Ref.6

Mutagenesis

175

1

E → A: Almost abolishes enzyme activity. Ref.6

Mutagenesis

206

1

H → N: Almost abolishes enzyme activity. Ref.6

Mutagenesis

373

1

H → A: Almost abolishes enzyme activity. Ref.6

Secondary structure

1

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408

Helix Strand Turn

Details...

Helix

11 – 20

10

Helix

31 – 45

15

Beta strand

48 – 55

8

Beta strand

58 – 65

8

Beta strand

74 – 80

7

Helix

88 – 90

3

Turn

95 – 97

3

Beta strand

104 – 107

4

Turn

109 – 114

6

Helix

115 – 130

16

Beta strand

139 – 145

7

Helix

147 – 149

3

Turn

152 – 154

3

Helix

155 – 158

4

Helix

162 – 165

4

Beta strand

169 – 174

6

Beta strand

180 – 188

9

Helix

194 – 196

3

Helix

322 – 333

12

Beta strand

338 – 342

5

Helix

348 – 354

7

Beta strand

359 – 362

4

Beta strand

378 – 380

3

Helix

381 – 399

19

Helix

405 – 407

3

Sequences

	Sequence		Length	Mass (Da)
	Q03154 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: 293350CD7759826C	FASTA	408	45,885
	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

References

	« Hide 'large scale' referencesShow '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].
[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]. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Lung and Skin.
[5]	"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].
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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. , 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.
[10]	"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.
[11]	"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.
BC000545 mRNA. Translation: AAH00545.1.
BC003023 mRNA. Translation: AAH03023.1.
BC014112 mRNA. Translation: AAH14112.1.

IPI

IPI00940464.

PIR

A47488.

RefSeq

NP_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.

UniGene

Hs.334707.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q7L	X-ray	1.40	A/C	1-198	[»]
			B/D	321-408	[»]

ProteinModelPortal

Q03154.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q03154. 5 interactions.

MINT

MINT-4999851.

STRING

9606.ENSP00000232907.

Protein family/group databases

MEROPS

M20.973.

PTM databases

PhosphoSite

Q03154.

Polymorphism databases

DMDM

461466.

2D gel databases

REPRODUCTION-2DPAGE

IPI00009268.

Proteomic databases

PaxDb

Q03154.

PeptideAtlas

Q03154.

PRIDE

Q03154.

Protocols and materials databases

DNASU

95.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000404366; ENSP00000384296; ENSG00000243989.

GeneID

95.

KEGG

hsa:95.

UCSC

uc003dcp.3. human.

Organism-specific databases

CTD

95.

GeneCards

GC03P052017.

HGNC

HGNC:177. ACY1.

HPA

CAB003695.
HPA036174.
HPA036175.

MIM

104620. gene.
609924. phenotype.

neXtProt

NX_Q03154.

Orphanet

137754. Neurological conditions associated with aminoacylase 1 deficiency.

PharmGKB

PA24497.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0624.

HOGENOM

HOG000021196.

HOVERGEN

HBG000982.

InParanoid

Q03154.

KO

K14677.

OrthoDB

EOG46143V.

PhylomeDB

Q03154.

Enzyme and pathway databases

BioCyc

MetaCyc:HS03800-MONOMER.

BRENDA

3.5.1.14. 2681.

SABIO-RK

Q03154.

Gene expression databases

ArrayExpress

Q03154.

Bgee

Q03154.

CleanEx

HS_ACY1.

Genevestigator

Q03154.

GermOnline

ENSG00000114786. Homo sapiens.

Family and domain databases

InterPro

IPR001261. ArgE/DapE_CS.
IPR010159. N-acyl_aa_amidohydrolase.
IPR002933. Peptidase_M20.
IPR011650. Peptidase_M20_dimer.
[Graphical view]

Pfam

PF07687. M20_dimer. 1 hit.
PF01546. Peptidase_M20. 1 hit.
[Graphical view]

PIRSF

PIRSF036696. ACY-1. 1 hit.

SUPFAM

SSF55031. Peptidase_M20_dimer. 1 hit.

TIGRFAMs

TIGR01880. Ac-peptdase-euk. 1 hit.

PROSITE

PS00758. ARGE_DAPE_CPG2_1. 1 hit.
PS00759. ARGE_DAPE_CPG2_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ACY1. human.

DrugBank

DB00128. L-Aspartic Acid.

EvolutionaryTrace

Q03154.

GenomeRNAi

95.

NextBio

361.

SOURCE

Search...

Entry information

Entry name

ACY1_HUMAN

Accession

Primary (citable) accession number: Q03154

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 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.