ACY1

Protein identityUniProt · HPA

UniProt accession

Q03154

Gene

ACY1

Ensembl

ENSG00000243989

Chromosome

3

Canonical length

408 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a cytosolic, homodimeric, zinc-binding enzyme that catalyzes the hydrolysis of acylated L-amino acids to L-amino acids and an acyl group, and has been postulated to function in the catabolism and salvage of acylated amino acids. This gene is located on chromosome 3p21.1, a region reduced to homozygosity in small-cell lung cancer (SCLC), and its expression has been reported to be reduced or undetectable in SCLC cell lines and tumors. The amino acid sequence of human aminoacylase-1 is highly homologous to the porcine counterpart, and this enzyme is the first member of a new family of zinc-binding enzymes. Mutations in this gene cause aminoacylase-1 deficiency, a metabolic disorder characterized by central nervous system defects and increased urinary excretion of N-acetylated amino acids. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ABHD14A (abhydrolase domain containing 14A) gene, as represented in GeneID:100526760. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Nov 2010]

Canonical amino-acid sequenceUniProt

408 residues, UniProt reviewed canonical sequence.

>Q03154|ACY1
     1  MTSKGPEEEH PSVTLFRQYL RIRTVQPKPD YGAAVAFFEE TARQLGLGCQ KVEVAPGYVV
    61  TVLTWPGTNP TLSSILLNSH TDVVPVFKEH WSHDPFEAFK DSEGYIYARG AQDMKCVSIQ
   121  YLEAVRRLKV EGHRFPRTIH MTFVPDEEVG GHQGMELFVQ RPEFHALRAG FALDEGIANP
   181  TDAFTVFYSE RSPWWVRVTS TGRPGHASRF MEDTAAEKLH KVVNSILAFR EKEWQRLQSN
   241  PHLKEGSVTS VNLTKLEGGV AYNVIPATMS ASFDFRVAPD VDFKAFEEQL QSWCQAAGEG
   301  VTLEFAQKWM HPQVTPTDDS NPWWAAFSRV CKDMNLTLEP EIMPAATDNR YIRAVGVPAL
   361  GFSPMNRTPV LLHDHDERLH EAVFLRGVDI YTRLLPALAS VPALPSDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACY1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

421 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACY1.

Disease | AllUniProt

Conditions ACY1 is implicated in, by any mechanism.

• Aminoacylase-1 deficiency (ACY1D) MIM:609924

Disease | GeneticClinVar

13 pathogenic / likely-pathogenic of 190 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aminoacylase 1 deficiency
• ACY1-related disorder

ReferencesPubMed · IEDB

Publications for ACY1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.06

gnomAD pLI

0

gnomAD missense Z

0.1

DepMap mean gene effect

0.12

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amino acid metabolic process

Molecular functions

• aminoacylase activity
• identical protein binding
• metal ion binding

Cellular components

• cytosol
• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• ArgE/DapE/ACY1/CPG2/YscS, conserved site
• Peptidase M20
• Peptidase M20, dimerisation domain
• Bacterial exopeptidase dimerisation domain
• Peptidase family M20/M25/M40
• Peptidase dimerisation domain
• N-acyl-L-amino-acid amidohydrolase
• Aminoacylase-1 peptidase M20A

KeywordsUniProt

• Cytoplasm
• Hydrolase
• Metal-binding
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ACY1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SPHK1
• NUDT1