APEH acylaminoacyl-peptide hydrolase [Homo sapiens (human)] - Gene

Summary

Official Symbol: APEHprovided by HGNC
Official Full Name: acylaminoacyl-peptide hydrolaseprovided by HGNC
Primary source: HGNC:HGNC:586
See related: Ensembl:ENSG00000164062 MIM:102645; AllianceGenome:HGNC:586
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APH; OPH; AARE; ACPH; D3S48E; D3F15S2; DNF15S2
Summary: This gene encodes the enzyme acylpeptide hydrolase, which catalyzes the hydrolysis of the terminal acetylated amino acid preferentially from small acetylated peptides. The acetyl amino acid formed by this hydrolase is further processed to acetate and a free amino acid by an aminoacylase. This gene is located within the same region of chromosome 3 (3p21) as the aminoacylase gene, and deletions at this locus are also associated with a decrease in aminoacylase activity. The acylpeptide hydrolase is a homotetrameric protein of 300 kDa with each subunit consisting of 732 amino acid residues. It can play an important role in destroying oxidatively damaged proteins in living cells. Deletions of this gene locus are found in various types of carcinomas, including small cell lung carcinoma and renal cell carcinoma. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in kidney (RPKM 28.3), thyroid (RPKM 22.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (49673117..49683971)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (49702408..49713255)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (49711784..49721404)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7-APEH-Proteasome Axis in High-grade Serous Ovarian Carcinoma.
Title: Deubiquitinase UCHL1 Maintains Protein Homeostasis through the PSMA7-APEH-Proteasome Axis in High-grade Serous Ovarian Carcinoma.
Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target?
Title: Selective inhibition of acylpeptide hydrolase in SAOS-2 osteosarcoma cells: is this enzyme a viable anticancer target?
APEH knockdown abrogated RAS-RAF-MAPK signaling in cells expressing the constitutively active (oncogenic) mutant of KRAS (KRASG12V), and selectively inhibited the proliferation of KRAS-transformed pancreatic cancer cells. Taken together, these results identify APEH as a novel drug target for a potential anti-KRAS therapeutic.
Title: Acylpeptide hydrolase is a novel regulator of KRAS plasma membrane localization and function.
Although APEH is primarily localized in the cytoplasm, a sub-fraction of this enzyme is sequestered at sites of nuclear damage following UVA irradiation or following oxidative stress. APEH interacts with the amino-terminal domain of XRCC1, and APEH facilitates both single-strand break repair and cell survival following exposure to H2O2. Thus, APEH as a novel proteolytic component of the DNA damage response.
Title: Acylpeptide hydrolase is a component of the cellular response to DNA damage.
APEH polymorphism has significant influence on valproic acid pharmacokinetics in Chinese population
Title: Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients.
Studies indicate that the cylindromatosis/turban tumor syndrome gene (CYLD) ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4).
Title: Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review.
Observational study of gene-disease association. (HuGE Navigator)
Title: Evaluation of candidate genes for cholinesterase activity in farmworkers exposed to organophosphorus pesticides: association of single nucleotide polymorphisms in BCHE.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

APEH (e-PCR)
- UniSTS:253958

GDB:181206 (e-PCR)
- UniSTS:155174

GDB:512856 (e-PCR)
- UniSTS:157533

APEH (e-PCR)
- UniSTS:265936

WI-16108 (e-PCR)
- UniSTS:2785

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables omega peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in amyloid-beta metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in translational termination	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: acylamino-acid-releasing enzyme

Names: N-acylaminoacyl-peptide hydrolase; acyl-peptide hydrolase; acylaminoacyl-peptidase; oxidized protein hydrolase

NP_001631.3

EC 3.4.19.1

XP_005265154.1

EC 3.4.19.1

XP_011531960.1

EC 3.4.19.1

XP_016861774.1

EC 3.4.19.1

XP_047304021.1

EC 3.4.19.1

XP_047304022.1

EC 3.4.19.1

XP_054202382.1

EC 3.4.19.1

XP_054202383.1

EC 3.4.19.1

XP_054202384.1

EC 3.4.19.1

XP_054202385.1

EC 3.4.19.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011438.1 RefSeqGene

Range

5350..14970

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001640.4 → NP_001631.3 acylamino-acid-releasing enzyme

See identical proteins and their annotated locations for NP_001631.3

Status: REVIEWED

Source sequence(s)

AC099668

Consensus CDS

CCDS2801.1

UniProtKB/Swiss-Prot

P13798, Q9BQ33, Q9P0Y2

UniProtKB/TrEMBL

C9JIF9

Related

ENSP00000296456.5, ENST00000296456.10

Conserved Domains (1) summary

COG1506
Location:157 → 732

DAP2; Dipeptidyl aminopeptidase/acylaminoacyl peptidase [Amino acid transport and metabolism]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

49673117..49683971

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448065.1 → XP_047304021.1 acylamino-acid-releasing enzyme isoform X2

UniProtKB/TrEMBL

C9JIF9
XM_011533658.4 → XP_011531960.1 acylamino-acid-releasing enzyme isoform X1

UniProtKB/TrEMBL

C9JIF9

Conserved Domains (3) summary

pfam05934
Location:10 → 127

MCLC; Mid-1-related chloride channel (MCLC)

pfam12146
Location:538 → 754

Hydrolase_4; Serine aminopeptidase, S33

cl21494
Location:555 → 777

Abhydrolase; alpha/beta hydrolases
XM_017006285.2 → XP_016861774.1 acylamino-acid-releasing enzyme isoform X3

UniProtKB/TrEMBL

C9JIF9
XM_005265097.3 → XP_005265154.1 acylamino-acid-releasing enzyme isoform X4

UniProtKB/TrEMBL

C9JIF9

Conserved Domains (2) summary

pfam12146
Location:447 → 663

Hydrolase_4; Serine aminopeptidase, S33

cl21494
Location:464 → 686

Abhydrolase; alpha/beta hydrolases
XM_047448066.1 → XP_047304022.1 acylamino-acid-releasing enzyme isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

49702408..49713255

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346407.1 → XP_054202382.1 acylamino-acid-releasing enzyme isoform X1

UniProtKB/TrEMBL

C9JIF9
XM_054346409.1 → XP_054202384.1 acylamino-acid-releasing enzyme isoform X3

UniProtKB/TrEMBL

C9JIF9
XM_054346408.1 → XP_054202383.1 acylamino-acid-releasing enzyme isoform X2

UniProtKB/TrEMBL

C9JIF9
XM_054346410.1 → XP_054202385.1 acylamino-acid-releasing enzyme isoform X5