XPNPEP2 X-prolyl aminopeptidase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: XPNPEP2provided by HGNC
Official Full Name: X-prolyl aminopeptidase 2provided by HGNC
Primary source: HGNC:HGNC:12823
See related: Ensembl:ENSG00000122121 MIM:300145; AllianceGenome:HGNC:12823
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: APP2; AEACEI
Summary: Aminopeptidase P is a hydrolase specific for N-terminal imido bonds, which are common to several collagen degradation products, neuropeptides, vasoactive peptides, and cytokines. Structurally, the enzyme is a member of the 'pita bread fold' family and occurs in mammalian tissues in both soluble and GPI-anchored membrane-bound forms. A membrane-bound and soluble form of this enzyme have been identified as products of two separate genes. [provided by RefSeq, Jul 2008]
Expression: Biased expression in small intestine (RPKM 88.3), kidney (RPKM 85.4) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: Xq26.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (129738979..129769536)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (128057775..128088323)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (128872955..128903512)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
Title: XPNPEP2 is associated with lymph node metastasis in prostate cancer patients.
The XPNPEP2 c-2399A and the ACE insertion/deletion polymorphisms analyzed in a population of patients with hereditary angioedema with F12 mutation were not a major determinant of disease expression.
Title: Hereditary angioedema with F12 mutation: Clinical features and enzyme polymorphisms in 9 Southwestern Spanish families.
we demonstrated that XPNPEP2 had significant effects on the metastasis of xenografted tumors in vivo. Collectively, our findings identify the novel function of XPNPEP2 in the metastasis of cervical cancer and suggest that XPNPEP2 could be a novel potential therapeutic target for the treatment of cervical cancer
Title: XPNPEP2 is overexpressed in cervical cancer and promotes cervical cancer metastasis.
A C-2399A SNP assay was applied to patients with acute hypotensive transfusion reactions. In a pilot study, 2 patients (50%) were found to possess C-2399A polymorphisms. One was found to be homozygous, and the other was heterozygous.
Title: The development of a novel molecular assay examining the role of aminopeptidase P polymorphisms in acute hypotensive transfusion reactions.
the genetic regulation of the XPNPEP2 gene and identify the genetic factors contributing to variance in plasma aminopeptidase P activity and ACEi-angioedema (XPNPEP2)
Title: A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P and increased risk of ACE inhibitor-induced angioedema.
XPNPEP2 C-2399A polymorphism associates with angiotensin-converting enzyme inhibitor-associated angioedema in men but not women.
Title: Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema.
Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Identification of genetic factors associated with susceptibility to angiotensin-converting enzyme inhibitors-induced cough.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema.
females have polymorphisms associated with lower levels of APP & ACE; study suggests multiple genes may contribute to this disease
Title: Genetic analysis of Factor XII and bradykinin catabolic enzymes in a family with estrogen-dependent inherited angioedema.
Structural comparisons suggest mechanisms for substrate selectivity in different X-prolyl peptidases.
Title: Structure of human cytosolic X-prolyl aminopeptidase: a double Mn(II)-dependent dimeric enzyme with a novel three-domain subunit.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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

Associated conditions

Description	Tests
Susceptibility to angioedema induced by ACE inhibitors MedGen: C3806711 OMIM: 300909 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound (XPNPEP2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AL032550 (e-PCR)
- UniSTS:93266

AL008958 (e-PCR)
- UniSTS:59236

SHGC-57484 (e-PCR)
- UniSTS:54659

GDB:316041 (e-PCR)
- UniSTS:156566

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables aminopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloaminopeptidase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in proteolysis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in side of membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: xaa-Pro aminopeptidase 2

Names: X-Pro aminopeptidase 2; X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound; aminoacylproline aminopeptidase; mAmP; membrane-bound APP; membrane-bound AmP; membrane-bound aminopeptidase P

NP_003390.4

EC 3.4.11.9

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_011479.2 RefSeqGene

Range

5002..35559

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003399.6 → NP_003390.4 xaa-Pro aminopeptidase 2 precursor

See identical proteins and their annotated locations for NP_003390.4

Status: REVIEWED

Source sequence(s)

AL023653, BF830085, BP270314, BQ224207, BX386512, CD617070, U90724

Consensus CDS

CCDS14613.1

UniProtKB/Swiss-Prot

A0AV16, O43895, O75994

UniProtKB/TrEMBL

B7ZLM6

Related

ENSP00000360147.3, ENST00000371106.4

Conserved Domains (5) summary

COG0006
Location:348 → 601

PepP; Xaa-Pro aminopeptidase [Amino acid transport and metabolism]

cd01085
Location:365 → 583

APP; X-Prolyl Aminopeptidase 2. E.C. 3.4.11.9. Also known as X-Pro aminopeptidase, proline aminopeptidase, aminopeptidase P, and aminoacylproline aminopeptidase. Catalyses release of any N-terminal amino acid, including proline, that is linked with proline, ...

pfam01321
Location:54 → 184

Creatinase_N; Creatinase/Prolidase N-terminal domain

pfam16188
Location:585 → 648

Peptidase_M24_C; C-terminal region of peptidase_M24

pfam16189
Location:202 → 361

Creatinase_N_2; Creatinase/Prolidase N-terminal domain