MEP1A meprin A subunit alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: MEP1Aprovided by HGNC
Official Full Name: meprin A subunit alphaprovided by HGNC
Primary source: HGNC:HGNC:7015
See related: Ensembl:ENSG00000112818 MIM:600388; AllianceGenome:HGNC:7015
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PPHA
Summary: Enables metallodipeptidase activity. Involved in epidermal growth factor receptor ligand maturation. Located in extracellular exosome. Part of meprin A complex. Is active in plasma membrane. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in small intestine (RPKM 216.8), duodenum (RPKM 122.1) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 6p12.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (46793389..46845984)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (46631036..46683461)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (46761126..46807515)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

Mep1A is overexpressed in most hepatocellular carcinomas and induces tumor cell migration and invasion. Mep1A expression is regulated by Reptin, and Mep1A mediates Reptin-induced migration.
Title: Metalloproteinase meprin α regulates migration and invasion of human hepatocarcinoma cells and is a mediator of the oncoprotein Reptin.
In this review we report on recent findings that summarize the complex molecular regulation of meprins, particular folding, activation and shedding. Dysregulation of meprin alpha and meprin beta is often associated with pathological conditions such as neurodegeneration, inflammatory bowel disease and fibrosis
Title: Meprin metalloproteases: Molecular regulation and function in inflammation and fibrosis.
Results showed that MEP1A expression was elevated in colorectal cancer (CRC) tissues at both the mRNA and protein levels, and provided evidence for its functionally crucial role in CRC carcinogenesis as tumor proliferation and invasion.
Title: Metalloproteases meprin-ɑ (MEP1A) is a prognostic biomarker and promotes proliferation and invasion of colorectal cancer.
Variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism in overweight/obese central European women with polycystic ovary syndrome.
Title: Association of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome.
Meprin metalloproteases A and B inactivate interleukin 6
Title: Meprin metalloproteases inactivate interleukin 6.
Proteolytically active meprinalpha leads to an increase in EGFR and ERK1/2 phosphorylation and subsequently enhances cell proliferation and migration
Title: Meprinα transactivates the epidermal growth factor receptor (EGFR) via ligand shedding, thereby enhancing colorectal cancer cell proliferation and migration.
The present results indicate that a TNF-alpha-mediated down-regulation of CDX2 can be related to suppressed expression of MEP1A during intestinal inflammation.
Title: TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis.
Meprin-alpha activity is regulated differently in primary tumors and metastases of colorectal cancer. By virtue of its pro-migratory and pro-angiogenic activity, meprin-alpha may promote tumor progression in colorectal cancer.
Title: Enhanced activity of meprin-α, a pro-migratory and pro-angiogenic protease, in colorectal cancer.
Cystatin C was an inhibitor for human meprin alpha(K(i) = 8.5 x 10(-6) M) but, interestingly, not for meprin beta.
Title: Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases.
meprins could be important players in several remodeling processes involving collagen fiber deposition
Title: Processing of procollagen III by meprins: new players in extracellular matrix assembly?

Submit: New GeneRIF Correction See all GeneRIFs (15)

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

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

D6S2059 (e-PCR)
- UniSTS:31509

STS-M82962 (e-PCR)
- UniSTS:75806

RH65261 (e-PCR)
- UniSTS:84200

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metallodipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in epidermal growth factor receptor ligand maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in signaling receptor ligand precursor processing	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular space	TAS Traceable Author Statement more info	PubMed
part_of meprin A complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: meprin A subunit alpha

Names: N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit alpha; PABA peptide hydrolase; PPH alpha; bA268F1.1 (meprin A alpha (PABA peptide hydrolase)); endopeptidase-2; meprin A, alpha (PABA peptide hydrolase)

NP_005579.2

EC 3.4.24.18

XP_011512930.1

EC 3.4.24.18

XP_011512931.1

EC 3.4.24.18

XP_054211437.1

EC 3.4.24.18

XP_054211438.1

EC 3.4.24.18

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.

mRNA and Protein(s)

NM_005588.3 → NP_005579.2 meprin A subunit alpha precursor

See identical proteins and their annotated locations for NP_005579.2

Status: VALIDATED

Source sequence(s)

AF478685, DA432559

Consensus CDS

CCDS4918.1

UniProtKB/Swiss-Prot

A2RRM4, B0AZP9, B2RCS2, Q16819, Q8TDC9, Q9H1R1

Related

ENSP00000230588.4, ENST00000230588.9

Conserved Domains (6) summary

cd06263
Location:269 → 431

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

smart00137
Location:264 → 431

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

cd00054
Location:672 → 710

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd03783
Location:431 → 594

MATH_Meprin_Alpha; Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, ...

cd04282
Location:30 → 259

ZnMc_meprin; Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted extracellular proteases, which cleave a variety of targets, including peptides such as parathyroid hormone, gastrin, and cholecystokinin, cytokines such as ...

pfam01400
Location:73 → 261

Astacin; Astacin (Peptidase family M12A)

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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

46793389..46845984

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011514629.3 → XP_011512931.1 meprin A subunit alpha isoform X2

Conserved Domains (6) summary

cd06263
Location:269 → 431

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

smart00137
Location:264 → 431

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

cd03783
Location:431 → 594

MATH_Meprin_Alpha; Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, ...

cd04282
Location:30 → 259

ZnMc_meprin; Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted extracellular proteases, which cleave a variety of targets, including peptides such as parathyroid hormone, gastrin, and cholecystokinin, cytokines such as ...

pfam00008
Location:674 → 695

EGF; EGF-like domain

pfam01400
Location:73 → 261

Astacin; Astacin (Peptidase family M12A)
XM_011514628.2 → XP_011512930.1 meprin A subunit alpha isoform X1

See identical proteins and their annotated locations for XP_011512930.1

UniProtKB/TrEMBL

B7ZL91

Related

ENSP00000480465.1, ENST00000611727.2

Conserved Domains (6) summary

cd06263
Location:297 → 459

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

smart00137
Location:292 → 459

MAM; Domain in meprin, A5, receptor protein tyrosine phosphatase mu (and others)

cd00054
Location:700 → 738

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd03783
Location:459 → 622

MATH_Meprin_Alpha; Meprin family, Alpha subunit, MATH domain; Meprins are multidomain extracellular metalloproteases capable of cleaving growth factors, cytokines, extracellular matrix proteins, and biologically active peptides. They are composed of two related subunits, ...

cd04282
Location:58 → 287

ZnMc_meprin; Zinc-dependent metalloprotease, meprin_like subfamily. Meprins are membrane-bound or secreted extracellular proteases, which cleave a variety of targets, including peptides such as parathyroid hormone, gastrin, and cholecystokinin, cytokines such as ...

pfam01400
Location:101 → 289

Astacin; Astacin (Peptidase family M12A)