Mme membrane metallo endopeptidase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mmeprovided by MGI
Official Full Name: membrane metallo endopeptidaseprovided by MGI
Primary source: MGI:MGI:97004
See related: Ensembl:ENSMUSG00000027820 AllianceGenome:MGI:97004
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: NEP; SFE; CD10; CALLA; 6030454K05Rik
Summary: Enables peptidase activity. Involved in amyloid-beta clearance; positive regulation of long-term synaptic potentiation; and sensory perception of pain. Acts upstream of or within amyloid-beta metabolic process. Located in several cellular components, including dendrite; neuron projection terminus; and synaptic vesicle. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; liver and biliary system; and mammary gland. Used to study Alzheimer's disease. Human ortholog(s) of this gene implicated in Alzheimer's disease; Charcot-Marie-Tooth disease axonal type 2T; cerebellar ataxia type 43; cerebral amyloid angiopathy; and membranous glomerulonephritis. Orthologous to human MME (membrane metalloendopeptidase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in limb E14.5 (RPKM 8.6), kidney adult (RPKM 7.9) and 18 other tissues See more
Orthologs: human all
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Genomic context

Location:: 3 E1; 3 29.97 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
109	current	GRCm39 (GCF_000001635.27)	3	NC_000069.7 (63202632..63291134)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	3	NC_000069.6 (63295211..63383713)

Chromosome 3 - NC_000069.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Local Action of Neprilysin Exacerbates Pressure Overload Induced Cardiac Remodeling.
Title: Local Action of Neprilysin Exacerbates Pressure Overload Induced Cardiac Remodeling.
LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes.
Title: LncRNA ANRIL Silencing Alleviates High Glucose-Induced Inflammation, Oxidative Stress, and Apoptosis via Upregulation of MME in Podocytes.
Study identified neutral endopeptidase (NEP) that is upregulated in human abdominal aortic aneurysm (AAA) tissue as a major enzyme that metabolizes and inactivates APLN17 peptide. NEP cleavage resistant APLN17 analog ameliorated Ang II-mediated adverse aortic remodeling and AAA formation in mouse model of AAA. Study defines a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs.
Title: Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs.
Results suggest that although the expression of MME in the mouse is dysregulated after injury in a NRG1 dependent manner it does not appear to modulate the rate of nerve repair. It does, however, appear to have a role in moderating excessive responses to noxious stimuli.
Title: Membrane metallo-endopeptidase is dispensable for repair after nerve injury.
Following low-fat feeding, NEP(-/-) mice exhibited lower beta- and alpha-cell mass compared with wild-type controls. A high-fat diet had no effect on these parameters in wild-type mice, but in NEP(-/-) mice, it resulted in the expansion of beta-cell mass.
Title: Neprilysin Deficiency Is Associated With Expansion of Islet β-Cell Mass in High Fat-Fed Mice.
feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Abeta accumulation in the hippocampus and cortex.
Title: Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer's disease.
The abundance of elastic fibers was reduced and fragmented in obesity, suggesting that the reduction in elastic fibers is initially caused by increased neprilysin and decreased fibrillin-1 expression, which may inhibit formation and stabilization of elastic fibers, resulting in skin fragility in obesity.
Title: Reduction and fragmentation of elastic fibers in the skin of obese mice is associated with altered mRNA expression levels of fibrillin-1 and neprilysin.
results indicate that NEP accelerates adipogenesis through enhancement of insulin-mediated PI3K-Akt activation and imply a high therapeutic value of NEP in treating obesity and obesity-related disorders.
Title: Neprilysin facilitates adipogenesis through potentiation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies
Title: Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.
Amyloid beta (Abeta)-degrading effects of overexpressed neprilysin can block deleterious BACE1-elevating mechanisms that accelerate Abeta production
Title: A combination Alzheimer's therapy targeting BACE1 and neprilysin in 5XFAD transgenic mice.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (1)
Targeted (1) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Mme (e-PCR), detects polymorphism
- UniSTS:143877

RH127173 (e-PCR)
- UniSTS:207500

39.MHAa90d3.seq (e-PCR)
- UniSTS:159122

Homology

Homologs of the Mme gene: The Mme gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, and chicken.
Orthologs from Annotation Pipeline: 342 organisms have orthologs with human gene Mme
Orthologs

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cardiolipin binding	ISO Inferred from Sequence Orthology more info
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables exopeptidase activity	ISO Inferred from Sequence Orthology more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables metalloendopeptidase activity	ISO Inferred from Sequence Orthology more info
enables metallopeptidase activity	IEA Inferred from Electronic Annotation more info
enables oligopeptidase activity	ISO Inferred from Sequence Orthology more info
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptide binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylserine binding	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in amyloid-beta clearance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in amyloid-beta clearance	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta clearance	ISO Inferred from Sequence Orthology more info
involved_in amyloid-beta clearance by cellular catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within amyloid-beta metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in bradykinin catabolic process	ISO Inferred from Sequence Orthology more info
involved_in cellular response to UV-A	ISO Inferred from Sequence Orthology more info
involved_in cellular response to UV-B	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cytokine stimulus	ISO Inferred from Sequence Orthology more info
involved_in creatinine metabolic process	ISO Inferred from Sequence Orthology more info
involved_in hormone catabolic process	ISO Inferred from Sequence Orthology more info
involved_in learning or memory	ISO Inferred from Sequence Orthology more info
involved_in neuropeptide processing	ISO Inferred from Sequence Orthology more info
involved_in peptide metabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of long-term synaptic potentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of neurogenesis	ISO Inferred from Sequence Orthology more info
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
involved_in response to estrogen	ISO Inferred from Sequence Orthology more info
involved_in sensory perception of pain	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in substance P catabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon	ISO Inferred from Sequence Orthology more info
located_in brush border	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic vesicle	ISO Inferred from Sequence Orthology more info
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in membrane raft	ISO Inferred from Sequence Orthology more info
located_in neuron projection terminus	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in presynapse	ISO Inferred from Sequence Orthology more info
located_in synapse	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: neprilysin

Names: atriopeptidase; common acute lymphoblastic leukemia antigen; enkephalinase; neutral endopeptidase 24.11; skin fibroblast elastase

NP_001276391.1

EC 3.4.24.11

NP_001276392.1

EC 3.4.24.11

NP_001344264.1

EC 3.4.24.11

NP_032630.2

EC 3.4.24.11

XP_006501161.1

EC 3.4.24.11

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_001289462.1 → NP_001276391.1 neprilysin

See identical proteins and their annotated locations for NP_001276391.1

Status: VALIDATED

Source sequence(s)

AC121840, AK031446, AK076908, BY145991

Consensus CDS

CCDS17381.1

UniProtKB/Swiss-Prot

Q61391, Q8K251

UniProtKB/TrEMBL

A0A8C6ICD4

Related

ENSMUSP00000141544.2, ENSMUST00000194150.6

Conserved Domains (1) summary

cd08662
Location:77 → 748

M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I
NM_001289463.1 → NP_001276392.1 neprilysin

See identical proteins and their annotated locations for NP_001276392.1

Status: VALIDATED

Source sequence(s)

AC121840, AC121993, AK031446, AK033824

Consensus CDS

CCDS17381.1

UniProtKB/Swiss-Prot

Q61391, Q8K251

UniProtKB/TrEMBL

A0A8C6ICD4

Related

ENSMUSP00000029400.2, ENSMUST00000029400.7

Conserved Domains (1) summary

cd08662
Location:77 → 748

M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I
NM_001357335.1 → NP_001344264.1 neprilysin

Status: VALIDATED

Source sequence(s)

AC121840, AC121993

Consensus CDS

CCDS17381.1

UniProtKB/Swiss-Prot

Q8K251

UniProtKB/TrEMBL

A0A8C6ICD4

Conserved Domains (1) summary

cd08662
Location:77 → 748

M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I
NM_008604.4 → NP_032630.2 neprilysin

See identical proteins and their annotated locations for NP_032630.2

Status: VALIDATED

Source sequence(s)

AC121840, AK031446

Consensus CDS

CCDS17381.1

UniProtKB/Swiss-Prot

Q61391, Q8K251

UniProtKB/TrEMBL

A0A8C6ICD4

Related

ENSMUSP00000142205.2, ENSMUST00000194134.6

Conserved Domains (1) summary

cd08662
Location:77 → 748

M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I

RefSeqs of Annotated Genomes: Mus musculus Annotation Release 109 details...

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

Reference GRCm39 C57BL/6J

Genomic

NC_000069.7 Reference GRCm39 C57BL/6J

Range

63202632..63291134

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006501098.4 → XP_006501161.1 neprilysin isoform X1

See identical proteins and their annotated locations for XP_006501161.1

UniProtKB/Swiss-Prot

Q61391, Q8K251

UniProtKB/TrEMBL

A0A8C6ICD4

Conserved Domains (1) summary

cd08662
Location:77 → 748

M13; Peptidase family M13 includes neprilysin and endothelin-converting enzyme I