The protein encoded by this gene is a member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mai... See more...

Aliases for MMEL1 Gene

Aliases for MMEL1 Gene

  • Membrane Metalloendopeptidase Like 1 2 3 5
  • Membrane Metallo-Endopeptidase-Like 2 2 3 4
  • Membrane Metallo-Endopeptidase-Like 1 3 4
  • Neprilysin II 3 4
  • Neprilysin-2 3 4
  • EC 3.4.24.11 4 52
  • NEP2(M) 3 4
  • MMEL2 3 4
  • NEPII 3 4
  • NEP2 3 4
  • NL2 3 4
  • Soluble Secreted Endopeptidase 3
  • Zinc Metallopeptidase 3
  • Neprilysin-II 2
  • Neprilysin 2 2
  • EC 3.4.24 52
  • MELL1 4
  • NL1 3
  • SEP 3

External Ids for MMEL1 Gene

Previous HGNC Symbols for MMEL1 Gene

  • MMEL2

Previous GeneCards Identifiers for MMEL1 Gene

  • GC00U990694
  • GC01M002557
  • GC01M001803

Summaries for MMEL1 Gene

Entrez Gene Summary for MMEL1 Gene

  • The protein encoded by this gene is a member of the neutral endopeptidase (NEP) or membrane metallo-endopeptidase (MME) family. Family members play important roles in pain perception, arterial pressure regulation, phosphate metabolism and homeostasis. This protein is a type II transmembrane protein and is thought to be expressed as a secreted protein. This gene is expressed mainly in testis with weak expression in the brain, kidney, and heart. [provided by RefSeq, Jul 2008]

GeneCards Summary for MMEL1 Gene

MMEL1 (Membrane Metalloendopeptidase Like 1) is a Protein Coding gene. Diseases associated with MMEL1 include Primary Biliary Cirrhosis and Schwartz-Jampel Syndrome, Type 1. Among its related pathways are A-beta Pathways: Plaque Formation and APP Metabolism and A-beta Pathways: Uptake and Degradation. Gene Ontology (GO) annotations related to this gene include metalloendopeptidase activity. An important paralog of this gene is MME.

UniProtKB/Swiss-Prot Summary for MMEL1 Gene

  • Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond (By similarity).

Additional gene information for MMEL1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MMEL1 Gene

Genomics for MMEL1 Gene

GeneHancer (GH) Regulatory Elements for MMEL1 Gene

Promoters and enhancers for MMEL1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J002631 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 532.2 +0.4 400 3.1 NCOR1 ZBTB26 KLF9 TFDP1 SAP130 SMAD4 GLIS1 HNF4A RAD21 NFATC1 MMEL1 ENSG00000237058 MMEL1-AS1 lnc-TTC34-6 PRXL2B ENSG00000224387 ENSG00000229393
GH01J002629 Promoter/Enhancer 0.9 EPDnew Ensembl 532.5 +4.3 4313 1.5 ZIC2 ZNF341 EZH2 ZFHX2 ZNF335 MAZ SUZ12 ZBTB8A GLIS2 ZBTB20 MMEL1 PRXL2B ENSG00000237058 RF00017-009
GH01J002640 Promoter/Enhancer 1.7 FANTOM5 ENCODE CraniofacialAtlas 41.7 -9.6 -9575 2.5 HNRNPK ZBTB40 EP300 SIN3A NRF1 USF1 POLR2G SP1 PHF8 JUND MMEL1 ACTRT2 PRXL2B MORN1 PANK4 lnc-TTC34-5 AB372589-001 TTC34
GH01J002580 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 30.5 +48.3 48330 7.8 ZBTB40 SIN3A NRF1 POLR2G USF1 SP1 TEAD4 PHB2 ZFX ZNF10 PRXL2B MMEL1 CDK11A ENSG00000228037 lnc-MMEL1-2 LOC100996583
GH01J002574 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 27.7 +56.2 56198 5 ZBTB40 POLR2G SP1 NCOR1 POLR2A KDM6A RFX1 RELA TGIF2 SKI MMEL1 TNFRSF14 PRXL2B SKI ENSG00000228037 lnc-MMEL1-1 lnc-TNFRSF14-3 LOC100996583
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MMEL1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MMEL1

Top Transcription factor binding sites by QIAGEN in the MMEL1 gene promoter:
  • AREB6
  • GR
  • GR-alpha
  • GR-beta
  • ZID

Genomic Locations for MMEL1 Gene

Genomic Locations for MMEL1 Gene
chr1:2,590,639-2,633,042
(GRCh38/hg38)
Size:
42,404 bases
Orientation:
Minus strand
chr1:2,522,078-2,564,481
(GRCh37/hg19)
Size:
42,404 bases
Orientation:
Minus strand

Genomic View for MMEL1 Gene

Genes around MMEL1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MMEL1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MMEL1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MMEL1 Gene

Proteins for MMEL1 Gene

  • Protein details for MMEL1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q495T6-MMEL1_HUMAN
    Recommended name:
    Membrane metallo-endopeptidase-like 1
    Protein Accession:
    Q495T6
    Secondary Accessions:
    • B9DI79
    • Q495T7
    • Q495T8
    • Q5SZS6
    • Q96PH9

    Protein attributes for MMEL1 Gene

    Size:
    779 amino acids
    Molecular mass:
    89367 Da
    Cofactor:
    Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAI01028.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAI01031.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAL08942.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for MMEL1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MMEL1 Gene

Selected DME Specific Peptides for MMEL1 Gene

Q495T6:
  • SIKTDVHSP
  • AVVNAFYS
  • FACGGWLRRH
  • VIGHEITHGFDD
  • FPAGILQ
  • TLGENIADNGG
  • FPAGILQPPFFS

Post-translational modifications for MMEL1 Gene

  • N-glycosylated.
  • Glycosylation at Asn177, Asn350, Asn207, Asn530, and Asn657
  • Modification sites at PhosphoSitePlus

Domains & Families for MMEL1 Gene

Gene Families for MMEL1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for MMEL1 Gene

Blocks:
  • Neprilysin metalloprotease (M13) family signature
  • Peptidase M13
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MMEL1 Gene

GenScript: Design optimal peptide antigens:
  • Neprilysin-2 (MMEL1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q495T6

UniProtKB/Swiss-Prot:

MMEL1_HUMAN :
  • Belongs to the peptidase M13 family.
Family:
  • Belongs to the peptidase M13 family.
genes like me logo Genes that share domains with MMEL1: view

Function for MMEL1 Gene

Molecular function for MMEL1 Gene

UniProtKB/Swiss-Prot Function:
Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by thiorphan and phosphoramidon.

Enzyme Numbers (IUBMB) for MMEL1 Gene

Phenotypes From GWAS Catalog for MMEL1 Gene

Gene Ontology (GO) - Molecular Function for MMEL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IDA 18539150
GO:0004222 metalloendopeptidase activity IEA --
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with MMEL1: view
genes like me logo Genes that share phenotypes with MMEL1: view

Human Phenotype Ontology for MMEL1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MMEL1 Gene

MGI Knock Outs for MMEL1:

Animal Model Products

CRISPR Products

miRNA for MMEL1 Gene

miRTarBase miRNAs that target MMEL1

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMEL1

No data available for Transcription Factor Targets and HOMER Transcription for MMEL1 Gene

Localization for MMEL1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MMEL1 Gene

Membrane; Single-pass type II membrane protein. Secreted. Note=A secreted form produced by proteolytic cleavage also exists. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MMEL1 gene
Compartment Confidence
extracellular 5
plasma membrane 3
endoplasmic reticulum 2
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for MMEL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 18539150
GO:0016020 membrane IDA 18539150
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with MMEL1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MMEL1 Gene

Pathways & Interactions for MMEL1 Gene

genes like me logo Genes that share pathways with MMEL1: view

Pathways by source for MMEL1 Gene

Interacting Proteins for MMEL1 Gene

;

Gene Ontology (GO) - Biological Process for MMEL1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IDA 18539150
genes like me logo Genes that share ontologies with MMEL1: view

No data available for SIGNOR curated interactions for MMEL1 Gene

Drugs & Compounds for MMEL1 Gene

(1) Drugs for MMEL1 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Racecadotril Investigational Pharma 8

(1) ApexBio Compounds for MMEL1 Gene

Compound Action Cas Number
Racecadotril 81110-73-8
genes like me logo Genes that share compounds with MMEL1: view

Drug Products

Transcripts for MMEL1 Gene

mRNA/cDNA for MMEL1 Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MMEL1

Alternative Splicing Database (ASD) splice patterns (SP) for MMEL1 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d · 2e ^ 3a · 3b
SP1: -
SP2: -
SP3:
SP4: -

Relevant External Links for MMEL1 Gene

GeneLoc Exon Structure for
MMEL1

Expression for MMEL1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MMEL1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MMEL1 Gene

This gene is overexpressed in Testis (x23.0).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MMEL1

SOURCE GeneReport for Unigene cluster for MMEL1 Gene:

Hs.591453

mRNA Expression by UniProt/SwissProt for MMEL1 Gene:

Q495T6-MMEL1_HUMAN
Tissue specificity: Predominantly expressed in testis. Weakly expressed in brain, kidney and heart.
genes like me logo Genes that share expression patterns with MMEL1: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for MMEL1 Gene

Orthologs for MMEL1 Gene

This gene was present in the common ancestor of animals.

Orthologs for MMEL1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MMEL1 31 30
  • 96.87 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MMEL1 31 30
  • 86.78 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MMEL1 31 30
  • 86.14 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Mmel1 17 31 30
  • 81.18 (n)
rat
(Rattus norvegicus)
Mammalia Mmel1 30
  • 81.18 (n)
oppossum
(Monodelphis domestica)
Mammalia MMEL1 31
  • 66 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MMEL1 31
  • 65 (a)
OneToOne
chicken
(Gallus gallus)
Aves MMEL1 31 30
  • 67.46 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mmel1 30
  • 65.37 (n)
Str.13545 30
zebrafish
(Danio rerio)
Actinopterygii mmel1 30
  • 64.14 (n)
MMEL1 31
  • 61 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003106 30
  • 55.72 (n)
fruit fly
(Drosophila melanogaster)
Insecta Nep4 31 30
  • 54.34 (n)
ManyToMany
Nep1 31
  • 36 (a)
ManyToMany
Nep2 31
  • 36 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea nep-2 31 30
  • 49.41 (n)
ManyToMany
nep-1 31
  • 32 (a)
ManyToMany
nep-11 31
  • 32 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 39 (a)
OneToMany
Species where no ortholog for MMEL1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MMEL1 Gene

ENSEMBL:
Gene Tree for MMEL1 (if available)
TreeFam:
Gene Tree for MMEL1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MMEL1: view image

Paralogs for MMEL1 Gene

Paralogs for MMEL1 Gene

(6) SIMAP similar genes for MMEL1 Gene using alignment to 2 proteins:

  • MMEL1_HUMAN
  • J3KRD2_HUMAN
genes like me logo Genes that share paralogs with MMEL1: view

Variants for MMEL1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MMEL1 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
708734 Likely Benign: not provided 2,592,689(-) A/G MISSENSE_VARIANT
712823 Benign: not provided 2,604,193(-) T/C MISSENSE_VARIANT
719695 Benign: not provided 2,592,725(-) G/A INTRON_VARIANT
719696 Benign: not provided 2,593,833(-) C/T SYNONYMOUS_VARIANT
719937 Benign: not provided 2,591,922(-) C/T INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for MMEL1 Gene

Structural Variations from Database of Genomic Variants (DGV) for MMEL1 Gene

Variant ID Type Subtype PubMed ID
dgv19e59 CNV duplication 20981092
esv3582248 CNV gain 25503493
esv3585029 CNV loss 21293372
nsv1136059 CNV deletion 24896259
nsv1144338 CNV deletion 24896259
nsv428399 CNV gain 18775914
nsv470684 CNV loss 18288195
nsv545077 CNV gain 21841781
nsv545082 CNV loss 21841781
nsv545083 CNV gain 21841781
nsv7171 OTHER inversion 18451855
nsv829648 CNV loss 17160897
nsv951592 CNV deletion 24416366
nsv951593 CNV deletion 24416366

Variation tolerance for MMEL1 Gene

Residual Variation Intolerance Score: 88% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.06; 50.59% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MMEL1 Gene

Human Gene Mutation Database (HGMD)
MMEL1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MMEL1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MMEL1 Gene

Disorders for MMEL1 Gene

MalaCards: The human disease database

(4) MalaCards diseases for MMEL1 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
primary biliary cirrhosis
  • pbc
schwartz-jampel syndrome, type 1
  • kniest-like dysplasia with pursed lips and ectopia lentis
nemaline myopathy 2
  • nem2
celiac disease 1
  • celiac disease, susceptibility to, 1
- elite association - COSMIC cancer census association via MalaCards
Search MMEL1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MMEL1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MMEL1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MMEL1 Gene

Publications for MMEL1 Gene

  1. Molecular cloning, tissue distribution, and chromosomal localization of MMEL2, a gene coding for a novel human member of the neutral endopeptidase-24.11 family. (PMID: 11560781) Bonvouloir N … DesGroseillers L (DNA and cell biology 2001) 2 3 4 23 54
  2. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A … Murray JC (PloS one 2010) 3 41 54
  3. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. (PMID: 20453842) Stahl EA … Plenge RM (Nature genetics 2010) 3 41 54
  4. Multiple common variants for celiac disease influencing immune gene expression. (PMID: 20190752) Dubois PC … van Heel DA (Nature genetics 2010) 3 41 54
  5. A functionally relevant IRF5 haplotype is associated with reduced risk to Wegener's granulomatosis. (PMID: 20049410) Wieczorek S … Epplen JT (Journal of molecular medicine (Berlin, Germany) 2010) 3 41 54

Products for MMEL1 Gene

Sources for MMEL1 Gene