Human Gene MME (ENST00000360490.7_6) from GENCODE V47lift37
  Description: membrane metalloendopeptidase, transcript variant 2b (from RefSeq NM_007289.4)
Gencode Transcript: ENST00000360490.7_6
Gencode Gene: ENSG00000196549.13_11
Transcript (Including UTRs)
   Position: hg19 chr3:154,798,108-154,901,493 Size: 103,386 Total Exon Count: 23 Strand: +
Coding Region
   Position: hg19 chr3:154,801,957-154,898,248 Size: 96,292 Coding Exon Count: 22 

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Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:154,798,108-154,901,493)mRNA (may differ from genome)Protein (750 aa)
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-  Comments and Description Text from UniProtKB
  ID: NEP_HUMAN
DESCRIPTION: RecName: Full=Neprilysin; EC=3.4.24.11; AltName: Full=Atriopeptidase; AltName: Full=Common acute lymphocytic leukemia antigen; Short=CALLA; AltName: Full=Enkephalinase; AltName: Full=Neutral endopeptidase 24.11; Short=NEP; Short=Neutral endopeptidase; AltName: Full=Skin fibroblast elastase; Short=SFE; AltName: CD_antigen=CD10;
FUNCTION: Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV- inducible elastase activity toward skin preelastic and elastic fibers.
CATALYTIC ACTIVITY: Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.
COFACTOR: Binds 1 zinc ion per subunit.
ENZYME REGULATION: Inhibited in a dose dependent manner by opiorphin.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=55.1 uM for angiotensin-1; KM=179 uM for angiotensin-2; KM=111.4 uM for angiotensin 1-9;
INTERACTION: P08107:HSPA1B; NbExp=3; IntAct=EBI-353759, EBI-629985; P04792:HSPB1; NbExp=4; IntAct=EBI-353759, EBI-352682;
SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane protein.
PTM: Myristoylation is a determinant of membrane targeting.
MISCELLANEOUS: Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.
SIMILARITY: Belongs to the peptidase M13 family.
SEQUENCE CAUTION: Sequence=CAA30157.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MMEID41386ch3q25.html";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MME
Diseases sorted by gene-association score: spinocerebellar ataxia 43* (1279), charcot-marie-tooth disease, axonal, type 2t* (1240), charcot-marie-tooth disease type 2t* (350), acute lymphocytic leukemia (41), adenosarcoma (32), atypical polypoid adenomyoma (23), adenomyoma (23), adenofibroma (23), cystadenoma (17), perivascular epithelioid cell tumor (17), cystic nephroma (17), acute diarrhea (16), mixed endometrial stromal and smooth muscle tumor (15), ovarian endometrioid adenofibroma (15), fallopian tube endometrioid adenocarcinoma (14), breast myofibroblastoma (14), t-cell adult acute lymphocytic leukemia (14), endometrial stromal sarcoma (14), follicular lymphoma (14), angioimmunoblastic t-cell lymphoma (13), pancreatic mucinous cystadenoma (12), mixed cell type cancer (11), b-cell lymphomas (11), cerebral amyloid angiopathy (11), central nervous system leukemia (11), t-cell/histiocyte rich large b cell lymphoma (11), renal oncocytoma (11), renal clear cell carcinoma (10), precursor t-lymphoblastic lymphoma/leukemia (10), membranous nephropathy (10), balloon cell malignant melanoma (10), tracheal lymphoma (10), pleomorphic rhabdomyosarcoma (10), angioedema (9), chromophobe renal cell carcinoma (9), collecting duct carcinoma (9), oxyphilic adenoma (9), endometrial stromal nodule (9), diffuse large b-cell lymphoma (9), phyllode tumor (8), diarrhea (8), encapsulated thymoma (8), congestive heart failure (8), clear cell papillary renal cell carcinoma (8), psammomatous meningioma (8), extrahepatic bile duct adenocarcinoma (8), acute lymphoblastic leukemia, childhood (8), lung combined type small cell carcinoma (8), cervix endometriosis (7), kidney benign neoplasm (7), intravascular large b-cell lymphoma (7), ovarian lymphoma (7), leukemia (7), heart lymphoma (7), precursor lymphoblastic lymphoma/leukemia (7), schizoid personality disorder (7), cervical adenoma malignum (7), cervical carcinosarcoma (7), invasive malignant thymoma (7), lymphoblastic lymphoma (7), malignant leydig cell tumor (7), leiomyoma (7), complex regional pain syndrome (7), fallopian tube adenocarcinoma (7), intravenous leiomyomatosis (7), clear cell hidradenoma (7), benign breast phyllodes tumor (6), hydronephrosis (6), histrionic personality disorder (6), mantle cell lymphoma (6), peroneal neuropathy (6), schwartz-jampel syndrome, type 1 (6), adrenal cortical adenocarcinoma (6), gastrointestinal lymphoma (6), sweat gland cancer (6), cervical mucinous adenocarcinoma (6), orbital plasma cell granuloma (6), cll/sll (6), breast adenomyoepithelioma (5), breast myoepithelial neoplasm (5), mature b-cell neoplasm (5), nephrogenic adenofibroma (5), marginal zone b-cell lymphoma (5), bladder lymphoma (5), folic acid deficiency anemia (5), childhood disintegrative disease (5), dependent personality disorder (5), infiltrative basal cell carcinoma (5), papillary hidradenoma (5), tooth disease (5), dermis tumor (5), alzheimer disease (5), breast fibroadenoma (5), rete testis adenocarcinoma (5), spermatocele (5), charcot-marie-tooth disease (5), integumentary system benign neoplasm (5), renal cell carcinoma, papillary (5), lymphoma, malt, somatic (5), breast benign neoplasm (5), thoracic benign neoplasm (5), breast papillary carcinoma (5), mucinous tubular and spindle renal cell carcinoma (5), osmotic diarrhea (4), cardiovascular cancer (4), cystadenofibroma (4), chronic orbital inflammation (4), rete testis neoplasm (4), ovarian brenner tumor (4), meningeal melanocytoma (4), breast metaplastic carcinoma (4), uterine sarcoma (4), avoidant personality disorder (4), bare lymphocyte syndrome, type i (3), pediatric lymphoma (3), leukemia, acute lymphoblastic 3 (3), renal cell carcinoma (3), endometrial cancer (2), hepatocellular carcinoma (2), organ system benign neoplasm (1), myocardial infarction (1), lymphoma, non-hodgkin (1), hypertension, essential (1), leukemia, acute myeloid (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 247.12 RPKM in Cells - Cultured fibroblasts
Total median expression: 413.49 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -39.10158-0.247 Picture PostScript Text
3' UTR -777.703245-0.240 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR024079 - MetalloPept_cat_dom
IPR000718 - Peptidase_M13
IPR018497 - Peptidase_M13_C
IPR008753 - Peptidase_M13_N

Pfam Domains:
PF01431 - Peptidase family M13
PF05649 - Peptidase family M13

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases
55486 - Metalloproteases ("zincins"), catalytic domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1DL9 - Model 1DMT - X-ray 1QVD - Model 1R1H - X-ray 1R1I - X-ray 1R1J - X-ray 1Y8J - X-ray 2QPJ - X-ray 2YB9 - X-ray


ModBase Predicted Comparative 3D Structure on P08473
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004175 endopeptidase activity
GO:0004222 metalloendopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008238 exopeptidase activity
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0042277 peptide binding
GO:0046872 metal ion binding

Biological Process:
GO:0001822 kidney development
GO:0002003 angiotensin maturation
GO:0006508 proteolysis
GO:0006518 peptide metabolic process
GO:0019233 sensory perception of pain
GO:0043312 neutrophil degranulation
GO:0046449 creatinine metabolic process
GO:0050435 beta-amyloid metabolic process
GO:0071345 cellular response to cytokine stimulus
GO:0071492 cellular response to UV-A
GO:0071493 cellular response to UV-B
GO:0090399 replicative senescence
GO:0097242 beta-amyloid clearance

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005903 brush border
GO:0005925 focal adhesion
GO:0008021 synaptic vesicle
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0030667 secretory granule membrane
GO:0044306 neuron projection terminus
GO:0045202 synapse
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK291761 - Homo sapiens cDNA FLJ75497 complete cds, highly similar to Homo sapiens membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10) (MME), transcript variant 2b, mRNA.
AK310664 - Homo sapiens cDNA, FLJ17706.
BX647134 - Homo sapiens mRNA; cDNA DKFZp686O16152 (from clone DKFZp686O16152).
BC106070 - Homo sapiens membrane metallo-endopeptidase, mRNA (cDNA clone IMAGE:4360784), complete cds.
Y00811 - Human mRNA for common acute lymphocytic leukemia antigen CALLA (EC 3.4.24.11).
JD515592 - Sequence 496616 from Patent EP1572962.
JD251372 - Sequence 232396 from Patent EP1572962.
JD348228 - Sequence 329252 from Patent EP1572962.
BC101632 - Homo sapiens membrane metallo-endopeptidase, mRNA (cDNA clone MGC:126681 IMAGE:8069138), complete cds.
BC143465 - Homo sapiens membrane metallo-endopeptidase, mRNA (cDNA clone MGC:176990 IMAGE:9051973), complete cds.
BC101658 - Homo sapiens membrane metallo-endopeptidase, mRNA (cDNA clone MGC:126707 IMAGE:8069164), complete cds.
JD480191 - Sequence 461215 from Patent EP1572962.
J03779 - Human common acute lymphoblastic leukemia antigen (CALLA) mRNA, complete cds.
KJ891626 - Synthetic construct Homo sapiens clone ccsbBroadEn_01020 MME gene, encodes complete protein.
X07166 - Human mRNA for enkephalinase (EC 3.4.24.11).
KC143287 - Homo sapiens neprilysin-411 (MME) mRNA, partial cds, alternatively spliced.
KC143288 - Homo sapiens neprilysin-390 (MME) mRNA, partial cds, alternatively spliced.
AL833459 - Homo sapiens mRNA; cDNA DKFZp686L15116 (from clone DKFZp686L15116).
JD242466 - Sequence 223490 from Patent EP1572962.
JD506837 - Sequence 487861 from Patent EP1572962.
JD045770 - Sequence 26794 from Patent EP1572962.
JD547259 - Sequence 528283 from Patent EP1572962.
JD360033 - Sequence 341057 from Patent EP1572962.
JD301825 - Sequence 282849 from Patent EP1572962.
JD039080 - Sequence 20104 from Patent EP1572962.
JD550101 - Sequence 531125 from Patent EP1572962.
JD501118 - Sequence 482142 from Patent EP1572962.
JD236286 - Sequence 217310 from Patent EP1572962.
JD562598 - Sequence 543622 from Patent EP1572962.
JD449511 - Sequence 430535 from Patent EP1572962.
JD553445 - Sequence 534469 from Patent EP1572962.
JD460939 - Sequence 441963 from Patent EP1572962.
JD048308 - Sequence 29332 from Patent EP1572962.
JD086663 - Sequence 67687 from Patent EP1572962.
JD306013 - Sequence 287037 from Patent EP1572962.
JD433881 - Sequence 414905 from Patent EP1572962.
JD166287 - Sequence 147311 from Patent EP1572962.
JD295776 - Sequence 276800 from Patent EP1572962.
JD415480 - Sequence 396504 from Patent EP1572962.
JD254819 - Sequence 235843 from Patent EP1572962.
JD323814 - Sequence 304838 from Patent EP1572962.
JD091655 - Sequence 72679 from Patent EP1572962.
JD561515 - Sequence 542539 from Patent EP1572962.
JD159987 - Sequence 141011 from Patent EP1572962.
JD172046 - Sequence 153070 from Patent EP1572962.
JD055928 - Sequence 36952 from Patent EP1572962.
JD297854 - Sequence 278878 from Patent EP1572962.
JD554958 - Sequence 535982 from Patent EP1572962.
JD237838 - Sequence 218862 from Patent EP1572962.
JD072866 - Sequence 53890 from Patent EP1572962.
JD251417 - Sequence 232441 from Patent EP1572962.
JD078880 - Sequence 59904 from Patent EP1572962.
JD126602 - Sequence 107626 from Patent EP1572962.
JD525242 - Sequence 506266 from Patent EP1572962.
AJ270689 - Homo sapiens partial unknown mRNA from drug-resistant melanoma cells, 3'UTR, clone DSM-5.
JD304542 - Sequence 285566 from Patent EP1572962.
JD085528 - Sequence 66552 from Patent EP1572962.
JD531136 - Sequence 512160 from Patent EP1572962.
JD267000 - Sequence 248024 from Patent EP1572962.
JD422274 - Sequence 403298 from Patent EP1572962.
JD156865 - Sequence 137889 from Patent EP1572962.
JD521946 - Sequence 502970 from Patent EP1572962.
JD244225 - Sequence 225249 from Patent EP1572962.
JD090634 - Sequence 71658 from Patent EP1572962.
JD546933 - Sequence 527957 from Patent EP1572962.
JD163568 - Sequence 144592 from Patent EP1572962.
JD228436 - Sequence 209460 from Patent EP1572962.
JD219821 - Sequence 200845 from Patent EP1572962.
JD085303 - Sequence 66327 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P08473 (Reactome details) participates in the following event(s):

R-HSA-6798743 Exocytosis of secretory granule membrane proteins
R-HSA-2022368 Neprilysin hydrolyzes Angiotensin-(1-9) to Angiotensin-(1-7)
R-HSA-2022396 Neprilysin hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-7)
R-HSA-6798695 Neutrophil degranulation
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-168249 Innate Immune System
R-HSA-2980736 Peptide hormone metabolism
R-HSA-168256 Immune System
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8K6U6, D3DNJ9, ENST00000360490.1, ENST00000360490.2, ENST00000360490.3, ENST00000360490.4, ENST00000360490.5, ENST00000360490.6, EPN, MME , NEP_HUMAN, NM_007289, P08473, Q3MIX4, uc318bov.1, uc318bov.2
UCSC ID: ENST00000360490.7_6
RefSeq Accession: NM_007289.4
Protein: P08473 (aka NEP_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MME:
ataxias (Hereditary Ataxia Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.