Reactome | UniProt:P08473 MME

chain	initiator methionine:1 chain:2-750
checksum	BCF3827C39898630
comment	FUNCTION Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:6208535, PubMed:6349683, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991, PubMed:6349683). Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (PubMed:6208535). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675, PubMed:6349683). Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:16254193, PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).CATALYTIC ACTIVITY Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.CATALYTIC ACTIVITY substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2CATALYTIC ACTIVITY substance P + H2O = substance P(1-7) + L-Phe-Gly-L-Leu-L-Met-NH2CATALYTIC ACTIVITY neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucineCATALYTIC ACTIVITY neurotensin + H2O = neurotensin(1-10) + L-tyrosyl-L-isoleucyl-L-leucineCOFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Inhibited in a dose dependent manner by opiorphin (PubMed:17101991). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059).BIOPHYSICOCHEMICAL PROPERTIES Myristoylation is a determinant of membrane targeting.PTM Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.SIMILARITY Belongs to the peptidase M13 family.SEQUENCE CAUTION Truncated N-terminus.
crossReference	[DatabaseIdentifier:12206314] PDB:4CTH [DatabaseIdentifier:12818203] ZINC - World Drugs:NEP_HUMAN [DatabaseIdentifier:12816365] ZINC target:P08473 [DatabaseIdentifier:12812969] ZINC - Substances:NEP_HUMAN [DatabaseIdentifier:12808668] ZINC - Predictions - Purchasable:NEP_HUMAN [DatabaseIdentifier:12807981] ZINC - Metabolites:NEP_HUMAN [DatabaseIdentifier:12806696] ZINC - Investigational:NEP_HUMAN [DatabaseIdentifier:12804483] ZINC - Biogenic:NEP_HUMAN [DatabaseIdentifier:12379954] RefSeq:XP_054202545.1 [DatabaseIdentifier:12379948] RefSeq:NP_009218.2 [DatabaseIdentifier:12379951] RefSeq:XP_054202547.1 [DatabaseIdentifier:12379947] RefSeq:XP_006713710.1 [DatabaseIdentifier:12379952] RefSeq:XP_054202546.1 [DatabaseIdentifier:12379942] RefSeq:NP_000893.2 [DatabaseIdentifier:12379950] RefSeq:XP_011511158.1 [DatabaseIdentifier:12379955] RefSeq:XP_054202544.1 [DatabaseIdentifier:12379946] RefSeq:NP_001341571.1 [DatabaseIdentifier:12379945] RefSeq:NP_009219.2 [DatabaseIdentifier:12379949] RefSeq:XP_011511159.1 [DatabaseIdentifier:12379953] RefSeq:NP_009220.2 [DatabaseIdentifier:12379943] RefSeq:XP_047304113.1 [DatabaseIdentifier:12379944] RefSeq:NP_001341572.1 [DatabaseIdentifier:12288935] Pharos - Targets:P08473 [DatabaseIdentifier:12270545] PRO:P08473 [DatabaseIdentifier:12206317] PDB:6THP [DatabaseIdentifier:12206312] PDB:5JMY [DatabaseIdentifier:12206306] PDB:1R1J [DatabaseIdentifier:12206305] PDB:1DMT [DatabaseIdentifier:12206303] PDB:2YB9 [DatabaseIdentifier:12206307] PDB:1Y8J [DatabaseIdentifier:12206316] PDB:6SH1 [DatabaseIdentifier:12206310] PDB:1R1H [DatabaseIdentifier:12206309] PDB:2QPJ [DatabaseIdentifier:12206304] PDB:6SUK [DatabaseIdentifier:12206308] PDB:1R1I [DatabaseIdentifier:11477722] ENSEMBL:ENSG00000196549 [DatabaseIdentifier:11577460] ENSEMBL:ENSP00000420389 [DatabaseIdentifier:11577463] ENSEMBL:ENSP00000505690 [DatabaseIdentifier:11577465] ENSEMBL:ENSP00000353679 [DatabaseIdentifier:11577464] ENSEMBL:ENSP00000417079 [DatabaseIdentifier:11577458] ENSEMBL:ENSP00000418791 [DatabaseIdentifier:11577457] ENSEMBL:ENSP00000502021 [DatabaseIdentifier:11577462] ENSEMBL:ENSP00000419653 [DatabaseIdentifier:11577456] ENSEMBL:ENSP00000505211 [DatabaseIdentifier:11577459] ENSEMBL:ENSP00000420542 [DatabaseIdentifier:11577461] ENSEMBL:ENSP00000418525 [DatabaseIdentifier:11700162] ENSEMBL:ENST00000493237 [DatabaseIdentifier:11700164] ENSEMBL:ENST00000491026 [DatabaseIdentifier:11700155] ENSEMBL:ENST00000460393 [DatabaseIdentifier:11700157] ENSEMBL:ENST00000360490 [DatabaseIdentifier:11700163] ENSEMBL:ENST00000473730 [DatabaseIdentifier:11700161] ENSEMBL:ENST00000675418 [DatabaseIdentifier:11700158] ENSEMBL:ENST00000680057 [DatabaseIdentifier:11700160] ENSEMBL:ENST00000680282 [DatabaseIdentifier:11700159] ENSEMBL:ENST00000492661 [DatabaseIdentifier:11700156] ENSEMBL:ENST00000462745 [DatabaseIdentifier:11779195] Guide to Pharmacology - Targets:1611 [DatabaseIdentifier:11791091] GeneCards:MME [DatabaseIdentifier:11832471] HMDB Protein:HMDBP02539 [DatabaseIdentifier:11844096] HPA:ENSG00000196549-MME [DatabaseIdentifier:12128715] OpenTargets:ENSG00000196549 [DatabaseIdentifier:12136964] Orphanet:MME [DatabaseIdentifier:12206302] PDB:6XVP [DatabaseIdentifier:12206315] PDB:6SH2 [DatabaseIdentifier:12206311] PDB:6GID [DatabaseIdentifier:12206313] PDB:6SVY
databaseName	UniProt
dbId	60073
description	recommendedName: fullName evidence="27"Neprilysin ecNumber evidence="9 20 24 25 26"3.4.24.11 alternativeName: Atriopeptidase alternativeName: Common acute lymphocytic leukemia antigen shortName: CALLA alternativeName: fullName evidence="31"Enkephalinase alternativeName: fullName evidence="29"Neutral endopeptidase 24.11 shortName: NEP shortName: Neutral endopeptidase alternativeName: Skin fibroblast elastase shortName: SFE cdAntigenName evidence="28"CD10/cdAntigenName
displayName	UniProt:P08473 MME
geneName	MME EPN
identifier	P08473
isSequenceChanged	false
keyword	3D-structure Cell membrane Charcot-Marie-Tooth disease Disease variant Disulfide bond Glycoprotein Hydrolase Lipoprotein Membrane Metal-binding Metalloprotease Myristate Neurodegeneration Neuropathy Phosphoprotein Protease Proteomics identification Reference proteome Signal-anchor Spinocerebellar ataxia Transmembrane Transmembrane helix Zinc
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	MME
otherIdentifier	11720022_a_at 11741562_a_at 11747693_a_at 11755860_a_at 11761628_a_at 1389_at 16947173 203434_PM_s_at 203434_s_at 203435_PM_s_at 203435_s_at 2648678 2648679 2648680 2648681 2648682 2648683 2648684 2648685 2648686 2648687 2648688 2648701 2648702 2648703 2648705 2648706 2648707 2648708 2648709 2648710 2648715 2648716 2648717 2648718 2648720 2648721 2648724 2648725 2648727 2648729 2648731 2648732 2648733 2648734 2648736 2648742 2648743 2648744 2648745 2648746 4311 8083494 A_14_P114532 A_23_P212061 A_24_P260101 A_33_P3290707 A_33_P3370094 GE58450 GO:0001786 GO:0001822 GO:0001890 GO:0002003 GO:0004175 GO:0004181 GO:0004222 GO:0005515 GO:0005576 GO:0005654 GO:0005737 GO:0005768 GO:0005769 GO:0005802 GO:0005813 GO:0005815 GO:0005829 GO:0005886 GO:0005903 GO:0005925 GO:0006508 GO:0006518 GO:0007611 GO:0007613 GO:0008021 GO:0008233 GO:0008237 GO:0008238 GO:0008270 GO:0009986 GO:0010814 GO:0010815 GO:0016020 GO:0016485 GO:0016787 GO:0019233 GO:0021764 GO:0021766 GO:0030163 GO:0030324 GO:0030424 GO:0030425 GO:0030667 GO:0031410 GO:0035264 GO:0036064 GO:0042277 GO:0042447 GO:0042803 GO:0043025 GO:0043627 GO:0044306 GO:0045121 GO:0045202 GO:0046449 GO:0046872 GO:0048856 GO:0050435 GO:0050769 GO:0050877 GO:0061837 GO:0070012 GO:0070062 GO:0071345 GO:0071492 GO:0071493 GO:0090399 GO:0097242 GO:0098793 GO:0150094 GO:1900273 GO:1901612 HMNXSV003013972 Hs.1298.2.S1_3p_a_at ILMN_1678170 ILMN_1696162 ILMN_1751943 ILMN_1786319 J03779_at PH_hs_0023672 TC03000846.hg g6042199_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-2022342] MME [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6806156] MME [secretory granule membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000196549] ENSEMBL:ENSG00000196549 MME [ReferenceDNASequence:12741119] UCSC:P08473 MME [ReferenceDNASequence:11343172] BioGPS Gene:4311 MME [ReferenceDNASequence:11399958] COSMIC - genes:MME MME [ReferenceDNASequence:11418694] CTD Gene:4311 MME [ReferenceDNASequence:11437024] dbSNP Gene:4311 MME [ReferenceDNASequence:11822757] HGNC:7154 MME [ReferenceDNASequence:11883669] KEGG:hsa:4311 MME [ReferenceDNASequence:11972961] Monarch:4311 MME [ReferenceDNASequence:12057054] NCBI Gene:4311 MME [ReferenceDNASequence:12113448] OMIM:120520 MME
referenceTranscript	[ReferenceRNASequence:12561722] RefSeq:XM_011512856.3 MME [ReferenceRNASequence:12561724] RefSeq:NM_007288.3 MME [ReferenceRNASequence:12561731] RefSeq:XM_054346572.1 MME [ReferenceRNASequence:12561723] RefSeq:NM_007287.4 MME [ReferenceRNASequence:12561729] RefSeq:XM_054346569.1 MME [ReferenceRNASequence:12561727] RefSeq:NM_001354642.2 MME [ReferenceRNASequence:12561725] RefSeq:XM_011512857.3 MME [ReferenceRNASequence:12561719] RefSeq:XM_006713647.5 MME [ReferenceRNASequence:12561730] RefSeq:XM_054346570.1 MME [ReferenceRNASequence:12561732] RefSeq:XM_054346571.1 MME [ReferenceRNASequence:12561720] RefSeq:NM_007289.4 MME [ReferenceRNASequence:12561721] RefSeq:NM_000902.5 MME [ReferenceRNASequence:12561728] RefSeq:NM_001354643.1 MME [ReferenceRNASequence:12561726] RefSeq:XM_047448157.1 MME
schemaClass	ReferenceGeneProduct
secondaryIdentifier	NEP_HUMAN A8K6U6 D3DNJ9 Q3MIX4
sequenceLength	750
species	[Species:48887] Homo sapiens
stId	uniprot:P08473
url	http://purl.uniprot.org/uniprot/P08473

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-2022342] MME [plasma membrane] [EntityWithAccessionedSequence:R-HSA-6806156] MME [secretory granule membrane]
(interactor)	[UndirectedInteraction:11183115] UniProt:P04792 <-> UniProt:P08473 (IntAct) [UndirectedInteraction:11210039] UniProt:A0PJW6 <-> UniProt:P08473 (IntAct) [UndirectedInteraction:11273649] UniProt:P05067 <-> UniProt:P08473 (IntAct) [UndirectedInteraction:11300995] UniProt:P21926 <-> UniProt:P08473 (IntAct)

UniProt:P08473 MME Show undefined attributes

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