Protein detail
NEP
Neprilysin (EC 3.4.24.11) (Atriopeptidase) (Common acute lymphocytic leukemia antigen) (CALLA) (Enkephalinase) (Neutral endopeptidase 24.11) (NEP) (Neutral endopeptidase) (Skin fibroblast elastase) (SFE) (CD antigen CD10)
Entry name NEP | UniProt ID | EVMP confidence score 0.50 |
Supporting publications (n) 4 | Transmembrane count 1 | Protein classification Cancer-related genesCandidate cardiovascular disease genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information13
Protein Names
Neprilysin (EC 3.4.24.11) (Atriopeptidase) (Common acute lymphocytic leukemia antigen) (CALLA) (Enkephalinase) (Neutral endopeptidase 24.11) (NEP) (Neutral endopeptidase) (Skin fibroblast elastase) (SFE) (CD antigen CD10)
Protein Class (10)
Cancer-related genesCandidate cardiovascular disease genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins
Protein Function (10)
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- CD markers
- Candidate cardiovascular disease genes
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- ENZYME proteins:Hydrolases
- Peptidases:Metallopeptidases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Transmembrane
29..51; Helical; Signal-anchor for type II membrane protein
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym (3)
CALLACD10NEP
Gene Description
Membrane metalloendopeptidase
Chromosome
3
Position
155024124-155183704
Supporting publications (n)
4
EVMP confidence score
0.50
Fluorescence & Localization3
Tissue SpecificbrainCell SpecificAdrenal cortex cellsSingle-Nuclei Brain Specificastrocyte
Function & Pathway7
Protein Function (10)
- Predicted intracellular proteins
- Human disease related genes:Nervous system diseases:Neurodegenerative diseases
- CD markers
- Candidate cardiovascular disease genes
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- ENZYME proteins:Hydrolases
- Peptidases:Metallopeptidases
- Disease related genes
- FDA approved drug targets:Small molecule drugs
Cellular Component (19)
- GO:0005737 cytoplasm
- GO:0005769 early endosome
- GO:0005802 trans-Golgi network
- GO:0005886 plasma membrane
- GO:0005903 brush border
- GO:0005925 focal adhesion
- GO:0008021 synaptic vesicle
- GO:0009986 cell surface
- GO:0016020 membrane
- GO:0030424 axon
Page 1 of 2
Molecular Function (10)
- GO:0001786 phosphatidylserine binding
- GO:0004175 endopeptidase activity
- GO:0004222 metalloendopeptidase activity
- GO:0005515 protein binding
- GO:0008238 exopeptidase activity
- GO:0008270 zinc ion binding
- GO:0042277 peptide binding
- GO:0042803 protein homodimerization activity
- GO:0070012 oligopeptidase activity
- GO:1901612 cardiolipin binding
Biological Process (3)
KEGG (4)
Reactome (11)
- R-hsa-5576891 cardiac conduction
- R-hsa-9734767 developmental cell lineages
- R-hsa-9734779 developmental cell lineages of the integumentary system
- R-hsa-9924644 developmental lineages of the mammary gland
- R-hsa-9927432 developmental lineage of mammary gland myoepithelial cells
- R-hsa-168249 innate immune system
- R-hsa-2022377 metabolism of angiotensinogen to angiotensins
- R-hsa-397014 muscle contraction
- R-hsa-6798695 neutrophil degranulation
- R-hsa-2980736 peptide hormone metabolism
Page 1 of 2
Mediation Categories (6)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence38
Enzyme-Mediated Modification (3)
3 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| MME | CSNK2B | P67870 | S | 6 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPProtMapperHPRDKEASIGNOR_ProtMapper | ProtMapper:8943850HPRD:18578522HPRD:8943850KEA:8943850HPRD:20166139 |
| MME | CSNK2B | P67870 | T | 25 | phosphorylation | KEA | KEA:8943850 |
| MME | CSNK2A1 | P68400 | S | 6 | phosphorylation | PhosphoSite_MIMPMIMPHPRD_MIMPProtMapperSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20957047 |
Ligand-Receptor Signaling (31)
31 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | Yes | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | Yes | No |
| plasma_membrane_transmembrane | plasma_membrane_transmembrane | CSPA | No | No | No | Yes | No |
| plasma_membrane_transmembrane | plasma_membrane_transmembrane | OmniPath | No | No | No | Yes | No |
| cell_surface | cell_surface | Surfaceome | No | No | No | Yes | No |
| cell_surface | cell_surface | OmniPath | No | No | No | Yes | No |
| receptor | receptor | scConnect | No | Yes | No | Yes | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | No | Yes | No |
| transmembrane_phobius | transmembrane_predicted | Almen2009 | No | No | No | Yes | No |
| transmembrane_sosui | transmembrane_predicted | Almen2009 | No | No | No | Yes | No |
Regulatory Interaction Network (2)
2 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| CSK21 | P68400 | NEP | P08473 | Yes | Yes | Yes | WangPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperHINTSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper | ProtMapper:20957047PhosphoSite:22767595HINT:8943850SIGNOR:20957047HINT:20957047 |
| CSK2B | P67870 | NEP | P08473 | Yes | No | No | PhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetSIGNORProtMapperHPRDPhosphoSite_KEAKEAHPRD_KEASIGNOR_ProtMapperHPRD-phos | ProtMapper:8943850HPRD-phos:8943850ProtMapper:18578522HPRD:8943850HPRD-phos:18578522KEA:8943850ProtMapper:20166139SIGNOR:8943850HPRD-phos:20166139 |
Protein Complex Composition (1)
Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | Mass spectrometry | 1 | 37980468 |
Sequence, Structure & Domains13
Sequences
Length
750
Mass
85,514
Sequence
MGKSESQMDITDINTPKPKKKQRWTPLEISLSVLVLLLTIIAVTMIALYATYDDGICKSSDCIKSAARLIQNMDATTEPCTDFFKYACGGWLKRNVIPETSSRYGNFDILRDELEVVLKDVLQEPKTEDIVAVQKAKALYRSCINESAIDSRGGEPLLKLLPDIYGWPVATENWEQKYGASWTAEKAIAQLNSKYGKKVLINLFVGTDDKNSVNHVIHIDQPRLGLPSRDYYECTGIYKEACTAYVDFMISVARLIRQEERLPIDENQLALEMNKVMELEKEIANATAKPEDRNDPMLLYNKMTLAQIQNNFSLEINGKPFSWLNFTNEIMSTVNISITNEEDVVVYAPEYLTKLKPILTKYSARDLQNLMSWRFIMDLVSSLSRTYKESRNAFRKALYGTTSETATWRRCANYVNGNMENAVGRLYVEAAFAGESKHVVEDLIAQIREVFIQTLDDLTWMDAETKKRAEEKALAIKERIGYPDDIVSNDNKLNNEYLELNYKEDEYFENIIQNLKFSQSKQLKKLREKVDKDEWISGAAVVNAFYSSGRNQIVFPAGILQPPFFSAQQSNSLNYGGIGMVIGHEITHGFDDNGRNFNKDGDLVDWWTQQSASNFKEQSQCMVYQYGNFSWDLAGGQHLNGINTLGENIADNGGLGQAYRAYQNYIKKNGEEKLLPGLDLNHKQLFFLNFAQVWCGTYRPEYAVNSIKTDVHSPGNFRIIGTLQNSAEFSEAFHCRKNSYMNPEKKCRVW
3D Structural Models
Turn
79..81; 152..154; 178..181; 497..499; 525..527; 548..551; 562..564; 641..644
Helix
60..72; 83..94; 106..122; 131..144; 146..151; 155..160; 161..164; 168..170; 174..177; 184..195; 229..233; 236..238; 239..259; 266..286; 290..293; 296..299; 305..311; 323..331; 332..334; 349..359; 364..379; 380..382; 385..389; 392..399; 407..418; 420..431; 436..457; 463..475; 485..488; 490..496; 507..524; 557..559; 571..576; 578..588; 594..596; 609..627; 632..634; 645..669; 682..692; 700..709; 715..724; 727..732
Beta Strand
102..105; 171..173; 200..208; 211..220; 225..228; 302..304; 316..319; 343..347; 459..461; 477..481; 545..547; 552..556; 567..569; 636..638; 696..698
3D Structure
X-ray crystallography (16)
Domain & Motif Annotations
Compositional Bias
1..14; Polar residues
Motif
16..23; Stop-transfer sequence
Domain (FT)
56..750; Peptidase M13
Region
1..20; Disordered
Protein Families
Peptidase M13 family
Sequence Similarities
Belongs to the peptidase M13 family.
Clinical Relevance9
Disease Involvement (7)
Cancer-related genesCharcot-Marie-Tooth diseaseDisease variantFDA approved drug targetsNeurodegenerationNeuropathySpinocerebellar ataxia
Related Diseases (17)
Biomarker
Phase 2; Phase 1; Discontinued in Phase 2/3; Terminated; Approved; Phase 3; Discontinued in Phase 2
Drug Targets
FDA approved drug targets
Drugs (12)
Interaction Protein
ENSG00000106211
Interaction Count
1
Interaction Dataset
intact_biogrid
Supporting Publications4
| PMID | Title | Abstract |
|---|---|---|
| 33592500 | A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia-Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia. | No abstract available |
| 37322475 | Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration. | No abstract available |
| 41068253 | Identification of plasma extracellular vesicle protein biomarkers in diabetic retinopathy progression. | No abstract available |
| 41307968 | Extracellular Vesicles Define Discrete Nano-Based Niches Within the Human Haematopoietic System. | No abstract available |