ID F7B8E7_HORSE Unreviewed; 750 AA. AC F7B8E7; DT 27-JUL-2011, integrated into UniProtKB/TrEMBL. DT 27-JUL-2011, sequence version 1. DT 27-MAR-2024, entry version 68. DE RecName: Full=Neprilysin {ECO:0000256|ARBA:ARBA00022077}; DE EC=3.4.24.11 {ECO:0000256|ARBA:ARBA00012521}; DE AltName: Full=Atriopeptidase {ECO:0000256|ARBA:ARBA00032584}; DE AltName: Full=Enkephalinase {ECO:0000256|ARBA:ARBA00031362}; DE AltName: Full=Neutral endopeptidase 24.11 {ECO:0000256|ARBA:ARBA00031127}; DE AltName: Full=Skin fibroblast elastase {ECO:0000256|ARBA:ARBA00031486}; GN Name=MME {ECO:0000313|Ensembl:ENSECAP00000007949.1, GN ECO:0000313|VGNC:VGNC:20220}; OS Equus caballus (Horse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus. OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000007949.1, ECO:0000313|Proteomes:UP000002281}; RN [1] {ECO:0000313|Ensembl:ENSECAP00000007949.1, ECO:0000313|Proteomes:UP000002281} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000007949.1, RC ECO:0000313|Proteomes:UP000002281}; RX PubMed=19892987; DOI=10.1126/science.1178158; RG Broad Institute Genome Sequencing Platform; RG Broad Institute Whole Genome Assembly Team; RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F., RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O., RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T., RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T., RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S., RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G., RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R., RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A., RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J., RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.; RT "Genome sequence, comparative analysis, and population genetics of the RT domestic horse."; RL Science 326:865-867(2009). RN [2] {ECO:0000313|Ensembl:ENSECAP00000007949.1} RP IDENTIFICATION. RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000007949.1}; RG Ensembl; RL Submitted (NOV-2023) to UniProtKB. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + neurotensin = L-isoleucyl-L-leucine + neurotensin(1-11); CC Xref=Rhea:RHEA:71475, ChEBI:CHEBI:15377, ChEBI:CHEBI:147362, CC ChEBI:CHEBI:190704, ChEBI:CHEBI:190706; CC Evidence={ECO:0000256|ARBA:ARBA00034019}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476; CC Evidence={ECO:0000256|ARBA:ARBA00034019}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + neurotensin = L-tyrosyl-L-isoleucyl-L-leucine + CC neurotensin(1-10); Xref=Rhea:RHEA:71479, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:147362, ChEBI:CHEBI:190705, ChEBI:CHEBI:190707; CC Evidence={ECO:0000256|ARBA:ARBA00033995}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71480; CC Evidence={ECO:0000256|ARBA:ARBA00033995}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + substance P = L-Leu-L-Met-NH2 + substance P(1-9); CC Xref=Rhea:RHEA:71459, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692, CC ChEBI:CHEBI:190693, ChEBI:CHEBI:190700; CC Evidence={ECO:0000256|ARBA:ARBA00034071}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460; CC Evidence={ECO:0000256|ARBA:ARBA00034071}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + substance P = L-Phe-Gly-L-Leu-L-Met-NH2 + substance P(1- CC 7); Xref=Rhea:RHEA:71467, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692, CC ChEBI:CHEBI:190695, ChEBI:CHEBI:190698; CC Evidence={ECO:0000256|ARBA:ARBA00033985}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71468; CC Evidence={ECO:0000256|ARBA:ARBA00033985}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Preferential cleavage of polypeptides between hydrophobic CC residues, particularly with Phe or Tyr at P1'.; EC=3.4.24.11; CC Evidence={ECO:0000256|ARBA:ARBA00000716}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000256|ARBA:ARBA00001947}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR RefSeq; XP_005601073.1; XM_005601016.2. DR RefSeq; XP_014587415.1; XM_014731929.1. DR AlphaFoldDB; F7B8E7; -. DR SMR; F7B8E7; -. DR STRING; 9796.ENSECAP00000007949; -. DR MEROPS; M13.001; -. DR GlyCosmos; F7B8E7; 4 sites, No reported glycans. DR PaxDb; 9796-ENSECAP00000007949; -. DR Ensembl; ENSECAT00000010316.3; ENSECAP00000007949.1; ENSECAG00000009138.4. DR GeneID; 100053541; -. DR KEGG; ecb:100053541; -. DR CTD; 4311; -. DR VGNC; VGNC:20220; MME. DR GeneTree; ENSGT00940000156745; -. DR HOGENOM; CLU_006187_8_0_1; -. DR InParanoid; F7B8E7; -. DR OMA; YECTGVY; -. DR OrthoDB; 202716at2759; -. DR TreeFam; TF315192; -. DR Proteomes; UP000002281; Chromosome 16. DR Bgee; ENSECAG00000009138; Expressed in adult mammalian kidney and 21 other cell types or tissues. DR ExpressionAtlas; F7B8E7; baseline. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005903; C:brush border; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005769; C:early endosome; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; IEA:Ensembl. DR GO; GO:0044306; C:neuron projection terminus; ISS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0045202; C:synapse; ISS:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl. DR GO; GO:1901612; F:cardiolipin binding; IEA:Ensembl. DR GO; GO:0008238; F:exopeptidase activity; IEA:Ensembl. DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB. DR GO; GO:0042277; F:peptide binding; ISS:UniProtKB. DR GO; GO:0001786; F:phosphatidylserine binding; IEA:Ensembl. DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0097242; P:amyloid-beta clearance; IBA:GO_Central. DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IEA:Ensembl. DR GO; GO:0050435; P:amyloid-beta metabolic process; ISS:UniProtKB. DR GO; GO:0010815; P:bradykinin catabolic process; IEA:Ensembl. DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS:UniProtKB. DR GO; GO:0071492; P:cellular response to UV-A; ISS:UniProtKB. DR GO; GO:0071493; P:cellular response to UV-B; ISS:UniProtKB. DR GO; GO:0046449; P:creatinine metabolic process; ISS:UniProtKB. DR GO; GO:0042447; P:hormone catabolic process; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; ISS:UniProtKB. DR GO; GO:0007611; P:learning or memory; IEA:Ensembl. DR GO; GO:0061837; P:neuropeptide processing; IEA:Ensembl. DR GO; GO:0006518; P:peptide metabolic process; ISS:UniProtKB. DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl. DR GO; GO:0016485; P:protein processing; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB. DR GO; GO:0090399; P:replicative senescence; ISS:UniProtKB. DR GO; GO:0019233; P:sensory perception of pain; ISS:UniProtKB. DR GO; GO:0010814; P:substance P catabolic process; IEA:Ensembl. DR CDD; cd08662; M13; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 1.10.1380.10; Neutral endopeptidase , domain2; 1. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR000718; Peptidase_M13. DR InterPro; IPR018497; Peptidase_M13_C. DR InterPro; IPR042089; Peptidase_M13_dom_2. DR InterPro; IPR008753; Peptidase_M13_N. DR PANTHER; PTHR11733:SF114; NEPRILYSIN; 1. DR PANTHER; PTHR11733; ZINC METALLOPROTEASE FAMILY M13 NEPRILYSIN-RELATED; 1. DR Pfam; PF01431; Peptidase_M13; 1. DR Pfam; PF05649; Peptidase_M13_N; 1. DR PRINTS; PR00786; NEPRILYSIN. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS51885; NEPRILYSIN; 1. PE 1: Evidence at protein level; KW Hydrolase {ECO:0000256|ARBA:ARBA00022801}; KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288}; KW Membrane {ECO:0000256|SAM:Phobius}; KW Metal-binding {ECO:0000256|ARBA:ARBA00022723}; KW Metalloprotease {ECO:0000256|ARBA:ARBA00023049}; KW Myristate {ECO:0000256|ARBA:ARBA00022707}; KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553}; KW Protease {ECO:0000256|ARBA:ARBA00022670}; KW Proteomics identification {ECO:0007829|PeptideAtlas:F7B8E7}; KW Reference proteome {ECO:0000313|Proteomes:UP000002281}; KW Transmembrane {ECO:0000256|SAM:Phobius}; KW Transmembrane helix {ECO:0000256|SAM:Phobius}; KW Zinc {ECO:0000256|ARBA:ARBA00022833}. FT TRANSMEM 29..52 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" FT DOMAIN 79..483 FT /note="Peptidase M13 N-terminal" FT /evidence="ECO:0000259|Pfam:PF05649" FT DOMAIN 543..749 FT /note="Peptidase M13 C-terminal" FT /evidence="ECO:0000259|Pfam:PF01431" SQ SEQUENCE 750 AA; 85407 MW; E03A3D0F9D600D2D CRC64; MGRSESQMDI TDINTPKPKK QQRWTPLEVS LSVLVVLLTV IAVTTIALYA TYDDGICKSS DCIKSAARLI QNMDATAEPC ANFFKYACGG WLKRNIIPET SSRYGNFDIL RDELEVVLKD VLQETKTEDI AAVQKAKTLY RSCVNESVID SRGGEPLLRL LPDIYDWPVA TENWEQVYGT SWTAEKSIAQ LNSKYGKKVI INFFVGTDDK NSMNHIIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI SVAKLIRQEK GLPIDENQLS SEMNKVMELE KEIANATAKP EDRNDPILLY NKMTLAQIQS NFSLEINGKP FSWANFTNEI MSTVNINIPN EEDVVVYAPE YLTKLKLILT KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV ENLIAQIREV FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDEIISND SKLDNEYLEL NYKEDEYFEN IIQNLKFSQN KQLKKLREKV DKDEWISGAA VVNAFYSSGR NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD GDLVDWWTQQ SANNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA DNGGIGQAYR AYQNYVKKNG EEKLLPGIDL NHKQLFFLNF AQVWCGTYRP EYAINSIKTD VHSPGSFRII GTLQNSPEFS EAFHCPKNSY MNPEKKCRVW //