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P0C1T0

- MMEL1_RAT

UniProt

P0C1T0 - MMEL1_RAT

Protein

Membrane metallo-endopeptidase-like 1

Gene

Mmel1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 60 (01 Oct 2014)
      Sequence version 1 (05 Sep 2006)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

    Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

    Inhibited by thiorphan and phosphoramidon.

    Kineticsi

    1. KM=62 µM for Tyrosyl-D-Ala(2)-Leu(5)-enkephalin2 Publications
    2. KM=27 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
    3. KM=50 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications
    4. KM=40 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
    5. KM=100 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications
    6. KM=23 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
    7. KM=35 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei72 – 732CleavageBy similarity
    Binding sitei131 – 1311Substrate carboxylCurated
    Metal bindingi608 – 6081Zinc; catalyticPROSITE-ProRule annotation
    Metal bindingi612 – 6121Zinc; catalyticPROSITE-ProRule annotation
    Active sitei615 – 6151PROSITE-ProRule annotation
    Metal bindingi671 – 6711Zinc; catalyticPROSITE-ProRule annotation
    Active sitei675 – 6751Proton donorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: RGD
    2. zinc ion binding Source: RGD

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Membrane metallo-endopeptidase-like 1 (EC:3.4.24.11)
    Alternative name(s):
    NEP2(m)
    Neprilysin II
    Short name:
    NEPII
    Neprilysin-2
    Short name:
    NEP2
    Short name:
    NL2
    Cleaved into the following chain:
    Alternative name(s):
    Neprilysin-2 secreted
    Short name:
    NEP2(s)
    Gene namesi
    Name:Mmel1
    Synonyms:Mell1, Nep2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 5

    Organism-specific databases

    RGDi1309299. Mmel1.

    Subcellular locationi

    Membrane; Single-pass type II membrane protein. Secreted
    Note: A secreted form produced by proteollytic cleavage also exists.Curated

    GO - Cellular componenti

    1. endoplasmic reticulum Source: Ensembl
    2. extracellular space Source: RGD
    3. Golgi apparatus Source: Ensembl
    4. integral component of membrane Source: UniProtKB-KW
    5. membrane Source: RGD

    Keywords - Cellular componenti

    Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi131 – 1311R → M: Impairs binding of free carboxylate group of substrates. 1 Publication
    Mutagenesisi133 – 1331S → G: Impairs both substrate-binding and enzyme activity. 1 Publication
    Mutagenesisi567 – 5671N → G: Impairs the enzyme specificity. 1 Publication
    Mutagenesisi739 – 7391L → G: Impairs both substrate-binding and enzyme activity. 1 Publication
    Mutagenesisi751 – 7511P → A: Loss of function. 1 Publication
    Mutagenesisi764 – 7641P → Y: Induces a 3-fold decrease of specific activity. 1 Publication
    Mutagenesisi774 – 7741W → F: No effect. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 774774Membrane metallo-endopeptidase-like 1PRO_0000248419Add
    BLAST
    Chaini73 – 774702Membrane metallo-endopeptidase-like 1, soluble formBy similarityPRO_0000248420Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi85 ↔ 90By similarity
    Disulfide bondi108 ↔ 759By similarity
    Disulfide bondi116 ↔ 719By similarity
    Disulfide bondi171 ↔ 434By similarity
    Glycosylationi173 – 1731N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi239 – 2391N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi633 – 6331N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi645 ↔ 771By similarity
    Glycosylationi652 – 6521N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi703 – 7031N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.1 Publication

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP0C1T0.
    PRIDEiP0C1T0.

    Expressioni

    Tissue specificityi

    Specifically expressed in testis and central nervous system (CNS) (at protein level). Restricted to developing and differentiating fields of the CNS. The soluble form is expressed in round spermatides.2 Publications

    Gene expression databases

    GenevestigatoriP0C1T0.

    Interactioni

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000063235.

    Structurei

    3D structure databases

    ProteinModelPortaliP0C1T0.
    SMRiP0C1T0. Positions 83-774.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2626CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini48 – 774727LumenalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei27 – 4721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili532 – 55827Sequence AnalysisAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi14 – 218Stop-transfer sequenceSequence Analysis

    Sequence similaritiesi

    Belongs to the peptidase M13 family.Curated

    Keywords - Domaini

    Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG3590.
    GeneTreeiENSGT00650000093248.
    HOGENOMiHOG000245574.
    HOVERGENiHBG005554.
    OMAiDGNMLDW.
    OrthoDBiEOG7PZRWQ.

    Family and domain databases

    Gene3Di3.40.390.10. 2 hits.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view]
    PANTHERiPTHR11733. PTHR11733. 1 hit.
    PfamiPF01431. Peptidase_M13. 1 hit.
    PF05649. Peptidase_M13_N. 1 hit.
    [Graphical view]
    PRINTSiPR00786. NEPRILYSIN.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P0C1T0-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGKSESSVGM MERADNCGRR RLGFVECGLL VLLTLLLMGA IVTLGVFYSI    50
    GKQLPLLNSL LHVSRHERTV VKRVLRDSSQ KSDICTTPSC VIAAARILQN 100
    MDQSKKPCDN FYQYACGGWL RHHVIPETNS RYSVFDILRD ELEVILKGVL 150
    EDSSVQHRPA VEKAKTLYRS CMNQSVIEKR DSEPLLNVLD MIGGWPVAMD 200
    KWNETMGPKW ELERQLAVLN SQFNRRVLID LFIWNDDQNS SRHVIYIDQP 250
    TLGMPSREYY FKEDSHRVRE AYLQFMTSVA TMLRRDLNLP GETDLVQEEM 300
    AQVLHLETHL ANATVPQEKR HDVTALYHRM GLEELQERFG LKGFNWTLFI 350
    QNVLSSVQVE LLPNEEVVVY GIPYLENLEE IIDVFPAQTL QNYLVWRLVL 400
    DRIGSLSQRF KEARVDYRKA LYGTTMEEVR WRECVSYVNS NMESAVGSLY 450
    IKRAFSKDSK SIVSELIEKI RSVFVDNLDE LNWMDEESKK KAQEKALNIR 500
    EQIGYPDYIL EDNNRHLDEE YSSLTFSEDL YFENGLQNLK NNAQRSLKKL 550
    REKVDQNLWI IGAAVVNAFY SPNRNLIVFP AGILQPPFFS KDQPQALNFG 600
    GIGMVIGHEI THGFDDNGRN FDKNGNMLDW WSNFSARHFR QQSQCMIYQY 650
    SNFSWELADN QNVNGFSTLG ENIADNGGVR QAYKAYLQWL AEGGRDQRLP 700
    GLNLTYAQLF FINYAQVWCG SYRPEFAIQS IKTDVHSPLN AQVLGSLQNL 750
    PGFSEAFHCP RGSPMHPMNR CRIW 774
    Length:774
    Mass (Da):89,197
    Last modified:September 5, 2006 - v1
    Checksum:iF95E2088CA4B64AD
    GO
    Isoform 2 (identifier: P0C1T0-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         51-73: Missing.

    Show »
    Length:751
    Mass (Da):86,533
    Checksum:i1995504DF1EFCDDF
    GO
    Isoform 3 (identifier: P0C1T0-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         246-267: Missing.

    Show »
    Length:752
    Mass (Da):86,482
    Checksum:iA7E932880187EFFE
    GO
    Isoform 4 (identifier: P0C1T0-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         303-313: Missing.

    Show »
    Length:763
    Mass (Da):87,997
    Checksum:i60A7053E8AE2D62A
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei51 – 7323Missing in isoform 2. 1 PublicationVSP_020292Add
    BLAST
    Alternative sequencei246 – 26722Missing in isoform 3. 1 PublicationVSP_020293Add
    BLAST
    Alternative sequencei303 – 31311Missing in isoform 4. CuratedVSP_020294Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AABR03040205 Genomic DNA. No translation available.
    UniGeneiRn.50873.

    Genome annotation databases

    EnsembliENSRNOT00000017957; ENSRNOP00000017957; ENSRNOG00000012593. [P0C1T0-1]
    ENSRNOT00000064738; ENSRNOP00000063235; ENSRNOG00000012593. [P0C1T0-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AABR03040205 Genomic DNA. No translation available.
    UniGenei Rn.50873.

    3D structure databases

    ProteinModelPortali P0C1T0.
    SMRi P0C1T0. Positions 83-774.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000063235.

    Proteomic databases

    PaxDbi P0C1T0.
    PRIDEi P0C1T0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000017957 ; ENSRNOP00000017957 ; ENSRNOG00000012593 . [P0C1T0-1 ]
    ENSRNOT00000064738 ; ENSRNOP00000063235 ; ENSRNOG00000012593 . [P0C1T0-2 ]

    Organism-specific databases

    RGDi 1309299. Mmel1.

    Phylogenomic databases

    eggNOGi COG3590.
    GeneTreei ENSGT00650000093248.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.
    OMAi DGNMLDW.
    OrthoDBi EOG7PZRWQ.

    Miscellaneous databases

    PROi P0C1T0.

    Gene expression databases

    Genevestigatori P0C1T0.

    Family and domain databases

    Gene3Di 3.40.390.10. 2 hits.
    InterProi IPR024079. MetalloPept_cat_dom.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view ]
    PANTHERi PTHR11733. PTHR11733. 1 hit.
    Pfami PF01431. Peptidase_M13. 1 hit.
    PF05649. Peptidase_M13_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00786. NEPRILYSIN.
    PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Neprilysin II: a putative novel metalloprotease and its isoforms in CNS and testis."
      Ouimet T., Facchinetti P., Rose C., Bonhomme M.-C., Gros C., Schwartz J.-C.
      Biochem. Biophys. Res. Commun. 271:565-570(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
    2. Erratum
      Ouimet T., Facchinetti P., Rose C., Bonhomme M.-C., Gros C., Schwartz J.-C.
      Biochem. Biophys. Res. Commun. 275:247-247(2000)
    3. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
      Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
      , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
      Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Brown Norway.
    4. "Ontogeny, regional and cellular distribution of the novel metalloprotease neprilysin 2 in the rat: a comparison with neprilysin and endothelin-converting enzyme-1."
      Facchinetti P., Rose C., Schwartz J.C., Ouimet T.
      Neuroscience 118:627-639(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    5. "A three-dimensional model of the neprilysin 2 active site based on the X-ray structure of neprilysin. Identification of residues involved in substrate hydrolysis and inhibitor binding of neprilysin 2."
      Voisin S., Rognan D., Gros C., Ouimet T.
      J. Biol. Chem. 279:46172-46181(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-131; SER-133; ASN-567 AND LEU-739.
    6. "Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared with neprilysin."
      Rose C., Voisin S., Gros C., Schwartz J.-C., Ouimet T.
      Biochem. J. 363:697-705(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES.
    7. "The ultimate tryptophan residue of neprilysin 2 is not involved in protein maturation and enzymatic activity."
      Voisin S., Ouimet T.
      Biochem. Biophys. Res. Commun. 335:356-360(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF PRO-751; PRO-764 AND TRP-774.

    Entry informationi

    Entry nameiMMEL1_RAT
    AccessioniPrimary (citable) accession number: P0C1T0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: September 5, 2006
    Last modified: October 1, 2014
    This is version 60 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Peptidase families
      Classification of peptidase families and list of entries
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3