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Q9JLI3

- MMEL1_MOUSE

UniProt

Q9JLI3 - MMEL1_MOUSE

Protein

Membrane metallo-endopeptidase-like 1

Gene

Mmel1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      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.2 Publications

    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.1 Publication

    Kineticsi

    1. KM=18 µM for D-Ala(2)-Leu(5)-enkephalin1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei62 – 632CleavageCurated
    Binding sitei121 – 1211Substrate carboxylBy similarity
    Metal bindingi599 – 5991Zinc; catalyticPROSITE-ProRule annotation
    Metal bindingi603 – 6031Zinc; catalyticPROSITE-ProRule annotation
    Active sitei606 – 6061PROSITE-ProRule annotation
    Metal bindingi662 – 6621Zinc; catalyticPROSITE-ProRule annotation
    Active sitei666 – 6661Proton donorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: MGI
    2. zinc ion binding Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Protein family/group databases

    MEROPSiM13.008.

    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
    Neprilysin-like 1
    Short name:
    NL-1
    Neprilysin-like peptidase
    Short name:
    NEPLP
    Soluble secreted endopeptidase
    Cleaved into the following chain:
    Alternative name(s):
    Neprilysin-2 secreted
    Short name:
    NEP2(s)
    Gene namesi
    Name:Mmel1
    Synonyms:Nep2, Nl1, Sep
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:1351603. Mmel1.

    Subcellular locationi

    Membrane 1 Publication; Single-pass type II membrane protein 1 Publication. Secreted 1 Publication
    Note: A secreted form produced by proteollytic cleavage also exists.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Membrane, Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Mice are viable and develop normally. However, males produce smaller litters, indicating specific male fertility problems.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi62 – 632KR → NG: Abolishes formation the soluble form. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 765765Membrane metallo-endopeptidase-like 1PRO_0000248417Add
    BLAST
    Chaini63 – 765703Membrane metallo-endopeptidase-like 1, soluble formCuratedPRO_0000248418Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi75 ↔ 80By similarity
    Disulfide bondi98 ↔ 750By similarity
    Disulfide bondi106 ↔ 710By similarity
    Disulfide bondi161 ↔ 425By similarity
    Glycosylationi163 – 1631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi279 – 2791N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi303 – 3031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi636 ↔ 762By similarity
    Glycosylationi694 – 6941N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9JLI3.
    PRIDEiQ9JLI3.

    PTM databases

    PhosphoSiteiQ9JLI3.

    Expressioni

    Tissue specificityi

    Highly expressed in testis. Also expressed in ovary. Weakly or not expressed in brain, lung, heart, liver, kidney, adrenal gland and intestine.1 Publication

    Gene expression databases

    BgeeiQ9JLI3.
    CleanExiMM_MMEL1.
    GenevestigatoriQ9JLI3.

    Interactioni

    Protein-protein interaction databases

    IntActiQ9JLI3. 2 interactions.
    MINTiMINT-4129130.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JLI3.
    SMRiQ9JLI3. Positions 74-765.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1919CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini41 – 765725LumenalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei20 – 4021Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili523 – 54927Sequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase M13 family.Curated

    Keywords - Domaini

    Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG3590.
    HOGENOMiHOG000245574.
    HOVERGENiHBG005554.
    KOiK08635.

    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 (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9JLI3-1) [UniParc]FASTAAdd to Basket

    Also known as: Beta

    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

    MVERAGWCRK KSPGFVEYGL MVLLLLLLGA IVTLGVFYSI GKQLPLLTSL    50
    LHFSWDERTV VKRALRDSSL KSDICTTPSC VIAAARILEN MDQSRNPCEN 100
    FYQYACGGWL RHHVIPETNS RYSVFDILRD ELEVILKGVL EDSTSQHRPA 150
    VEKAKTLYRS CMNQSVIEKR DSEPLLSVLK MVGGWPVAMD KWNETMGLKW 200
    ELERQLAVLN SQFNRRVLID LFIWNDDQNS SRHVIYIDQP TLGMPSREYY 250
    FQEDNNHKVR KAYLEFMTSV ATMLRKDQNL SKESAMVREE MAEVLELETH 300
    LANATVPQEK RHDVTALYHR MDLMELQERF GLKGFNWTLF IQNVLSSVEV 350
    ELFPDEEVVV YGIPYLENLE DIIDSYSART MQNYLVWRLV LDRIGSLSQR 400
    FKEARVDYRK ALYGTTVEEV RWRECVSYVN SNMESAVGSL YIKRAFSKDS 450
    KSTVRELIEK IRSVFVDNLD ELNWMDEESK KKAQEKAMNI REQIGYPDYI 500
    LEDNNKHLDE EYSSLTFYED LYFENGLQNL KNNAQRSLKK LREKVDQNLW 550
    IIGAAVVNAF YSPNRNQIVF PAGILQPPFF SKDQPQSLNF GGIGMVIGHE 600
    ITHGFDDNGR NFDKNGNMLD WWSNFSARHF QQQSQCMIYQ YGNFSWELAD 650
    NQNVNGFSTL GENIADNGGV RQAYKAYLRW LADGGKDQRL PGLNLTYAQL 700
    FFINYAQVWC GSYRPEFAVQ SIKTDVHSPL KYRVLGSLQN LPGFSEAFHC 750
    PRGSPMHPMK RCRIW 765
    Length:765
    Mass (Da):88,700
    Last modified:October 1, 2000 - v1
    Checksum:iD3662F1CE5B957F7
    GO
    Isoform 2 (identifier: Q9JLI3-2) [UniParc]FASTAAdd to Basket

    Also known as: Alpha, Delta

    The sequence of this isoform differs from the canonical sequence as follows:
         41-63: Missing.

    Show »
    Length:742
    Mass (Da):85,994
    Checksum:i4A44EAD211B2499F
    GO
    Isoform 3 (identifier: Q9JLI3-3) [UniParc]FASTAAdd to Basket

    Also known as: Gamma

    The sequence of this isoform differs from the canonical sequence as follows:
         41-63: Missing.
         330-330: F → FGLKDRVSLCSPGCPGTHSVDQAGLELGNPPASDSRVL

    Show »
    Length:779
    Mass (Da):89,710
    Checksum:i5E48CA530828584B
    GO

    Sequence cautioni

    The sequence BAE32538.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti189 – 1891M → L in AAF13152. (PubMed:10542292)Curated
    Sequence conflicti189 – 1891M → L in AAF13153. (PubMed:10542292)Curated
    Sequence conflicti264 – 2641L → P in AAF13152. (PubMed:10542292)Curated
    Sequence conflicti264 – 2641L → P in AAF13153. (PubMed:10542292)Curated
    Sequence conflicti659 – 6591T → S in AAF13152. (PubMed:10542292)Curated
    Sequence conflicti659 – 6591T → S in AAF13153. (PubMed:10542292)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei41 – 6323Missing in isoform 2 and isoform 3. 2 PublicationsVSP_020290Add
    BLAST
    Alternative sequencei330 – 3301F → FGLKDRVSLCSPGCPGTHSV DQAGLELGNPPASDSRVL in isoform 3. CuratedVSP_020291

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF157105 mRNA. Translation: AAF13152.1.
    AF157106 mRNA. Translation: AAF13153.1.
    AF176569 mRNA. Translation: AAF69247.1.
    AF302075 mRNA. Translation: AAG18446.1.
    AF302076 mRNA. Translation: AAG18447.1.
    AF302077 mRNA. Translation: AAG18448.1.
    AK154366 mRNA. Translation: BAE32538.1. Different initiation.
    RefSeqiNP_038811.2. NM_013783.2.
    UniGeneiMm.116944.

    Genome annotation databases

    GeneIDi27390.
    KEGGimmu:27390.
    UCSCiuc008wcg.1. mouse. [Q9JLI3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF157105 mRNA. Translation: AAF13152.1 .
    AF157106 mRNA. Translation: AAF13153.1 .
    AF176569 mRNA. Translation: AAF69247.1 .
    AF302075 mRNA. Translation: AAG18446.1 .
    AF302076 mRNA. Translation: AAG18447.1 .
    AF302077 mRNA. Translation: AAG18448.1 .
    AK154366 mRNA. Translation: BAE32538.1 . Different initiation.
    RefSeqi NP_038811.2. NM_013783.2.
    UniGenei Mm.116944.

    3D structure databases

    ProteinModelPortali Q9JLI3.
    SMRi Q9JLI3. Positions 74-765.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi Q9JLI3. 2 interactions.
    MINTi MINT-4129130.

    Protein family/group databases

    MEROPSi M13.008.

    PTM databases

    PhosphoSitei Q9JLI3.

    Proteomic databases

    PaxDbi Q9JLI3.
    PRIDEi Q9JLI3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 27390.
    KEGGi mmu:27390.
    UCSCi uc008wcg.1. mouse. [Q9JLI3-1 ]

    Organism-specific databases

    CTDi 79258.
    MGIi MGI:1351603. Mmel1.

    Phylogenomic databases

    eggNOGi COG3590.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.
    KOi K08635.

    Miscellaneous databases

    NextBioi 305354.
    PROi Q9JLI3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9JLI3.
    CleanExi MM_MMEL1.
    Genevestigatori Q9JLI3.

    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. "Molecular identification and characterization of novel membrane-bound metalloprotease, the soluble secreted form of which hydrolyzes a variety of vasoactive peptides."
      Ikeda K., Emoto N., Raharjo S.B., Nurhantari Y., Saiki K., Yokoyama M., Matsuo M.
      J. Biol. Chem. 274:32469-32477(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Testis.
    2. "Molecular cloning and biochemical characterization of a new mouse testis soluble zinc-metallopeptidase of the neprilysin family."
      Ghaddar G., Ruchon A.F., Carpentier M., Marcinkiewicz M., Seidah N.G., Crine P., DesGroseillers L., Boileau G.
      Biochem. J. 347:419-429(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF 62-LYS-ARG-63.
      Tissue: Testis.
    3. "Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases."
      Shirotani K., Tsubuki S., Iwata N., Takaki Y., Harigaya W., Maruyama K., Kiryu-Seo S., Kiyama H., Iwata H., Tomita T., Iwatsubo T., Saido T.C.
      J. Biol. Chem. 276:21895-21901(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME REGULATION.
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-765.
      Strain: NOD.
    5. Cited for: DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiMMEL1_MOUSE
    AccessioniPrimary (citable) accession number: Q9JLI3
    Secondary accession number(s): Q3U495
    , Q9ERK2, Q9ERK3, Q9QZV6, Q9QZV7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: October 1, 2000
    Last modified: October 1, 2014
    This is version 89 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3