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Protein

Membrane metallo-endopeptidase-like 1

Gene

Mmel1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Activity regulationi

Inhibited by thiorphan and phosphoramidon.1 Publication

Kineticsi

  1. KM=18 µM for D-Ala2-Leu5-enkephalin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei121Substrate carboxylBy similarity1
    Metal bindingi599Zinc; catalyticPROSITE-ProRule annotation1
    Metal bindingi603Zinc; catalyticPROSITE-ProRule annotation1
    Active sitei606PROSITE-ProRule annotation1
    Metal bindingi662Zinc; catalyticPROSITE-ProRule annotation1
    Active sitei666Proton donorPROSITE-ProRule annotation1

    GO - Molecular functioni

    • metalloendopeptidase activity Source: MGI
    • zinc ion binding Source: MGI

    Keywordsi

    Molecular functionHydrolase, Metalloprotease, Protease
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.24.B14 3474

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Unplaced

    Organism-specific databases

    MGIiMGI:1351603 Mmel1

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 19CytoplasmicSequence analysisAdd BLAST19
    Transmembranei20 – 40Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
    Topological domaini41 – 765LumenalSequence analysisAdd BLAST725

    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)DescriptionActionsGraphical viewLength
    Mutagenesisi62 – 63KR → NG: Abolishes formation the soluble form. 1 Publication2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002484171 – 765Membrane metallo-endopeptidase-like 1Add BLAST765
    ChainiPRO_000024841863 – 765Membrane metallo-endopeptidase-like 1, soluble formCuratedAdd BLAST703

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi75 ↔ 80By similarity
    Disulfide bondi98 ↔ 750By similarity
    Disulfide bondi106 ↔ 710By similarity
    Disulfide bondi161 ↔ 425By similarity
    Glycosylationi163N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi279N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi303N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi336N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi636 ↔ 762By similarity
    Glycosylationi694N-linked (GlcNAc...) asparagineSequence analysis1

    Post-translational modificationi

    N-glycosylated.2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei62 – 63CleavageCurated2

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9JLI3
    PRIDEiQ9JLI3

    PTM databases

    iPTMnetiQ9JLI3
    PhosphoSitePlusiQ9JLI3

    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

    CleanExiMM_MMEL1

    Interactioni

    Protein-protein interaction databases

    IntActiQ9JLI3, 2 interactors
    MINTiQ9JLI3
    STRINGi10090.ENSMUSP00000131753

    Structurei

    3D structure databases

    ProteinModelPortaliQ9JLI3
    SMRiQ9JLI3
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Coiled coili523 – 549Sequence analysisAdd BLAST27

    Sequence similaritiesi

    Belongs to the peptidase M13 family.Curated

    Keywords - Domaini

    Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3624 Eukaryota
    COG3590 LUCA
    HOGENOMiHOG000245574
    HOVERGENiHBG005554
    InParanoidiQ9JLI3
    KOiK08635

    Family and domain databases

    CDDicd08662 M13, 1 hit
    Gene3Di3.40.390.10, 1 hit
    InterProiView protein in InterPro
    IPR024079 MetalloPept_cat_dom_sf
    IPR029735 MMEL1
    IPR000718 Peptidase_M13
    IPR018497 Peptidase_M13_C
    IPR008753 Peptidase_M13_N
    PANTHERiPTHR11733 PTHR11733, 1 hit
    PTHR11733:SF141 PTHR11733:SF141, 1 hit
    PfamiView protein in Pfam
    PF01431 Peptidase_M13, 1 hit
    PF05649 Peptidase_M13_N, 1 hit
    PRINTSiPR00786 NEPRILYSIN
    PROSITEiView protein in PROSITE
    PS00142 ZINC_PROTEASE, 1 hit

    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. AlignAdd to basket

    This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

    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
            10         20         30         40         50
    MVERAGWCRK KSPGFVEYGL MVLLLLLLGA IVTLGVFYSI GKQLPLLTSL
    60 70 80 90 100
    LHFSWDERTV VKRALRDSSL KSDICTTPSC VIAAARILEN MDQSRNPCEN
    110 120 130 140 150
    FYQYACGGWL RHHVIPETNS RYSVFDILRD ELEVILKGVL EDSTSQHRPA
    160 170 180 190 200
    VEKAKTLYRS CMNQSVIEKR DSEPLLSVLK MVGGWPVAMD KWNETMGLKW
    210 220 230 240 250
    ELERQLAVLN SQFNRRVLID LFIWNDDQNS SRHVIYIDQP TLGMPSREYY
    260 270 280 290 300
    FQEDNNHKVR KAYLEFMTSV ATMLRKDQNL SKESAMVREE MAEVLELETH
    310 320 330 340 350
    LANATVPQEK RHDVTALYHR MDLMELQERF GLKGFNWTLF IQNVLSSVEV
    360 370 380 390 400
    ELFPDEEVVV YGIPYLENLE DIIDSYSART MQNYLVWRLV LDRIGSLSQR
    410 420 430 440 450
    FKEARVDYRK ALYGTTVEEV RWRECVSYVN SNMESAVGSL YIKRAFSKDS
    460 470 480 490 500
    KSTVRELIEK IRSVFVDNLD ELNWMDEESK KKAQEKAMNI REQIGYPDYI
    510 520 530 540 550
    LEDNNKHLDE EYSSLTFYED LYFENGLQNL KNNAQRSLKK LREKVDQNLW
    560 570 580 590 600
    IIGAAVVNAF YSPNRNQIVF PAGILQPPFF SKDQPQSLNF GGIGMVIGHE
    610 620 630 640 650
    ITHGFDDNGR NFDKNGNMLD WWSNFSARHF QQQSQCMIYQ YGNFSWELAD
    660 670 680 690 700
    NQNVNGFSTL GENIADNGGV RQAYKAYLRW LADGGKDQRL PGLNLTYAQL
    710 720 730 740 750
    FFINYAQVWC GSYRPEFAVQ SIKTDVHSPL KYRVLGSLQN LPGFSEAFHC
    760
    PRGSPMHPMK RCRIW
    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

    Computationally mapped potential isoform sequencesi

    There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    E9PVK7E9PVK7_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    766Annotation score:
    B1AS17B1AS17_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    782Annotation score:
    B1AS15B1AS15_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    768Annotation score:
    B1AS16B1AS16_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    745Annotation score:
    E9QPA9E9QPA9_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    780Annotation score:
    B1AS18B1AS18_MOUSE
    Membrane metallo-endopeptidase-like...
    Mmel1
    150Annotation score:

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti189M → L in AAF13152 (PubMed:10542292).Curated1
    Sequence conflicti189M → L in AAF13153 (PubMed:10542292).Curated1
    Sequence conflicti264L → P in AAF13152 (PubMed:10542292).Curated1
    Sequence conflicti264L → P in AAF13153 (PubMed:10542292).Curated1
    Sequence conflicti659T → S in AAF13152 (PubMed:10542292).Curated1
    Sequence conflicti659T → S in AAF13153 (PubMed:10542292).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_02029041 – 63Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST23
    Alternative sequenceiVSP_020291330F → FGLKDRVSLCSPGCPGTHSV DQAGLELGNPPASDSRVL in isoform 3. Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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

    3D structure databases

    ProteinModelPortaliQ9JLI3
    SMRiQ9JLI3
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ9JLI3, 2 interactors
    MINTiQ9JLI3
    STRINGi10090.ENSMUSP00000131753

    Protein family/group databases

    MEROPSiM13.008

    PTM databases

    iPTMnetiQ9JLI3
    PhosphoSitePlusiQ9JLI3

    Proteomic databases

    PaxDbiQ9JLI3
    PRIDEiQ9JLI3

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi79258
    MGIiMGI:1351603 Mmel1

    Phylogenomic databases

    eggNOGiKOG3624 Eukaryota
    COG3590 LUCA
    HOGENOMiHOG000245574
    HOVERGENiHBG005554
    InParanoidiQ9JLI3
    KOiK08635

    Enzyme and pathway databases

    BRENDAi3.4.24.B14 3474

    Miscellaneous databases

    ChiTaRSiEphx2 mouse
    PROiPR:Q9JLI3
    SOURCEiSearch...

    Gene expression databases

    CleanExiMM_MMEL1

    Family and domain databases

    CDDicd08662 M13, 1 hit
    Gene3Di3.40.390.10, 1 hit
    InterProiView protein in InterPro
    IPR024079 MetalloPept_cat_dom_sf
    IPR029735 MMEL1
    IPR000718 Peptidase_M13
    IPR018497 Peptidase_M13_C
    IPR008753 Peptidase_M13_N
    PANTHERiPTHR11733 PTHR11733, 1 hit
    PTHR11733:SF141 PTHR11733:SF141, 1 hit
    PfamiView protein in Pfam
    PF01431 Peptidase_M13, 1 hit
    PF05649 Peptidase_M13_N, 1 hit
    PRINTSiPR00786 NEPRILYSIN
    PROSITEiView protein in PROSITE
    PS00142 ZINC_PROTEASE, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMMEL1_MOUSE
    AccessioniPrimary (citable) accession number: Q9JLI3
    Secondary accession number(s): Q3U495
    , Q9ERK2, Q9ERK3, Q9QZV6, Q9QZV7
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: October 1, 2000
    Last modified: November 7, 2018
    This is version 112 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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