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Protein

Membrane metallo-endopeptidase-like 1

Gene

Mmel1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)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

    • metal ion binding Source: UniProtKB-KW
    • metalloendopeptidase activity Source: MGI
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Unplaced

    Organism-specific databases

    MGIiMGI:1351603. Mmel1.

    Subcellular locationi

    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

    GO - Cellular componenti

    • endoplasmic reticulum Source: MGI
    • extracellular space Source: MGI
    • Golgi apparatus Source: MGI
    • integral component of membrane Source: UniProtKB-KW
    Complete GO annotation...

    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...)Sequence analysis1
    Glycosylationi279N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi303N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi336N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi636 ↔ 762By similarity
    Glycosylationi694N-linked (GlcNAc...)Sequence 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

    BgeeiENSMUSG00000058183.
    CleanExiMM_MMEL1.

    Interactioni

    Protein-protein interaction databases

    IntActiQ9JLI3. 2 interactors.
    MINTiMINT-4129130.
    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. 2 hits.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR029735. MMEL1.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view]
    PANTHERiPTHR11733. PTHR11733. 2 hits.
    PTHR11733:SF141. PTHR11733:SF141. 2 hits.
    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. AlignAdd to basket

    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

    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

    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.
    MINTiMINT-4129130.
    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

    PROiQ9JLI3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000058183.
    CleanExiMM_MMEL1.

    Family and domain databases

    CDDicd08662. M13. 1 hit.
    Gene3Di3.40.390.10. 2 hits.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR029735. MMEL1.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view]
    PANTHERiPTHR11733. PTHR11733. 2 hits.
    PTHR11733:SF141. PTHR11733:SF141. 2 hits.
    PfamiPF01431. Peptidase_M13. 1 hit.
    PF05649. Peptidase_M13_N. 1 hit.
    [Graphical view]
    PRINTSiPR00786. NEPRILYSIN.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    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: November 2, 2016
    This is version 103 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.