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Q495T6

- MMEL1_HUMAN

UniProt

Q495T6 - MMEL1_HUMAN

Protein

Membrane metallo-endopeptidase-like 1

Gene

MMEL1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 2 (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.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei73 – 742CleavageBy similarity
    Binding sitei135 – 1351Substrate carboxylBy similarity
    Metal bindingi613 – 6131Zinc; catalyticPROSITE-ProRule annotation
    Metal bindingi617 – 6171Zinc; catalyticPROSITE-ProRule annotation
    Active sitei620 – 6201PROSITE-ProRule annotation
    Metal bindingi676 – 6761Zinc; catalyticPROSITE-ProRule annotation
    Active sitei680 – 6801Proton donorPROSITE-ProRule annotation

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: Ensembl
    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):
    Membrane metallo-endopeptidase-like 2
    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, MMEL2, NEP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:14668. MMEL1.

    Subcellular locationi

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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Membrane, Secreted

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti186. Primary biliary cirrhosis.
    PharmGKBiPA30865.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 779779Membrane metallo-endopeptidase-like 1PRO_0000248415Add
    BLAST
    Chaini74 – 779706Membrane metallo-endopeptidase-like 1, soluble formBy similarityPRO_0000248416Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi89 ↔ 94By similarity
    Disulfide bondi112 ↔ 764By similarity
    Disulfide bondi120 ↔ 724By similarity
    Disulfide bondi175 ↔ 439By similarity
    Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi207 – 2071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi350 – 3501N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi530 – 5301N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi650 ↔ 776By similarity
    Glycosylationi657 – 6571N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylated.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ495T6.
    PRIDEiQ495T6.

    PTM databases

    PhosphoSiteiQ495T6.

    Expressioni

    Tissue specificityi

    Predominantly expressed in testis. Weakly expressed in brain, kidney and heart.1 Publication

    Gene expression databases

    ArrayExpressiQ495T6.
    BgeeiQ495T6.
    CleanExiHS_MMEL1.
    GenevestigatoriQ495T6.

    Organism-specific databases

    HPAiCAB020786.
    HPA007876.
    HPA008205.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000288709.

    Structurei

    3D structure databases

    ProteinModelPortaliQ495T6.
    SMRiQ495T6. Positions 88-779.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2727CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini49 – 779731LumenalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei28 – 4821Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili515 – 56046Sequence 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.
    InParanoidiQ495T6.
    KOiK08635.
    OMAiDGNMLDW.
    OrthoDBiEOG7PZRWQ.
    PhylomeDBiQ495T6.
    TreeFamiTF315192.

    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: Q495T6-1) [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

    MGKSEGPVGM VESAGRAGQK RPGFLEGGLL LLLLLVTAAL VALGVLYADR    50
    RGKQLPRLAS RLCFLQEERT FVKRKPRGIP EAQEVSEVCT TPGCVIAAAR 100
    ILQNMDPTTE PCDDFYQFAC GGWLRRHVIP ETNSRYSIFD VLRDELEVIL 150
    KAVLENSTAK DRPAVEKART LYRSCMNQSV IEKRGSQPLL DILEVVGGWP 200
    VAMDRWNETV GLEWELERQL ALMNSQFNRR VLIDLFIWND DQNSSRHIIY 250
    IDQPTLGMPS REYYFNGGSN RKVREAYLQF MVSVATLLRE DANLPRDSCL 300
    VQEDMVQVLE LETQLAKATV PQEERHDVIA LYHRMGLEEL QSQFGLKGFN 350
    WTLFIQTVLS SVKIKLLPDE EVVVYGIPYL QNLENIIDTY SARTIQNYLV 400
    WRLVLDRIGS LSQRFKDTRV NYRKALFGTM VEEVRWRECV GYVNSNMENA 450
    VGSLYVREAF PGDSKSMVRE LIDKVRTVFV ETLDELGWMD EESKKKAQEK 500
    AMSIREQIGH PDYILEEMNR RLDEEYSNLN FSEDLYFENS LQNLKVGAQR 550
    SLRKLREKVD PNLWIIGAAV VNAFYSPNRN QIVFPAGILQ PPFFSKEQPQ 600
    ALNFGGIGMV IGHEITHGFD DNGRNFDKNG NMMDWWSNFS TQHFREQSEC 650
    MIYQYGNYSW DLADEQNVNG FNTLGENIAD NGGVRQAYKA YLKWMAEGGK 700
    DQQLPGLDLT HEQLFFINYA QVWCGSYRPE FAIQSIKTDV HSPLKYRVLG 750
    SLQNLAAFAD TFHCARGTPM HPKERCRVW 779
    Length:779
    Mass (Da):89,367
    Last modified:September 5, 2006 - v2
    Checksum:i08C41819F4E81CBD
    GO
    Isoform 2 (identifier: Q495T6-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         583-611: VFPAGILQPPFFSKEQPQALNFGGIGMVI → AYSLSRPWGQYSLPGSSSPPSSARSSHRP
         612-779: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:611
    Mass (Da):69,930
    Checksum:iE3275B5EB05886BE
    GO
    Isoform 3 (identifier: Q495T6-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         159-315: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:622
    Mass (Da):71,092
    Checksum:i1D6C960EE827051A
    GO

    Sequence cautioni

    The sequence AAL08942.1 differs from that shown. Reason: Frameshift at positions 7 and 8.
    The sequence AAI01028.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence AAI01031.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti351 – 3511W → R in AAI01029. (PubMed:15489334)Curated
    Sequence conflicti489 – 4891M → I in AAI01031. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti518 – 5181M → T.1 Publication
    Corresponds to variant rs3748816 [ dbSNP | Ensembl ].
    VAR_027348

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei159 – 315157Missing in isoform 3. 1 PublicationVSP_020287Add
    BLAST
    Alternative sequencei583 – 61129VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2. 1 PublicationVSP_020288Add
    BLAST
    Alternative sequencei612 – 779168Missing in isoform 2. 1 PublicationVSP_020289Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF336981 mRNA. Translation: AAL08942.1. Frameshift.
    AL139246, AL589746, AL831784 Genomic DNA. Translation: CAX30814.1.
    AL589746, AL831784 Genomic DNA. Translation: CAI22652.1.
    AL831784, AL589746 Genomic DNA. Translation: CAI17336.1.
    CH471183 Genomic DNA. Translation: EAW56082.1.
    BC101027 mRNA. Translation: AAI01028.2. Different initiation.
    BC101028 mRNA. Translation: AAI01029.2.
    BC101029 mRNA. Translation: AAI01030.1.
    BC101030 mRNA. Translation: AAI01031.2. Different initiation.
    CCDSiCCDS30569.2. [Q495T6-1]
    RefSeqiNP_258428.2. NM_033467.3. [Q495T6-1]
    UniGeneiHs.591453.

    Genome annotation databases

    EnsembliENST00000378412; ENSP00000367668; ENSG00000142606. [Q495T6-1]
    ENST00000502556; ENSP00000422492; ENSG00000142606. [Q495T6-3]
    ENST00000504800; ENSP00000425477; ENSG00000142606. [Q495T6-2]
    GeneIDi79258.
    KEGGihsa:79258.
    UCSCiuc001ajy.2. human. [Q495T6-1]

    Polymorphism databases

    DMDMi114150028.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF336981 mRNA. Translation: AAL08942.1 . Frameshift.
    AL139246 , AL589746 , AL831784 Genomic DNA. Translation: CAX30814.1 .
    AL589746 , AL831784 Genomic DNA. Translation: CAI22652.1 .
    AL831784 , AL589746 Genomic DNA. Translation: CAI17336.1 .
    CH471183 Genomic DNA. Translation: EAW56082.1 .
    BC101027 mRNA. Translation: AAI01028.2 . Different initiation.
    BC101028 mRNA. Translation: AAI01029.2 .
    BC101029 mRNA. Translation: AAI01030.1 .
    BC101030 mRNA. Translation: AAI01031.2 . Different initiation.
    CCDSi CCDS30569.2. [Q495T6-1 ]
    RefSeqi NP_258428.2. NM_033467.3. [Q495T6-1 ]
    UniGenei Hs.591453.

    3D structure databases

    ProteinModelPortali Q495T6.
    SMRi Q495T6. Positions 88-779.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000288709.

    Protein family/group databases

    MEROPSi M13.008.

    PTM databases

    PhosphoSitei Q495T6.

    Polymorphism databases

    DMDMi 114150028.

    Proteomic databases

    PaxDbi Q495T6.
    PRIDEi Q495T6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000378412 ; ENSP00000367668 ; ENSG00000142606 . [Q495T6-1 ]
    ENST00000502556 ; ENSP00000422492 ; ENSG00000142606 . [Q495T6-3 ]
    ENST00000504800 ; ENSP00000425477 ; ENSG00000142606 . [Q495T6-2 ]
    GeneIDi 79258.
    KEGGi hsa:79258.
    UCSCi uc001ajy.2. human. [Q495T6-1 ]

    Organism-specific databases

    CTDi 79258.
    GeneCardsi GC01M002557.
    H-InvDB HIX0000061.
    HGNCi HGNC:14668. MMEL1.
    HPAi CAB020786.
    HPA007876.
    HPA008205.
    neXtProti NX_Q495T6.
    Orphaneti 186. Primary biliary cirrhosis.
    PharmGKBi PA30865.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3590.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.
    InParanoidi Q495T6.
    KOi K08635.
    OMAi DGNMLDW.
    OrthoDBi EOG7PZRWQ.
    PhylomeDBi Q495T6.
    TreeFami TF315192.

    Miscellaneous databases

    GenomeRNAii 79258.
    NextBioi 68218.
    PROi Q495T6.

    Gene expression databases

    ArrayExpressi Q495T6.
    Bgeei Q495T6.
    CleanExi HS_MMEL1.
    Genevestigatori Q495T6.

    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 cloning, tissue distribution, and chromosomal localization of MMEL2, a gene coding for a novel human member of the neutral endopeptidase-24.11 family."
      Bonvouloir N., Lemieux N., Crine P., Boileau G., DesGroseillers L.
      DNA Cell Biol. 20:493-498(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    2. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT THR-518.

    Entry informationi

    Entry nameiMMEL1_HUMAN
    AccessioniPrimary (citable) accession number: Q495T6
    Secondary accession number(s): B9DI79
    , Q495T7, Q495T8, Q5SZS6, Q96PH9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: September 5, 2006
    Last modified: October 1, 2014
    This is version 91 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3