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Protein

Meprin A subunit alpha

Gene

MEP1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

Hydrolysis of protein and peptide substrates preferentially on carboxyl side of hydrophobic residues.

Cofactori

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

Enzyme regulationi

Inhibited by several hydroxamate compounds, the most potent inhibitor is actinonin.1 Publication

Kineticsi

  1. KM=110 µM for GRP1 Publication
  2. KM=18.0 µM for PTH 12-341 Publication
  3. KM=33.9 µM for secretin1 Publication
  4. KM=41.3 µM for substance P1 Publication
  5. KM=56.5 µM for LHRH1 Publication
  6. KM=73.2 µM for orcokinin1 Publication
  7. KM=292 µM for alpha-MSH1 Publication
  8. KM=125 µM for bradykinin1 Publication
  9. KM=200 µM for gastrin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi58Zinc; catalyticPROSITE-ProRule annotation1
    Metal bindingi155Zinc; via tele nitrogen; catalyticBy similarity1
    Active sitei156PROSITE-ProRule annotation1
    Metal bindingi159Zinc; via tele nitrogen; catalyticBy similarity1
    Metal bindingi165Zinc; via tele nitrogen; catalyticBy similarity1

    GO - Molecular functioni

    • metalloendopeptidase activity Source: ProtInc
    • zinc ion binding Source: InterPro

    GO - Biological processi

    • digestion Source: ProtInc
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000112818-MONOMER.
    BRENDAi3.4.24.18. 2681.
    SignaLinkiQ16819.

    Protein family/group databases

    MEROPSiM12.002.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Meprin A subunit alpha (EC:3.4.24.18)
    Alternative name(s):
    Endopeptidase-2
    N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit alpha
    PABA peptide hydrolase
    PPH alpha
    Gene namesi
    Name:MEP1A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:7015. MEP1A.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini66 – 712ExtracellularSequence analysisAdd BLAST647
    Transmembranei713 – 740HelicalSequence analysisAdd BLAST28
    Topological domaini741 – 746CytoplasmicSequence analysis6

    GO - Cellular componenti

    • extracellular exosome Source: UniProtKB
    • extracellular space Source: ProtInc
    • integral component of plasma membrane Source: ProtInc
    • meprin A complex Source: Ensembl
    Complete GO annotation...

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi4224.
    OpenTargetsiENSG00000112818.
    PharmGKBiPA30749.

    Polymorphism and mutation databases

    BioMutaiMEP1A.
    DMDMi205830902.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 21By similarityAdd BLAST21
    PropeptideiPRO_000002887722 – 65By similarityAdd BLAST44
    ChainiPRO_000002887866 – 746Meprin A subunit alphaAdd BLAST681

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi107 ↔ 259PROSITE-ProRule annotation
    Disulfide bondi128 ↔ 147PROSITE-ProRule annotation
    Glycosylationi140N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi222N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi258N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi269 ↔ 431PROSITE-ProRule annotation
    Disulfide bondi277InterchainPROSITE-ProRule annotation
    Disulfide bondi308InterchainPROSITE-ProRule annotation
    Glycosylationi414N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi440N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi447N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi539N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi674 ↔ 685PROSITE-ProRule annotation
    Disulfide bondi679 ↔ 694PROSITE-ProRule annotation
    Disulfide bondi696 ↔ 709PROSITE-ProRule annotation

    Post-translational modificationi

    N-glycosylated; contains GlcNAc, galactose, mannose and a small amount of fucose.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    PaxDbiQ16819.
    PeptideAtlasiQ16819.
    PRIDEiQ16819.

    PTM databases

    iPTMnetiQ16819.
    PhosphoSitePlusiQ16819.

    Expressioni

    Gene expression databases

    BgeeiENSG00000112818.
    CleanExiHS_MEP1A.
    ExpressionAtlasiQ16819. baseline and differential.
    GenevisibleiQ16819. HS.

    Organism-specific databases

    HPAiCAB025163.
    HPA029416.

    Interactioni

    Subunit structurei

    Homotetramer consisting of disulfide-linked alpha subunits, homooligomer consisting of disulfide-linked alpha subunit homodimers, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers (By similarity). Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity (By similarity).By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MMP9P147802EBI-8153734,EBI-1382326

    Protein-protein interaction databases

    BioGridi110387. 12 interactors.
    IntActiQ16819. 1 interactor.
    STRINGi9606.ENSP00000230588.

    Structurei

    3D structure databases

    ProteinModelPortaliQ16819.
    SMRiQ16819.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini264 – 433MAMPROSITE-ProRule annotationAdd BLAST170
    Domaini434 – 593MATHPROSITE-ProRule annotationAdd BLAST160
    Domaini670 – 710EGF-likePROSITE-ProRule annotationAdd BLAST41

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni66 – 263MetalloproteaseAdd BLAST198

    Sequence similaritiesi

    Belongs to the peptidase M12A family.Curated
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 1 MAM domain.PROSITE-ProRule annotation
    Contains 1 MATH domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3714. Eukaryota.
    ENOG410ZPX7. LUCA.
    GeneTreeiENSGT00760000119227.
    HOVERGENiHBG052457.
    InParanoidiQ16819.
    KOiK01395.
    PhylomeDBiQ16819.
    TreeFamiTF315280.

    Family and domain databases

    CDDicd06263. MAM. 1 hit.
    Gene3Di2.60.210.10. 1 hit.
    3.40.390.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR000742. EGF-like_dom.
    IPR000998. MAM_dom.
    IPR002083. MATH/TRAF_dom.
    IPR008294. Meprin.
    IPR024079. MetalloPept_cat_dom.
    IPR001506. Peptidase_M12A.
    IPR006026. Peptidase_Metallo.
    IPR008974. TRAF-like.
    [Graphical view]
    PANTHERiPTHR10127:SF311. PTHR10127:SF311. 1 hit.
    PfamiPF01400. Astacin. 1 hit.
    PF00008. EGF. 1 hit.
    PF00629. MAM. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001196. Meprin. 1 hit.
    PRINTSiPR00480. ASTACIN.
    PR00020. MAMDOMAIN.
    SMARTiSM00137. MAM. 1 hit.
    SM00061. MATH. 1 hit.
    SM00235. ZnMc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49599. SSF49599. 1 hit.
    SSF49899. SSF49899. 1 hit.
    PROSITEiPS50026. EGF_3. 1 hit.
    PS00740. MAM_1. 1 hit.
    PS50060. MAM_2. 1 hit.
    PS50144. MATH. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    Q16819-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAWIRSTCIL FFTLLFAHIA AVPIKYLPEE NVHDADFGEQ KDISEINLAA
    60 70 80 90 100
    GLDLFQGDIL LQKSRNGLRD PNTRWTFPIP YILADNLGLN AKGAILYAFE
    110 120 130 140 150
    MFRLKSCVDF KPYEGESSYI IFQQFDGCWS EVGDQHVGQN ISIGQGCAYK
    160 170 180 190 200
    AIIEHEILHA LGFYHEQSRT DRDDYVNIWW DQILSGYQHN FDTYDDSLIT
    210 220 230 240 250
    DLNTPYDYES LMHYQPFSFN KNASVPTITA KIPEFNSIIG QRLDFSAIDL
    260 270 280 290 300
    ERLNRMYNCT TTHTLLDHCT FEKANICGMI QGTRDDTDWA HQDSAQAGEV
    310 320 330 340 350
    DHTLLGQCTG AGYFMQFSTS SGSAEEAALL ESRILYPKRK QQCLQFFYKM
    360 370 380 390 400
    TGSPSDRLVV WVRRDDSTGN VRKLVKVQTF QGDDDHNWKI AHVVLKEEQK
    410 420 430 440 450
    FRYLFQGTKG DPQNSTGGIY LDDITLTETP CPTGVWTVRN FSQVLENTSK
    460 470 480 490 500
    GDKLQSPRFY NSEGYGFGVT LYPNSRESSG YLRLAFHVCS GENDAILEWP
    510 520 530 540 550
    VENRQVIITI LDQEPDVRNR MSSSMVFTTS KSHTSPAIND TVIWDRPSRV
    560 570 580 590 600
    GTYHTDCNCF RSIDLGWSGF ISHQMLKRRS FLKNDDLIIF VDFEDITHLS
    610 620 630 640 650
    QTEVPTKGKR LSPQGLILQG QEQQVSEEGS GKAMLEEALP VSLSQGQPSR
    660 670 680 690 700
    QKRSVENTGP LEDHNWPQYF RDPCDPNPCQ NDGICVNVKG MASCRCISGH
    710 720 730 740
    AFFYTGERCQ AVQVHGSVLG MVIGGTAGVI FLTFSIIAIL SQRPRK
    Length:746
    Mass (Da):84,419
    Last modified:July 22, 2008 - v2
    Checksum:iB5F0812F2850F958
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti26Y → H in AAA21338 (Ref. 1) Curated1
    Sequence conflicti162G → V in AAL85339 (Ref. 2) Curated1
    Sequence conflicti306G → E in BAF98731 (PubMed:14702039).Curated1
    Sequence conflicti426L → P in BAF98731 (PubMed:14702039).Curated1
    Sequence conflicti518R → Q in BAG37669 (PubMed:14702039).Curated1
    Sequence conflicti546R → S in BAF98731 (PubMed:14702039).Curated1
    Sequence conflicti638A → V in BAF98731 (PubMed:14702039).Curated1
    Sequence conflicti711 – 713AVQ → SAE in AAA21338 (Ref. 1) Curated3
    Sequence conflicti711 – 713AVQ → SAE no nucleotide entry (PubMed:8262185).Curated3

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_020056469V → L.2 PublicationsCorresponds to variant rs2274658dbSNPEnsembl.1
    Natural variantiVAR_033492476R → G.1 PublicationCorresponds to variant rs12197930dbSNPEnsembl.1
    Natural variantiVAR_051583606T → S.2 PublicationsCorresponds to variant rs2297020dbSNPEnsembl.1
    Natural variantiVAR_021846634M → V.Corresponds to variant rs2297019dbSNPEnsembl.1
    Natural variantiVAR_033493726T → M.1 PublicationCorresponds to variant rs1804211dbSNPEnsembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M82962 mRNA. Translation: AAA21338.1.
    AF478685 mRNA. Translation: AAL85339.1.
    AK290282 mRNA. Translation: BAF82971.1.
    AK315246 mRNA. Translation: BAG37669.1.
    AK315840 mRNA. Translation: BAF98731.1.
    AL161618 Genomic DNA. Translation: CAC21508.1.
    CH471081 Genomic DNA. Translation: EAX04306.1.
    BC131714 mRNA. Translation: AAI31715.1.
    CCDSiCCDS4918.1.
    PIRiS60193. HYHUMA.
    RefSeqiNP_005579.2. NM_005588.2.
    UniGeneiHs.179704.

    Genome annotation databases

    EnsembliENST00000230588; ENSP00000230588; ENSG00000112818.
    GeneIDi4224.
    KEGGihsa:4224.
    UCSCiuc010jzh.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M82962 mRNA. Translation: AAA21338.1.
    AF478685 mRNA. Translation: AAL85339.1.
    AK290282 mRNA. Translation: BAF82971.1.
    AK315246 mRNA. Translation: BAG37669.1.
    AK315840 mRNA. Translation: BAF98731.1.
    AL161618 Genomic DNA. Translation: CAC21508.1.
    CH471081 Genomic DNA. Translation: EAX04306.1.
    BC131714 mRNA. Translation: AAI31715.1.
    CCDSiCCDS4918.1.
    PIRiS60193. HYHUMA.
    RefSeqiNP_005579.2. NM_005588.2.
    UniGeneiHs.179704.

    3D structure databases

    ProteinModelPortaliQ16819.
    SMRiQ16819.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110387. 12 interactors.
    IntActiQ16819. 1 interactor.
    STRINGi9606.ENSP00000230588.

    Protein family/group databases

    MEROPSiM12.002.

    PTM databases

    iPTMnetiQ16819.
    PhosphoSitePlusiQ16819.

    Polymorphism and mutation databases

    BioMutaiMEP1A.
    DMDMi205830902.

    Proteomic databases

    PaxDbiQ16819.
    PeptideAtlasiQ16819.
    PRIDEiQ16819.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000230588; ENSP00000230588; ENSG00000112818.
    GeneIDi4224.
    KEGGihsa:4224.
    UCSCiuc010jzh.2. human.

    Organism-specific databases

    CTDi4224.
    DisGeNETi4224.
    GeneCardsiMEP1A.
    H-InvDBHIX0032798.
    HGNCiHGNC:7015. MEP1A.
    HPAiCAB025163.
    HPA029416.
    MIMi600388. gene.
    neXtProtiNX_Q16819.
    OpenTargetsiENSG00000112818.
    PharmGKBiPA30749.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3714. Eukaryota.
    ENOG410ZPX7. LUCA.
    GeneTreeiENSGT00760000119227.
    HOVERGENiHBG052457.
    InParanoidiQ16819.
    KOiK01395.
    PhylomeDBiQ16819.
    TreeFamiTF315280.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000112818-MONOMER.
    BRENDAi3.4.24.18. 2681.
    SignaLinkiQ16819.

    Miscellaneous databases

    GeneWikiiMEP1A.
    GenomeRNAii4224.
    PROiQ16819.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000112818.
    CleanExiHS_MEP1A.
    ExpressionAtlasiQ16819. baseline and differential.
    GenevisibleiQ16819. HS.

    Family and domain databases

    CDDicd06263. MAM. 1 hit.
    Gene3Di2.60.210.10. 1 hit.
    3.40.390.10. 1 hit.
    InterProiIPR013320. ConA-like_dom.
    IPR000742. EGF-like_dom.
    IPR000998. MAM_dom.
    IPR002083. MATH/TRAF_dom.
    IPR008294. Meprin.
    IPR024079. MetalloPept_cat_dom.
    IPR001506. Peptidase_M12A.
    IPR006026. Peptidase_Metallo.
    IPR008974. TRAF-like.
    [Graphical view]
    PANTHERiPTHR10127:SF311. PTHR10127:SF311. 1 hit.
    PfamiPF01400. Astacin. 1 hit.
    PF00008. EGF. 1 hit.
    PF00629. MAM. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001196. Meprin. 1 hit.
    PRINTSiPR00480. ASTACIN.
    PR00020. MAMDOMAIN.
    SMARTiSM00137. MAM. 1 hit.
    SM00061. MATH. 1 hit.
    SM00235. ZnMc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49599. SSF49599. 1 hit.
    SSF49899. SSF49899. 1 hit.
    PROSITEiPS50026. EGF_3. 1 hit.
    PS00740. MAM_1. 1 hit.
    PS50060. MAM_2. 1 hit.
    PS50144. MATH. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMEP1A_HUMAN
    AccessioniPrimary (citable) accession number: Q16819
    Secondary accession number(s): A2RRM4
    , B0AZP9, B2RCS2, Q8TDC9, Q9H1R1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: July 22, 2008
    Last modified: November 2, 2016
    This is version 164 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 6
      Human chromosome 6: 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. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. 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.