ID   MEP1B_MOUSE             Reviewed;         704 AA.
AC   Q61847; Q059K0;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   13-JUL-2010, sequence version 2.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=Meprin A subunit beta;
DE            EC=3.4.24.63;
DE   AltName: Full=Endopeptidase-2;
DE   AltName: Full=Meprin B;
DE   Flags: Precursor;
GN   Name=Mep1b; Synonyms=Mep-1b;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 65-88;
RP   96-109; 329-345 AND 541-549.
RC   TISSUE=Kidney;
RX   PubMed=8407940; DOI=10.1016/s0021-9258(19)36890-5;
RA   Gorbea C.M., Marchand P., Jiang W., Copeland N.G., Gilbert D.J.,
RA   Jenkins N.A., Bond J.S.;
RT   "Cloning, expression, and chromosomal localization of the mouse meprin beta
RT   subunit.";
RL   J. Biol. Chem. 268:21035-21043(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC   TISSUE=Kidney;
RX   PubMed=8567689; DOI=10.1074/jbc.271.4.2271;
RA   Dietrich J.M., Bond J.S., Jiang W.;
RT   "A novel meprin beta' mRNA in mouse embryonal and human colon carcinoma
RT   cells.";
RL   J. Biol. Chem. 271:2271-2278(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   PROTEIN SEQUENCE OF 21-30 (ISOFORM 1), CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND GLYCOSYLATION.
RC   STRAIN=C3H/He; TISSUE=Kidney;
RX   PubMed=1894622; DOI=10.1016/s0021-9258(19)47380-8;
RA   Kounnas M.Z., Wolz R.L., Gorbea C.M., Bond J.S.;
RT   "Meprin-A and -B. Cell surface endopeptidases of the mouse kidney.";
RL   J. Biol. Chem. 266:17350-17357(1991).
RN   [6]
RP   SUBUNIT.
RX   PubMed=1929422; DOI=10.1016/0003-9861(91)90580-c;
RA   Gorbea C.M., Flannery A.V., Bond J.S.;
RT   "Homo- and heterotetrameric forms of the membrane-bound
RT   metalloendopeptidases meprin A and B.";
RL   Arch. Biochem. Biophys. 290:549-553(1991).
RN   [7]
RP   CATALYTIC ACTIVITY.
RX   PubMed=11278902; DOI=10.1074/jbc.m011414200;
RA   Bertenshaw G.P., Turk B.E., Hubbard S.J., Matters G.L., Bylander J.E.,
RA   Crisman J.M., Cantley L.C., Bond J.S.;
RT   "Marked differences between metalloproteases meprin A and B in substrate
RT   and peptide bond specificity.";
RL   J. Biol. Chem. 276:13248-13255(2001).
RN   [8]
RP   INTERACTION WITH MBL2.
RX   PubMed=16116208; DOI=10.4049/jimmunol.175.5.3177;
RA   Hirano M., Ma B.Y., Kawasaki N., Okimura K., Baba M., Nakagawa T., Miwa K.,
RA   Kawasaki N., Oka S., Kawasaki T.;
RT   "Mannan-binding protein blocks the activation of metalloproteases meprin
RT   alpha and beta.";
RL   J. Immunol. 175:3177-3185(2005).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Membrane metallopeptidase that sheds many membrane-bound
CC       proteins. Exhibits a strong preference for acidic amino acids at the
CC       P1' position (PubMed:11278902). Known substrates include: FGF19, VGFA,
CC       IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10,
CC       tenascin-C. The presence of several pro-inflammatory cytokine among
CC       substrates implicate MEP1B in inflammation. It is also involved in
CC       tissue remodeling due to its capability to degrade extracellular matrix
CC       components (By similarity). {ECO:0000250|UniProtKB:Q16820,
CC       ECO:0000269|PubMed:11278902}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of proteins, including azocasein, and peptides.
CC         Hydrolysis of 5-His-|-Leu-6, 6-Leu-|-Cys-7, 14-Ala-|-Leu-15 and 19-
CC         Cys-|-Gly-20 bonds in insulin B chain.; EC=3.4.24.63;
CC         Evidence={ECO:0000269|PubMed:11278902, ECO:0000269|PubMed:1894622};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU01211};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC       ProRule:PRU01211};
CC   -!- ACTIVITY REGULATION: Strongly inhibited by fetuin-A/AHSG (By
CC       similarity). Inhibited by cysteine and by the metal ion chelators EDTA
CC       and 1,10-phenanthroline. Not inhibited by 3,4-dichloroisocourmarin,
CC       soybean trypsin inhibitor, or the cysteine proteinase inhibitors
CC       iodoacetic acid and E-64. {ECO:0000250, ECO:0000269|PubMed:1894622}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Temperature dependence:
CC         The half-life at 58 degrees Celsius is less than 3 minutes.
CC         {ECO:0000269|PubMed:1894622};
CC   -!- SUBUNIT: Homotetramer consisting of disulfide-linked beta subunits, or
CC       heterotetramer of two alpha and two beta subunits formed by non-
CC       covalent association of two disulfide-linked heterodimers. Interacts
CC       with MBL2 through its carbohydrate moiety. This interaction may inhibit
CC       its catalytic activity. {ECO:0000269|PubMed:16116208,
CC       ECO:0000269|PubMed:1929422}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q16820};
CC       Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q16820}.
CC       Secreted {ECO:0000250|UniProtKB:Q16820}. Note=Homodimers are
CC       essentially membrane bound but may also be shed from the surface by
CC       ADAM-10 and ADAM-17. {ECO:0000250|UniProtKB:Q16820}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Beta;
CC         IsoId=Q61847-1; Sequence=Displayed;
CC       Name=2; Synonyms=Beta';
CC         IsoId=Q61847-2; Sequence=VSP_005460;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is expressed in kidney, intestinal brush
CC       borders, and salivary ducts. Isoform 2 has been found in carcinoma
CC       cells.
CC   -!- INDUCTION: By retinoic acid.
CC   -!- PTM: Proteolytically activated by trypsin in the intestinal lumen and
CC       kallikrein-related peptidases in other tissues. {ECO:0000250}.
CC   -!- PTM: N-glycosylated; contains high mannose and/or complex biantennary
CC       structures. {ECO:0000269|PubMed:1894622}.
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DR   EMBL; L15193; AAA75234.1; -; mRNA.
DR   EMBL; CH466557; EDK96962.1; -; Genomic_DNA.
DR   EMBL; BC125627; AAI25628.1; -; mRNA.
DR   EMBL; BC145979; AAI45980.1; -; mRNA.
DR   CCDS; CCDS37747.1; -. [Q61847-1]
DR   PIR; A48040; A48040.
DR   RefSeq; NP_032612.2; NM_008586.2. [Q61847-1]
DR   AlphaFoldDB; Q61847; -.
DR   SMR; Q61847; -.
DR   BioGRID; 201397; 2.
DR   IntAct; Q61847; 1.
DR   STRING; 10090.ENSMUSP00000080866; -.
DR   MEROPS; M12.004; -.
DR   GlyCosmos; Q61847; 9 sites, 14 glycans.
DR   GlyGen; Q61847; 9 sites.
DR   PhosphoSitePlus; Q61847; -.
DR   jPOST; Q61847; -.
DR   MaxQB; Q61847; -.
DR   PaxDb; 10090-ENSMUSP00000080866; -.
DR   PeptideAtlas; Q61847; -.
DR   ProteomicsDB; 295925; -. [Q61847-1]
DR   ProteomicsDB; 295926; -. [Q61847-2]
DR   Antibodypedia; 22196; 89 antibodies from 19 providers.
DR   DNASU; 17288; -.
DR   Ensembl; ENSMUST00000082235.5; ENSMUSP00000080866.5; ENSMUSG00000024313.9. [Q61847-1]
DR   GeneID; 17288; -.
DR   KEGG; mmu:17288; -.
DR   UCSC; uc008eff.1; mouse. [Q61847-1]
DR   AGR; MGI:96964; -.
DR   CTD; 4225; -.
DR   MGI; MGI:96964; Mep1b.
DR   VEuPathDB; HostDB:ENSMUSG00000024313; -.
DR   eggNOG; KOG3714; Eukaryota.
DR   GeneTree; ENSGT00950000183111; -.
DR   HOGENOM; CLU_021966_0_0_1; -.
DR   InParanoid; Q61847; -.
DR   OMA; VYCTRKR; -.
DR   OrthoDB; 2876645at2759; -.
DR   PhylomeDB; Q61847; -.
DR   TreeFam; TF315280; -.
DR   BRENDA; 3.4.24.63; 3474.
DR   BioGRID-ORCS; 17288; 1 hit in 77 CRISPR screens.
DR   PRO; PR:Q61847; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q61847; Protein.
DR   Bgee; ENSMUSG00000024313; Expressed in small intestine Peyer's patch and 54 other cell types or tissues.
DR   ExpressionAtlas; Q61847; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0017090; C:meprin A complex; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd00054; EGF_CA; 1.
DR   CDD; cd06263; MAM; 1.
DR   Gene3D; 2.60.120.200; -; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR000998; MAM_dom.
DR   InterPro; IPR002083; MATH/TRAF_dom.
DR   InterPro; IPR008294; Meprin.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001506; Peptidase_M12A.
DR   InterPro; IPR006026; Peptidase_Metallo.
DR   InterPro; IPR008974; TRAF-like.
DR   InterPro; IPR049342; TRAF_MEP1_MATH_dom.
DR   PANTHER; PTHR10127; DISCOIDIN, CUB, EGF, LAMININ , AND ZINC METALLOPROTEASE DOMAIN CONTAINING; 1.
DR   PANTHER; PTHR10127:SF814; MEPRIN A SUBUNIT BETA; 1.
DR   Pfam; PF01400; Astacin; 1.
DR   Pfam; PF00629; MAM; 1.
DR   Pfam; PF21355; TRAF-mep_MATH; 1.
DR   PIRSF; PIRSF001196; Meprin; 1.
DR   PRINTS; PR00480; ASTACIN.
DR   PRINTS; PR00020; MAMDOMAIN.
DR   SMART; SM00137; MAM; 1.
DR   SMART; SM00061; MATH; 1.
DR   SMART; SM00235; ZnMc; 1.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF49599; TRAF domain-like; 1.
DR   PROSITE; PS51864; ASTACIN; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   PROSITE; PS00740; MAM_1; 1.
DR   PROSITE; PS50060; MAM_2; 1.
DR   PROSITE; PS50144; MATH; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; Q61847; MM.
PE   1: Evidence at protein level;
KW   Alternative promoter usage; Alternative splicing; Cell membrane;
KW   Direct protein sequencing; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Hydrolase; Inflammatory response; Membrane; Metal-binding; Metalloprotease;
KW   Protease; Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Zinc; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..64
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028885"
FT   CHAIN           65..704
FT                   /note="Meprin A subunit beta"
FT                   /id="PRO_0000028886"
FT   TOPO_DOM        21..654
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        655..678
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        679..704
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          63..257
FT                   /note="Peptidase M12A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DOMAIN          261..430
FT                   /note="MAM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT   DOMAIN          431..586
FT                   /note="MATH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT   DOMAIN          607..647
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   ACT_SITE        154
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         153
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         157
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   SITE            239
FT                   /note="Mediates preference for acidic residues at subsite
FT                   P1'"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        219
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        255
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        316
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        422
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        437
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        529
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        548
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        593
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        104..256
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DISULFID        125..145
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DISULFID        266..428
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        274
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        306
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        493
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        611..622
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        616..631
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        633..646
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   VAR_SEQ         1..27
FT                   /note="MDARHQPWFLVFATFLLVSGLPAPEKF -> MNSTAGPASRSRHSFKCRMKL
FT                   LKAPRDGMYMMTFG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:8567689"
FT                   /id="VSP_005460"
FT   CONFLICT        18
FT                   /note="V -> A (in Ref. 1; AAA75234)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        26
FT                   /note="K -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        29
FT                   /note="K -> S (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        470
FT                   /note="S -> Y (in Ref. 1; AAA75234 and 2; no nucleotide
FT                   entry)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   704 AA;  79501 MW;  04F92C493F701525 CRC64;
     MDARHQPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINQGLGLDL FEGDIKLEAN
     GKNSIIGDHK RWPHTIPYVL EDSLEMNAKG VILNAFERYR LKTCIDFKPW SGEANYISVF
     KGSGCWSSVG NIHAGKQELS IGTNCDRIAT VQHEFLHALG FWHEQSRADR DDYVIIVWDR
     IQPGKEHNFN IYNDSVSDSL NVPYDYTSVM HYSKTAFQNG TESTIVTRIS EFEDVIGQRM
     DFSDYDLLKL NQLYNCTSSL SFMDSCDFEL ENICGMIQSS GDSADWQRVS QVLSGPESDH
     SKMGQCKDSG FFMHFNTSIL NEGATAMLES RLLYPKRGFQ CLEFYLYNSG SGNDQLNIYT
     REYTTGQQGG VLTLQRQIKE VPIGSWQLHY VTLQVTKKFR VVFEGLRGPG TSSGGLSIDD
     INLSETRCPH HIWHIQNFTQ ILGGQDTSVY SPPFYSSKGY AFQIYMDLRS STNVGIYFHL
     ISGANDDQLQ WPCPWQQATM TLLDQNPDIR QRMFNQRSIT TDPTMTSDNG SYFWDRPSKV
     GVTDVFPNGT QFSRGIGYGT TVFITRERLK SREFIKGDDI YILLTVEDIS HLNSTSAVPD
     PVPTLAVHNA CSEVVCQNGG ICVVQDGRAE CKCPAGEDWW YMGKRCEKRG STRDTVIIAV
     SSTVTVFAVM LIITLVSVYC TRRKYRKKAR ANTAAMTLEN QHAF
//