MEP1B_MOUSE
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 03-AUG-2022, entry version 188.
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;
CC Evidence={ECO:0000255|PROSITE-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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; Q61847; 9 sites.
DR PhosphoSitePlus; Q61847; -.
DR jPOST; Q61847; -.
DR MaxQB; Q61847; -.
DR PaxDb; Q61847; -.
DR PeptideAtlas; Q61847; -.
DR PRIDE; Q61847; -.
DR ProteomicsDB; 295925; -. [Q61847-1]
DR ProteomicsDB; 295926; -. [Q61847-2]
DR Antibodypedia; 22196; 74 antibodies from 19 providers.
DR DNASU; 17288; -.
DR Ensembl; ENSMUST00000082235; ENSMUSP00000080866; ENSMUSG00000024313. [Q61847-1]
DR GeneID; 17288; -.
DR KEGG; mmu:17288; -.
DR UCSC; uc008eff.1; mouse. [Q61847-1]
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; GPNDHNL; -.
DR OrthoDB; 241999at2759; -.
DR PhylomeDB; Q61847; -.
DR TreeFam; TF315280; -.
DR BRENDA; 3.4.24.63; 3474.
DR BioGRID-ORCS; 17288; 1 hit in 72 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 52 other tissues.
DR ExpressionAtlas; Q61847; baseline and differential.
DR Genevisible; Q61847; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0017090; C:meprin A complex; 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 GO; GO:1901998; P:toxin transport; IMP:MGI.
DR CDD; cd06263; MAM; 1.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.40.390.10; -; 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; IPR034302; Meprin_beta.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR008974; TRAF-like.
DR PANTHER; PTHR10127:SF814; PTHR10127:SF814; 1.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00629; MAM; 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; SSF49899; 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.
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
