MEP1B_RAT
ID MEP1B_RAT Reviewed; 704 AA.
AC P28826; Q642D0;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 03-AUG-2022, entry version 163.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=1377685; DOI=10.1016/s0021-9258(18)42240-5;
RA Johnson G.D., Hersh L.B.;
RT "Cloning a rat meprin cDNA reveals the enzyme is a heterodimer.";
RL J. Biol. Chem. 267:13505-13512(1992).
RN [2]
RP ERRATUM OF PUBMED:1377685, AND RETRACTION NOTICE OF PUBMED:1377685.
RA Johnson G.D., Hersh L.B.;
RL J. Biol. Chem. 268:17647-17647(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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].
RC STRAIN=Brown Norway; TISSUE=Kidney;
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 INTERCHAIN DISULFIDE BOND.
RX PubMed=8760356; DOI=10.1042/bj3170731;
RA Chevallier S., Ahn J., Boileau G., Crine P.;
RT "Identification of the cysteine residues implicated in the formation of
RT alpha 2 and alpha/beta dimers of rat meprin.";
RL Biochem. J. 317:731-738(1996).
RN [6]
RP DISULFIDE BONDS, AND MUTAGENESIS OF CYS-274; CYS-306 AND CYS-492.
RX PubMed=15695509; DOI=10.1074/jbc.m414218200;
RA Ishmael F.T., Shier V.K., Ishmael S.S., Bond J.S.;
RT "Intersubunit and domain interactions of the meprin B metalloproteinase.
RT Disulfide bonds and protein-protein interactions in the MAM and TRAF
RT domains.";
RL J. Biol. Chem. 280:13895-13901(2005).
CC -!- FUNCTION: Membrane metallopeptidase that sheds many membrane-bound
CC proteins. Exhibits a strong preference for acidic amino acids at the
CC P1' position. Known substrates include: FGF19, VGFA, IL1B, IL18,
CC procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C.
CC The presence of several pro-inflammatory cytokine among substrates
CC implicate MEP1B in inflammation. It is also involved in tissue
CC remodeling due to its capability to degrade extracellular matrix
CC components. {ECO:0000250|UniProtKB:Q61847}.
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:0000250|UniProtKB:Q61847};
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.
CC {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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 -!- TISSUE SPECIFICITY: Kidney, intestinal brush borders and salivary
CC ducts.
CC -!- PTM: N-glycosylated; contains high mannose and/or complex biantennary
CC structures. {ECO:0000250}.
CC -!- PTM: Proteolytically activated by trypsin in the intestinal lumen and
CC kallikrein-related peptidases in other tissues. {ECO:0000250}.
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DR EMBL; M88601; AAA41587.1; -; mRNA.
DR EMBL; CH473974; EDL76105.1; -; Genomic_DNA.
DR EMBL; BC081833; AAH81833.1; -; mRNA.
DR PIR; A42908; A42908.
DR RefSeq; NP_037315.1; NM_013183.2.
DR AlphaFoldDB; P28826; -.
DR SMR; P28826; -.
DR BioGRID; 247756; 2.
DR STRING; 10116.ENSRNOP00000063916; -.
DR MEROPS; M12.004; -.
DR GlyGen; P28826; 8 sites.
DR PaxDb; P28826; -.
DR GeneID; 25727; -.
DR KEGG; rno:25727; -.
DR CTD; 4225; -.
DR RGD; 3081; Mep1b.
DR VEuPathDB; HostDB:ENSRNOG00000049345; -.
DR eggNOG; KOG3714; Eukaryota.
DR HOGENOM; CLU_021966_0_0_1; -.
DR InParanoid; P28826; -.
DR OMA; GPNDHNL; -.
DR OrthoDB; 241999at2759; -.
DR PhylomeDB; P28826; -.
DR BRENDA; 3.4.24.63; 5301.
DR PRO; PR:P28826; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Proteomes; UP000234681; Chromosome 18.
DR Bgee; ENSRNOG00000049345; Expressed in jejunum and 9 other tissues.
DR Genevisible; P28826; RN.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0017090; C:meprin A complex; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:RGD.
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; NAS:RGD.
DR GO; GO:1901998; P:toxin transport; ISO:RGD.
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; 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 Cell membrane; Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Inflammatory response; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..64
FT /id="PRO_0000028887"
FT CHAIN 65..704
FT /note="Meprin A subunit beta"
FT /id="PRO_0000028888"
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..585
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 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 528
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 592
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 104..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:15695509"
FT DISULFID 125..145
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211,
FT ECO:0000269|PubMed:15695509"
FT DISULFID 266..428
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:15695509"
FT DISULFID 274
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:15695509"
FT DISULFID 306
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:15695509"
FT DISULFID 492
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:15695509"
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 MUTAGEN 274
FT /note="C->A: Predominantly occurs as a monomer, less than
FT 10% occurs as dimer."
FT /evidence="ECO:0000269|PubMed:15695509"
FT MUTAGEN 306
FT /note="C->A: Only occurs as a monomer."
FT /evidence="ECO:0000269|PubMed:15695509"
FT MUTAGEN 492
FT /note="C->A: Only occurs as a monomer."
FT /evidence="ECO:0000269|PubMed:15695509"
FT CONFLICT 324
FT /note="V -> I (in Ref. 1; AAA41587)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 79236 MW; 1B40FFDD4D9965E5 CRC64;
MDARHWPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINEDLGLDL FEGDIKLEAS
GRNSIIGDNY RWPHTIPYVL EDSLEMNAKG VILNAFERYR LKTCIDFKPW SGEENYISVF
KGSGCWSSVG NIHAGKQELS IGTNCDRIAT VQHEFLHALG FWHEQSRADR DDYITIVWDR
ILSGKEHNFN IYNDSVSDSL NVPYDYTSVM HYSKTAFQNG TESTIITKIS DFEDVIGQRM
DFSDYDLLKL NQLYSCTSSL SFMDSCDFEL ENICGMIQSS QDSADWQRLS QVLSGPENDH
SNMGQCKDSG FFMHFNTSTG NGGVTAMLES RVLYPKRGFQ CVEFYLYNSG SGNGQLNVYT
REYTAGHQDG VLTLQREIRD IPTGSWQLYY VTLQVTEKFR VVFEGVGGPG ASSGGLSIDD
INLSETRCPH HIWHIQNFTQ LLGGQTTVYS PPFYSSKGYA FQINLDLTSP TNVGLYFHLI
SGANDDQLQW PCPWQQATMT LLDQNPDIRQ RMSNQRSITT DPKMTDDNGS YLWDRPSKVG
VEAFFPNGTQ FSRGRGYGTS VFITQERLKS REFLKGDDVY ILLTVEDISH LNSTAAVPGP
VPTTSTVHNA CSEVECQNGG ICTLQEGRAE CKCPAGEDWW YMGKRCEKRG STKDTIVIAV
SSTVTVFAVM LIITLISVYC TRRKYRKKAS AKTAAMNLEN QHAF
