MEP1A_RAT
ID MEP1A_RAT Reviewed; 748 AA.
AC Q64230; Q642C9;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Meprin A subunit alpha;
DE EC=3.4.24.18;
DE AltName: Full=Endopeptidase-2;
DE AltName: Full=Endopeptidase-24.18 subunit alpha;
DE Short=E-24.18;
DE AltName: Full=MEP-1;
DE Flags: Precursor;
GN Name=Mep1a;
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].
RC TISSUE=Kidney;
RX PubMed=1505684; DOI=10.1016/0014-5793(92)81095-4;
RA Corbeil D., Gaudoux F., Wainwright S., Ingram J., Kenny A.J., Boileau G.,
RA Crine P.;
RT "Molecular cloning of the alpha-subunit of rat endopeptidase-24.18
RT (endopeptidase-2) and co-localization with endopeptidase-24.11 in rat
RT kidney by in situ hybridization.";
RL FEBS Lett. 309:203-208(1992).
RN [2]
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 [3]
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 [4]
RP ACTIVITY REGULATION.
RX PubMed=17976009; DOI=10.1515/bc.2007.156;
RA Bylander J.E., Bertenshaw G.P., Matters G.L., Hubbard S.J., Bond J.S.;
RT "Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate
RT and inhibitor specificities.";
RL Biol. Chem. 388:1163-1172(2007).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of protein and peptide substrates preferentially on
CC carboxyl side of hydrophobic residues.; EC=3.4.24.18;
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: Inhibited by actinonin.
CC {ECO:0000269|PubMed:17976009}.
CC -!- SUBUNIT: Homotetramer consisting of disulfide-linked alpha subunits,
CC homooligomer consisting of disulfide-linked alpha subunit homodimers,
CC or heterotetramer of two alpha and two beta subunits formed by non-
CC covalent association of two disulfide-linked heterodimers (By
CC similarity). Interacts with MBL2 through its carbohydrate moiety. This
CC interaction may inhibit its catalytic activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Colocalized with E-24.11 in proximal tubules of
CC juxtamedullary nephrons.
CC -!- PTM: N-glycosylated; contains GlcNAc, galactose, mannose and a small
CC amount of fucose. {ECO:0000250}.
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; S43408; AAB23030.1; -; mRNA.
DR EMBL; BC081834; AAH81834.1; -; mRNA.
DR PIR; S24134; S24134.
DR RefSeq; NP_037275.1; NM_013143.1.
DR AlphaFoldDB; Q64230; -.
DR SMR; Q64230; -.
DR STRING; 10116.ENSRNOP00000014791; -.
DR MEROPS; M12.002; -.
DR GlyGen; Q64230; 6 sites.
DR iPTMnet; Q64230; -.
DR PhosphoSitePlus; Q64230; -.
DR PaxDb; Q64230; -.
DR PRIDE; Q64230; -.
DR Ensembl; ENSRNOT00000014791; ENSRNOP00000014791; ENSRNOG00000011022.
DR GeneID; 25684; -.
DR KEGG; rno:25684; -.
DR UCSC; RGD:3080; rat.
DR CTD; 4224; -.
DR RGD; 3080; Mep1a.
DR eggNOG; KOG3714; Eukaryota.
DR GeneTree; ENSGT00950000183111; -.
DR HOGENOM; CLU_021966_1_0_1; -.
DR InParanoid; Q64230; -.
DR OMA; FEMFRLR; -.
DR OrthoDB; 241999at2759; -.
DR PhylomeDB; Q64230; -.
DR BRENDA; 3.4.24.18; 5301.
DR PRO; PR:Q64230; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000011022; Expressed in jejunum and 13 other tissues.
DR Genevisible; Q64230; RN.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0017090; C:meprin A complex; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0070573; F:metallodipeptidase activity; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; NAS:RGD.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; 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; IPR034301; Meprin_alpha.
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:SF824; PTHR10127:SF824; 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 Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT PROPEP 21..66
FT /evidence="ECO:0000250"
FT /id="PRO_0000028881"
FT CHAIN 67..748
FT /note="Meprin A subunit alpha"
FT /id="PRO_0000028882"
FT TOPO_DOM 67..719
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 720..739
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 740..748
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 67..261
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DOMAIN 265..434
FT /note="MAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT DOMAIN 435..596
FT /note="MATH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT DOMAIN 672..712
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 641..668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 641..661
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 108..260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 129..148
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 270..432
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 278
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 309
FT /note="Interchain"
FT DISULFID 676..687
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 681..696
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 698..711
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CONFLICT 78
FT /note="L -> P (in Ref. 1; AAB23030)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="A -> S (in Ref. 1; AAB23030)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="C -> R (in Ref. 1; AAB23030)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="R -> E (in Ref. 1; AAB23030)"
FT /evidence="ECO:0000305"
FT CONFLICT 610
FT /note="P -> S (in Ref. 1; AAB23030)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 748 AA; 85123 MW; BCAE2DCD53B8C6A4 CRC64;
MLWTLPVCLL SLSFSAHIAA VSIQHLSTGH DHDDVDVGEQ QKDISEINSA AGLNLFQGDI
LLPRTRNALR DPSSRWKLPI PYILADNLDL NAKGAILNAF EMFRLKSCVD FKPYEGESSY
IIFQQFSGCW SMVGDQHVGQ NISIGEGCDY KAIIEHEILH ALGFFHEQSR TDRDDYVNIW
WNEIMTDYEH NFNTYDDKTI TDLNTPYDYE SLMHYGPFSF NKNETIPTIT TKIPEFNAII
GQRLDFSATD LTRLNRMYNC TRTHTLLDHC AFEKTNICGM IQGTRDDADW VHEDSSQPGQ
VDHTLVGRCK AAGYFMYFNT SSGVTGEVAL LESRILYPKR KQQCLQFFYK MTGSPADRLL
IWVRRDDNTG NVCQLAKIQT FQGDSDHNWK IAHVTLNEEK KFRYVFQGTK GDPGNSDGGI
YLDDITLTET PCPTGVWTIR NISQVLENTV KGDRLVSPRF YNSEGYGFGV TLYPNGRITS
NSGYLGLAFH LYSGDNDVIL EWPVENRQAI MTILDQEPDA RNRMSLSLMF TTSKYQTSSA
INGSVIWDRP TKVGVYDKDC DCFRSIDWGW GQAISHQMLM RRNFLKDDTL IIFVDFKDLT
HLRQTEVPIP SRSVIPRGLL LQGQEPLALG DSRIAMMEES LPRRLDQRQP SRPKRSVENT
GPMEDHNWPQ YFRDPCDPNP CQNEGTCVNV KGMASCRCVS GHAFFYTGER CQAMHVHGSL
LGLLIGCITA LIFLTFITFS NTYQKLRQ
