LGMN_RAT
ID LGMN_RAT Reviewed; 435 AA.
AC Q9R0J8; Q9JLN3;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Legumain;
DE EC=3.4.22.34;
DE AltName: Full=Asparaginyl endopeptidase;
DE AltName: Full=Protease, cysteine 1;
DE Flags: Precursor;
GN Name=Lgmn; Synonyms=Prsc1;
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=Liver;
RA Ishidoh K.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Neumann J., Koehler B., Reske K.;
RT "Cloning and expression of rat legumain.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9742219; DOI=10.1042/bj3350111;
RA Chen J.-M., Dando P.M., Stevens R.A.E., Fortunato M., Barrett A.J.;
RT "Cloning and expression of mouse legumain, a lysosomal endopeptidase.";
RL Biochem. J. 335:111-117(1998).
CC -!- FUNCTION: Has a strict specificity for hydrolysis of asparaginyl bonds.
CC Can also cleave aspartyl bonds slowly, especially under acidic
CC conditions. Required for normal lysosomal protein degradation in renal
CC proximal tubules. Required for normal degradation of internalized EGFR.
CC Plays a role in the regulation of cell proliferation via its role in
CC EGFR degradation. May be involved in the processing of proteins for MHC
CC class II antigen presentation in the lysosomal/endosomal system (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins and small molecule substrates at
CC -Asn-|-Xaa- bonds.; EC=3.4.22.34;
CC -!- SUBUNIT: Monomer after autocatalytic processing. Homodimer before
CC autocatalytic removal of the propeptide. May interact with integrins
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:9742219}.
CC -!- TISSUE SPECIFICITY: Detected in kidney cortex (at protein level).
CC {ECO:0000269|PubMed:9742219}.
CC -!- DOMAIN: In the zymogen form, the uncleaved propeptide blocks access to
CC the active site. {ECO:0000250}.
CC -!- PTM: Activated by autocatalytic processing at pH 4. {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C13 family. {ECO:0000305}.
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DR EMBL; AB032766; BAA84750.1; -; mRNA.
DR EMBL; AF154349; AAF73260.1; -; mRNA.
DR RefSeq; NP_071562.2; NM_022226.2.
DR AlphaFoldDB; Q9R0J8; -.
DR SMR; Q9R0J8; -.
DR STRING; 10116.ENSRNOP00000010101; -.
DR MEROPS; C13.004; -.
DR GlyGen; Q9R0J8; 5 sites.
DR iPTMnet; Q9R0J8; -.
DR PhosphoSitePlus; Q9R0J8; -.
DR jPOST; Q9R0J8; -.
DR PaxDb; Q9R0J8; -.
DR PRIDE; Q9R0J8; -.
DR GeneID; 63865; -.
DR KEGG; rno:63865; -.
DR UCSC; RGD:619832; rat.
DR CTD; 5641; -.
DR RGD; 619832; Lgmn.
DR eggNOG; KOG1348; Eukaryota.
DR InParanoid; Q9R0J8; -.
DR OrthoDB; 826971at2759; -.
DR PhylomeDB; Q9R0J8; -.
DR Reactome; R-RNO-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-RNO-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR PRO; PR:Q9R0J8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005770; C:late endosome; ISO:RGD.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:ARUK-UCL.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; ISO:RGD.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
DR GO; GO:0097061; P:dendritic spine organization; ISO:RGD.
DR GO; GO:0007613; P:memory; ISO:RGD.
DR GO; GO:1901185; P:negative regulation of ERBB signaling pathway; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:RGD.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISO:RGD.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISS:UniProtKB.
DR GO; GO:0032801; P:receptor catabolic process; ISS:UniProtKB.
DR GO; GO:0003014; P:renal system process; ISS:UniProtKB.
DR GO; GO:0010447; P:response to acidic pH; ISO:RGD.
DR GO; GO:0097264; P:self proteolysis; ISO:RGD.
DR GO; GO:0006624; P:vacuolar protein processing; IBA:GO_Central.
DR InterPro; IPR043577; AE.
DR InterPro; IPR001096; Peptidase_C13.
DR PANTHER; PTHR12000; PTHR12000; 1.
DR Pfam; PF01650; Peptidase_C13; 1.
DR PIRSF; PIRSF500139; AE; 1.
DR PIRSF; PIRSF019663; Legumain; 1.
DR PRINTS; PR00776; HEMOGLOBNASE.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Protease;
KW Reference proteome; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250"
FT CHAIN 18..325
FT /note="Legumain"
FT /id="PRO_0000026506"
FT PROPEP 326..435
FT /evidence="ECO:0000250"
FT /id="PRO_0000026507"
FT ACT_SITE 150
FT /evidence="ECO:0000250"
FT ACT_SITE 191
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT SITE 325..326
FT /note="Cleavage; by autolysis"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 380..414
FT /evidence="ECO:0000250"
FT DISULFID 392..431
FT /evidence="ECO:0000250"
FT CONFLICT 2..4
FT /note="TWR -> IWK (in Ref. 2; AAF73260)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 435 AA; 49466 MW; E835F21C13F17A98 CRC64;
MTWRVAVLLS LVLGAGAVHI GVDDPEDGGK HWVVIVAGSN GWYNYRHQAD ACHAYQIIHR
NGIPDEQIIV MMYDDIANNE ENPTPGVVIN RPNGTDVYKG VPKDYTGEDV TPENFLAVLR
GDEEAVKGKG SGKVLKSGPR DHVFVYFTDH GATGILVFPN EDLHVKDLNK TIRYMYEHKM
YQKMVFYIEA CESGSMMNHL PDDIDVYATT AANPNESSYA CYYDEERSTY LGDWYSVNWM
EDSDVEDLTK ETLHKQYHLV KSHTNTSHVM QYGNKSISTM KVMQFQGMKH RASSPISLPP
VTHLDLTPSP DVPLTILKRK LLRTNNMKES QVLVGQIQHL LDARHIIEKS VQKIVSLLAG
FGETAQKHLS ERAMLTAHDC HQEAVTHFRT HCFNWHSVTY EHALRYLYVL ANLCEKPYPI
DRIKMAMDKV CLSHY
