ID   LGMN_PONAB              Reviewed;         433 AA.
AC   Q5R5D9;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 56.
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   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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:0000250}.
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; CR860922; CAH93027.1; -; mRNA.
DR   RefSeq; NP_001126789.1; NM_001133317.1.
DR   AlphaFoldDB; Q5R5D9; -.
DR   SMR; Q5R5D9; -.
DR   STRING; 9601.ENSPPYP00000006913; -.
DR   MEROPS; C13.004; -.
DR   GeneID; 100173793; -.
DR   KEGG; pon:100173793; -.
DR   CTD; 5641; -.
DR   eggNOG; KOG1348; Eukaryota.
DR   InParanoid; Q5R5D9; -.
DR   OrthoDB; 826971at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:1901185; P:negative regulation of ERBB signaling pathway; ISS:UniProtKB.
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   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   2: Evidence at transcript 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..323
FT                   /note="Legumain"
FT                   /id="PRO_0000259474"
FT   PROPEP          324..433
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000259475"
FT   ACT_SITE        148
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        189
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   SITE            323..324
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        91
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        272
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        378..412
FT                   /evidence="ECO:0000250"
FT   DISULFID        390..429
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   433 AA;  49309 MW;  C509F72F1D155E8A CRC64;
     MVWKVAVFLS AALVIGAVPI DDPEDGGKHW VVIVAGSNGW YNYRHQADAC HAYQIIHRNG
     IPDEQIVVMM YDDIAYSEDN PTPGIVINRP NGTDVYQGVP KDYTGEDVTP QNFLAVLRGD
     AEAVKGIGSG KVLKSGPQDH VFVYSTDHGS TGILVFPNED LHVEDLNETI HYMYKHKMYR
     KMVFYIEACE SGSMMNHLPD NINVYATTAA NPRESSYACY YDEKRSTYLG DWYSVNWMED
     SDVEDLTKET LHKQYHLVKS HTNTSHVMQY GNKTISTMKV MQFQGMKHKA SSPISLPPVT
     HLDLTPSPDV PLTIMKRKLM NTNDLEESRQ LTEEIQQHLD ARHLIEKSVR KIVSLLAASE
     AEVEQLLSER APLTGHSCYP EALLHFRTHC FNWHSPTYEY ALRHLYVLVN LCEKPYPLHR
     IKLSMDHVCL GHY