ID LGMN_BOVIN Reviewed; 433 AA.
AC Q95M12; Q2TA48;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 24-JAN-2024, entry version 89.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-51, FUNCTION, CATALYTIC
RP ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=11983426; DOI=10.1016/s0167-4838(02)00209-1;
RA Yamane T., Takeuchi K., Yamamoto Y., Li Y.-H., Fujiwara M., Nishi K.,
RA Takahashi S., Ohkubo I.;
RT "Legumain from bovine kidney: its purification, molecular cloning,
RT immunohistochemical localization and degradation of annexin II and vitamin
RT D-binding protein.";
RL Biochim. Biophys. Acta 1596:108-120(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Has a strict specificity for hydrolysis of asparaginyl bonds
CC (PubMed:11983426). Can also cleave aspartyl bonds slowly, especially
CC under acidic conditions (By similarity). Involved in the processing of
CC proteins for MHC class II antigen presentation in the
CC lysosomal/endosomal system (By similarity). Also involved in MHC class
CC I antigen presentation in cross-presenting dendritic cells by mediating
CC cleavage and maturation of Perforin-2 (MPEG1), thereby promoting
CC antigen translocation in the cytosol (By similarity). Required for
CC normal lysosomal protein degradation in renal proximal tubules (By
CC similarity). Required for normal degradation of internalized EGFR (By
CC similarity). Plays a role in the regulation of cell proliferation via
CC its role in EGFR degradation (By similarity).
CC {ECO:0000250|UniProtKB:O89017, ECO:0000250|UniProtKB:Q99538,
CC ECO:0000269|PubMed:11983426}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins and small molecule substrates at
CC -Asn-|-Xaa- bonds.; EC=3.4.22.34;
CC Evidence={ECO:0000269|PubMed:11983426};
CC -!- SUBUNIT: Homodimer before autocatalytic removal of the propeptide.
CC Monomer after autocatalytic processing. May interact with integrins.
CC {ECO:0000250|UniProtKB:Q99538}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:11983426}.
CC -!- TISSUE SPECIFICITY: Detected in kidney (at protein level).
CC {ECO:0000269|PubMed:11983426}.
CC -!- DOMAIN: In the zymogen form, the uncleaved propeptide blocks access to
CC the active site. {ECO:0000250|UniProtKB:Q99538}.
CC -!- PTM: Activated by autocatalytic processing at pH 4.
CC {ECO:0000250|UniProtKB:Q99538}.
CC -!- SIMILARITY: Belongs to the peptidase C13 family. {ECO:0000305}.
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; AB060129; BAB69947.1; -; mRNA.
DR EMBL; BC111117; AAI11118.1; -; mRNA.
DR RefSeq; NP_776526.1; NM_174101.2.
DR AlphaFoldDB; Q95M12; -.
DR SMR; Q95M12; -.
DR STRING; 9913.ENSBTAP00000053922; -.
DR ChEMBL; CHEMBL3286062; -.
DR MEROPS; C13.004; -.
DR GlyCosmos; Q95M12; 4 sites, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000053922; -.
DR PeptideAtlas; Q95M12; -.
DR GeneID; 281281; -.
DR KEGG; bta:281281; -.
DR CTD; 5641; -.
DR eggNOG; KOG1348; Eukaryota.
DR HOGENOM; CLU_024160_2_0_1; -.
DR InParanoid; Q95M12; -.
DR OrthoDB; 2951493at2759; -.
DR TreeFam; TF313403; -.
DR BRENDA; 3.4.22.34; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0043202; C:lysosomal lumen; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; 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 GO; GO:0006624; P:vacuolar protein processing; IBA:GO_Central.
DR CDD; cd21115; legumain_C; 1.
DR Gene3D; 1.10.132.130; -; 1.
DR Gene3D; 3.40.50.1460; -; 1.
DR InterPro; IPR043577; AE.
DR InterPro; IPR048501; Legum_prodom.
DR InterPro; IPR046427; Legumain_prodom_sf.
DR InterPro; IPR001096; Peptidase_C13.
DR PANTHER; PTHR12000; HEMOGLOBINASE FAMILY MEMBER; 1.
DR PANTHER; PTHR12000:SF42; LEGUMAIN; 1.
DR Pfam; PF20985; Legum_prodom; 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 Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Lysosome; Protease; Reference proteome; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:Q99538"
FT PROPEP 18..25
FT /evidence="ECO:0000269|PubMed:11983426"
FT /id="PRO_0000259469"
FT CHAIN 26..323
FT /note="Legumain"
FT /id="PRO_0000259470"
FT PROPEP 324..433
FT /evidence="ECO:0000250|UniProtKB:O89017"
FT /id="PRO_0000259471"
FT ACT_SITE 148
FT /evidence="ECO:0000250|UniProtKB:O89017"
FT ACT_SITE 189
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O89017"
FT SITE 323..324
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:O89017"
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|UniProtKB:O89017"
FT DISULFID 390..429
FT /evidence="ECO:0000250|UniProtKB:O89017"
FT CONFLICT 5
FT /note="F -> V (in Ref. 2; AAI11118)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 433 AA; 49284 MW; 48B2CF9844206AB4 CRC64;
MIWEFTVLLS LVLGTGAVPL EDPEDGGKHW VVIVAGSNGW YNYRHQADAC HAYQIVHRNG
IPDEQIIVMM YDDIANSEDN PTPGIVINRP NGSDVYQGVL KDYTGEDVTP KNFLAVLRGD
AEAVKGVGSG KVLKSGPRDH VFVYFTDHGA TGILVFPNED LHVKDLNETI RYMYEHKMYQ
KMVFYIEACE SGSMMNHLPP DINVYATTAA NPRESSYACY YDEQRSTFLG DWYSVNWMED
SDVEDLTKET LHKQYQLVKS HTNTSHVMQY GNKSISAMKL MQFQGLKHQA SSPISLPAVS
RLDLTPSPEV PLSIMKRKLM STNDLQESRR LVQKIDRHLE ARNIIEKSVR KIVTLVSGSA
AEVDRLLSQR APLTEHACYQ TAVSHFRSHC FNWHNPTYEY ALRHLYVLVN LCENPYPIDR
IKLSMNKVCH GYY
//
