ID   LAMP2_CRIGR             Reviewed;         410 AA.
AC   P49130;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 94.
DE   RecName: Full=Lysosome-associated membrane glycoprotein 2;
DE            Short=LAMP-2;
DE            Short=Lysosome-associated membrane protein 2;
DE   AltName: Full=CD107 antigen-like family member B;
DE   AltName: Full=Lysosomal membrane glycoprotein B;
DE            Short=LGP-B;
DE   AltName: CD_antigen=CD107b;
DE   Flags: Precursor;
GN   Name=LAMP2; Synonyms=LGPB;
OS   Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Cricetulus.
OX   NCBI_TaxID=10029;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX   PubMed=8867788;
RA   Uthayakumar S., Granger B.L.;
RT   "Cell surface accumulation of overexpressed hamster lysosomal membrane
RT   glycoproteins.";
RL   Cell. Mol. Biol. Res. 41:405-420(1995).
CC   -!- FUNCTION: Lysosomal membrane glycoprotein which plays an important role
CC       in lysosome biogenesis, lysosomal pH regulation and autophagy. Acts as
CC       an important regulator of lysosomal lumen pH regulation by acting as a
CC       direct inhibitor of the proton channel TMEM175, facilitating lysosomal
CC       acidification for optimal hydrolase activity. Plays an important role
CC       in chaperone-mediated autophagy, a process that mediates lysosomal
CC       degradation of proteins in response to various stresses and as part of
CC       the normal turnover of proteins with a long biological half-live.
CC       Functions by binding target proteins, such as GAPDH, NLRP3 and MLLT11,
CC       and targeting them for lysosomal degradation. In the chaperone-mediated
CC       autophagy, acts downstream of chaperones, such as HSPA8/HSC70, which
CC       recognize and bind substrate proteins and mediate their recruitment to
CC       lysosomes, where target proteins bind LAMP2. Plays a role in lysosomal
CC       protein degradation in response to starvation. Required for the fusion
CC       of autophagosomes with lysosomes during autophagy. Cells that lack
CC       LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on
CC       autophagosomes, which is the most likely explanation for the lack of
CC       fusion between autophagosomes and lysosomes. Required for normal
CC       degradation of the contents of autophagosomes. Required for efficient
CC       MHC class II-mediated presentation of exogenous antigens via its
CC       function in lysosomal protein degradation; antigenic peptides generated
CC       by proteases in the endosomal/lysosomal compartment are captured by
CC       nascent MHC II subunits. Is not required for efficient MHC class II-
CC       mediated presentation of endogenous antigens (By similarity).
CC       {ECO:0000250|UniProtKB:P13473, ECO:0000250|UniProtKB:P17046}.
CC   -!- SUBUNIT: Monomer. Forms large homooligomers (By similarity). Interacts
CC       (via its cytoplasmic region) with HSPA8; HSPA8 mediates recruitment of
CC       proteins with a KFERQ motif to the surface of the lysosome for
CC       chaperone-mediated autophagy (By similarity). Interacts with HSP90 in
CC       the lysosome lumen; this enhances LAMP2 stability (By similarity).
CC       Interacts with MLLT11 (By similarity). Interacts with ABCB9 (By
CC       similarity). Interacts with FURIN (By similarity). Interacts with CT55;
CC       this interaction may be important for LAMP2 protein stability (By
CC       similarity). Interacts with TMEM175; inhibiting the proton channel
CC       activity of TMEM175 (By similarity). {ECO:0000250|UniProtKB:P13473,
CC       ECO:0000250|UniProtKB:P17046}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000255|PROSITE-
CC       ProRule:PRU00740, ECO:0000269|PubMed:8867788}; Single-pass type I
CC       membrane protein {ECO:0000255|PROSITE-ProRule:PRU00740}. Endosome
CC       membrane {ECO:0000250|UniProtKB:P13473}; Single-pass type I membrane
CC       protein {ECO:0000255|PROSITE-ProRule:PRU00740}. Cell membrane
CC       {ECO:0000269|PubMed:8867788}; Single-pass type I membrane protein
CC       {ECO:0000255|PROSITE-ProRule:PRU00740}. Cytoplasmic vesicle,
CC       autophagosome membrane {ECO:0000250|UniProtKB:P17047}. Note=This
CC       protein shuttles between lysosomes, endosomes, and the plasma membrane.
CC       {ECO:0000250|UniProtKB:P13473}.
CC   -!- PTM: Extensively N-glycosylated. Contains a minor proportion of O-
CC       linked glycans. {ECO:0000250|UniProtKB:P17046}.
CC   -!- SIMILARITY: Belongs to the LAMP family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00740}.
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DR   EMBL; L19357; AAC37683.1; -; mRNA.
DR   RefSeq; NP_001233678.1; NM_001246749.1.
DR   AlphaFoldDB; P49130; -.
DR   SMR; P49130; -.
DR   GlyCosmos; P49130; 17 sites, No reported glycans.
DR   PaxDb; 10029-NP_001233678-1; -.
DR   GeneID; 100689316; -.
DR   KEGG; cge:100689316; -.
DR   CTD; 3920; -.
DR   eggNOG; KOG4818; Eukaryota.
DR   OrthoDB; 5317371at2759; -.
DR   Proteomes; UP000694386; Unplaced.
DR   Proteomes; UP001108280; Chromosome X.
DR   GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008200; F:ion channel inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0097352; P:autophagosome maturation; ISS:UniProtKB.
DR   GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR   GO; GO:0061684; P:chaperone-mediated autophagy; ISS:UniProtKB.
DR   GO; GO:0007042; P:lysosomal lumen acidification; ISS:UniProtKB.
DR   GO; GO:1905146; P:lysosomal protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0050821; P:protein stabilization; ISS:CAFA.
DR   GO; GO:0006605; P:protein targeting; ISS:UniProtKB.
DR   GO; GO:0061740; P:protein targeting to lysosome involved in chaperone-mediated autophagy; ISS:UniProtKB.
DR   Gene3D; 2.40.160.110; -; 2.
DR   InterPro; IPR048528; Lamp2-like_luminal.
DR   InterPro; IPR048524; Lamp2-like_TM.
DR   InterPro; IPR018134; LAMP_CS.
DR   InterPro; IPR002000; Lysosome-assoc_membr_glycop.
DR   PANTHER; PTHR11506:SF28; FI04419P; 1.
DR   PANTHER; PTHR11506; LYSOSOME-ASSOCIATED MEMBRANE GLYCOPROTEIN; 1.
DR   Pfam; PF01299; Lamp; 2.
DR   Pfam; PF21222; Lamp2_2nd; 1.
DR   PRINTS; PR00336; LYSASSOCTDMP.
DR   PROSITE; PS00310; LAMP_1; 1.
DR   PROSITE; PS00311; LAMP_2; 1.
DR   PROSITE; PS51407; LAMP_3; 1.
PE   2: Evidence at transcript level;
KW   Autophagy; Cell membrane; Cytoplasmic vesicle; Disulfide bond; Endosome;
KW   Glycoprotein; Lysosome; Membrane; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..410
FT                   /note="Lysosome-associated membrane glycoprotein 2"
FT                   /id="PRO_0000017113"
FT   TOPO_DOM        29..375
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        376..399
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   TOPO_DOM        400..410
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   REGION          29..192
FT                   /note="First lumenal domain"
FT   REGION          193..228
FT                   /note="Hinge"
FT   REGION          229..375
FT                   /note="Second lumenal domain"
FT   REGION          401..404
FT                   /note="Important for binding and subsequent lysosomal
FT                   degradation of target proteins"
FT                   /evidence="ECO:0000250|UniProtKB:P13473"
FT   CARBOHYD        48
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        75
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        99
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        119
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        123
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        179
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        222
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        275
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        307
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        317
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        40..79
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   DISULFID        153..189
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   DISULFID        232..265
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT   DISULFID        331..368
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
SQ   SEQUENCE   410 AA;  45028 MW;  ADA8EBF04285C406 CRC64;
     MMCFRLSPVS GSGLVLSCLL LGAVQSYAFE LNLPDSKATC LFAKWKMNFT ISYETTTNKT
     LKTVTISEPH NVTYNGSSCG DDQGVAKIAV QFGSTVSWNV TFTKEESHYV IGSIWLVYNT
     SDNTTFPGAI PKGSATVISS QSIEIPLDDI FRCNSLLTFK TGNVVQNYWD IHLQAFVQNG
     TVSKEEFVCE EDKSVTTVRP IIHTTVPPPT TTPTPLPPKV GNYSVSNGNA TCLLATMGLQ
     LNVTEEKVPF IFNINPSTTN FTGSCHPQTA QLRLNNSQIK YLDFIFAVKS ESHFYLKEVN
     VSMYMANGSV FSVANNNLSF WDAPLGSSYM CNKEQVVSVS RTFQINTFNL KVQPFNVTKG
     KYATAQDCSA DEDNFLVPIA VGAALAGVLA LVLLAYFIGL KRHHTGYEQF
//