LAMP3_HUMAN
ID LAMP3_HUMAN Reviewed; 416 AA.
AC Q9UQV4; D3DNS4; O94781; Q8NEC8;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Lysosome-associated membrane glycoprotein 3;
DE Short=LAMP-3;
DE Short=Lysosomal-associated membrane protein 3;
DE AltName: Full=DC-lysosome-associated membrane glycoprotein;
DE Short=DC LAMP;
DE AltName: Full=Protein TSC403;
DE AltName: CD_antigen=CD208;
DE Flags: Precursor;
GN Name=LAMP3; Synonyms=DCLAMP, TSC403;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT VAL-318.
RC TISSUE=Lung;
RX PubMed=9721848;
RA Ozaki K., Nagata M., Suzuki M., Fujiwara T., Ueda K., Miyoshi Y.,
RA Takahashi E., Nakamura Y.;
RT "Isolation and characterization of a novel human lung-specific gene
RT homologous to lysosomal membrane glycoprotein 1 and 2; significantly
RT increased expression in cancers of various tissues.";
RL Cancer Res. 58:3499-3503(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9768752; DOI=10.1016/s1074-7613(00)80615-9;
RA de Saint-Vis B.M., Vincent J., Vandenabeele S., Vanbervliet B., Pin J.J.,
RA Ait-Yahia S., Patel S., Mattei M.-G., Banchereau J., Zurawski S.,
RA Davoust J., Caux C., Lebecque S.;
RT "A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon
RT DC maturation, is transiently expressed in MHC class II compartment.";
RL Immunity 9:325-336(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-318.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-32.
RC TISSUE=Testis;
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 [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21930964; DOI=10.4049/jimmunol.1100600;
RA Duchez S., Rodrigues M., Bertrand F., Valitutti S.;
RT "Reciprocal polarization of T and B cells at the immunological synapse.";
RL J. Immunol. 187:4571-4580(2011).
RN [6]
RP FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=21810281; DOI=10.1186/1743-422x-8-384;
RA Zhou Z., Xue Q., Wan Y., Yang Y., Wang J., Hung T.;
RT "Lysosome-associated membrane glycoprotein 3 is involved in influenza A
RT virus replication in human lung epithelial (A549) cells.";
RL Virol. J. 8:384-384(2011).
RN [7]
RP FUNCTION.
RX PubMed=24434718; DOI=10.1530/erc-13-0183;
RA Nagelkerke A., Sieuwerts A.M., Bussink J., Sweep F.C., Look M.P.,
RA Foekens J.A., Martens J.W., Span P.N.;
RT "LAMP3 is involved in tamoxifen resistance in breast cancer cells through
RT the modulation of autophagy.";
RL Endocr. Relat. Cancer 21:101-112(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY ATF4.
RX PubMed=25681212; DOI=10.1016/j.ejcb.2015.01.003;
RA Dominguez-Bautista J.A., Klinkenberg M., Brehm N., Subramaniam M., Kern B.,
RA Roeper J., Auburger G., Jendrach M.;
RT "Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular
RT vulnerability against proteasomal inhibition.";
RL Eur. J. Cell Biol. 94:148-161(2015).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), INDUCTION BY SALMONELLA (MICROBIAL
RP INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=27329040; DOI=10.14348/molcells.2016.0112;
RA Lee E.J., Park K.S., Jeon I.S., Choi J.W., Lee S.J., Choy H.E., Song K.D.,
RA Lee H.K., Choi J.K.;
RT "LAMP-3 (Lysosome-Associated Membrane Protein 3) Promotes the Intracellular
RT Proliferation of Salmonella typhimurium.";
RL Mol. Cells 39:566-572(2016).
RN [10]
RP FUNCTION.
RX PubMed=29056532; DOI=10.1016/j.mce.2017.10.010;
RA Liao X., Song L., Zhang L., Wang H., Tong Q., Xu J., Yang G., Yang S.,
RA Zheng H.;
RT "LAMP3 regulates hepatic lipid metabolism through activating PI3K/Akt
RT pathway.";
RL Mol. Cell. Endocrinol. 470:160-167(2018).
RN [11]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH FURIN, AND INTERACTION
RP WITH MUMPS VIRURS PROTEIN F (MICROBIAL INFECTION).
RX PubMed=32295904; DOI=10.1128/jvi.00050-20;
RA Ueo A., Kubota M., Shirogane Y., Ohno S., Hashiguchi T., Yanagi Y.;
RT "Lysosome-Associated Membrane Proteins Support the Furin-Mediated
RT Processing of the Mumps Virus Fusion Protein.";
RL J. Virol. 94:0-0(2020).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 222-381, SUBUNIT, GLYCOSYLATION
RP AT ASN-291, AND DISULFIDE BONDS.
RX PubMed=22809326; DOI=10.1186/1741-7007-10-62;
RA Wilke S., Krausze J., Bussow K.;
RT "Crystal structure of the conserved domain of the DC lysosomal associated
RT membrane protein: implications for the lysosomal glycocalyx.";
RL BMC Biol. 10:62-62(2012).
CC -!- FUNCTION: Lysosomal membrane glycoprotein which plays a role in the
CC unfolded protein response (UPR) that contributes to protein degradation
CC and cell survival during proteasomal dysfunction (PubMed:25681212).
CC Plays a role in the process of fusion of the lysosome with the
CC autophagosome, thereby modulating the autophagic process
CC (PubMed:24434718). Promotes hepatocellular lipogenesis through
CC activation of the PI3K/Akt pathway (PubMed:29056532). May also play a
CC role in dendritic cell function and in adaptive immunity
CC (PubMed:9768752). {ECO:0000269|PubMed:24434718,
CC ECO:0000269|PubMed:25681212, ECO:0000269|PubMed:29056532,
CC ECO:0000269|PubMed:9768752}.
CC -!- FUNCTION: (Microbial infection) Plays a positive role in post-entry
CC steps of influenza A virus replication, either virus uncoating,
CC cytosolic transport, or nuclear import of viral components, and
CC promotes nuclear accumulation of influenza nucleoprotein/NP at early
CC stages of viral infection. {ECO:0000269|PubMed:21810281}.
CC -!- FUNCTION: (Microbial infection) Supports the FURIN-mediated cleavage of
CC mumps virus fusion protein F by interacting with both FURIN and the
CC unprocessed form but not the processed form of the viral protein F.
CC {ECO:0000269|PubMed:32295904}.
CC -!- FUNCTION: (Microbial infection) Promotes the intracellular
CC proliferation of Salmonella typhimuium. {ECO:0000269|PubMed:27329040}.
CC -!- SUBUNIT: Monomer (PubMed:22809326). Interacts with FURIN
CC (PubMed:32295904). {ECO:0000269|PubMed:22809326,
CC ECO:0000269|PubMed:32295904}.
CC -!- SUBUNIT: (Microbial infection) Interacts with mumps virus protein F;
CC this interaction promotes protein F cleavage by FURIN.
CC {ECO:0000269|PubMed:32295904}.
CC -!- SUBCELLULAR LOCATION: Cell surface {ECO:0000269|PubMed:27329040}.
CC Lysosome membrane {ECO:0000269|PubMed:21930964,
CC ECO:0000269|PubMed:9768752}; Single-pass type I membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:9768752}; Single-pass type I membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:21810281};
CC Single-pass type I membrane protein {ECO:0000255}. Note=During
CC dendritic cell maturation, detected on cytoplasmic vesicles (the MHC II
CC compartment) that contain MHC II proteins, LAMP1, LAMP2 and LAMP3
CC (PubMed:9768752). Detected on lysosomes in mature dendritic cells
CC (PubMed:9768752). {ECO:0000269|PubMed:9768752}.
CC -!- TISSUE SPECIFICITY: Detected in tonsil interdigitating dendritic cells,
CC in spleen, lymph node, Peyer's patches in the small instestine, in
CC thymus medulla and in B-cells (at protein level). Expressed in lymphoid
CC organs and dendritic cells. Expressed in lung. Up-regulated in
CC carcinomas of the esophagus, colon, rectum, ureter, stomach, breast,
CC fallopian tube, thyroid and parotid tissues.
CC {ECO:0000269|PubMed:21930964, ECO:0000269|PubMed:9721848,
CC ECO:0000269|PubMed:9768752}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated during dendritic cell maturation.
CC -!- INDUCTION: By UPR transcription factor ATF4 signaling.
CC {ECO:0000269|PubMed:25681212}.
CC -!- INDUCTION: (Microbial infection) Upon Salmonella typhimurium infection,
CC at both transcriptional and translational levels.
CC {ECO:0000269|PubMed:27329040}.
CC -!- SIMILARITY: Belongs to the LAMP family. {ECO:0000255|PROSITE-
CC ProRule:PRU00740}.
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DR EMBL; AB013924; BAA34533.1; -; mRNA.
DR EMBL; AJ005766; CAA06691.1; -; mRNA.
DR EMBL; CH471052; EAW78337.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78338.1; -; Genomic_DNA.
DR EMBL; BC032940; AAH32940.1; -; mRNA.
DR CCDS; CCDS3242.1; -.
DR RefSeq; NP_055213.2; NM_014398.3.
DR PDB; 4AKM; X-ray; 2.69 A; A/B=222-381.
DR PDBsum; 4AKM; -.
DR AlphaFoldDB; Q9UQV4; -.
DR SMR; Q9UQV4; -.
DR BioGRID; 117983; 493.
DR IntAct; Q9UQV4; 69.
DR MINT; Q9UQV4; -.
DR STRING; 9606.ENSP00000265598; -.
DR GlyGen; Q9UQV4; 8 sites, 2 O-linked glycans (1 site).
DR iPTMnet; Q9UQV4; -.
DR PhosphoSitePlus; Q9UQV4; -.
DR SwissPalm; Q9UQV4; -.
DR BioMuta; LAMP3; -.
DR DMDM; 126302564; -.
DR EPD; Q9UQV4; -.
DR jPOST; Q9UQV4; -.
DR MassIVE; Q9UQV4; -.
DR PaxDb; Q9UQV4; -.
DR PeptideAtlas; Q9UQV4; -.
DR PRIDE; Q9UQV4; -.
DR ProteomicsDB; 85575; -.
DR Antibodypedia; 33770; 592 antibodies from 39 providers.
DR DNASU; 27074; -.
DR Ensembl; ENST00000265598.8; ENSP00000265598.3; ENSG00000078081.8.
DR GeneID; 27074; -.
DR KEGG; hsa:27074; -.
DR MANE-Select; ENST00000265598.8; ENSP00000265598.3; NM_014398.4; NP_055213.2.
DR UCSC; uc003flh.5; human.
DR CTD; 27074; -.
DR DisGeNET; 27074; -.
DR GeneCards; LAMP3; -.
DR HGNC; HGNC:14582; LAMP3.
DR HPA; ENSG00000078081; Tissue enriched (lung).
DR MIM; 605883; gene.
DR neXtProt; NX_Q9UQV4; -.
DR OpenTargets; ENSG00000078081; -.
DR PharmGKB; PA30286; -.
DR VEuPathDB; HostDB:ENSG00000078081; -.
DR eggNOG; KOG4818; Eukaryota.
DR GeneTree; ENSGT00940000164015; -.
DR InParanoid; Q9UQV4; -.
DR OMA; ECFSDRN; -.
DR OrthoDB; 829830at2759; -.
DR PhylomeDB; Q9UQV4; -.
DR TreeFam; TF316339; -.
DR PathwayCommons; Q9UQV4; -.
DR SignaLink; Q9UQV4; -.
DR BioGRID-ORCS; 27074; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; LAMP3; human.
DR GeneWiki; LAMP3; -.
DR GenomeRNAi; 27074; -.
DR Pharos; Q9UQV4; Tbio.
DR PRO; PR:Q9UQV4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UQV4; protein.
DR Bgee; ENSG00000078081; Expressed in lower lobe of lung and 135 other tissues.
DR ExpressionAtlas; Q9UQV4; baseline and differential.
DR Genevisible; Q9UQV4; HS.
DR GO; GO:0097233; C:alveolar lamellar body membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031902; C:late endosome membrane; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0072594; P:establishment of protein localization to organelle; IBA:GO_Central.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010506; P:regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903900; P:regulation of viral life cycle; IMP:ParkinsonsUK-UCL.
DR GO; GO:0035455; P:response to interferon-alpha; IMP:ParkinsonsUK-UCL.
DR InterPro; IPR002000; Lysosome-assoc_membr_glycop.
DR PANTHER; PTHR11506; PTHR11506; 1.
DR Pfam; PF01299; Lamp; 1.
DR PRINTS; PR00336; LYSASSOCTDMP.
DR PROSITE; PS51407; LAMP_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cytoplasmic vesicle; Disulfide bond;
KW Endosome; Glycoprotein; Host-virus interaction; Immunity; Lysosome;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..416
FT /note="Lysosome-associated membrane glycoprotein 3"
FT /id="PRO_0000223695"
FT TOPO_DOM 28..381
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 382..402
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT TOPO_DOM 403..416
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00740"
FT REGION 136..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 139..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22809326"
FT DISULFID 237..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00740,
FT ECO:0000269|PubMed:22809326"
FT DISULFID 339..376
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00740,
FT ECO:0000269|PubMed:22809326"
FT VARIANT 32
FT /note="E -> G (in dbSNP:rs17853113)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030827"
FT VARIANT 318
FT /note="I -> V (in dbSNP:rs482912)"
FT /evidence="ECO:0000269|PubMed:9721848, ECO:0000269|Ref.3"
FT /id="VAR_025343"
FT CONFLICT 145
FT /note="T -> A (in Ref. 1; BAA34533)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="V -> D (in Ref. 1; BAA34533)"
FT /evidence="ECO:0000305"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 235..248
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:4AKM"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 276..285
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 301..311
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 318..323
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 343..346
FT /evidence="ECO:0007829|PDB:4AKM"
FT STRAND 348..363
FT /evidence="ECO:0007829|PDB:4AKM"
SQ SEQUENCE 416 AA; 44346 MW; D615895D382B8F88 CRC64;
MPRQLSAAAA LFASLAVILH DGSQMRAKAF PETRDYSQPT AAATVQDIKK PVQQPAKQAP
HQTLAARFMD GHITFQTAAT VKIPTTTPAT TKNTATTSPI TYTLVTTQAT PNNSHTAPPV
TEVTVGPSLA PYSLPPTITP PAHTTGTSSS TVSHTTGNTT QPSNQTTLPA TLSIALHKST
TGQKPVQPTH APGTTAAAHN TTRTAAPAST VPGPTLAPQP SSVKTGIYQV LNGSRLCIKA
EMGIQLIVQD KESVFSPRRY FNIDPNATQA SGNCGTRKSN LLLNFQGGFV NLTFTKDEES
YYISEVGAYL TVSDPETIYQ GIKHAVVMFQ TAVGHSFKCV SEQSLQLSAH LQVKTTDVQL
QAFDFEDDHF GNVDECSSDY TIVLPVIGAI VVGLCLMGMG VYKIRLRCQS SGYQRI
