LAG3_HUMAN
ID LAG3_HUMAN Reviewed; 525 AA.
AC P18627; A8K7T9; Q7Z643;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 07-JUL-2009, sequence version 5.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Lymphocyte activation gene 3 protein {ECO:0000303|PubMed:1692078};
DE Short=LAG-3 {ECO:0000303|PubMed:1692078};
DE AltName: CD_antigen=CD223;
DE Contains:
DE RecName: Full=Secreted lymphocyte activation gene 3 protein {ECO:0000305};
DE Short=sLAG-3 {ECO:0000250|UniProtKB:Q61790};
DE Flags: Precursor;
GN Name=LAG3 {ECO:0000312|HGNC:HGNC:6476}; Synonyms=FDC;
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] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND VARIANT THR-455.
RX PubMed=1692078; DOI=10.1084/jem.171.5.1393;
RA Triebel F., Jitsukawa S., Baixeras E., Roman-Roman S., Genevee C.,
RA Viegas-Pequignot E., Hercend T.;
RT "LAG-3, a novel lymphocyte activation gene closely related to CD4.";
RL J. Exp. Med. 171:1393-1405(1990).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Triebel F.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-455.
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT THR-455.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
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 [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=1380059; DOI=10.1084/jem.176.2.327;
RA Baixeras E., Huard B., Miossec C., Jitsukawa S., Martin M., Hercend T.,
RA Auffray C., Triebel F., Piatier-Tonneau D.;
RT "Characterization of the lymphocyte activation gene 3-encoded protein. A
RT new ligand for human leukocyte antigen class II antigens.";
RL J. Exp. Med. 176:327-337(1992).
RN [8]
RP FUNCTION.
RX PubMed=7805750; DOI=10.1002/eji.1830241246;
RA Huard B., Tournier M., Hercend T., Triebel F., Faure F.;
RT "Lymphocyte-activation gene 3/major histocompatibility complex class II
RT interaction modulates the antigenic response of CD4+ T lymphocytes.";
RL Eur. J. Immunol. 24:3216-3221(1994).
RN [9]
RP INTERACTION WITH MHC-II.
RX PubMed=7589152; DOI=10.1002/eji.1830250949;
RA Huard B., Prigent P., Tournier M., Bruniquel D., Triebel F.;
RT "CD4/major histocompatibility complex class II interaction analyzed with
RT CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins.";
RL Eur. J. Immunol. 25:2718-2721(1995).
RN [10]
RP FUNCTION, AND INTERACTION WITH MHC-II.
RX PubMed=8647185; DOI=10.1002/eji.1830260533;
RA Huard B., Prigent P., Pages F., Bruniquel D., Triebel F.;
RT "T cell major histocompatibility complex class II molecules down-regulate
RT CD4+ T cell clone responses following LAG-3 binding.";
RL Eur. J. Immunol. 26:1180-1186(1996).
RN [11]
RP INTERACTION WITH MHC-II, AND MUTAGENESIS OF GLN-35; ASP-52; HIS-78; HIS-85;
RP ARG-95; ARG-97; ARG-98; TYR-99; ARG-110; ARG-125; ARG-129; ASP-131;
RP ARG-137; 155-ASP-ARG-156 AND ASP-247.
RX PubMed=9159144; DOI=10.1073/pnas.94.11.5744;
RA Huard B., Mastrangeli R., Prigent P., Bruniquel D., Donini S., El-Tayar N.,
RA Maigret B., Dreano M., Triebel F.;
RT "Characterization of the major histocompatibility complex class II binding
RT site on LAG-3 protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:5744-5749(1997).
RN [12]
RP INDUCTION.
RX PubMed=9634475; DOI=10.1007/s002510050411;
RA Bruniquel D., Borie N., Hannier S., Triebel F.;
RT "Regulation of expression of the human lymphocyte activation gene-3 (LAG-3)
RT molecule, a ligand for MHC class II.";
RL Immunogenetics 48:116-124(1998).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20421648; DOI=10.4049/jimmunol.0903879;
RA Camisaschi C., Casati C., Rini F., Perego M., De Filippo A., Triebel F.,
RA Parmiani G., Belli F., Rivoltini L., Castelli C.;
RT "LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T
RT cells that are expanded at tumor sites.";
RL J. Immunol. 184:6545-6551(2010).
RN [14]
RP INTERACTION WITH FGL1, AND MUTAGENESIS OF TYR-99.
RX PubMed=30580966; DOI=10.1016/j.cell.2018.11.010;
RA Wang J., Sanmamed M.F., Datar I., Su T.T., Ji L., Sun J., Chen L., Chen Y.,
RA Zhu G., Yin W., Zheng L., Zhou T., Badri T., Yao S., Zhu S., Boto A.,
RA Sznol M., Melero I., Vignali D.A.A., Schalper K., Chen L.;
RT "Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3.";
RL Cell 0:0-0(2018).
CC -!- FUNCTION: Lymphocyte activation gene 3 protein: Inhibitory receptor on
CC antigen activated T-cells (PubMed:7805750, PubMed:8647185,
CC PubMed:20421648). Delivers inhibitory signals upon binding to ligands,
CC such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3
CC and is responsible for LAG3 T-cell inhibitory function (By similarity).
CC Following TCR engagement, LAG3 associates with CD3-TCR in the
CC immunological synapse and directly inhibits T-cell activation (By
CC similarity). May inhibit antigen-specific T-cell activation in synergy
CC with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (By
CC similarity). Negatively regulates the proliferation, activation,
CC effector function and homeostasis of both CD8(+) and CD4(+) T-cells
CC (PubMed:7805750, PubMed:8647185, PubMed:20421648). Also mediates immune
CC tolerance: constitutively expressed on a subset of regulatory T-cells
CC (Tregs) and contributes to their suppressive function (By similarity).
CC Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs)
CC activation (By similarity). Binds MHC class II (MHC-II); the precise
CC role of MHC-II-binding is however unclear (PubMed:8647185).
CC {ECO:0000250|UniProtKB:Q61790, ECO:0000269|PubMed:20421648,
CC ECO:0000269|PubMed:7805750, ECO:0000269|PubMed:8647185}.
CC -!- FUNCTION: [Secreted lymphocyte activation gene 3 protein]: May function
CC as a ligand for MHC class II (MHC-II) on antigen-presenting cells
CC (APC), promoting APC activation/maturation and driving Th1 immune
CC response. {ECO:0000250|UniProtKB:Q61790}.
CC -!- SUBUNIT: Interacts with MHC class II (MHC-II); selectively recognizes
CC stable complexes of peptide and MHC-II (PubMed:1692078, PubMed:7589152,
CC PubMed:8647185, PubMed:9159144). Interacts with FGL1 (via the
CC Fibrinogen C-terminal domain) (PubMed:30580966).
CC {ECO:0000269|PubMed:1692078, ECO:0000269|PubMed:30580966,
CC ECO:0000269|PubMed:7589152, ECO:0000269|PubMed:8647185,
CC ECO:0000269|PubMed:9159144}.
CC -!- SUBCELLULAR LOCATION: [Lymphocyte activation gene 3 protein]: Cell
CC membrane {ECO:0000269|PubMed:1380059, ECO:0000269|PubMed:1692078,
CC ECO:0000269|PubMed:9634475}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Secreted lymphocyte activation gene 3 protein]:
CC Secreted {ECO:0000250|UniProtKB:Q61790}. Note=Produced following
CC cleavage of the main chain. {ECO:0000250|UniProtKB:Q61790}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P18627-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P18627-2; Sequence=VSP_056311, VSP_056312;
CC -!- TISSUE SPECIFICITY: Primarily expressed in activated T-cells and a
CC subset of natural killer (NK) cells. {ECO:0000269|PubMed:1380059,
CC ECO:0000269|PubMed:1692078, ECO:0000269|PubMed:20421648}.
CC -!- INDUCTION: Expression is induced by interleukin-2 (IL2), interleukin-7
CC (IL7) and interleukin-12 (IL12A and IL12B) on activated T-cells.
CC {ECO:0000269|PubMed:9634475}.
CC -!- DOMAIN: [Lymphocyte activation gene 3 protein]: The KIEELE motif is
CC required for interaction with downstream signaling molecules.
CC {ECO:0000250|UniProtKB:Q61790}.
CC -!- PTM: [Lymphocyte activation gene 3 protein]: Proteolytically cleaved by
CC ADAM10 and ADAM17 within the connecting peptide region, leading to
CC release of Secreted lymphocyte activation gene 3 protein (sLAG-3).
CC ADAM10 mediates constitutive cleavage, but cleavage increases following
CC T-cell activation, whereas shedding by ADAM17 is induced by TCR
CC signaling in a PRKCQ-dependent manner. {ECO:0000250|UniProtKB:Q61790}.
CC -!- SIMILARITY: Belongs to the LAG3 family. {ECO:0000305}.
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DR EMBL; X51985; CAA36243.3; -; mRNA.
DR EMBL; AK292104; BAF84793.1; -; mRNA.
DR EMBL; AC125494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88741.1; -; Genomic_DNA.
DR EMBL; BC052589; AAH52589.1; -; mRNA.
DR CCDS; CCDS8561.1; -. [P18627-1]
DR PIR; S11246; S11246.
DR RefSeq; NP_002277.4; NM_002286.5. [P18627-1]
DR AlphaFoldDB; P18627; -.
DR BioGRID; 110097; 25.
DR IntAct; P18627; 4.
DR STRING; 9606.ENSP00000203629; -.
DR ChEMBL; CHEMBL4630881; -.
DR GlyGen; P18627; 4 sites.
DR iPTMnet; P18627; -.
DR PhosphoSitePlus; P18627; -.
DR BioMuta; LAG3; -.
DR DMDM; 251757512; -.
DR MassIVE; P18627; -.
DR PaxDb; P18627; -.
DR PeptideAtlas; P18627; -.
DR PRIDE; P18627; -.
DR ProteomicsDB; 53604; -. [P18627-1]
DR ProteomicsDB; 69373; -.
DR ABCD; P18627; 81 sequenced antibodies.
DR Antibodypedia; 2267; 1053 antibodies from 38 providers.
DR DNASU; 3902; -.
DR Ensembl; ENST00000203629.3; ENSP00000203629.2; ENSG00000089692.9. [P18627-1]
DR Ensembl; ENST00000441671.6; ENSP00000413825.2; ENSG00000089692.9. [P18627-2]
DR GeneID; 3902; -.
DR KEGG; hsa:3902; -.
DR MANE-Select; ENST00000203629.3; ENSP00000203629.2; NM_002286.6; NP_002277.4.
DR UCSC; uc001qqs.4; human. [P18627-1]
DR CTD; 3902; -.
DR DisGeNET; 3902; -.
DR GeneCards; LAG3; -.
DR HGNC; HGNC:6476; LAG3.
DR HPA; ENSG00000089692; Tissue enhanced (lymphoid tissue, ovary).
DR MIM; 153337; gene.
DR neXtProt; NX_P18627; -.
DR OpenTargets; ENSG00000089692; -.
DR PharmGKB; PA30265; -.
DR VEuPathDB; HostDB:ENSG00000089692; -.
DR eggNOG; ENOG502S2HD; Eukaryota.
DR GeneTree; ENSGT01050000244846; -.
DR HOGENOM; CLU_041154_0_0_1; -.
DR InParanoid; P18627; -.
DR OMA; LWVAPVE; -.
DR OrthoDB; 862925at2759; -.
DR PhylomeDB; P18627; -.
DR TreeFam; TF335942; -.
DR PathwayCommons; P18627; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR SignaLink; P18627; -.
DR BioGRID-ORCS; 3902; 8 hits in 1071 CRISPR screens.
DR GeneWiki; LAG3; -.
DR GenomeRNAi; 3902; -.
DR Pharos; P18627; Tbio.
DR PRO; PR:P18627; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P18627; protein.
DR Bgee; ENSG00000089692; Expressed in granulocyte and 88 other tissues.
DR Genevisible; P18627; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0003823; F:antigen binding; TAS:ProtInc.
DR GO; GO:0042289; F:MHC class II protein binding; IDA:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; IEA:Ensembl.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0002270; P:plasmacytoid dendritic cell activation; ISS:UniProtKB.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0050776; P:regulation of immune response; ISS:UniProtKB.
DR GO; GO:0042110; P:T cell activation; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR015621; IL-1_rcpt_fam.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR SMART; SM00409; IG; 3.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunity; Immunoglobulin domain; Membrane;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..525
FT /note="Lymphocyte activation gene 3 protein"
FT /id="PRO_0000014631"
FT CHAIN 23..?
FT /note="Secreted lymphocyte activation gene 3 protein"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT /id="PRO_0000446642"
FT TOPO_DOM 23..450
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 451..471
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 472..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..167
FT /note="Ig-like V-type"
FT DOMAIN 168..252
FT /note="Ig-like C2-type 1"
FT DOMAIN 265..343
FT /note="Ig-like C2-type 2"
FT DOMAIN 348..419
FT /note="Ig-like C2-type 3"
FT REGION 37..252
FT /note="Interaction with FGL1"
FT /evidence="ECO:0000269|PubMed:30580966,
FT ECO:0000269|PubMed:9159144"
FT REGION 62..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..450
FT /note="Connecting peptide"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT REGION 487..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..524
FT /note="12 X 2 AA tandem repeats of E-X"
FT MOTIF 498..503
FT /note="KIEELE motif"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT COMPBIAS 72..91
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..525
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 250
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..160
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 189..241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 282..333
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 369..412
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 353..360
FT /note="VTPKSFGS -> GQPQVGKE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056311"
FT VAR_SEQ 361..525
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056312"
FT VARIANT 455
FT /note="I -> T (in dbSNP:rs870849)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:1692078, ECO:0000269|Ref.5"
FT /id="VAR_058295"
FT MUTAGEN 35
FT /note="Q->A: Does not affect binding to MHC class II (MHC-
FT II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 52
FT /note="D->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 78
FT /note="H->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 78
FT /note="H->F: Does not significantly affect binding to MHC
FT class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 85
FT /note="H->A,F: Does not affect binding to MHC class II
FT (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 95
FT /note="R->E: Increased binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 97
FT /note="R->A,E: Increased binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 98
FT /note="R->E: Increased binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 99
FT /note="Y->F: Abolishes binding to MHC class II (MHC-II)
FT without affecting interaction with FGL1."
FT /evidence="ECO:0000269|PubMed:30580966,
FT ECO:0000269|PubMed:9159144"
FT MUTAGEN 110
FT /note="R->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 125
FT /note="R->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 129
FT /note="R->K: Does not affect binding to MHC class II (MHC-
FT II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 131
FT /note="D->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 137
FT /note="R->A: Reduced binding to MHC class II (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 155..156
FT /note="DR->AA: Slightly affects binding to MHC class II
FT (MHC-II)."
FT /evidence="ECO:0000269|PubMed:9159144"
FT MUTAGEN 247
FT /note="D->L: Does not affect binding to MHC class II (MHC-
FT II)."
FT /evidence="ECO:0000269|PubMed:9159144"
SQ SEQUENCE 525 AA; 57449 MW; 5E0BDEF20E9E36D2 CRC64;
MWEAQFLGLL FLQPLWVAPV KPLQPGAEVP VVWAQEGAPA QLPCSPTIPL QDLSLLRRAG
VTWQHQPDSG PPAAAPGHPL APGPHPAAPS SWGPRPRRYT VLSVGPGGLR SGRLPLQPRV
QLDERGRQRG DFSLWLRPAR RADAGEYRAA VHLRDRALSC RLRLRLGQAS MTASPPGSLR
ASDWVILNCS FSRPDRPASV HWFRNRGQGR VPVRESPHHH LAESFLFLPQ VSPMDSGPWG
CILTYRDGFN VSIMYNLTVL GLEPPTPLTV YAGAGSRVGL PCRLPAGVGT RSFLTAKWTP
PGGGPDLLVT GDNGDFTLRL EDVSQAQAGT YTCHIHLQEQ QLNATVTLAI ITVTPKSFGS
PGSLGKLLCE VTPVSGQERF VWSSLDTPSQ RSFSGPWLEA QEAQLLSQPW QCQLYQGERL
LGAAVYFTEL SSPGAQRSGR APGALPAGHL LLFLILGVLS LLLLVTGAFG FHLWRRQWRP
RRFSALEQGI HPPQAQSKIE ELEQEPEPEP EPEPEPEPEP EPEQL
