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Tbio Lymphocyte activation gene 3 protein

Involved in lymphocyte activation. Binds to HLA class-II antigens.

Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. [provided by RefSeq, Jul 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 36
PubMed Score 286.95
PubTator Score 97.23

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (2)

Disease Target Count Z-score Confidence
Cancer 2346 3.773 1.9

Expression

  Differential Expression (7)

Disease log2 FC p
cutaneous lupus erythematosus 2.000 1.6e-03
osteosarcoma -1.195 4.1e-03
medulloblastoma 1.200 5.0e-06
atypical teratoid / rhabdoid tumor 1.200 1.8e-06
medulloblastoma, large-cell 1.200 9.2e-04
Common variable immunodeficiency 1.185 3.8e-03
psoriasis 1.700 3.0e-48

Synonym

Accession P18627 A8K7T9 Q7Z643 LAG-3
Symbols CD223

Gene

LAG3

PANTHER Protein Class (3)

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (12)

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 GO Function (3)

 GO Component (2)

 GO Process (4)

 Compartment GO Term (6)

 MGI Phenotype (2)

 HCA RNA Cell Line (54)

See all...

Pathway (3)

Protein-protein Interaction (23)

HLA-DRB3   HLA-DRB1   HLA-DRB1   HLA-DRB5   HLA-DRB1   HLA-DRB1   HLA-DRB1   HLA-DRB1   HLA-DRB1   CELSR1   FAT4   FREM2   FRAS1   FAT3   FAT1   FBXO11   ADGRV1   PCDH20   FBXO2   ITIH2   COL14A1   PCDH7   CELSR2  

Gene RIF (28)

PMID Text
27053622 LAG-3 is highly expressed in peripheral blood CD8+ T cells in chronic HBV-infected patients.
26927558 Data indicate that in recurrent spontaneous abortion patients, the expression levels of CD49b and LAG-3 (CD223) on CD14(+) mononuclear cells and the plasma level of transforming growth factor beta (TGF-beta) decreased obviously compared with normal females.
26013006 An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy.
25810006 iNKT cytokine production is profoundly altered by both HIV infection and treatment, and LAG-3, but not PD-1, expression is associated with a reduction in iNKT IFNgamma production.
25780040 the LAG-3/MHC class II pathway may synergize with PD-1/PD ligand to enhance T cell-mediated immune responses.
25154740 The elevated expression of LAG-3 at the genital tract suggests it may regulate T-cell activation, and identify cells susceptible to HIV infection. The enrichment of LAG-3 on double negative T cells suggests LAG-3 may contribute to the immunoregulatory activity of these cells.
25108024 LAG-3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells.
25006012 NFKB1, CD27, LAG3 and IKZF3 are new susceptibility genes for psoriasis.
24441096 These results suggest that LAG-3-mediated activation of plasmacytoid dendritic cells takes place in vivo at tumor sites, and it is in part responsible for directing an immune-suppressive environment.
23261718 Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients.
21441454 our data suggest that the LAG-3-MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma
20568250 Multiple myeloma was associated with 2 SNPs in intron regions of LAG3 within 20 k base pairs 5' upstream of the candidate CD4 gene. The variant in LAG3 gene itself may play a role in susceptibility of MM.
20421648 LAG-3 defines an active CD4(+)CD25(high)Foxp3(+) regulatory T cell subset whose frequency is enhanced in the PBMCs of patients with cancer
20385810 Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.
20331378 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
20228263 Analysis identified a gene-set (LAG3, LPL, ZAP70) whose overexpression is assigned to unmutated immunoglobulin variable heavy chain region with 90% specificity.
19773279 Observational study of gene-disease association. (HuGE Navigator)
18322184 Soluble human recombinant fusion protein (hLAG-3Ig) used in vitro as a single maturation agent induces phenotypic maturation of monocyte-derived dendritic cells and promotes the production of chemokines and TNF-alpha inflammatory cytokine.
17020785 Observational study of gene-disease association. (HuGE Navigator)
17020785 The result, including a total of 2640 MS patients and 2194 controls shows no significant association with CD4 and LAG3 and MS. We conclude that these genes are of minor importance in regard of genetic predisposition to the MS.
16757686 regulatory T cells and LAG-3 have pivotal roles in the suppression of EBV-specific cell-mediated immunity in Hodgkin lymphoma
16519819 Observational study of gene-disease association. (HuGE Navigator)
15674389 Observational study of gene-disease association. (HuGE Navigator)
14644131 LAG-3 activates antigen-presenting cells through MHC class II signalling, leading to increased antigen-specific T-cell responses in vivo.
12825348 LAG3 may mediate sphingolipid metabolism
12775570 LAG-3 induces rapid protein phosphorylation of phospholipase Cgamma2 and p72syk as well as activation of phosphatidyl inositol 3-kinase/Akt, p42/44 extracellular signal-regulated protein kinase, and p38 mitogen-activated protein kinase pathways.
11937541 MHC class II-mediated signals induced by the natural ligand, LAG-3, lead to complete maturation of monocyte-derived dendritic cells, which acquire the capacity to trigger naive T cells and drive polarized Th1 responses.

AA Sequence 

MWEAQFLGLLFLQPLWVAPVKPLQPGAEVPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAGVTWQHQPDSG      1 - 70
PPAAAPGHPLAPGPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPLQPRVQLDERGRQRGDFSLWLRPAR     71 - 140
RADAGEYRAAVHLRDRALSCRLRLRLGQASMTASPPGSLRASDWVILNCSFSRPDRPASVHWFRNRGQGR    141 - 210
VPVRESPHHHLAESFLFLPQVSPMDSGPWGCILTYRDGFNVSIMYNLTVLGLEPPTPLTVYAGAGSRVGL    211 - 280
PCRLPAGVGTRSFLTAKWTPPGGGPDLLVTGDNGDFTLRLEDVSQAQAGTYTCHIHLQEQQLNATVTLAI    281 - 350
ITVTPKSFGSPGSLGKLLCEVTPVSGQERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERL    351 - 420
LGAAVYFTELSSPGAQRSGRAPGALPAGHLLLFLILGVLSLLLLVTGAFGFHLWRRQWRPRRFSALEQGI    421 - 490
HPPQAQSKIEELEQEPEPEPEPEPEPEPEPEPEQL                                       491 - 525
//

Text Mined References (39)

PMID Year Title
27053622 2016 [Elevated expression of lymphocyte activation gene-3 on peripheral blood CD8(+) T lymphocytes in patients with chronic hepatitis B virus infection].
26927558 2016 [Decreased expression levels of LAG-3 and CD49b on CD14+ cells in peripheral blood of patients with recurrent spontaneous abortion].
26013006 2016 An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy.
25810006 2015 Elevated expression of LAG-3, but not PD-1, is associated with impaired iNKT cytokine production during chronic HIV-1 infection and treatment.
25780040 2015 The upregulation of LAG-3 on T cells defines a subpopulation with functional exhaustion and correlates with disease progression in HIV-infected subjects.
25154740 2014 Enrichment of LAG-3, but not PD-1, on double negative T cells at the female genital tract.
25108024 2014 Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling.
25006012 2014 Sequencing-based approach identified three new susceptibility loci for psoriasis.
24441096 2014 Alternative activation of human plasmacytoid DCs in vitro and in melanoma lesions: involvement of LAG-3.
23261718 2013 Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8(+) T cell in HCC patients.
21441454 2011 MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis.
20568250 2010 Common single nucleotide polymorphisms in immunoregulatory genes and multiple myeloma risk among women in Connecticut.
20421648 2010 LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites.
20385810 2010 Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.
20331378 2010 Large-scale candidate gene analysis of spontaneous clearance of hepatitis C virus.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20228263 2010 High expression of lymphocyte-activation gene 3 (LAG3) in chronic lymphocytic leukemia cells is associated with unmutated immunoglobulin variable heavy chain region (IGHV) gene and reduced treatment-free survival.
19773279 2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity.
18322184 2008 Human lymphocyte activation gene-3 molecules expressed by activated T cells deliver costimulation signal for dendritic cell activation.
17020785 2006 Association analysis of the LAG3 and CD4 genes in multiple sclerosis in two independent populations.
16757686 2006 Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients.
16541075 2006 The finished DNA sequence of human chromosome 12.
16519819 2006 Analysis of polymorphisms in 16 genes in type 1 diabetes that have been associated with other immune-mediated diseases.
15674389 2005 Two genes encoding immune-regulatory molecules (LAG3 and IL7R) confer susceptibility to multiple sclerosis.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14644131 2003 LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination.
12825348 2003 Molecular cloning, characterisation and tissue-specific expression of human LAG3, a member of the novel Lag1 protein family.
12775570 2003 MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223).
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11592063 2001 LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a repeated EP motif in the intracellular region of LAG-3, may participate in the down-regulation of the CD3/TCR activation pathway.
10545478 1999 The MHC class II ligand lymphocyte activation gene-3 is co-distributed with CD8 and CD3-TCR molecules after their engagement by mAb or peptide-MHC class I complexes.
9780176 1998 CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling.
9634475 1998 Regulation of expression of the human lymphocyte activation gene-3 (LAG-3) molecule, a ligand for MHC class II.
9382927 1997 Genomic organization of the human LAG-3/CD4 locus.
9159144 1997 Characterization of the major histocompatibility complex class II binding site on LAG-3 protein.
8097522 1993 Reconstitution of the subclass-specific expression of CD4 in thymocytes and peripheral T cells of transgenic mice: identification of a human CD4 enhancer.
1692078 1990 LAG-3, a novel lymphocyte activation gene closely related to CD4.
1380059 1992 Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens.