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Aliases for LAG3 Gene

Aliases for LAG3 Gene

  • Lymphocyte Activating 3 2 3 5
  • Lymphocyte Activation Gene 3 Protein 3 4
  • Lymphocyte-Activation Gene 3 2 3
  • CD223 Antigen 4
  • CD223 3
  • LAG-3 4
  • FDC 4

External Ids for LAG3 Gene

Previous GeneCards Identifiers for LAG3 Gene

  • GC12M006669
  • GC12M006794
  • GC12P006760
  • GC12P006751
  • GC12P006881

Summaries for LAG3 Gene

Entrez Gene Summary for LAG3 Gene

  • 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]

CIViC summary for LAG3 Gene

GeneCards Summary for LAG3 Gene

LAG3 (Lymphocyte Activating 3) is a Protein Coding gene. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include transmembrane signaling receptor activity and MHC class II protein binding. An important paralog of this gene is IL1R1.

UniProtKB/Swiss-Prot for LAG3 Gene

  • Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (By similarity). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (By similarity). Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:8647185).
  • Secreted lymphocyte activation gene 3 protein: May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response.

Gene Wiki entry for LAG3 Gene

Additional gene information for LAG3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LAG3 Gene

Genomics for LAG3 Gene

GeneHancer (GH) Regulatory Elements for LAG3 Gene

Promoters and enhancers for LAG3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J006771 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 600.7 +1.6 1559 4.1 ELF3 CEBPG RERE TFE3 SP1 HNF1A PPARG SP5 KAT8 IKZF1 LAG3 ING4 GC12M006781
GH12J006772 Enhancer 0.7 ENCODE dbSUPER 600.7 -1.2 -1233 0.2 ZNF600 SP1 POLR2A SIN3A LAG3 MLF2
GH12J006770 Enhancer 0.4 dbSUPER 600.7 -2.0 -1958 0.6 PATZ1 ZNF513 LAG3 MLF2 PTMS
GH12J006530 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 21.1 -235.4 -235387 12.8 HDGF ZNF652 SP1 ZFX ELF3 CC2D1A CTCF ZNF148 NKRF POLR2A GAPDH ENSG00000269968 GPR162 ZNF384 CHD4 ENSG00000219410 ENSG00000247853 NOP2 NCAPD2 ATN1
GH12J006602 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 19.1 -166.8 -166755 7.4 SP1 CC2D1A ZKSCAN8 ZNF148 NKRF POLR2A MLLT1 CSDE1 ZNF687 ZSCAN21 CHD4 ENSG00000285238 ZNF384 ENSG00000219410 ENSG00000247853 NCAPD2 NOP2 EMG1 ING4 SPSB2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LAG3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the LAG3 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA
  • AREB6
  • p300
  • STAT3
  • TBP
  • Zic1

Genomic Locations for LAG3 Gene

Genomic Locations for LAG3 Gene
chr12:6,772,483-6,778,455
(GRCh38/hg38)
Size:
5,973 bases
Orientation:
Plus strand
chr12:6,881,670-6,887,621
(GRCh37/hg19)
Size:
5,952 bases
Orientation:
Plus strand

Genomic View for LAG3 Gene

Genes around LAG3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LAG3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LAG3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LAG3 Gene

Proteins for LAG3 Gene

  • Protein details for LAG3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P18627-LAG3_HUMAN
    Recommended name:
    Lymphocyte activation gene 3 protein
    Protein Accession:
    P18627
    Secondary Accessions:
    • A8K7T9
    • Q7Z643

    Protein attributes for LAG3 Gene

    Size:
    525 amino acids
    Molecular mass:
    57449 Da
    Quaternary structure:
    • Interacts with MHC class II (MHC-II); selectively recognizes stable complexes of peptide and MHC-II (PubMed:1692078, PubMed:7589152, PubMed:8647185, PubMed:9159144). Interacts with FGL1 (via the Fibrinogen C-terminal domain) (PubMed:30580966).

    Alternative splice isoforms for LAG3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LAG3 Gene

Post-translational modifications for LAG3 Gene

  • Lymphocyte activation gene 3 protein: Proteolytically cleaved by ADAM10 and ADAM17 within the connecting peptide region, leading to release of Secreted lymphocyte activation gene 3 protein (sLAG-3). ADAM10 mediates constitutive cleavage, but cleavage increases following T-cell activation, whereas shedding by ADAM17 is induced by TCR signaling in a PRKCQ-dependent manner.
  • Glycosylation at isoforms=2343, posLast=250250, isoforms=2188, and posLast=256256
  • Modification sites at PhosphoSitePlus

Other Protein References for LAG3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Santa Cruz Biotechnology (SCBT) Antibodies for LAG3

Protein Products

No data available for DME Specific Peptides for LAG3 Gene

Domains & Families for LAG3 Gene

Gene Families for LAG3 Gene

HGNC:
Human Protein Atlas (HPA):
  • CD markers
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for LAG3 Gene

Suggested Antigen Peptide Sequences for LAG3 Gene

GenScript: Design optimal peptide antigens:
  • Protein FDC (LAG3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P18627

UniProtKB/Swiss-Prot:

LAG3_HUMAN :
  • Lymphocyte activation gene 3 protein: The KIEELE motif is required for interaction with downstream signaling molecules.
  • Belongs to the LAG3 family.
Domain:
  • Lymphocyte activation gene 3 protein: The KIEELE motif is required for interaction with downstream signaling molecules.
Family:
  • Belongs to the LAG3 family.
genes like me logo Genes that share domains with LAG3: view

Function for LAG3 Gene

Molecular function for LAG3 Gene

UniProtKB/Swiss-Prot Function:
Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Delivers inhibitory signals upon binding to ligands, such as FGL1 (By similarity). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (By similarity). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:7805750, PubMed:8647185, PubMed:20421648). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (By similarity). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (By similarity). Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:8647185).
UniProtKB/Swiss-Prot Function:
Secreted lymphocyte activation gene 3 protein: May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response.
UniProtKB/Swiss-Prot Induction:
Expression is induced by interleukin-2 (IL2), interleukin-7 (IL7) and interleukin-12 (IL12A and IL12B) on activated T-cells.
GENATLAS Biochemistry:
lymphocyte activation gene-3,with three transcriptional initiation sites,highly homolog to CD4,expressed exclusively in activated T and NK lymphocytes,major histocompatibility complex (MHC) class 2 ligand potentially involved in the regulation of immune response

Phenotypes From GWAS Catalog for LAG3 Gene

Gene Ontology (GO) - Molecular Function for LAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003823 antigen binding TAS 1692078
GO:0004888 transmembrane signaling receptor activity IEA,IBA 21873635
GO:0005515 protein binding IPI 30580966
GO:0042289 MHC class II protein binding IDA 9159144
genes like me logo Genes that share ontologies with LAG3: view
genes like me logo Genes that share phenotypes with LAG3: view

Animal Models for LAG3 Gene

MGI Knock Outs for LAG3:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LAG3

Clone Products

  • Applied Biological Materials (abm): Clones for LAG3 - Now 50% OFF >
  • * LAG3 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * LAG3 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for LAG3 Gene

Localization for LAG3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LAG3 Gene

Lymphocyte activation gene 3 protein: Cell membrane; Single-pass type I membrane protein.
Secreted lymphocyte activation gene 3 protein: Secreted. Note=Produced following cleavage of the main chain. {ECO:0000250 UniProtKB:Q61790}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LAG3 gene
Compartment Confidence
plasma membrane 5
extracellular 4
mitochondrion 1
peroxisome 1
nucleus 1
endoplasmic reticulum 1
cytosol 1

Gene Ontology (GO) - Cellular Components for LAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005886 plasma membrane TAS --
GO:0009897 external side of plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with LAG3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for LAG3 Gene

Pathways & Interactions for LAG3 Gene

genes like me logo Genes that share pathways with LAG3: view

Pathways by source for LAG3 Gene

1 Cell Signaling Technology pathway for LAG3 Gene

Interacting Proteins for LAG3 Gene

Gene Ontology (GO) - Biological Process for LAG3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002250 adaptive immune response IEA --
GO:0002270 plasmacytoid dendritic cell activation ISS --
GO:0007166 cell surface receptor signaling pathway ISS,IEA --
GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II TAS --
GO:0045085 negative regulation of interleukin-2 biosynthetic process IEA --
genes like me logo Genes that share ontologies with LAG3: view

No data available for SIGNOR curated interactions for LAG3 Gene

Transcripts for LAG3 Gene

mRNA/cDNA for LAG3 Gene

(1) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(4) Selected AceView cDNA sequences:
(4) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Unigene Clusters for LAG3 Gene

Lymphocyte-activation gene 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LAG3

Clone Products

  • Applied Biological Materials (abm): Clones for LAG3 - Now 50% OFF >
  • * LAG3 as ready-to-use vector or virus: ORF | Lenti- | Retro- | Adeno- | AAV- | Protein Vector - Browse All
  • * LAG3 tags and reporters available: His, HA, Myc, Flag, GFP, RFP, Luciferase - Browse All

Alternative Splicing Database (ASD) splice patterns (SP) for LAG3 Gene

No ASD Table

Relevant External Links for LAG3 Gene

GeneLoc Exon Structure for
LAG3
ECgene alternative splicing isoforms for
LAG3

Expression for LAG3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for LAG3 Gene

mRNA differential expression in normal tissues according to GTEx for LAG3 Gene

This gene is overexpressed in Ovary (x6.9), Spleen (x6.3), and Whole Blood (x4.8).

NURSA nuclear receptor signaling pathways regulating expression of LAG3 Gene:

LAG3

SOURCE GeneReport for Unigene cluster for LAG3 Gene:

Hs.409523

mRNA Expression by UniProt/SwissProt for LAG3 Gene:

P18627-LAG3_HUMAN
Tissue specificity: Primarily expressed in activated T-cells and a subset of natural killer (NK) cells.

Evidence on tissue expression from TISSUES for LAG3 Gene

  • Spleen(4.5)
  • Blood(2.5)
  • Lymph node(2.5)
genes like me logo Genes that share expression patterns with LAG3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for LAG3 Gene

Orthologs for LAG3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for LAG3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LAG3 35 34
  • 99.2 (n)
OneToOne
cow
(Bos Taurus)
Mammalia LAG3 35 34
  • 82.47 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Lag3 17 35 34
  • 79.36 (n)
rat
(Rattus norvegicus)
Mammalia Lag3 34
  • 78.55 (n)
dog
(Canis familiaris)
Mammalia LAG3 35
  • 64 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia LAG3 35
  • 48 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LAG3 35
  • 36 (a)
OneToOne
chicken
(Gallus gallus)
Aves LAG3 35 34
  • 48.16 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LAG3 35
  • 27 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia lag3 34
  • 43.9 (n)
Species where no ortholog for LAG3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for LAG3 Gene

ENSEMBL:
Gene Tree for LAG3 (if available)
TreeFam:
Gene Tree for LAG3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LAG3: view image

Paralogs for LAG3 Gene

genes like me logo Genes that share paralogs with LAG3: view

Variants for LAG3 Gene

Sequence variations from dbSNP and Humsavar for LAG3 Gene

SNP ID Clin Chr 12 pos Variation AA Info Type
rs1000009184 -- 6,772,489(+) G/A 5_prime_UTR_variant, genic_upstream_transcript_variant, upstream_transcript_variant
rs1000012718 -- 6,777,672(+) T/C intron_variant
rs1003580236 -- 6,771,452(+) T/C upstream_transcript_variant
rs1003858223 -- 6,777,167(+) C/T intron_variant
rs1003991491 -- 6,773,777(+) C/G coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for LAG3 Gene

Variant ID Type Subtype PubMed ID
dgv2323n54 CNV loss 21841781
esv3580394 CNV gain 25503493
nsv557257 CNV loss 21841781
nsv593 CNV deletion 18451855
nsv832323 CNV loss 17160897

Variation tolerance for LAG3 Gene

Residual Variation Intolerance Score: 75.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.05; 50.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LAG3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
LAG3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LAG3 Gene

Disorders for LAG3 Gene

Additional Disease Information for LAG3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for LAG3 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for LAG3 Gene

Publications for LAG3 Gene

  1. LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites. (PMID: 20421648) Camisaschi C … Castelli C (Journal of immunology (Baltimore, Md. : 1950) 2010) 3 4 23 58
  2. Regulation of expression of the human lymphocyte activation gene-3 (LAG-3) molecule, a ligand for MHC class II. (PMID: 9634475) Bruniquel D … Triebel F (Immunogenetics 1998) 3 4 23 58
  3. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. (PMID: 9159144) Huard B … Triebel F (Proceedings of the National Academy of Sciences of the United States of America 1997) 3 4 23 58
  4. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. (PMID: 1380059) Baixeras E … Piatier-Tonneau D (The Journal of experimental medicine 1992) 3 4 23 58
  5. LAG-3, a novel lymphocyte activation gene closely related to CD4. (PMID: 1692078) Triebel F … Hercend T (The Journal of experimental medicine 1990) 3 4 23 58

Products for LAG3 Gene

Sources for LAG3 Gene

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