Lag3
entrez
16768
canonical
uniprot
Q61790
canonical
ensembl
ENSMUSG00000030124
resolver
ensp
ENSMUSP00000032217
resolver
enst
ENSMUST00000032217
resolver
genesymbol
Lag3
resolver
uniprot
Q0VBL2
resolver
uniprot_entry
LAG3_MOUSE
resolver
uniprot_sec
Q0VBL2
resolver
amino_acid_sequence
MREDLLLGFLLLGLLWEAPVVSSGPGKELPVVWAQEGAPVHLPCSLKSPNLDPNFLRRGGVIWQHQPDSGQPTPIPALDLHQGMPSPRQPAPGRYTVLSVAPGGLRSGRQPLHPHVQLEERGLQRGDFSLWLRPALRTDAGEYHATVRLPNRALSCSLRLRVGQASMIASPSGVLKLSDWVLLNCSFSRPDRPVSVHWFQGQNRVPVYNSPRHFLAETFLLLPQVSPLDSGTWGCVLTYRDGFNVSITYNLKVLGLEPVAPLTVYAAEGSRVELPCHLPPGVGTPSLLIAKWTPPGGGPELPVAGKSGNFTLHLEAVGLAQAGTYTCSIHLQGQQLNATVTLAVITVTPKSFGLPGSRGKLLCEVTPASGKERFVWRPLNNLSRSCPGPVLEIQEARLLAERWQCQLYEGQRLLGATVYAAESSSGAHSARRISGDLKGGHLVLVLILGALSLFLLVAGAFGFHWWRKQLLLRRFSALEHGIQPFPAQRKIEELERELETEMGQEPEPEPEPQLEPEPRQL
uniprot
proteins
function
FUNCTION: [Lymphocyte activation gene 3 protein]: Inhibitory receptor on antigen activated T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887, PubMed:30580966, PubMed:35413245, PubMed:35761082, PubMed:38483996, PubMed:39209860). Delivers inhibitory signals upon binding to ligands, such as MHC class II, its main ligand present at the surface of antigen-presenting cells (APCs), and FGL1, which is secreted by hepatocytes and certain types of tumor cells (PubMed:12209638, PubMed:12421911, PubMed:30349037, PubMed:30580966, PubMed:35413245, PubMed:35761082, PubMed:39209860). Ligand-binding initiates a signaling that inhibits the T-cell receptor (TCR) in the immunological synapse, preventing T-cell activation (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). Mechanistically, ligand-binding promotes (1) ubiquitination of the KIEELE motif, unleashing the RRFSALE motif from the membrane and (2) leading to the formation of condensates with the TCR component CD3E, thereby disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:40101708, PubMed:40592325). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1 (PubMed:21300912). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (PubMed:15485628). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (PubMed:19201841). {ECO:0000269|PubMed:12209638, ECO:0000269|PubMed:12421911, ECO:0000269|PubMed:12672063, ECO:0000269|PubMed:15100286, ECO:0000269|PubMed:15485628, ECO:0000269|PubMed:15634887, ECO:0000269|PubMed:19201841, ECO:0000269|PubMed:21300912, ECO:0000269|PubMed:30349037, ECO:0000269|PubMed:30580966, ECO:0000269|PubMed:35413245, ECO:0000269|PubMed:35761082, ECO:0000269|PubMed:38483996, ECO:0000269|PubMed:39209860, ECO:0000269|PubMed:40101708, ECO:0000269|PubMed:40592325}.; FUNCTION: The LAG3-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival. {ECO:0000269|PubMed:35413245}.; 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. {ECO:0000269|PubMed:11937541}.
uniprot
proteins
mass_dalton
56978
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="L->Q: Abolished binding to FGL1 without affecting binding to MHC class II; does not affect ability to inhibit T-cell activation; when associated with A-20 and E-27."; /evidence="ECO:0000269|PubMed:35413245"; MUTAGEN 20; /note="V->A: Abolished binding to FGL1 without affecting binding to MHC class II; does not affect ability to inhibit T-cell activation; when associated with Q-14 and E-27."; /evidence="ECO:0000269|PubMed:35413245"; MUTAGEN 27; /note="K->E: Abolished binding to FGL1 without affecting binding to MHC class II; does not affect ability to inhibit T-cell activation; when associated with Q-14 and A-20."; /evidence="ECO:0000269|PubMed:35413245"; MUTAGEN 94; /note="R->E: Decreased binding to MHC class II."; /evidence="ECO:0000269|PubMed:12421911"; MUTAGEN 95; /note="Y->F: No significant effect on MHC class II-binding."; /evidence="ECO:0000269|PubMed:12421911"; MUTAGEN 103; /note="G->R: Abolished binding to MHC class II without affecting binding to FGL1; abolished ability to inhibit T-cell activation; when associated with A-111."; /evidence="ECO:0000269|PubMed:35413245, ECO:0000269|PubMed:39209860"; MUTAGEN 106; /note="R->A: Abolished binding to MHC class II."; /evidence="ECO:0000269|PubMed:39209860"; MUTAGEN 111; /note="P->A: Abolished binding to MHC class II without affecting binding to FGL1; abolished ability to inhibit T-cell activation; when associated with R-103."; /evidence="ECO:0000269|PubMed:35413245, ECO:0000269|PubMed:39209860"; MUTAGEN 121; /note="R->A: No significant effect on MHC class II-binding."; /evidence="ECO:0000269|PubMed:12421911"; MUTAGEN 125; /note="R->A: Decreased binding to MHC class II."; /evidence="ECO:0000269|PubMed:39209860"; MUTAGEN 180; /note="W->D: Decreased homodimerization."; /evidence="ECO:0000269|PubMed:38483996"; MUTAGEN 184; /note="N->Q: Slightly decreased homodimerization."; /evidence="ECO:0000269|PubMed:38483996"; MUTAGEN 475..478; /note="FSAL->ASAA: Abolished ability to prevent TCR activation."; /evidence="ECO:0000269|PubMed:40592325"; MUTAGEN 490; /note="K->A: Abolished ability to inhibit T-cell activation."; /evidence="ECO:0000269|PubMed:12421911"; MUTAGEN 490; /note="K->R: Knockin mice show abolished ubiquitination."; /evidence="ECO:0000269|PubMed:40101708
uniprot
proteins
post_translational_modification
PTM: [Lymphocyte activation gene 3 protein]: Ubiquitinated by CBL and CBLB in response to ligand-binding, initiating a signaling that prevents TCR activation: ubiquitination at Lys-490 via 'Lys-63'-linked ubiquitin chains unleashes the RRFSALE motif from the membrane (PubMed:40101708). MHC class II and membrane-bound FGL1 promote ubiquitination by CBL and CBLB; in contrast secreted FGL1 is not able to trigger LAG3 ubiquitination (By similarity). {ECO:0000250|UniProtKB:P18627, ECO:0000269|PubMed:40101708}.; PTM: [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) (PubMed:17245433). 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 (PubMed:17245433). {ECO:0000269|PubMed:17245433}.
uniprot
proteins
protein_family
LAG3 family
uniprot
proteins
pubmed
11937541
uniprot
proteins
pubmed
12209638
uniprot
proteins
pubmed
12421911
uniprot
proteins
pubmed
12672063
uniprot
proteins
pubmed
15100286
uniprot
proteins
pubmed
15485628
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15557174
uniprot
proteins
pubmed
15634887
uniprot
proteins
pubmed
17245433
uniprot
proteins
pubmed
19201841
uniprot
proteins
pubmed
21300912
uniprot
proteins
pubmed
21873518
uniprot
proteins
pubmed
30349037
uniprot
proteins
pubmed
30580966
uniprot
proteins
pubmed
35413245
uniprot
proteins
pubmed
35761082
uniprot
proteins
pubmed
38483996
uniprot
proteins
pubmed
39209860
uniprot
proteins
pubmed
40101708
uniprot
proteins
pubmed
40592325
uniprot
proteins
pubmed
8602528
uniprot
proteins
pubmed
8921170
uniprot
proteins
sequence_length
521
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Lymphocyte activation gene 3 protein]: Cell membrane {ECO:0000269|PubMed:35761082, ECO:0000269|PubMed:8602528}; Single-pass type I membrane protein {ECO:0000269|PubMed:35761082}. Note=Clusters on the T-cell surface following ligand-binding. {ECO:0000269|PubMed:35761082}.; SUBCELLULAR LOCATION: [Secreted lymphocyte activation gene 3 protein]: Secreted {ECO:0000269|PubMed:15557174, ECO:0000269|PubMed:17245433}. Note=Produced following cleavage of the main chain. {ECO:0000269|PubMed:17245433}.
uniprot
proteins
transmembrane_region
TRANSMEM 443..463; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins