LAG3

Protein identityUniProt · HPA

UniProt accession

P18627

Gene

LAG3

Ensembl

ENSG00000089692

Chromosome

12

Canonical length

525 aa

Protein class

CD markers, FDA approved drug targets, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

525 residues, UniProt reviewed canonical sequence.

>P18627|LAG3
     1  MWEAQFLGLL FLQPLWVAPV KPLQPGAEVP VVWAQEGAPA QLPCSPTIPL QDLSLLRRAG
    61  VTWQHQPDSG PPAAAPGHPL APGPHPAAPS SWGPRPRRYT VLSVGPGGLR SGRLPLQPRV
   121  QLDERGRQRG DFSLWLRPAR RADAGEYRAA VHLRDRALSC RLRLRLGQAS MTASPPGSLR
   181  ASDWVILNCS FSRPDRPASV HWFRNRGQGR VPVRESPHHH LAESFLFLPQ VSPMDSGPWG
   241  CILTYRDGFN VSIMYNLTVL GLEPPTPLTV YAGAGSRVGL PCRLPAGVGT RSFLTAKWTP
   301  PGGGPDLLVT GDNGDFTLRL EDVSQAQAGT YTCHIHLQEQ QLNATVTLAI ITVTPKSFGS
   361  PGSLGKLLCE VTPVSGQERF VWSSLDTPSQ RSFSGPWLEA QEAQLLSQPW QCQLYQGERL
   421  LGAAVYFTEL SSPGAQRSGR APGALPAGHL LLFLILGVLS LLLLVTGAFG FHLWRRQWRP
   481  RRFSALEQGI HPPQAQSKIE ELEQEPEPEP EPEPEPEPEP EPEQL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LAG3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

22 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for LAG3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.5

gnomAD pLI

0.28

gnomAD missense Z

0.51

DepMap mean gene effect

-0.04

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adaptive immune response
• cell surface receptor signaling pathway
• innate immune response
• natural killer cell mediated cytotoxicity
• negative regulation of interleukin-2 production
• negative regulation of regulatory T cell differentiation
• negative regulation of T cell activation
• negative regulation of T cell mediated immune response to tumor cell
• negative regulation of T cell receptor signaling pathway
• plasmacytoid dendritic cell activation
• positive regulation of natural killer cell mediated cytotoxicity
• regulation of immune response
• T cell activation

Molecular functions

• antigen binding
• MHC class II protein binding
• transmembrane signaling receptor activity

Cellular components

• cell surface
• external side of plasma membrane
• extracellular region
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin-like fold
• Interleukin-1 receptor family
• Immunoglobulin-like domain superfamily

KeywordsUniProt

• Adaptive immunity
• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunity
• Immunoglobulin domain
• Isopeptide bond
• Membrane
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of LAG3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD3E