LAG3_RAT
ID LAG3_RAT Reviewed; 525 AA.
AC Q5BK54;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Lymphocyte activation gene 3 protein;
DE Short=LAG-3;
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Lewis.1W;
RA Haudebourg T., Coulon F., Vanhove B.;
RT "Coding sequence of rat LAG-3 (CD223), LEWIS.1W (RT1u) strain.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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).
CC -!- FUNCTION: Lymphocyte activation gene 3 protein: Inhibitory receptor on
CC antigen activated T-cells. Delivers inhibitory signals upon binding to
CC ligands, such as FGL1. FGL1 constitutes a major ligand of LAG3 and is
CC responsible for LAG3 T-cell inhibitory function. Following TCR
CC engagement, LAG3 associates with CD3-TCR in the immunological synapse
CC and directly inhibits T-cell activation. May inhibit antigen-specific
CC T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a
CC coreceptor for PDCD1/PD-1. Negatively regulates the proliferation,
CC activation, effector function and homeostasis of both CD8(+) and CD4(+)
CC T-cells. Also mediates immune tolerance: constitutively expressed on a
CC subset of regulatory T-cells (Tregs) and contributes to their
CC suppressive function. Also acts as a negative regulator of plasmacytoid
CC dendritic cell (pDCs) activation. Binds MHC class II (MHC-II); the
CC precise role of MHC-II-binding is however unclear.
CC {ECO:0000250|UniProtKB:Q61790}.
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. Interacts with FGL1 (via the
CC Fibrinogen C-terminal domain). {ECO:0000250|UniProtKB:Q61790}.
CC -!- SUBCELLULAR LOCATION: [Lymphocyte activation gene 3 protein]: Cell
CC membrane {ECO:0000250|UniProtKB:Q61790}; Single-pass type I membrane
CC protein {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 -!- 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; DQ438937; ABE68618.1; -; mRNA.
DR EMBL; BC091201; AAH91201.1; -; mRNA.
DR RefSeq; NP_997678.2; NM_212513.2.
DR RefSeq; XP_008761504.1; XM_008763282.2.
DR AlphaFoldDB; Q5BK54; -.
DR STRING; 10116.ENSRNOP00000036771; -.
DR GlyGen; Q5BK54; 3 sites.
DR PaxDb; Q5BK54; -.
DR PRIDE; Q5BK54; -.
DR Ensembl; ENSRNOT00000028965; ENSRNOP00000036771; ENSRNOG00000021334.
DR GeneID; 297596; -.
DR KEGG; rno:297596; -.
DR UCSC; RGD:1302990; rat.
DR CTD; 3902; -.
DR RGD; 1302990; Lag3.
DR eggNOG; ENOG502S2HD; Eukaryota.
DR GeneTree; ENSGT01050000244846; -.
DR HOGENOM; CLU_041154_1_0_1; -.
DR InParanoid; Q5BK54; -.
DR OMA; LWVAPVE; -.
DR OrthoDB; 862925at2759; -.
DR PhylomeDB; Q5BK54; -.
DR TreeFam; TF335942; -.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR PRO; PR:Q5BK54; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000021334; Expressed in thymus and 14 other tissues.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042289; F:MHC class II protein binding; ISO:RGD.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0045590; P:negative regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISO:RGD.
DR GO; GO:0002270; P:plasmacytoid dendritic cell activation; ISS:UniProtKB.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:RGD.
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; IPR003598; Ig_sub2.
DR InterPro; IPR015621; IL-1_rcpt_fam.
DR InterPro; IPR013151; Immunoglobulin.
DR PANTHER; PTHR11890; PTHR11890; 1.
DR Pfam; PF00047; ig; 2.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 2.
DR SUPFAM; SSF48726; SSF48726; 3.
DR PROSITE; PS50835; IG_LIKE; 2.
PE 2: Evidence at transcript level;
KW Adaptive immunity; Cell membrane; Disulfide bond; Glycoprotein; Immunity;
KW Immunoglobulin domain; Membrane; Reference proteome; Repeat; Secreted;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..525
FT /note="Lymphocyte activation gene 3 protein"
FT /id="PRO_0000253042"
FT CHAIN 24..?
FT /note="Secreted lymphocyte activation gene 3 protein"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT /id="PRO_0000446644"
FT TOPO_DOM 24..442
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..525
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..163
FT /note="Ig-like V-type"
FT DOMAIN 164..246
FT /note="Ig-like C2-type 1"
FT DOMAIN 258..341
FT /note="Ig-like C2-type 2"
FT DOMAIN 345..412
FT /note="Ig-like C2-type 3"
FT REGION 37..246
FT /note="Interaction with FGL1"
FT /evidence="ECO:0000250|UniProtKB:P18627"
FT REGION 422..442
FT /note="Connecting peptide"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT REGION 483..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..522
FT /note="15 X 2 AA tandem repeats of E-X"
FT MOTIF 490..495
FT /note="KIEELE motif"
FT /evidence="ECO:0000250|UniProtKB:Q61790"
FT COMPBIAS 498..515
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 185..235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 276..327
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 363..405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 525 AA; 57988 MW; 13CA457327052C4E CRC64;
MRQDLFLDLL LLQLLWEAPV VSSGPGKELS VVWAQEGAPV HLPCSLEFPH LDPNFLRRGW
VTWQHRPDSD QPASIPALDL LQGMPSTRRH PPHRYTVLSV APGGLRSGRQ PLLSHVQLEK
RGPQRGDFSL WLRPATRKDA GEYHAFVRLP DRDFSCSLRL RVGQASMIAS PPGTLKPSDW
VILNCSFSRP DRPVSVHWFQ GQSRVPVHNS PRHYLAESFL LLPQVSPLDS GTWGCVLTYR
DGFNVSITYN LKVQGLEPVA PLTVYAAEGS RVELPCHLPP VVGTPSLLIA KWTPPGGGPE
LPVTGKSGNF TLQLENVGRA QAGTYTCSIH LQGRQLSAAV TLAVITVTPK SFGLPGSPQK
LLCEVVPASG EGRFVWRPLS DLSRSSLGPV LELQEAKLLA EQWQCQLYEG QKLLGATVYT
AESSSGAWSA KRISGDLKGG HLFLSLILGA LALFLLVTGA FGFHLWRRQL LRRRFSALEH
GIRPPPVQSK IEELEREPET EMEPETEPDP EPQPEPELEP ESRQL
