Havcr2
entrez
171285
canonical
uniprot
Q8VIM0
canonical
ensembl
ENSMUSG00000020399
resolver
ensp
ENSMUSP00000020668
resolver
genesymbol
Havcr2
resolver
genesymbol_syn
Tim3
resolver
genesymbol_syn
Timd3
resolver
uniprot_entry
HAVR2_MOUSE
resolver
amino_acid_sequence
MFSGLTLNCVLLLLQLLLARSLENAYVFEVGKNAYLPCSYTLSTPGALVPMCWGKGFCPWSQCTNELLRTDERNVTYQKSSRYQLKGDLNKGDVSLIIKNVTLDDHGTYCCRIQFPGLMNDKKLELKLDIKAAKVTPAQTAHGDSTTASPRTLTTERNGSETQTLVTLHNNNGTKISTWADEIKDSGETIRTAIHIGVGVSAGLTLALIIGVLILKWYSCKKKKLSSLSLITLANLPPGGLANAGAVRIRSEENIYTIEENVYEVENSNEYYCYVNSQQPS
uniprot
proteins
function
FUNCTION: Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits (By similarity). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses (By similarity). Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6 (PubMed:22863785). Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged (By similarity). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF (PubMed:18006747). In tumor-infiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells and acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity (By similarity). Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993). {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556006, ECO:0000269|PubMed:17620455, ECO:0000269|PubMed:18006747, ECO:0000269|PubMed:19224762, ECO:0000269|PubMed:20083673, ECO:0000269|PubMed:20937702, ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22842346, ECO:0000269|PubMed:24567532, ECO:0000269|PubMed:25337993, ECO:0000305|PubMed:22863785}.
uniprot
proteins
mass_dalton
30934
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="W->A: Greatly decreases phosphatidylserine binding."; /evidence="ECO:0000269|PubMed:20083673"; MUTAGEN 60..62; /note="WSQ->VFE: Decreases phosphatidylserine binding."; /evidence="ECO:0000269|PubMed:20083673"; MUTAGEN 62; /note="Q->A: No effect on phagocytic activity."; /evidence="ECO:0000269|PubMed:19224762"; MUTAGEN 112; /note="R->A: Abolishes phagocytic activity."; /evidence="ECO:0000269|PubMed:19224762"; MUTAGEN 118..119; /note="LM->AA: Decreases phosphatidylserine binding."; /evidence="ECO:0000269|PubMed:20083673"; MUTAGEN 120..121; /note="ND->AA: Decreases phosphatidylserine binding, abolishes phagocytic activity."; /evidence="ECO:0000269|PubMed:19224762, ECO:0000269|PubMed:20083673"; MUTAGEN 256; /note="Y->F: Abolishes phosphorylation, disrupts interaction with PIK3R1 and PIK3R2, no LGALS9-mediated disruption of interaction with BAG6; when associated with F-263."; /evidence="ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22863785"; MUTAGEN 263; /note="Y->F: Abolishes phosphorylation, disrupts interaction with PIK3R1 and PIK3R2, no LGALS9-mediated disruption of interaction with BAG6; when associated with F-256."; /evidence="ECO:0000269|PubMed:21807895, ECO:0000269|PubMed:22863785
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmic domain by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by stimulation with ligand LGALS9 (By similarity). {ECO:0000250|UniProtKB:Q8TDQ0, ECO:0000269|PubMed:21807895}.; PTM: N-glycosylated. {ECO:0000269|PubMed:21807895}.
uniprot
proteins
protein_family
Immunoglobulin superfamily
uniprot
proteins
protein_family
TIM family
uniprot
proteins
pubmed
11725301
uniprot
proteins
pubmed
11823861
uniprot
proteins
pubmed
14556006
uniprot
proteins
pubmed
17620455
uniprot
proteins
pubmed
18006747
uniprot
proteins
pubmed
19224762
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20083673
uniprot
proteins
pubmed
20937702
uniprot
proteins
pubmed
21807895
uniprot
proteins
pubmed
22842346
uniprot
proteins
pubmed
22863785
uniprot
proteins
pubmed
24567532
uniprot
proteins
pubmed
25337993
uniprot
proteins
sequence_length
281
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Cell junction {ECO:0000250|UniProtKB:Q8TDQ0}. Note=Localizes to the immunological synapse between CD8+ T-cells and target cells. {ECO:0000250|UniProtKB:Q8TDQ0}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:14556006}.
uniprot
proteins
transmembrane_region
TRANSMEM 194..214; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins