SCUBA

HAVCR2 — Hepatitis A virus cellular receptor 2

HAVCR2 belongs to a gene co-expression module in 6 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.

HAVCR2's module in each cell type

Cell typeModuleShares the module with
CD4⁺ T cellsCytotoxic effector
Cytotoxicity
ADGRG1, ATP8B4, CCL3, CCL4, CCL4L2, CSF2, FASLG, GNLY +10 moreView in SCUBA
CD8⁺ T cellsTerminal Exhaustion
Exhaustion
ACP5, CARD16, CASP1, CD2, CD247, CD8A, CD8B, CHST12 +6 moreView in SCUBA
Gamma-delta T cellsNK-like Mature gd-T
cytotoxicity
ABHD2, ATG9A, CEP78, HSH2D, IFIT2, ITGAX, KIR2DL1, KIR2DL3 +14 more
MacrophagesMonocyte-Mac Iron Transport
Iron metabolism
ARFIP1, BCL2L1, CDS2, CLPB, EHD4, GNB4, IVNS1ABP, MINDY2 +9 moreView in SCUBA
MonocytesMonocyte Immune Tolerance
Tissue adaptation
ATP1B3, CTSL, EMP1, FCER1G, FTH1, INSIG1, MALT1, TIMP1 +1 moreView in SCUBA
Natural Killer cellsNK Cell Exhaustion
Immune regulation
CEBPB, CEMIP2, DENND3, FMNL1, IFNGR1, METRNL, PDE4D, PRNP +3 moreView in SCUBA

About the gene

SynonymsCD366, FLJ14428, Tim-3, TIM3, TIMD3
Chromosome5: 157085422-157142869
Predicted locationIntracellular, Membrane
Essential geneNo
Protein classCD markers, Disease related genes, Predicted intracellular proteins, Predicted membrane proteins
Biological processAdaptive immunity, Immunity, Inflammatory response, Innate immunity

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. Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. 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, and/or LGALS9-dependent recruitment of PTPRC to the immunological synapse. In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity). Expressed on Treg cells can inhibit Th17 cell responses. 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. 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 (By similarity). However, the function as receptor for LGALS9 has been challenged. Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll- like receptors promotes secretion of TNF-alpha. In tumor-imfiltrating 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 (By similarity). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity. Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity).

Human Protein Atlas · Open Targets · UniProt

Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.