General Information of Target

Target ID LDTP09447
Target Name Hepatitis A virus cellular receptor 2 (HAVCR2)
Gene Name HAVCR2
Gene ID 84868
Synonyms
TIM3; TIMD3; Hepatitis A virus cellular receptor 2; HAVcr-2; T-cell immunoglobulin and mucin domain-containing protein 3; TIMD-3; T-cell immunoglobulin mucin receptor 3; TIM-3; T-cell membrane protein 3; CD antigen CD366
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPV
FECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMND
EKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLA
NELRDSRLANDLRDSGATIRIGIYIGAGICAGLALALIFGALIFKWYSHSKEKIQNLSLI
SLANLPPSGLANAVAEGIRSEENIYTIEENVYEVEEPNEYYCYVSSRQQPSQPLGCRFAM
P
Target Type
Clinical trial
Target Bioclass
Immunoglobulin
Family
Immunoglobulin superfamily, TIM family
Subcellular location
Membrane
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. 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. 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. 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. 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.
TTD ID
T76233
Uniprot ID
Q8TDQ0
DrugMap ID
TT1RWL7
Ensemble ID
ENST00000307851.9
HGNC ID
HGNC:18437
ChEMBL ID
CHEMBL4630879

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
DANG SNV: p.Y77D .
HT SNV: p.L245P .
MDAMB231 SNV: p.D170H .
MOLT4 SNV: p.T198I .
NCIH1793 SNV: p.W53L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info 
C296(7.11)  LDD1704  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 T cell-activated C296(7.11)  LDD1704  [1]
 LDCM0024  KB05 T cell C296(7.63)  LDD1705  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Lysoplasmalogenase TMEM86A (TMEM86A) TMEM86 family Q8N2M4
Immunoglobulin
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) CEA family P13688
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Vesicle-trafficking protein SEC22a (SEC22A) Synaptobrevin family Q96IW7

The Drug(s) Related To This Target

Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Mbg453 . D0AE6Q
Phase 2
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bgb-a425 Antibody D7UIZ1
Gsk4069889 Antibody DZW53X
Ro7121661 Antibody DQM48O
Phase 1
Click To Hide/Show 4 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Incagn2390 Antibody DVA36E
Ly3415244 Antibody DC8HR6
Sym023 Antibody DEU8O6
Ly3321367 . D09YXT

References

1 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.