HAVCR2
entrez
84868
canonical
uniprot
Q8TDQ0
canonical
ensembl
ENSG00000135077
resolver
ensp
ENSP00000312002
resolver
genesymbol
HAVCR2
resolver
genesymbol_syn
TIM3
resolver
genesymbol_syn
TIMD3
resolver
hgnc
HGNC:18437
resolver
uniprot
B2RAY2
resolver
uniprot
Q8WW60
resolver
uniprot
Q96K94
resolver
uniprot_entry
HAVR2_HUMAN
resolver
uniprot_sec
B2RAY2
resolver
uniprot_sec
Q8WW60
resolver
uniprot_sec
Q96K94
resolver
amino_acid_sequence
MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDINLTQISTLANELRDSRLANDLRDSGATIRIGIYIGAGICAGLALALIFGALIFKWYSHSKEKIQNLSLISLANLPPSGLANAVAEGIRSEENIYTIEENVYEVEEPNEYYCYVSSRQQPSQPLGCRFAMP
uniprot
proteins
disease_involvement
DISEASE: Note=May be involved in T-cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV). {ECO:0000269|PubMed:19001139, ECO:0000269|PubMed:19587053}.; DISEASE: T-cell lymphoma, subcutaneous panniculitis-like (SPTCL) [MIM:618398]: An uncommon form of T-cell non-Hodgkin lymphoma, in which cytotoxic CD8+ T-cells infiltrate subcutaneous adipose tissue, and rimming adipocytes in a lace-like pattern. Affected individuals typically present with multiple subcutaneous nodules, systemic B-cell symptoms, and, in a subset of cases, autoimmune disorders, most commonly systemic lupus erythematosus. A subset of patients develop hemophagocytic lymphohistiocytosis. SPTCL transmission pattern is consistent with autosomal recessive inheritance with incomplete penetrance. {ECO:0000269|PubMed:30374066, ECO:0000269|PubMed:30792187, ECO:0000269|Ref.2}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
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:24825777). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005). 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 (PubMed:24337741, PubMed:26492563). 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 (PubMed:24838857). Receptor for LGALS9 (PubMed:16286920, PubMed:24337741). 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 (PubMed:23555261). 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. 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 (By similarity). Expressed on natural killer (NK) cells and acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453). In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801). Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity). {ECO:0000250|UniProtKB:Q8VIM0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556005, ECO:0000269|PubMed:16286920, ECO:0000269|PubMed:22323453, ECO:0000269|PubMed:23555261, ECO:0000269|PubMed:24838857, ECO:0000269|PubMed:26492563, ECO:0000269|PubMed:30374066, ECO:0000305|PubMed:24825777}.
uniprot
proteins
mass_dalton
33394
uniprot
proteins
mutagenesis
MUTAGEN 265; /note="Y->A: Abolishes TCR-induced NFAT activation; when associated with A-272."; /evidence="ECO:0000269|PubMed:26492563"; MUTAGEN 265; /note="Y->E: No effect on TCR-induced NFAT activation (phosphomimetic mutation); when associated with E-272."; /evidence="ECO:0000269|PubMed:26492563"; MUTAGEN 272; /note="Y->A: Abolishes TCR-induced NFAT activation; when associated with A-265."; /evidence="ECO:0000269|PubMed:26492563"; MUTAGEN 272; /note="Y->E: No effect on TCR-induced NFAT activation (phosphomimetic mutation); when associated with E-265."; /evidence="ECO:0000269|PubMed:26492563"; MUTAGEN 296; /note="C->A: Higher amount of polyubiquitination."; /evidence="ECO:0000269|PubMed:39546589
uniprot
proteins
post_translational_modification
PTM: O-glycosylated with core 1 or possibly core 8 glycans. {ECO:0000269|PubMed:22171320}.; PTM: Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmic domain by FYN (By similarity). Phosphorylation at Tyr-265 is increased by stimulation with ligand LGALS9. {ECO:0000250|UniProtKB:Q8VIM0, ECO:0000269|PubMed:17069754, ECO:0000269|PubMed:24337741}.; PTM: Palmitoylated by ZDHHC9 at Cys-296; palmitoylation stabilizes HAVCR2 by preventing binding to E3 ubiquitin ligase SYVN1, thereby suppressing its polyubiquitination and degradation. {ECO:0000269|PubMed:39546589}.; PTM: Ubiquitinated by SYVN1, leading to polyubiquitination and proteasomal degradation. {ECO:0000269|PubMed:39546589}.
uniprot
proteins
protein_family
Immunoglobulin superfamily
uniprot
proteins
protein_family
TIM family
uniprot
proteins
pubmed
11823861
uniprot
proteins
pubmed
14556005
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16286920
uniprot
proteins
pubmed
17069754
uniprot
proteins
pubmed
18006747
uniprot
proteins
pubmed
19001139
uniprot
proteins
pubmed
19587053
uniprot
proteins
pubmed
20083673
uniprot
proteins
pubmed
22171320
uniprot
proteins
pubmed
22323453
uniprot
proteins
pubmed
22383801
uniprot
proteins
pubmed
23555261
uniprot
proteins
pubmed
24337741
uniprot
proteins
pubmed
24825777
uniprot
proteins
pubmed
24838857
uniprot
proteins
pubmed
26492563
uniprot
proteins
pubmed
30374066
uniprot
proteins
pubmed
30429576
uniprot
proteins
pubmed
30792187
uniprot
proteins
pubmed
34110282
uniprot
proteins
pubmed
39546589
uniprot
proteins
sequence_length
301
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:39546589}; Single-pass type I membrane protein {ECO:0000305}. Cell junction {ECO:0000269|PubMed:24337741}. Cell membrane {ECO:0000269|PubMed:30374066}. Note=Localizes to the immunological synapse between CD8+ T-cells and target cells. {ECO:0000269|PubMed:24337741}.
uniprot
proteins
transmembrane_region
TRANSMEM 203..223; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins