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HAVCR2
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  • HAVCR2
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
Hippocampal formation Amygdala Basal ganglia Midbrain Spinal cord Cerebral cortex Cerebellum Hypothalamus Choroid plexus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Duodenum Small intestine Colon Rectum Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Thymus Tonsil Appendix Spleen Lymph node
HAVCR2 INFORMATION
Proteini

Full gene name according to HGNC.

Hepatitis A virus cellular receptor 2
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

HAVCR2 (CD366, FLJ14428, Tim-3, TIM3, TIMD3)
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

CD markers
Disease related genes
Protein evidence Evidence at protein level (all genes)
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

9
Protein interactions Interacting with 3 proteins
PROTEIN EXPRESSION AND LOCALIZATION
Tissue profilei

A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource.

"Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.
Cytoplasmic expression in a subset of lymphoid cells.
Subcellular locationi

Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.

Not available
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Membrane, Intracellular (different isoforms)
TISSUE RNA EXPRESSION
Tissue specificityi

The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.

Low tissue specificity
Tissue expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Lymphoid tissue - Immune response (mainly)
Brain specificityi

The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category

Low human brain regional specificity
Brain expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Macrophages & Microglia - Immune response (mainly)
CELL TYPE RNA EXPRESSION
Single cell type specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Cell type enhanced (Hofbauer cells, NK-cells, Schwann cells, Macrophages, Langerhans cells, Kupffer cells, Proximal tubular cells, granulocytes, monocytes)
Single cell type
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Dendritic cells - Antigen presentation (mainly)
Tissue cell type classificationi

Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.

Core cell type enriched (Macrophages)
Immune cell specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Group enriched (myeloid DC, NK-cell, intermediate monocyte, classical monocyte, non-classical monocyte)
Immune cell
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Monocytes & Neutrophils - Degranulation (mainly)
CANCER & CELL LINES
Prognostic summary HAVCR2 is a prognostic marker in Kidney renal clear cell carcinoma
Cancer specificityi

Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.

Cancer enhanced (Kidney Renal Clear Cell Carcinoma)
Cell line
expression clusteri

The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Lymphoma - Inflammatory response (mainly)
Cell line specificityi

RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.

Cancer enhanced (Lymphoma)
PROTEINS IN BLOOD
Upregulated in diseasei

A gene is classified as upregulated in a disease if the average concentration of all samples of that disease is significantly higher (adj P-value<0.005 and NPX difference>=1) than the average concentration of samples of all diseases as measured by PEA . For gender specific diseases the analysis includes only samples corresponding to the same gender from the other diseases.

Staphylococcus aureus bacteremia, Streptococcal soft tissue infection, Malaria, E.coli pyelonephritis, Pneumococcal pneumonia, Chronic liver disease, Alcohol-related liver disease, Myositis, Pancreatic cancer, Viral hepatitis related cirrhosis, Hepatocellular cancer, Pediatric systemic inflammatory disease, Systemic lupus erythematosus, Pediatric kidney tumor, Acute myeloid leukemia, Dengue fever
Disease prediction modeli

The disease(s) the gene is associated with and able to predict according to glmnet prediction models. To be included the gene has to be upregulated according to differential expression analysis and have more than 50% overall importance as indicated by the prediction models.

No
Detected in blood by
immunoassayi

The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.

No (not applicable)
Detected in blood by
mass spectrometryi

Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.

Yes
Proximity extension assayi

Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years.

Read more
Data available (High detectability)
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

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 1. Regulates macrophage activation 2. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance 3. 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 4, 5. 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 6. Receptor for LGALS9 7, 8. 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 9. 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 10. In contrast, shown to suppress NK cell-mediated cytotoxicity 11. Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity).... show less
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Adaptive immunity, Immunity, Inflammatory response, Innate immunity
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Metal-binding
Gene summary (Entrez)i

Useful information about the gene from Entrez

The protein encoded by this gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]... show less

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