Biomarker: Flt-4

Histology type: endometrial carcinoma

Country: Japan

Region: Hirosaki,

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 49

Subgroup 2 name: negative

Subgroup 2 number: 37

Conclusion: Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : overexpression

Expression elevation: a score was established corresponding to the sum of: (1) the percentage of positive cells (0, 0% immunopositive cells; 1, ,25% positive cells; 2, 26–50% positive cells; and 3, .50% positive cells); and (2) the staining intensity (0, negative; 1, weak; 2, moderate; 3, high). The sum for the assigned values of the positive cell percentage (1) and the staining intensity (2) was less than 6. Scores between 0 and 2 were regarded as negative, scores of 3 and 4 as weakly positive, and scores of 5 and 6 as strongly positive.

Funtion Uniprot: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'.

UniProt ID: P35916

UniProt Link: https://www.uniprot.org/uniprotkb/P35916/entry

Biological function from UniProt: #Angiogenesis

Molecular function from UniProt:

Tissue specificity from UniProt: Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney.

Subcellular UniProt: #Cell membrane #Cytoplasm #Membrane #Nucleus #Secreted

Alternative name from UniProt:

Catalytic activity: ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]

Activity regulation: Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by MAZ51.

Recommended name: Vascular endothelial growth factor receptor 3

Gene name from HGNC: FLT4 (PCL, VEGFR-3, VEGFR3)

HPA class: Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Metabolic proteins Plasma proteins RAS pathway related proteins

AlphaFold DB: P35916

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P35916

HPA link: https://www.proteinatlas.org/ENSG00000037280-FLT4

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Cytoplasmic and membranous expression in most tissues, including endothelial cells.

Single cell type specificity Group enriched (Hepatic stellate cells, Extravillous trophoblasts, Adipocytes, Endothelial cells)

Immune cell specificity: Immune cell enriched (MAIT T-cell)

Subcellular summary HPA Located in Nuclear speckles, Plasma membrane, Cell Junctions

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000037280-FLT4/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000037280-FLT4/pathology/endometrial+cancer

Phenotype ID: 153100;602089;618780;

Disease: Lymphatic malformation 1 (LMPHM1);Hemangioma, capillary infantile (HCI);No disease ID;Congenital heart defects, multiple types, 7 (CHTD7);

Note1: The disease is caused by variants affecting the gene represented in this entry;Disease susceptibility is associated with variants affecting the gene represented in this entry;Plays an important role in tumor lymphangiogenesis, in cancer cell survival, migration, and formation of metastases;The disease is caused by variants affecting the gene represented in this entry;

OMIM: 136352

OMIM link1: https://www.omim.org/entry/153100;https://www.omim.org/entry/602089;https://www.omim.org/entry/618780;

OMIM link2: https://www.omim.org/entry/136352

HGNC ID: HGNC:3767

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3767