UniProt functional annotation for P49767



	UniProt functional annotation for P49767

UniProt code: P49767.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors. {ECO:0000269|PubMed:20145116}.

Subunit: Homodimer; non-covalent and antiparallel (PubMed:20145116). Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation (PubMed:23878260). {ECO:0000269|PubMed:20145116, ECO:0000269|PubMed:23878260}.

Subcellular location: Secreted.

Tissue specificity: Spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine and fetal liver, lung and kidney, but not in peripheral blood lymphocyte.

Ptm: Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-227 and Ser-228 producing a heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non- covalent interactions.

Disease: Lymphatic malformation 4 (LMPHM4) [MIM:615907]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM4 is an autosomal dominant form with onset at birth or in early childhood. Affected individuals manifest lymphedema of lower limbs with prominent veins, and impaired lymphatic uptake and drainage. Additional features are nail dysplasia, skin hyperkeratosis and papillomatosis. {ECO:0000269|PubMed:23410910, ECO:0000269|PubMed:24744435}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the PDGF/VEGF growth factor family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors. {ECO:0000269\|PubMed:20145116}.


Subunit:		Homodimer; non-covalent and antiparallel (PubMed:20145116). Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation (PubMed:23878260). {ECO:0000269\|PubMed:20145116, ECO:0000269\|PubMed:23878260}.
Subcellular location:		Secreted.
Tissue specificity:		Spleen, lymph node, thymus, appendix, bone marrow, heart, placenta, ovary, skeletal muscle, prostate, testis, colon and small intestine and fetal liver, lung and kidney, but not in peripheral blood lymphocyte.
Ptm:		Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-227 and Ser-228 producing a heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non- covalent interactions.
Disease:		Lymphatic malformation 4 (LMPHM4) [MIM:615907]: A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM4 is an autosomal dominant form with onset at birth or in early childhood. Affected individuals manifest lymphedema of lower limbs with prominent veins, and impaired lymphatic uptake and drainage. Additional features are nail dysplasia, skin hyperkeratosis and papillomatosis. {ECO:0000269\|PubMed:23410910, ECO:0000269\|PubMed:24744435}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the PDGF/VEGF growth factor family. {ECO:0000305}.