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Developmental stage

Expressed in fetal lung and kidney (PubMed:8700872). Expressed in fetal liver (PubMed:28179430, PubMed:9247316).

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.

Involvement in disease

Lymphatic malformation 4

LMPHM4

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

Belongs to the PDGF/VEGF growth factor family.

Tissue specificity

Expressed in the spleen (PubMed:8700872, PubMed:9247316). Expressed in the lymph node, thymus, appendix and bone marrow (PubMed:9247316). Expressed in the heart, placenta, skeletal muscle, ovary and small intestine (PubMed:8617204, PubMed:8700872). Expressed in the prostate, testis and colon (PubMed:8700872).

Cellular localization

  • Secreted

Alternative names

Vascular endothelial growth factor C, VEGF-C, Flt4 ligand, Vascular endothelial growth factor-related protein, Flt4-L, VRP, VEGFC

Target type

Proteins

Primary research area

Oncology

Other research areas

  • Neuroscience

Molecular weight

46883Da