Alternative titles; symbols
HGNC Approved Gene Symbol: PROK1
Cytogenetic location: 1p13.3 Genomic coordinates (GRCh38) : 1:110,451,149-110,457,358 (from NCBI)
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) induces proliferation, migration, and fenestration in capillary endothelial cells derived from endocrine glands. Its expression is induced by hypoxia and is restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta). Its expression is often complementary to the expression of VEGF (192240), suggesting that these molecules function in a coordinated manner.
LeCouter et al. (2001) screened a library of purified human secreted proteins for the ability to induce proliferation in primary bovine adrenal cortex-derived capillary endothelial cells. EG-VEGF was capable of inducing a strong and reproducible mitogenic response. Mature EG-VEGF is a protein with a relative molecular mass of 8,600 encoded by a cDNA cloned from human ovary library. The 1.4-kb cDNA encodes a protein of 105 amino acids with a well defined signal sequence. The mature protein is predicted to have 86 amino acids, including 10 cysteines, and an expected isoelectric point of 8.46. These cysteines potentially form 5 disulfide bridges. EG-VEGF displays a high degree of homology to a nontoxic protein purified from the venom of the black mamba snake, venom protein A (VPRA). The structure of native VPRA was solved, and the disulfide bridge partners were revealed. The number and spacing of cysteines are completely conserved between VPRA and EG-VEGF. BV8, a human molecule closely related to a peptide isolated from the yellow-bellied toad, is 58% identical to the EG-VEGF mature protein. There is also significant homology to the carboxy-terminal sequence of Xenopus dickkopf (see 605189) and to colipase (120105).
Li et al. (2001) identified EG-VEGF as prokineticin-1.
EG-VEGF is mitogenic and chemoattractive and able to induce fenestration. EG-VEGF expression is induced by hypoxia, and there is an HIF1 (603348) binding site present on EG-VEGF. EG-VEGF is able to induce angiogenesis and ovarian cyst formation. Northern blot analysis demonstrated expression in testis, ovary, adrenal gland, and placenta. A signal was detectable in prostate after prolonged exposure.
The International Radiation Hybrid Mapping Consortium mapped the PROK1 gene to chromosome 1 (SHGC-16135).
LeCouter, J., Kowalski, J., Foster, J., Hass, P., Zhang, Z., Dillard-Telm, L., Frantz, G., Rangell, L., DeGuzman, L., Keller, G.-A., Peale, F., Gurney, P., Hillan, K. J., Ferrara, N. Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412: 877-884, 2001. [PubMed: 11528470] [Full Text: https://doi.org/10.1038/35091000]
Li, M., Bullock, C. M., Knauer, D. J., Ehlert, F. J., Zhou, Q. Y. Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. Molec. Pharm. 59: 692-698, 2001. [PubMed: 11259612] [Full Text: https://doi.org/10.1124/mol.59.4.692]