PROX1

Prospero homeobox protein 1 is a protein that in humans is encoded by the PROX1 gene. The Prox1 gene is critical for the development of multiple tissues. Prox1 activity is necessary and sufficient to specify a lymphatic endothelial cell fate in endothelial progenitors located in the embryonic veins.

PROX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LMD
Identifiers
Aliases	PROX1, prospero homeobox 1
External IDs	OMIM: 601546; MGI: 97772; HomoloGene: 2069; GeneCards: PROX1; OMA:PROX1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.3 Start 213,983,181 bp End 214,041,510 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 H6|1 95.85 cM Start 189,850,232 bp End 189,902,911 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve liver right lobe of liver right ventricle buccal mucosa cell corpus callosum biceps brachii islet of Langerhans Skeletal muscle tissue of biceps brachii body of pancreas Top expressed in lens neural layer of retina dentate gyrus of hippocampal formation granule cell subthalamus atrioventricular valve nucleus reuniens lumbar subsegment of spinal cord Rostral migratory stream white matter aortic valve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding transcription corepressor activity DNA binding domain binding DNA-binding transcription factor activity LBD domain binding DNA-binding transcription repressor activity, RNA polymerase II-specific core promoter sequence-specific DNA binding protein binding nuclear receptor binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component cytoplasm nucleus Biological process dorsal spinal cord development olfactory placode formation regulation of transcription, DNA-templated positive regulation of endothelial cell proliferation venous blood vessel morphogenesis kidney development lymphangiogenesis lung development dentate gyrus development rhythmic process ventricular septum morphogenesis cardiac muscle cell differentiation lymphatic endothelial cell differentiation positive regulation of sarcomere organization positive regulation of forebrain neuron differentiation endocardium formation hepatocyte differentiation negative regulation of transcription by RNA polymerase II negative regulation of DNA-binding transcription factor activity lymph vessel development hepatocyte cell migration transcription, DNA-templated lens placode formation involved in camera-type eye formation skeletal muscle thin filament assembly neuronal stem cell population maintenance positive regulation of endothelial cell migration positive regulation of transcription, DNA-templated positive regulation of heart growth ventricular cardiac muscle tissue morphogenesis positive regulation of neural precursor cell proliferation retina morphogenesis in camera-type eye multicellular organism development negative regulation of viral genome replication brain development branching involved in pancreas morphogenesis positive regulation of cell cycle lens development in camera-type eye response to nutrient levels hepatocyte proliferation positive regulation of cell cycle checkpoint regulation of circadian rhythm circadian rhythm acinar cell differentiation neural tube development neuron differentiation positive regulation of cell population proliferation lens morphogenesis in camera-type eye positive regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of bile acid biosynthetic process embryonic retina morphogenesis in camera-type eye regulation of gene expression cell fate determination pancreas development liver development atrial cardiac muscle tissue morphogenesis endothelial cell differentiation inner ear development negative regulation of transcription, DNA-templated ventricular cardiac myofibril assembly otic placode formation aorta smooth muscle tissue morphogenesis cerebellar granule cell differentiation negative regulation of cell population proliferation positive regulation of transcription by RNA polymerase II lens fiber cell morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5629 19130 Ensembl ENSG00000117707 ENSMUSG00000010175 UniProt Q92786 P48437 RefSeq (mRNA) NM_001270616 NM_002763 NM_008937 NM_001360827 RefSeq (protein) NP_001257545 NP_002754 NP_032963 NP_001347756 Location (UCSC) Chr 1: 213.98 – 214.04 Mb Chr 1: 189.85 – 189.9 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Interactions

PROX1 has been shown to interact with EP300.

Production

PROX1 is produced primarily in the dentate gyrus in the mouse, and in the dentate gyrus and white matter in humans. Gene expression data for mouse, human and macaque from the Allen Brain Atlases can be found here.

Clinical significance

PROX1 is used as a marker for lymphatic endothelium in biopsy samples.

Homologous gene

PROX2

Further reading

• Wigle JT, Chowdhury K, Gruss P, Oliver G (1999). "Prox1 function is crucial for mouse lens-fibre elongation". Nat. Genet. 21 (3): 318–22. doi:10.1038/6844. PMID 10080188. S2CID 23791417.
• Mouta Carreira C, Nasser SM, di Tomaso E, et al. (2001). "LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis". Cancer Res. 61 (22): 8079–84. PMID 11719431.
• Rodriguez-Niedenführ M, Papoutsi M, Christ B, et al. (2002). "Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts". Anat. Embryol. 204 (5): 399–406. doi:10.1007/s00429-001-0214-9. PMID 11789987. S2CID 21608393.
• Duncan MK, Cui W, Oh DJ, Tomarev SI (2002). "Prox1 is differentially localized during lens development". Mech. Dev. 112 (1–2): 195–8. doi:10.1016/S0925-4773(01)00645-1. PMID 11850194. S2CID 10074353.
• Chen Q, Dowhan DH, Liang D, et al. (2002). "CREB-binding protein/p300 co-activation of crystallin gene expression". J. Biol. Chem. 277 (27): 24081–9. doi:10.1074/jbc.M201821200. PMID 11943779.
• Wilting J, Papoutsi M, Christ B, et al. (2002). "The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues". FASEB J. 16 (10): 1271–3. doi:10.1096/fj.01-1010fje. PMID 12060670. S2CID 13013505.
• Petrova TV, Mäkinen T, Mäkelä TP, et al. (2002). "Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor". EMBO J. 21 (17): 4593–9. doi:10.1093/emboj/cdf470. PMC 125413. PMID 12198161.
• Hong YK, Harvey N, Noh YH, et al. (2003). "Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate". Dev. Dyn. 225 (3): 351–7. doi:10.1002/dvdy.10163. PMID 12412020.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003). "Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina". Nat. Genet. 34 (1): 53–8. doi:10.1038/ng1144. PMID 12692551. S2CID 6134008.
• Nagai H, Li Y, Hatano S, et al. (2003). "Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies". Genes Chromosomes Cancer. 38 (1): 13–21. doi:10.1002/gcc.10248. PMID 12874782. S2CID 35135526.
• Steffensen KR, Holter E, Båvner A, et al. (2005). "Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue". EMBO Rep. 5 (6): 613–9. doi:10.1038/sj.embor.7400147. PMC 1299067. PMID 15143342.
• Qin J, Gao DM, Jiang QF, et al. (2005). "Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-alpha-hydroxylase gene". Mol. Endocrinol. 18 (10): 2424–39. doi:10.1210/me.2004-0009. PMID 15205472.
• Dudas J, Papoutsi M, Hecht M, et al. (2005). "The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium". Anat. Embryol. 208 (5): 359–66. doi:10.1007/s00429-004-0403-4. PMID 15232737. S2CID 117581.
• Reis RM, Reis-Filho JS, Longatto Filho A, et al. (2006). "Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors". Pathol. Res. Pract. 201 (12): 771–6. doi:10.1016/j.prp.2005.08.010. hdl:1822/5789. PMID 16308102.
• Song KH, Li T, Chiang JY (2006). "A prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4 α that regulates the cholesterol 7α-hydroxylase gene". J. Biol. Chem. 281 (15): 10081–8. doi:10.1074/jbc.M513420200. PMC 1785292. PMID 16488887.
• Schneider M, Büchler P, Giese N, et al. (2006). "Role of lymphangiogenesis and lymphangiogenic factors during pancreatic cancer progression and lymphatic spread". Int. J. Oncol. 28 (4): 883–90. doi:10.3892/ijo.28.4.883. PMID 16525637.
• Shimoda M, Takahashi M, Yoshimoto T, et al. (2006). "A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma". Clin. Cancer Res. 12 (20 Pt 1): 6005–11. doi:10.1158/1078-0432.CCR-06-0712. hdl:2433/135812. PMID 17062673.
• Laerm A, Helmbold P, Goldberg M, et al. (2007). "Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system". J. Hepatol. 46 (1): 89–97. doi:10.1016/j.jhep.2006.07.033. PMID 17069925.

External links

• PROX1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: Q92786 (Prospero homeobox protein 1) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.