HOXA5

HOXA5
Identifiers
Aliases	HOXA5, HOX1, HOX1.3, HOX1C, homeobox A5
External IDs	OMIM: 142952; MGI: 96177; HomoloGene: 40726; GeneCards: HOXA5; OMA:HOXA5 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p15.2 Start 27,141,052 bp[1] End 27,143,681 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 B3|6 25.4 cM Start 52,178,734 bp[2] End 52,181,567 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in caput epididymis corpus epididymis renal medulla left uterine tube adrenal cortex right adrenal cortex left adrenal cortex mucosa of transverse colon mucosa of ileum right uterine tube Top expressed in axial skeleton human vertebral column cervical vertebral column thoracic vertebral column efferent ductule left lung lobe migratory enteric neural crest cell rib right lung lobe tail of embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding protein binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Cellular component nucleus Biological process embryonic skeletal system morphogenesis pattern specification process skeletal system development respiratory system process regulation of transcription, DNA-templated multicellular organism growth lung development trachea morphogenesis bronchiole development cell-cell signaling involved in mammary gland development regulation of mammary gland epithelial cell proliferation mammary gland alveolus development lung goblet cell differentiation transcription, DNA-templated mammary gland epithelial cell differentiation negative regulation of erythrocyte differentiation respiratory gaseous exchange by respiratory system trachea cartilage morphogenesis embryonic skeletal system development morphogenesis of an epithelium multicellular organism development thyroid gland development lobar bronchus epithelium development mesenchymal-epithelial cell signaling positive regulation of apoptotic process intestinal epithelial cell maturation negative regulation of angiogenesis cartilage morphogenesis lung alveolus development lung-associated mesenchyme development epithelial tube branching involved in lung morphogenesis cell migration positive regulation of myeloid cell differentiation anterior/posterior pattern specification positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3202 15402 Ensembl ENSG00000106004 ENSMUSG00000038253 UniProt P20719 P09021 RefSeq (mRNA) NM_019102 NM_010453 RefSeq (protein) NP_061975 NP_034583 Location (UCSC) Chr 7: 27.14 – 27.14 Mb Chr 6: 52.18 – 52.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.^[5][6][7]

Function

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis.^[7]

HoxA5 is controlled, at least in part, by DNA methylation.^[8] HoxA5 has been shown to upregulate the tumor suppressor p53 and AKT1 by downregulation of PTEN.^[9] Suppression of HoxA5 has been shown to attenuate hemangioma growth.^[10] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.^[11] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFα-inducible monocyte binding to HUVECs.^[12][13]

Comparison of the HoxA5 promoter methylation profile across cell types from the least differentiated (human embryonic stem cells) to the most endothelial-like (human umbilical vein endothelial cells, or HUVECs) shows that the HoxA5 promoter is normally heavily methylated in non-differentiated cells and becomes demethylated as cells differentiate down the endothelial lineage.^[14] HoxA5 contains a C-Amp Response Elements (CRE) in its promoter.^[8] POL2 and CTCF binding are enriched at the CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.^[14]

Clinical significance

HoxA5 is suppressed in acute myeloid leukemia (AML), and the DNMT inhibitor decitabine (5Aza) is used to treat this disease. While HoxA5 is known to be hypermethylated in AML, it has not yet been shown whether decitabine directly targets these genes for demethylation.^[15][16] HOXA5 has also been nominated as an oncogene in glioblastoma. ^[17]

See also

• Homeobox

References

1. GRCh38: Ensembl release 89: ENSG00000106004 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000038253 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. McAlpine PJ, Shows TB (Jul 1990). "Nomenclature for human homeobox genes". Genomics. 7 (3): 460. doi:10.1016/0888-7543(90)90186-X. PMID 1973146.
6. Scott MP (Nov 1992). "Vertebrate homeobox gene nomenclature". Cell. 71 (4): 551–3. doi:10.1016/0092-8674(92)90588-4. PMID 1358459. S2CID 13370372.
7. "Entrez Gene: HOXA5 homeobox A5".
8. Dunn J, Thabet S, Jo H (Jul 2015). "Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and Atherosclerosis". Arteriosclerosis, Thrombosis, and Vascular Biology. 35 (7): 1562–9. doi:10.1161/ATVBAHA.115.305042. PMC 4754957. PMID 25953647.
9. Arderiu G, Cuevas I, Chen A, Carrio M, East L, Boudreau NJ (2007). "HoxA5 stabilizes adherens junctions via increased Akt1". Cell Adhesion & Migration. 1 (4): 185–95. doi:10.4161/cam.1.4.5448. PMC 2634105. PMID 19262140.
10. Zhu Y, Cuevas IC, Gabriel RA, Su H, Nishimura S, Gao P, Fields A, Hao Q, Young WL, Yang GY, Boudreau NJ (Jun 2009). "Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain". Journal of Neuropathology and Experimental Neurology. 68 (6): 626–32. doi:10.1097/NEN.0b013e3181a491ce. PMC 2728585. PMID 19458547.
11. Chen H, Rubin E, Zhang H, Chung S, Jie CC, Garrett E, Biswal S, Sukumar S (May 2005). "Identification of transcriptional targets of HOXA5". The Journal of Biological Chemistry. 280 (19): 19373–80. doi:10.1074/jbc.M413528200. PMID 15757903.
12. Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH (Jul 2011). "Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation". Biochemical and Biophysical Research Communications. 410 (2): 312–6. doi:10.1016/j.bbrc.2011.05.139. PMID 21664342.
13. Chen Y, Gorski DH (Feb 2008). "Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5". Blood. 111 (3): 1217–26. doi:10.1182/blood-2007-07-104133. PMC 2214763. PMID 17957028.
14. Dunn J, Simmons R, Thabet S, Jo H (Oct 2015). "The role of epigenetics in the endothelial cell shear stress response and atherosclerosis". The International Journal of Biochemistry & Cell Biology. 67: 167–76. doi:10.1016/j.biocel.2015.05.001. PMC 4592147. PMID 25979369.
15. Strathdee G, Sim A, Soutar R, Holyoake TL, Brown R (Feb 2007). "HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia". Carcinogenesis. 28 (2): 299–309. doi:10.1093/carcin/bgl133. PMID 16861263.
16. Kim SY, Hwang SH, Song EJ, Shin HJ, Jung JS, Lee EY (Oct 2010). "Level of HOXA5 hypermethylation in acute myeloid leukemia is associated with short-term outcome". The Korean Journal of Laboratory Medicine. 30 (5): 469–73. doi:10.3343/kjlm.2010.30.5.469. PMID 20890077.
17. Cimino PJ, Kim Y, Wu HJ, Alexander J, Wirsching HG, Szulzewsky F, Pitter K, Ozawa T, Wang J, Vazquez J, Arora S, Rabadan R, Levine R, Michor F, Holland EC (2018). "Increased HOXA5 expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma". Genes & Development. 32 (7–8): 512–523. doi:10.1101/gad.312157.118. PMC 5959235. PMID 29632085.

External links

• HOXA5+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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