HOXA5
Identifiers
Aliases	HOXA5, HOX1, HOX1.3, HOX1C, homeobox A5
External IDs	OMIM: 142952 MGI: 96177 HomoloGene: 40726 GeneCards: HOXA5
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 uterine tube lower lobe of lung right lung nipple lactiferous duct Top expressed in axial skeleton vertebral column left lung lobe rib right lung lobe abdominal wall brown adipose tissue left colon thoracic diaphragm anterior horn of spinal cord 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
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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]