HOXA5: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Homeobox protein Hox-A5''' is a [[protein]] that in humans is encoded by the ''HOXA5'' [[gene]].<ref name="pmid1973146">{{cite journal | vauthors = McAlpine PJ, Shows TB | title = Nomenclature for human homeobox genes | journal = Genomics | volume = 7 | issue = 3 | pages = 460 | date = Jul 1990 | pmid = 1973146 | pmc =  | doi = 10.1016/0888-7543(90)90186-X }}</ref><ref name="pmid1358459">{{cite journal | vauthors = Scott MP | title = Vertebrate homeobox gene nomenclature | journal = Cell | volume = 71 | issue = 4 | pages = 551–3 | date = Nov 1992 | pmid = 1358459 | pmc = | doi = 10.1016/0092-8674(92)90588-4 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HOXA5 homeobox A5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3202| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_HOXA5_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1hom.
| PDB = {{PDB2|1hom}}, {{PDB2|1san}}
| Name = Homeobox A5
| HGNCid = 5106
| Symbol = HOXA5
| AltSymbols =; HOX1; HOX1.3; HOX1C; MGC9376
| OMIM = 142952
| ECnumber = 
| Homologene = 40726
| MGIid = 96177
| GeneAtlas_image1 = PBB_GE_HOXA5_213844_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0001501 |text = skeletal development}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007389 |text = pattern specification process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3202
    | Hs_Ensembl = ENSG00000106004
    | Hs_RefseqProtein = NP_061975
    | Hs_RefseqmRNA = NM_019102
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 27147521
    | Hs_GenLoc_end = 27149812
    | Hs_Uniprot = P20719
    | Mm_EntrezGene = 15402
    | Mm_Ensembl = ENSMUSG00000038253
    | Mm_RefseqmRNA = NM_010453
    | Mm_RefseqProtein = NP_034583
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 6
    | Mm_GenLoc_start = 52131337
    | Mm_GenLoc_end = 52134170
    | Mm_Uniprot = Q3UNA0
  }}
}}
'''Homeobox A5''', also known as '''HOXA5''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HOXA5 homeobox A5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3202| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
In vertebrates, the genes encoding the class of [[transcription factor]]s 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. [[Gene methylation|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]].<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: HOXA5 homeobox A5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3202| accessdate = }}</ref>
}}


==See also==
HoxA5 is controlled, at least in part, by [[DNA methylation]].<ref name="ReferenceA">{{cite journal | vauthors = Dunn J, Thabet S, Jo H | title = Flow-Dependent Epigenetic DNA Methylation in Endothelial Gene Expression and Atherosclerosis | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 35 | issue = 7 | pages = 1562–9 | date = Jul 2015 | pmid = 25953647 | doi = 10.1161/ATVBAHA.115.305042 | pmc=4754957}}</ref> HoxA5 has been shown to upregulate the tumor suppressor p53 and [[AKT1]] by downregulation of [[PTEN (gene)|PTEN]].<ref>{{cite journal | vauthors = Arderiu G, Cuevas I, Chen A, Carrio M, East L, Boudreau NJ | title = HoxA5 stabilizes adherens junctions via increased Akt1 | journal = Cell Adhesion & Migration | volume = 1 | issue = 4 | pages = 185–95 | pmid = 19262140 | doi=10.4161/cam.1.4.5448 | pmc=2634105}}</ref> Suppression of HoxA5 has been shown to attenuate [[hemangioma]] growth.<ref>{{cite journal | vauthors = Zhu Y, Cuevas IC, Gabriel RA, Su H, Nishimura S, Gao P, Fields A, Hao Q, Young WL, Yang GY, Boudreau NJ | title = Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain | journal = Journal of Neuropathology and Experimental Neurology | volume = 68 | issue = 6 | pages = 626–32 | date = Jun 2009 | pmid = 19458547 | doi = 10.1097/NEN.0b013e3181a491ce | pmc=2728585}}</ref> HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.<ref>{{cite journal | vauthors = Chen H, Rubin E, Zhang H, Chung S, Jie CC, Garrett E, Biswal S, Sukumar S | title = Identification of transcriptional targets of HOXA5 | journal = The Journal of Biological Chemistry | volume = 280 | issue = 19 | pages = 19373–80 | date = May 2005 | pmid = 15757903 | doi = 10.1074/jbc.M413528200 }}</ref>  HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of [[TNFα]]-inducible monocyte binding to [[HUVEC]]s.<ref>{{cite journal | vauthors = Lee JY, Park KS, Cho EJ, Joo HK, Lee SK, Lee SD, Park JB, Chang SJ, Jeon BH | title = Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation | journal = Biochemical and Biophysical Research Communications | volume = 410 | issue = 2 | pages = 312–6 | date = Jul 2011 | pmid = 21664342 | doi = 10.1016/j.bbrc.2011.05.139 }}</ref><ref>{{cite journal | vauthors = Chen Y, Gorski DH | title = Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5 | journal = Blood | volume = 111 | issue = 3 | pages = 1217–26 | date = Feb 2008 | pmid = 17957028 | doi = 10.1182/blood-2007-07-104133 | pmc=2214763}}</ref>
 
Comparison of the HoxA5 [[gene promoter|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 [[endothelium|endothelial lineage]].<ref name="Dunn_2015">{{cite journal | vauthors = Dunn J, Simmons R, Thabet S, Jo H | title = The role of epigenetics in the endothelial cell shear stress response and atherosclerosis | journal = The International Journal of Biochemistry & Cell Biology | volume = 67 | pages = 167–76 | date = Oct 2015 | pmid = 25979369 | doi = 10.1016/j.biocel.2015.05.001 | pmc=4592147}}</ref> HoxA5 contains a [[CREB#cAMP response element|C-Amp Response Elements]] (CRE) in its promoter.<ref name="ReferenceA"/>  POL2 and [[CTCF]] binding are enriched at the [[CpG site|CpG]]-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.<ref name="Dunn_2015"/>
 
== 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.<ref>{{cite journal | vauthors = Strathdee G, Sim A, Soutar R, Holyoake TL, Brown R | title = HOXA5 is targeted by cell-type-specific CpG island methylation in normal cells and during the development of acute myeloid leukaemia | journal = Carcinogenesis | volume = 28 | issue = 2 | pages = 299–309 | date = Feb 2007 | pmid = 16861263 | doi = 10.1093/carcin/bgl133 }}</ref><ref>{{cite journal | vauthors = Kim SY, Hwang SH, Song EJ, Shin HJ, Jung JS, Lee EY | title = Level of HOXA5 hypermethylation in acute myeloid leukemia is associated with short-term outcome | journal = The Korean Journal of Laboratory Medicine | volume = 30 | issue = 5 | pages = 469–73 | date = Oct 2010 | pmid = 20890077 | doi = 10.3343/kjlm.2010.30.5.469 }}</ref>
 
== See also ==
* [[Homeobox]]
* [[Homeobox]]
{{Clear}}


==References==
== References ==
{{reflist|2}}
{{reflist|33em}}
 
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Scott MP |title=Vertebrate homeobox gene nomenclature. |journal=Cell |volume=71 |issue= 4 |pages= 551-3 |year= 1992 |pmid= 1358459 |doi=  }}
*{{cite journal  | author=McAlpine PJ, Shows TB |title=Nomenclature for human homeobox genes. |journal=Genomics |volume=7 |issue= 3 |pages= 460 |year= 1990 |pmid= 1973146 |doi=  }}
*{{cite journal  | author=Tournier-Lasserve E, Odenwald WF, Garbern J, ''et al.'' |title=Remarkable intron and exon sequence conservation in human and mouse homeobox Hox 1.3 genes. |journal=Mol. Cell. Biol. |volume=9 |issue= 5 |pages= 2273-8 |year= 1989 |pmid= 2568583 |doi=  }}
*{{cite journal  | author=Boncinelli E, Acampora D, Pannese M, ''et al.'' |title=Organization of human class I homeobox genes. |journal=Genome |volume=31 |issue= 2 |pages= 745-56 |year= 1990 |pmid= 2576652 |doi=  }}
*{{cite journal  | author=Miano JM, Firulli AB, Olson EN, ''et al.'' |title=Restricted expression of homeobox genes distinguishes fetal from adult human smooth muscle cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 2 |pages= 900-5 |year= 1996 |pmid= 8570656 |doi=  }}
*{{cite journal  | author=Apiou F, Flagiello D, Cillo C, ''et al.'' |title=Fine mapping of human HOX gene clusters. |journal=Cytogenet. Cell Genet. |volume=73 |issue= 1-2 |pages= 114-5 |year= 1996 |pmid= 8646877 |doi=  }}
*{{cite journal  | author=Lu Q, Kamps MP |title=Structural determinants within Pbx1 that mediate cooperative DNA binding with pentapeptide-containing Hox proteins: proposal for a model of a Pbx1-Hox-DNA complex. |journal=Mol. Cell. Biol. |volume=16 |issue= 4 |pages= 1632-40 |year= 1996 |pmid= 8657138 |doi=  }}
*{{cite journal  | author=Stelnicki EJ, Kömüves LG, Kwong AO, ''et al.'' |title=HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development. |journal=J. Invest. Dermatol. |volume=110 |issue= 2 |pages= 110-5 |year= 1998 |pmid= 9457903 |doi= 10.1046/j.1523-1747.1998.00092.x }}
*{{cite journal  | author=Crooks GM, Fuller J, Petersen D, ''et al.'' |title=Constitutive HOXA5 expression inhibits erythropoiesis and increases myelopoiesis from human hematopoietic progenitors. |journal=Blood |volume=94 |issue= 2 |pages= 519-28 |year= 1999 |pmid= 10397719 |doi=  }}
*{{cite journal  | author=Dias Neto E, Correa RG, Verjovski-Almeida S, ''et al.'' |title=Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 7 |pages= 3491-6 |year= 2000 |pmid= 10737800 |doi=  }}
*{{cite journal  | author=Raman V, Tamori A, Vali M, ''et al.'' |title=HOXA5 regulates expression of the progesterone receptor. |journal=J. Biol. Chem. |volume=275 |issue= 34 |pages= 26551-5 |year= 2000 |pmid= 10875927 |doi= 10.1074/jbc.C000324200 }}
*{{cite journal  | author=Raman V, Martensen SA, Reisman D, ''et al.'' |title=Compromised HOXA5 function can limit p53 expression in human breast tumours. |journal=Nature |volume=405 |issue= 6789 |pages= 974-8 |year= 2000 |pmid= 10879542 |doi= 10.1038/35016125 }}
*{{cite journal  | author=Golpon HA, Geraci MW, Moore MD, ''et al.'' |title=HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema. |journal=Am. J. Pathol. |volume=158 |issue= 3 |pages= 955-66 |year= 2001 |pmid= 11238043 |doi=  }}
*{{cite journal  | author=Kosaki K, Kosaki R, Suzuki T, ''et al.'' |title=Complete mutation analysis panel of the 39 human HOX genes. |journal=Teratology |volume=65 |issue= 2 |pages= 50-62 |year= 2002 |pmid= 11857506 |doi= 10.1002/tera.10009 }}
*{{cite journal  | author=Foucher I, Volovitch M, Frain M, ''et al.'' |title=Hoxa5 overexpression correlates with IGFBP1 upregulation and postnatal dwarfism: evidence for an interaction between Hoxa5 and Forkhead box transcription factors. |journal=Development |volume=129 |issue= 17 |pages= 4065-74 |year= 2002 |pmid= 12163409 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Foucher I, Montesinos ML, Volovitch M, ''et al.'' |title=Joint regulation of the MAP1B promoter by HNF3beta/Foxa2 and Engrailed is the result of a highly conserved mechanism for direct interaction of homeoproteins and Fox transcription factors. |journal=Development |volume=130 |issue= 9 |pages= 1867-76 |year= 2003 |pmid= 12642491 |doi=  }}
*{{cite journal  | author=Scherer SW, Cheung J, MacDonald JR, ''et al.'' |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767-72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423 }}
*{{cite journal  | author=Hillier LW, Fulton RS, Fulton LA, ''et al.'' |title=The DNA sequence of human chromosome 7. |journal=Nature |volume=424 |issue= 6945 |pages= 157-64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 }}
*{{cite journal  | author=Chen H, Chung S, Sukumar S |title=HOXA5-induced apoptosis in breast cancer cells is mediated by caspases 2 and 8. |journal=Mol. Cell. Biol. |volume=24 |issue= 2 |pages= 924-35 |year= 2004 |pmid= 14701762 |doi=  }}
}}
{{refend}}


== External links ==
== External links ==
* {{MeshName|HOXA5+protein,+human}}
* {{MeshName|HOXA5+protein,+human}}
{{PDB Gallery|geneid=3202}}
{{Transcription factors|g3}}


{{NLM content}}
{{NLM content}}
{{protein-stub}}
 
{{Transcription factors}}
[[Category:Transcription factors]]
[[Category:Transcription factors]]
{{WikiDoc Sources}}
 
 
{{gene-7-stub}}

Latest revision as of 01:56, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.[1][2][3]

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.[3]

HoxA5 is controlled, at least in part, by DNA methylation.[4] HoxA5 has been shown to upregulate the tumor suppressor p53 and AKT1 by downregulation of PTEN.[5] Suppression of HoxA5 has been shown to attenuate hemangioma growth.[6] HoxA5 has far-reaching effects on gene expression, causing ~300 genes to become upregulated upon its induction in breast cancer cell lines.[7] HoxA5 protein transduction domain overexpression prevents inflammation shown by inhibition of TNFα-inducible monocyte binding to HUVECs.[8][9]

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.[10] HoxA5 contains a C-Amp Response Elements (CRE) in its promoter.[4] POL2 and CTCF binding are enriched at the CpG-dense HoxA5 promoter in HUVECs, demonstrating transcriptional activity.[10]

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.[11][12]

See also

References

  1. ↑ 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.
  2. ↑ Scott MP (Nov 1992). "Vertebrate homeobox gene nomenclature". Cell. 71 (4): 551–3. doi:10.1016/0092-8674(92)90588-4. PMID 1358459.
  3. ↑ 3.0 3.1 "Entrez Gene: HOXA5 homeobox A5".
  4. ↑ 4.0 4.1 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.
  5. ↑ Arderiu G, Cuevas I, Chen A, Carrio M, East L, Boudreau NJ. "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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 10.0 10.1 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.
  11. ↑ 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.
  12. ↑ 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.

External links

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


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