HIRA: 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
'''Protein HIRA''' is a [[protein]] that in humans is encoded by the ''HIRA'' [[gene]].<ref name="pmid8111380">{{cite journal | vauthors = Halford S, Wadey R, Roberts C, Daw SC, Whiting JA, O'Donnell H, Dunham I, Bentley D, Lindsay E, Baldini A | title = Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease | journal = Hum Mol Genet | volume = 2 | issue = 12 | pages = 2099–107 | date = Mar 1994 | pmid = 8111380 | pmc =  | doi = 10.1093/hmg/2.12.2099 }}</ref><ref name="pmid7633437">{{cite journal | vauthors = Lamour V, Lécluse Y, Desmaze C, Spector M, Bodescot M, Aurias A, Osley MA, Lipinski M | title = A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region | journal = Hum Mol Genet | volume = 4 | issue = 5 | pages = 791–9 | date = Sep 1995 | pmid = 7633437 | pmc =  | doi = 10.1093/hmg/4.5.791 }}</ref><ref name="pmid9731536">{{cite journal | vauthors = Magnaghi P, Roberts C, Lorain S, Lipinski M, Scambler PJ | title = HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3 | journal = Nat Genet | volume = 20 | issue = 1 | pages = 74–7 | date = Oct 1998 | pmid = 9731536 | pmc = | doi = 10.1038/1739 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7290| accessdate = }}</ref> This gene is mapped to 22q11.21, centromeric to [[Catechol-O-methyl transferase|COMT]].<ref name="entrez"/>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- 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_HIRA_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 2i32.
| PDB = {{PDB2|2i32}}
| Name = HIR histone cell cycle regulation defective homolog A (S. cerevisiae)
| HGNCid = 4916
| Symbol = HIRA
| AltSymbols =; DGCR1; TUP1; TUPLE1
| OMIM = 600237
| ECnumber = 
| Homologene = 48172
| MGIid = 99430
| GeneAtlas_image1 = PBB_GE_HIRA_217427_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0003714 |text = transcription corepressor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0000790 |text = nuclear chromatin}} {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006357 |text = regulation of transcription from RNA polymerase II promoter}} {{GNF_GO|id=GO:0007369 |text = gastrulation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7290
    | Hs_Ensembl = ENSG00000100084
    | Hs_RefseqProtein = NP_003316
    | Hs_RefseqmRNA = NM_003325
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 22
    | Hs_GenLoc_start = 17698224
    | Hs_GenLoc_end = 17799219
    | Hs_Uniprot = P54198
    | Mm_EntrezGene = 15260
    | Mm_Ensembl = ENSMUSG00000022702
    | Mm_RefseqmRNA = NM_001005228
    | Mm_RefseqProtein = NP_001005228
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 16
    | Mm_GenLoc_start = 18790313
    | Mm_GenLoc_end = 18883872
    | Mm_Uniprot = Q3TFY0
  }}
}}
'''HIR histone cell cycle regulation defective homolog A (S. cerevisiae)''', also known as '''HIRA''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7290| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The specific function of this protein has yet to be determined; however, it has been speculated to play a role in [[transcriptional regulation]] and/or [[chromatin]] and [[histone]] metabolism.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = The specific function of this gene has yet to be determined; however, it has been speculated to play a role in transcription regulation and/or chromatin and histone metabolism.  It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development.  This gene is mapped to 22q11.21, centromeric to COMT.<ref name="entrez">{{cite web | title = Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7290| accessdate = }}</ref>
}}


==References==
Research done by Salomé Adam, Sophie E. Polo, and Geneviève Almouzni indicate that HIRA proteins are involved in restarting transcription after UVC damage<ref>Adam, S., Polo, S. E., & Almouzni, G. (2013). Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA. Cell, 155(1), 94-106. Retrieved from http://www.cell.com/abstract/S0092-8674(13)01023-4</ref> Function of HIRA gene can be effectively examined by siRNA knockdown based on an independent validation.<ref>{{cite journal|last=Munkácsy|first=Gyöngyi|last2=Sztupinszki|first2=Zsófia|last3=Herman|first3=Péter|last4=Bán|first4=Bence|last5=Pénzváltó|first5=Zsófia|last6=Szarvas|first6=Nóra|last7=Győrffy|first7=Balázs|date=September 2016|title=Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056990/|journal=Molecular Therapy. Nucleic Acids|volume=5|issue=9|pages=e366|doi=10.1038/mtna.2016.66|issn=2162-2531|pmc=5056990|pmid=27673562}}</ref>
{{reflist|2}}
 
==Further reading==
== Clinical significance ==
 
It is considered the primary candidate gene in some [[haploinsufficiency]] syndromes such as [[DiGeorge syndrome]], and insufficient production of the gene may disrupt normal embryonic development.<ref name="entrez"/>
 
==Model organisms==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: right;" |
|+ ''Hira'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
 
|-
| [[Homozygote]] viability || bgcolor="#C40000"|Abnormal
|-
| Fertility || bgcolor="#488ED3"|Normal
|-
| Body weight || bgcolor="#488ED3"|Normal
|-
| [[Open Field (animal test)|Anxiety]] || bgcolor="#488ED3"|Normal
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
|-
| Grip strength || bgcolor="#488ED3"|Normal
|-
| [[Hot plate test|Hot plate]] || bgcolor="#488ED3"|Normal
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
|-
| Body temperature || bgcolor="#488ED3"|Normal
|-
| Eye morphology || bgcolor="#488ED3"|Normal
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
|-
| [[Haematology]] || bgcolor="#C40000"|Abnormal<ref name="Haematology">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MCBV/haematology-cbc/ |title=Haematology data for Hira |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| [[Peripheral blood lymphocyte]]s || bgcolor="#488ED3"|Normal
|-
| [[Micronucleus test]] || bgcolor="#488ED3"|Normal
|-
| Heart weight || bgcolor="#488ED3"|Normal
|-
| Eye Histopathology || bgcolor="#488ED3"|Normal
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal<ref name="''Salmonella'' infection">{{cite web |url=http://www.sanger.ac.uk/mouseportal/phenotyping/MCBV/salmonella-challenge/ |title=''Salmonella'' infection data for Hira |publisher=Wellcome Trust Sanger Institute}}</ref>
|-
| colspan=2; style="text-align: center;" | All tests and analysis from<ref name="mgp_reference">{{cite journal | doi = 10.1111/j.1755-3768.2010.4142.x | title = The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice | year = 2010 | author = Gerdin AK | journal = Acta Ophthalmologica | volume = 88 | pages =  925–7 }}</ref><ref>[http://www.sanger.ac.uk/mouseportal/ Mouse Resources Portal], Wellcome Trust Sanger Institute.</ref>
|}
[[Model organism]]s have been used in the study of HIRA function. A conditional [[knockout mouse]] line, called ''Hira<sup>tm1a(EUCOMM)Wtsi</sup>''<ref name="allele_ref">{{cite web |url=http://www.knockoutmouse.org/martsearch/search?query=Hira |title=International Knockout Mouse Consortium}}</ref><ref name="mgi_allele_ref">{{cite web |url=http://www.informatics.jax.org/searchtool/Search.do?query=MGI:4431679 |title=Mouse Genome Informatics}}</ref> was generated as part of the [[International Knockout Mouse Consortium]] program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–342 | year = 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | year = 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A Mouse for All Reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | year = 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref>
 
Male and female animals underwent a standardized [[phenotypic screen]] to determine the effects of deletion.<ref name="mgp_reference" /><ref name="pmid21722353">{{cite journal | vauthors = van der Weyden L, White JK, Adams DJ, Logan DW | title = The mouse genetics toolkit: revealing function and mechanism. | journal = Genome Biol | volume = 12 | issue = 6 | pages = 224 | year = 2011 | pmid = 21722353 | pmc = 3218837 | doi = 10.1186/gb-2011-12-6-224 }}</ref> Twenty two tests were carried out on [[mutant]] mice and two significant abnormalities were observed.<ref name="mgp_reference" /> No [[homozygous]] [[mutant]] mice survived until [[weaning]]. The remaining tests were carried out on [[heterozygous]] mutant adult mice and a decreased [[leukocyte]] cell number was recorded in male animals.<ref name="mgp_reference" />
 
== Interactions ==
 
HIRA has been shown to [[Protein-protein interaction|interact]] with [[HIST1H2BK]].<ref name="pmid9710638">{{cite journal | vauthors = Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M | title = Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA | journal = Mol. Cell. Biol. | volume = 18 | issue = 9 | pages = 5546–56 | date = September 1998 | pmid = 9710638 | pmc = 109139 | doi =  }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Lorain S, Demczuk S, Lamour V, Toth S, Aurias A, Roe BA, Lipinski M | title = Structural Organization of the WD repeat protein-encoding gene HIRA in the DiGeorge syndrome critical region of human chromosome 22. | journal = Genome Res. | volume = 6 | issue = 1 | pages = 43–50 | year = 1996 | pmid = 8681138 | doi = 10.1101/gr.6.1.43 }}
| citations =
* {{cite journal | vauthors = Llevadot R, Scambler P, Estivill X, Pritchard M | title = Genomic organization of TUPLE1/HIRA: a gene implicated in DiGeorge syndrome. | journal = Mamm. Genome | volume = 7 | issue = 12 | pages = 911–4 | year = 1997 | pmid = 8995764 | doi = 10.1007/s003359900268 }}
*{{cite journal  | author=Lamour V, Lécluse Y, Desmaze C, ''et al.'' |title=A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region. |journal=Hum. Mol. Genet. |volume=4 |issue= 5 |pages= 791-9 |year= 1995 |pmid= 7633437 |doi=  }}
* {{cite journal | vauthors = Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M | title = Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA. | journal = Mol. Cell. Biol. | volume = 18 | issue = 9 | pages = 5546–56 | year = 1998 | pmid = 9710638 | pmc = 109139 | doi = }}
*{{cite journal | author=Halford S, Wadey R, Roberts C, ''et al.'' |title=Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease. |journal=Hum. Mol. Genet. |volume=2 |issue= 12 |pages= 2099-107 |year= 1994 |pmid= 8111380 |doi=  }}
* {{cite journal | vauthors = Hall C, Nelson DM, Ye X, Baker K, DeCaprio JA, Seeholzer S, Lipinski M, Adams PD | title = HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression. | journal = Mol. Cell. Biol. | volume = 21 | issue = 5 | pages = 1854–65 | year = 2001 | pmid = 11238922 | pmc = 86753 | doi = 10.1128/MCB.21.5.1854-1865.2001 }}
*{{cite journal  | author=Lorain S, Demczuk S, Lamour V, ''et al.'' |title=Structural Organization of the WD repeat protein-encoding gene HIRA in the DiGeorge syndrome critical region of human chromosome 22. |journal=Genome Res. |volume=6 |issue= 1 |pages= 43-50 |year= 1996 |pmid= 8681138 |doi= }}
* {{cite journal | vauthors = Lorain S, Lécluse Y, Scamps C, Mattéi MG, Lipinski M | title = Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins. | journal = Biochim. Biophys. Acta | volume = 1517 | issue = 3 | pages = 376–83 | year = 2001 | pmid = 11342215 | doi = 10.1016/S0167-4781(00)00300-6 }}
*{{cite journal | author=Llevadot R, Scambler P, Estivill X, Pritchard M |title=Genomic organization of TUPLE1/HIRA: a gene implicated in DiGeorge syndrome. |journal=Mamm. Genome |volume=7 |issue= 12 |pages= 911-4 |year= 1997 |pmid= 8995764 |doi= }}
* {{cite journal | vauthors = Lehner B, Sanderson CM | title = A protein interaction framework for human mRNA degradation. | journal = Genome Res. | volume = 14 | issue = 7 | pages = 1315–23 | year = 2004 | pmid = 15231747 | pmc = 442147 | doi = 10.1101/gr.2122004 }}
*{{cite journal | author=Lorain S, Quivy JP, Monier-Gavelle F, ''et al.'' |title=Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA. |journal=Mol. Cell. Biol. |volume=18 |issue= 9 |pages= 5546-56 |year= 1998 |pmid= 9710638 |doi=  }}
* {{cite journal | vauthors = Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I | title = A genome annotation-driven approach to cloning the human ORFeome. | journal = Genome Biol. | volume = 5 | issue = 10 | pages = R84 | year = 2005 | pmid = 15461802 | pmc = 545604 | doi = 10.1186/gb-2004-5-10-r84 }}
*{{cite journal  | author=Magnaghi P, Roberts C, Lorain S, ''et al.'' |title=HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3. |journal=Nat. Genet. |volume=20 |issue= 1 |pages= 74-7 |year= 1998 |pmid= 9731536 |doi= 10.1038/1739 }}
* {{cite journal | vauthors = Gocke CB, Yu H, Kang J | title = Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates. | journal = J. Biol. Chem. | volume = 280 | issue = 6 | pages = 5004–12 | year = 2005 | pmid = 15561718 | doi = 10.1074/jbc.M411718200 }}
*{{cite journal | author=Hall C, Nelson DM, Ye X, ''et al.'' |title=HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression. |journal=Mol. Cell. Biol. |volume=21 |issue= 5 |pages= 1854-65 |year= 2001 |pmid= 11238922 |doi= 10.1128/MCB.21.5.1854-1865.2001 }}
* {{cite journal | vauthors = Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD | title = Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. | journal = Dev. Cell | volume = 8 | issue = 1 | pages = 19–30 | year = 2005 | pmid = 15621527 | doi = 10.1016/j.devcel.2004.10.019 }}
*{{cite journal | author=Lorain S, Lécluse Y, Scamps C, ''et al.'' |title=Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins. |journal=Biochim. Biophys. Acta |volume=1517 |issue= 3 |pages= 376-83 |year= 2001 |pmid= 11342215 |doi= }}
* {{cite journal | vauthors = Ahmad A, Kikuchi H, Takami Y, Nakayama T | title = Different roles of N-terminal and C-terminal halves of HIRA in transcription regulation of cell cycle-related genes that contribute to control of vertebrate cell growth. | journal = J. Biol. Chem. | volume = 280 | issue = 37 | pages = 32090–100 | year = 2005 | pmid = 16024922 | doi = 10.1074/jbc.M501426200 }}
*{{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 | vauthors = Tang Y, Poustovoitov MV, Zhao K, Garfinkel M, Canutescu A, Dunbrack R, Adams PD, Marmorstein R | title = Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. | journal = Nat. Struct. Mol. Biol. | volume = 13 | issue = 10 | pages = 921–9 | year = 2006 | pmid = 16980972 | pmc = 2933817 | doi = 10.1038/nsmb1147 }}
*{{cite journal | author=Lehner B, Sanderson CM |title=A protein interaction framework for human mRNA degradation. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1315-23 |year= 2004 |pmid= 15231747 |doi= 10.1101/gr.2122004 }}
* {{cite journal | vauthors = Zhang R, Chen W, Adams PD | title = Molecular dissection of formation of senescence-associated heterochromatin foci. | journal = Mol. Cell. Biol. | volume = 27 | issue = 6 | pages = 2343–58 | year = 2007 | pmid = 17242207 | pmc = 1820509 | doi = 10.1128/MCB.02019-06 }}
*{{cite journal | author=Collins JE, Wright CL, Edwards CA, ''et al.'' |title=A genome annotation-driven approach to cloning the human ORFeome. |journal=Genome Biol. |volume=5 |issue= 10 |pages= R84 |year= 2005 |pmid= 15461802 |doi= 10.1186/gb-2004-5-10-r84 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Gocke CB, Yu H, Kang J |title=Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates. |journal=J. Biol. Chem. |volume=280 |issue= 6 |pages= 5004-12 |year= 2005 |pmid= 15561718 |doi= 10.1074/jbc.M411718200 }}
*{{cite journal | author=Zhang R, Poustovoitov MV, Ye X, ''et al.'' |title=Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. |journal=Dev. Cell |volume=8 |issue= 1 |pages= 19-30 |year= 2005 |pmid= 15621527 |doi= 10.1016/j.devcel.2004.10.019 }}
*{{cite journal | author=Ahmad A, Kikuchi H, Takami Y, Nakayama T |title=Different roles of N-terminal and C-terminal halves of HIRA in transcription regulation of cell cycle-related genes that contribute to control of vertebrate cell growth. |journal=J. Biol. Chem. |volume=280 |issue= 37 |pages= 32090-100 |year= 2005 |pmid= 16024922 |doi= 10.1074/jbc.M501426200 }}
*{{cite journal | author=Tang Y, Poustovoitov MV, Zhao K, ''et al.'' |title=Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. |journal=Nat. Struct. Mol. Biol. |volume=13 |issue= 10 |pages= 921-9 |year= 2006 |pmid= 16980972 |doi= 10.1038/nsmb1147 }}
*{{cite journal | author=Zhang R, Chen W, Adams PD |title=Molecular dissection of formation of senescence-associated heterochromatin foci. |journal=Mol. Cell. Biol. |volume=27 |issue= 6 |pages= 2343-58 |year= 2007 |pmid= 17242207 |doi= 10.1128/MCB.02019-06 }}
}}
{{refend}}
{{refend}}


{{gene-22-stub}}
{{PDB Gallery|geneid=7290}}
{{WikiDoc Sources}}
 
[[Category:Genes mutated in mice]]

Revision as of 13:37, 31 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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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

Protein HIRA is a protein that in humans is encoded by the HIRA gene.[1][2][3][4] This gene is mapped to 22q11.21, centromeric to COMT.[4]

Function

The specific function of this protein has yet to be determined; however, it has been speculated to play a role in transcriptional regulation and/or chromatin and histone metabolism.[4]

Research done by Salomé Adam, Sophie E. Polo, and Geneviève Almouzni indicate that HIRA proteins are involved in restarting transcription after UVC damage[5] Function of HIRA gene can be effectively examined by siRNA knockdown based on an independent validation.[6]

Clinical significance

It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development.[4]

Model organisms

Model organisms have been used in the study of HIRA function. A conditional knockout mouse line, called Hiratm1a(EUCOMM)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty two tests were carried out on mutant mice and two significant abnormalities were observed.[9] No homozygous mutant mice survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased leukocyte cell number was recorded in male animals.[9]

Interactions

HIRA has been shown to interact with HIST1H2BK.[17]

References

  1. ↑ Halford S, Wadey R, Roberts C, Daw SC, Whiting JA, O'Donnell H, Dunham I, Bentley D, Lindsay E, Baldini A (Mar 1994). "Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease". Hum Mol Genet. 2 (12): 2099–107. doi:10.1093/hmg/2.12.2099. PMID 8111380.
  2. ↑ Lamour V, Lécluse Y, Desmaze C, Spector M, Bodescot M, Aurias A, Osley MA, Lipinski M (Sep 1995). "A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region". Hum Mol Genet. 4 (5): 791–9. doi:10.1093/hmg/4.5.791. PMID 7633437.
  3. ↑ Magnaghi P, Roberts C, Lorain S, Lipinski M, Scambler PJ (Oct 1998). "HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3". Nat Genet. 20 (1): 74–7. doi:10.1038/1739. PMID 9731536.
  4. ↑ 4.0 4.1 4.2 4.3 "Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)".
  5. ↑ Adam, S., Polo, S. E., & Almouzni, G. (2013). Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA. Cell, 155(1), 94-106. Retrieved from http://www.cell.com/abstract/S0092-8674(13)01023-4
  6. ↑ Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs (September 2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy. Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. ISSN 2162-2531. PMC 5056990. PMID 27673562.
  7. ↑ "Haematology data for Hira". Wellcome Trust Sanger Institute.
  8. ↑ "Salmonella infection data for Hira". Wellcome Trust Sanger Institute.
  9. ↑ 9.0 9.1 9.2 9.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  10. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ↑ "International Knockout Mouse Consortium".
  12. ↑ "Mouse Genome Informatics".
  13. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  14. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  15. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  16. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  17. ↑ Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M (September 1998). "Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA". Mol. Cell. Biol. 18 (9): 5546–56. PMC 109139. PMID 9710638.

Further reading

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