HIRA histone cell cycle regulator [Homo sapiens (human)] - Gene

Summary

Official Symbol: HIRAprovided by HGNC
Official Full Name: histone cell cycle regulatorprovided by HGNC
Primary source: HGNC:HGNC:4916
See related: Ensembl:ENSG00000100084 MIM:600237
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TUP1; DGCR1; TUPLE1
Summary: This gene encodes a histone chaperone that preferentially places the variant histone H3.3 in nucleosomes. Orthologs of this gene in yeast, flies, and plants are necessary for the formation of transcriptionally silent heterochomatin. This gene plays an important role in the formation of the senescence-associated heterochromatin foci. These foci likely mediate the irreversible cell cycle changes that occur in senescent cells. 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. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in thyroid (RPKM 43.4), bone marrow (RPKM 10.9) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 22q11.21

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	22	NC_000022.11 (19330701..19431696, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (19318221..19419247, complement)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

analysis of the trimeric HIRA, UBN1 and CABIN1 H3.3 histone chaperone complex
Title: Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.
These data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.
Title: Differential regulation of the histone chaperone HIRA during muscle cell differentiation by a phosphorylation switch.
Data show that histone chaperone HIRA co-localizes with viral genomes, binds to incoming viral and deposits histone H3.3 onto these.
Title: Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity.
Chromatin reassembly during double-strand break repair was dependent on the HIRA histone chaperone that is specific to the replication-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent canonical histones H3.1/H3.2.
Title: Nucleosome disassembly during human non-homologous end joining followed by concerted HIRA- and CAF-1-dependent reassembly.
RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation.
Title: RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.
H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements.
Title: H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements.
PHB has an unexpected nuclear role in human embryonic stem cells that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit.
Title: PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs.
The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of Tetralogy of Fallot.
Title: <i>HIRA</i> Gene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot.
These results support a model in which OGT modifies HIRA to regulate HIRA-H3.3 complex formation and H3.3 nucleosome assembly and reveal the mechanism by which OGT functions in cellular senescence.
Title: O-linked N-acetylglucosamine transferase (OGT) interacts with the histone chaperone HIRA complex and regulates nucleosome assembly and cellular senescence.
HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression.
Title: HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated (2012-08-28) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated (2012-08-28) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Cellular Senescence, organism-specific biosystem (from REACTOME)
Cellular Senescence, organism-specific biosystemCellular senescence involves irreversible growth arrest accompanied by phenotypic changes such as enlarged morphology, reorganization of chromatin through formation of senescence-associated heterochr...
Cellular responses to stress, organism-specific biosystem (from REACTOME)
Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
DNA Damage/Telomere Stress Induced Senescence, organism-specific biosystem (from REACTOME)
DNA Damage/Telomere Stress Induced Senescence, organism-specific biosystemReactive oxygen species (ROS), whose concentration increases in senescent cells due to oncogenic RAS-induced mitochondrial dysfunction (Moiseeva et al. 2009) or due to environmental stress, cause DNA...
Formation of Senescence-Associated Heterochromatin Foci (SAHF), organism-specific biosystem (from REACTOME)
Formation of Senescence-Associated Heterochromatin Foci (SAHF), organism-specific biosystemThe process of DNA damage/telomere stress induced senescence culminates in the formation of senescence associated heterochromatin foci (SAHF). These foci represent facultative heterochromatin that is...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:434686 (e-PCR)
- UniSTS:157206

STS-X89887 (e-PCR)
- UniSTS:14128

D22S609 (e-PCR)
- UniSTS:18525

D22S941 (e-PCR)
- UniSTS:150370

D22S942 (e-PCR)
- UniSTS:150371

RH27840 (e-PCR)
- UniSTS:84120

SHGC-58589 (e-PCR)
- UniSTS:94410

RH77784 (e-PCR)
- UniSTS:61133

D22S1095E (e-PCR)
- UniSTS:153811

D22S1039 (e-PCR)
- UniSTS:151775

D22S446 (e-PCR)
- UniSTS:259313

D22S447 (e-PCR)
- UniSTS:259314

D22S451 (e-PCR)
- UniSTS:259315

Homology

Homologs of the HIRA gene: The HIRA gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 258 organisms have orthologs with human gene HIRA
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
contributes_to nucleosome binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
DNA replication-independent nucleosome assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA replication-independent nucleosome assembly	IDA Inferred from Direct Assay more info	PubMed
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
chromatin silencing at centromere	IBA Inferred from Biological aspect of Ancestor more info	PubMed
gastrulation	IEA Inferred from Electronic Annotation more info
mitotic sister chromatid segregation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
muscle cell differentiation	IEA Inferred from Electronic Annotation more info
osteoblast differentiation	IEA Inferred from Electronic Annotation more info
regulation of chromatin silencing	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
transcription, DNA-templated	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
HIR complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
PML body	IEA Inferred from Electronic Annotation more info
chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
nuclear chromatin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear chromatin	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info
protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein HIRA

Names: DiGeorge critical region gene 1; HIR histone cell cycle regulation defective homolog A; TUP1-like enhancer of split protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009231.2 RefSeqGene

Range

5001..105996

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003325.4 → NP_003316.3 protein HIRA

See identical proteins and their annotated locations for NP_003316.3

Status: REVIEWED

Source sequence(s)

AC000079, AC000085, AC000092

Consensus CDS

CCDS13759.1

UniProtKB/Swiss-Prot

P54198

Related

ENSP00000263208.5, ENST00000263208.5

Conserved Domains (6) summary

COG2319
Location:7 → 372

WD40; WD40 repeat [General function prediction only]

cd00200
Location:7 → 352

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

pfam07569
Location:763 → 954

Hira; TUP1-like enhancer of split

pfam09453
Location:448 → 469

HIRA_B; HIRA B motif

pfam12341
Location:727 → 795

Mcl1_mid; Minichromosome loss protein, Mcl1, middle region

sd00039
Location:16 → 61

7WD40; WD40 repeat [structural motif]