HRK harakiri, BCL2 interacting protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: HRKprovided by HGNC
Official Full Name: harakiri, BCL2 interacting proteinprovided by HGNC
Primary source: HGNC:HGNC:5185
See related: Ensembl:ENSG00000135116 MIM:603447; AllianceGenome:HGNC:5185
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: DP5; HARAKIRI
Summary: This gene encodes a member of the BCL-2 protein family. Members of this family are involved in activating or inhibiting apoptosis. The encoded protein localizes to intracellular membranes. This protein promotes apoptosis by interacting with the apoptotic inhibitors BCL-2 and BCL-X(L) via its BH3 domain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]
Expression: Biased expression in brain (RPKM 5.1), thyroid (RPKM 2.9) and 3 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.22

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (116856144..116881441, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (116837255..116862509, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (117293949..117319246, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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 Functions

What's a GeneRIF?

Upregulated lncHRK2:1 prompts nucleus pulposus cell senescence in intervertebral disc degeneration.
Title: Upregulated lnc‑HRK‑2:1 prompts nucleus pulposus cell senescence in intervertebral disc degeneration.
YAP-Mediated Repression of HRK Regulates Tumor Growth, Therapy Response, and Survival Under Tumor Environmental Stress in Neuroblastoma.
Title: YAP-Mediated Repression of HRK Regulates Tumor Growth, Therapy Response, and Survival Under Tumor Environmental Stress in Neuroblastoma.
Characterization of an alternative BAK-binding site for BH3 peptides.
Title: Characterization of an alternative BAK-binding site for BH3 peptides.
In individuals with susceptible genetic backgrounds, Coxsackie B viral infection alters the epigenome to activate the pathological pathways leading to polymyositis-dermatomyositis via mitochondrial dysfunction and HRK up-regulation.
Title: Mitochondrial dysfunction and role of harakiri in the pathogenesis of myositis.
The apoptosis phenotype was partly dependent on HRK upregulation, as HRK knockdown significantly abrogated the sensitization. KDM2B-silenced tumors exhibited slower growth in vivo. Taken together, our findings suggest a novel mechanism, where the key apoptosis components are under epigenetic control of KDM2B in glioblastoma multiforme cells.
Title: KDM2B, an H3K36-specific demethylase, regulates apoptotic response of GBM cells to TRAIL.
miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human beta-cell apoptosis.
Title: MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.
our findings suggest that induction of the BH3-only protein Hrk is a critical step in 2-ME activation of the JNK-induced apoptotic pathway, targeting mitochondria by liberating proapoptotic protein Bak.
Title: Hrk mediates 2-methoxyestradiol-induced mitochondrial apoptotic signaling in prostate cancer cells.
SUZ12 promotes the proliferation of human EOC cells by inhibiting apoptosis and HRK is a novel SUZ12 target gene whose upregulation contributes to apoptosis induced by SUZ12 knockdown.
Title: SUZ12 promotes human epithelial ovarian cancer by suppressing apoptosis via silencing HRK.
Diva binds peptides derived from the BH3 domain of several other proapoptotic Bcl-2 proteins, including mouse Harakiri, Bid, Bak and Bmf.
Title: Nuclear magnetic resonance study of protein-protein interactions involving apoptosis regulator Diva (Boo) and the BH3 domain of proapoptotic Bcl-2 members.
The BH3-only protein harakiri (HRK) is transactivated by ATF4 in severe hypoxia through direct binding of ATF4 to the promoter region.
Title: ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia.

Submit: New GeneRIF Correction See all GeneRIFs (23)

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

EBI GWAS Catalog

Description
Common variants at 12q14 and 12q24 are associated with hippocampal volume. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of age-at-onset in Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of common variants associated with human hippocampal and intracranial volumes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:487026

SHGC-156031 (e-PCR)
- UniSTS:185002

SHGC-148297 (e-PCR)
- UniSTS:176305

NoName (e-PCR)
- UniSTS:485581

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: activator of apoptosis harakiri

Names: BH3-interacting domain-containing protein 3; activator of apoptosis Hrk; death protein 5; harakiri, BCL2 interacting protein (contains only BH3 domain); neuronal death protein DP5

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.

mRNA and Protein(s)

NM_003806.4 → NP_003797.1 activator of apoptosis harakiri

See identical proteins and their annotated locations for NP_003797.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the functional protein.

Source sequence(s)

AC083806, AK094730, BU623308, D83699, U76376

Consensus CDS

CCDS9181.1

UniProtKB/Swiss-Prot

O00198

Related

ENSP00000257572.4, ENST00000257572.5

Conserved Domains (1) summary

pfam15196
Location:1 → 91

Harakiri; Activator of apoptosis harakiri

RNA

NR_073189.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains three alternate internal exons, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC083806, AK094730, BE674890, BU623308, D83699