HRK harakiri, BCL2 interacting protein (contains only BH3 domain) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: HRKprovided by HGNC
Official Full Name: harakiri, BCL2 interacting protein (contains only BH3 domain)provided by HGNC
Primary source: HGNC:5185
See related: HPRD:04581; MIM:603447
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]

Genomic context

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Location :: 12q24.22

Sequence :: Chromosome: 12; NC_000012.11 (117299027..117319232, complement)

See HRK in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

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.
Data suggest that DP5 and PUMA/BBC3 (p53 up-regulated modulator of apoptosis/bcl-2-binding component 3) contribute to palmitate-induced apoptosis of pancreatic beta-cells via lipotoxic endoplasmic reticulum stress.
Title: Death protein 5 and p53-upregulated modulator of apoptosis mediate the endoplasmic reticulum stress-mitochondrial dialog triggering lipotoxic rodent and human β-cell apoptosis.
These results are used to propose a tentative structural model of how Harakiri works.
Title: Intrinsic order and disorder in the bcl-2 member harakiri: insights into its proapoptotic activity.
analysis of a novel interaction between Bcl-2 members Diva and Harakiri
Title: Characterization of a novel interaction between Bcl-2 members Diva and Harakiri.
Observational study of gene-disease association. (HuGE Navigator)
Title: Germline variation in apoptosis pathway genes and risk of non-Hodgkin's lymphoma.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Aberrant 5'-CpG methylation status and loss of heterozygosity on 12q13.1 are associated with HRK expression in human malignancies, including prostate cancers, astrocytic tumors and primary central nervous system lymphomas. Review.
Title: The role of HRK gene in human cancer.
HRK appears to be inactivated principally by promoter hypermethylation in prostate cancers and decreased expression may play an important role in tumor progression by modulating apoptotic cell death
Title: HRK inactivation associated with promoter methylation and LOH in prostate cancer.
in response to PAHs, Ahr-mediated activation of the harakiri, BCL2 interacting protein (contains only BH3 domain), was necessary for execution of cell death.
Title: Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri.

Submit: New GeneRIF Correction See all (15)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Common variants at 12q14 and 12q24 are associated with hippocampal volume.

Genome-wide association analysis of age-at-onset in Alzheimer's disease.

Identification of common variants associated with human hippocampal and intracranial volumes.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_003797.1	NP_000624.1	BCL2	BIND	PubMed	Hrk interacts with Bcl-2.
NP_003797.1	NP_000624.1	BCL2	BIND	PubMed	Hrk interacts with Bcl-2.
NP_003797.1	NP_004040.1	BCL2A1	BIND	PubMed	Hrk interacts with A1. This interaction was modelled on a demonstrated interaction between human Hrk and mouse A1.
NP_003797.1	NP_612815.1	BCL2L1	BIND	PubMed	Hrk interacts with Bcl-XL.
NP_003797.1	NP_612815.1	BCL2L1	BIND	PubMed	Bcl-XL interacts with Hrk. This interaction was modelled on a demonstrated interaction between Bcl-XL from an unspecified species and human Hrk.
NP_003797.1	NP_612815.1	BCL2L1	BIND	PubMed	Hrk interacts with Bcl-XL.
NP_003797.1	NP_004041.1	BCL2L2	BIND	PubMed	Hrk interacts with Bcl-w.
NP_003797.1	NP_001708.2	BNC1	BIND	PubMed	Hrk interacts with Mcl-1. This interaction was modelled on a demonstrated interaction between human Hrk and mouse Mcl-1.
O00198	Q92934	BAD	HPRD	PubMed
O00198	P10415	BCL2	HPRD	PubMed
O00198	Q16548	BCL2A1	HPRD	PubMed
O00198	Q07817	BCL2L1	HPRD	PubMed
O00198	Q92843	BCL2L2	HPRD	PubMed
O00198	Q07021	C1QBP	HPRD	PubMed
BioGRID:114276	BioGRID:107068	BCL2	BioGRID	PubMed	Affinity Capture-Western; Protein-peptide; Two-hybrid
BioGRID:114276	BioGRID:107069	BCL2A1	BioGRID	PubMed	Protein-peptide
BioGRID:114276	BioGRID:107070	BCL2L1	BioGRID	PubMed	Affinity Capture-Western; FRET; Two-hybrid
BioGRID:114276	BioGRID:107071	BCL2L2	BioGRID	PubMed	Protein-peptide
BioGRID:114276	BioGRID:108309	ELAVL1	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:114276	BioGRID:110338	MCL1	BioGRID	PubMed	Protein-peptide

Pathways from BioSystems

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ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
ATF-2 transcription factor network, organism-specific biosystem
ATF-2 transcription factor network
Apoptosis, organism-specific biosystem (from WikiPathways)
Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
Apoptosis Modulation and Signaling, organism-specific biosystem (from WikiPathways)
Apoptosis Modulation and Signaling, organism-specific biosystemApoptosis, or cell death program, can be activated by various mechanisms within the extrinsic and the intrinsic pathway. While activation of cell death receptors leads to the engagement of the extrin...

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

Homology

Homologs of the HRK gene: The HRK gene is conserved in chimpanzee, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
apoptotic process	IEA Inferred from Electronic Annotation more info
induction of apoptosis	TAS Traceable Author Statement more info	PubMed
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein homooligomerization	IDA Inferred from Direct Assay more info
positive regulation of release of cytochrome c from mitochondria	IDA Inferred from Direct Assay more info

Component	Evidence Code	Pubs
integral to membrane	IEA Inferred from Electronic Annotation more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: activator of apoptosis harakiri

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

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_003806.2 → NP_003797.1 activator of apoptosis harakiri

Status: REVIEWED

Description

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

Source sequence(s)

AC083806, U76376

Consensus CDS

CCDS9181.1

UniProtKB/Swiss-Prot

O00198

RNA

NR_073189.1 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, BE674890

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p10 Primary Assembly

Range

117299027..117319232, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

114308520..114328689, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018923.1 Alternate CHM1_1.0

Range

117094602..117114807, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01020022.1 (190362..210531)	None
genomic	AC083806.16 (80686..101693)	None
genomic	AMYH01004779.1 (261497..281702)	None
genomic	CH471054.1	EAW98093.1
mRNA	BE674890.1	None
mRNA	D83699.1	None
mRNA	U76376.1	AAC34931.1
other-genetic	BC111923.1	AAI11924.1