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HRK Gene

protein-coding GIFtS: 56

GC12M115761

harakiri, BCL2 interacting protein (contains only BH3 domain)
(Previous names: harakiri, BCL2-interacting protein (contains only BH3 domain) )
Symbol approved by the HUGO Gene Nomenclature Committee (HGNC) database

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc , and/or ⁷Ensembl, ⁸miRBase)
About This Section

Aliases
BID3 ^³
DP5 ^¹, ²
HARAKIRI ^²
harakiri ^²

Descriptions
BCL2-interacting protein ^²
BH3-interacting domain-containing protein 3 ^³
Neuronal death protein DP5 ^³
activator of apoptosis Hrk ^²
death protein 5 ^²
harakiri, BCL2 interacting protein (contains only BH3 domain) ^²
harakiri, BCL2-interacting protein (contains only BH3 domain) ^¹

External Ids
HGNC: 5185¹
Entrez Gene: 8739²
UniProtKB: O00198³
Ensembl: ENSG00000135116⁷

Search outside databases for aliases for HRK gene

Previous GC identifers: GC12M116138 GC12M116820 GC12M117081 GC12M115710

(According to Entrez Gene, Wikipedia's Gene Wiki,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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EntrezGene summary for HRK:

Activator of apoptosis Hrk regulates apoptosis through interaction with death-repressor proteins

Bcl-2 and Bcl-X(L). The HRK protein lacks significant homology to other BCL2 family members except

for an 8-amino acid region that was similar to the BCL2 homology domain-3 (BH3) motif of BIK. HRK

interacts with BCL2 and BCLXL via the BH3 domain, but not with the death-promoting BCL2-related

proteins BAX, BAK, or BCLXS. HRK localizes to membranes of intracellular organelles in a pattern

similar to that previously reported for BCL2 and BCLXL. [provided by RefSeq]

UniProtKB/Swiss-Prot: HRK_HUMAN, O00198

Function: Activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and

Bcl-X(L)

Gene Wiki entry for HRK

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 36),
and/or miRBase,
Genomic Views according to UCSC and Ensembl, Transcription factor binding sites according to SABiosciences)
About This Section

Genomic View:

UCSC Golden Path with GeneCards custom track

Transcription factor binding sites upstream to the HRK gene

Entrez Gene cytogenetic band: 12q24.22 Ensembl cytogenetic band: 12q24.22 HGNC cytogenetic band: 12q24.2

HRK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)

GeneLoc gene densities for chromosome 12 GeneLoc Exon Structure

GeneLoc location for GC12M115761: (about GC identifiers)

Start:	115,783,410 bp from pter
End:	115,803,615 bp from pter
Size:	20,206 bases
Orientation:	minus strand

RefSeq DNA sequence:

NC_000012.10 NT_009775.16

(According to ¹UniProtKB, and/or Ensembl, Phosphorylation sites according to ²Phosphosite, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Enzo Life Sciences, Abnova, OriGene and/or, Abcam,
Biochemical Assays by Invitrogen, Millipore, R&D Systems, Cell Signaling Technology, and/or Enzo Life Sciences, Ontologies according to Gene Ontology Consortium 01 Apr 2009 and Entrez Gene, Antibodies by Invitrogen, Millipore, Sigma-Aldrich, R&D Systems, Cell Signaling Technology, Abcam, Abnova, and/or Novus Biologicals)
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UniProtKB/Swiss-Prot: HRK_HUMAN, O00198 (See protein sequence)

Recommended Name: Activator of apoptosis harakiri

Size: 91 amino acids; 9884 Da

REFSEQ proteins: NP_003797.1

ENSEMBL proteins:

ENSP00000257572

Human Recombinant Proteins

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	R&D Systems Recombinant & Natural Proteins for HRK
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	Recombinant Proteins from Abcam (Hrk)
	Browse Abnova for Human Recombinant Proteins

OriGene Purified Recombinant Human Protein: HRK

Antibodies for HRK:

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	Browse Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Sigma-Aldrich Antibody Arrays and Antibodies for HRK
	R&D Systems Antibodies for HRK
	Antibodies from Abcam (Hrk), each with their Abpromise^SM
	Monoclonal and Polyclonal Antibodies from Abnova (HRK)
	Search Novus for antibodies for HRK

Assays for HRK:

	Browse Invitrogen for biochemical assays
	Browse Kits and Assays available from Millipore
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	Browse biochemical assays available from Enzo Life Sciences

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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Graphical View of Domain Structure for InterPro Entry O00198

ProtoNet protein and cluster: O00198

UniProtKB/Swiss-Prot: HRK_HUMAN, O00198

Domain: The BH3 motif is required for the induction of cell death

(According to MGI Jun 06 2009, UniProtKB, IUBMB,and/or Genatlas,
shRNA from OriGene, Sigma-Aldrich, RNAi from Sigma-Aldrich,
RNAi Products, Clones, and Q-PCR Products from Invitrogen, Millipore, OriGene, and/or Abnova, siRNAs from Applied Biosystems, SYBR primers from OriGene, Cell-based Assays from Millipore, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
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Inhib. RNA:		Browse Invitrogen for RNAi
		Browse for Gene Knock-down Tools from Millipore
		Browse Abnova for Chimera RNAi Products

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_003806

Applied Biosystems Silencer® siRNAs for HRK

Sigma-Aldrich siRNA and siRNA Panels for HRK

Sigma-Aldrich shRNA Panels and shRNA for HRK

Explore Sigma-Aldrich super-pooled esiRNAs

Clones:		Browse Clone Ranger at Invitrogen for clones
		Browse Clones for the Expression of Recombinant Proteins Available from Millipore

OriGene GFP tagged cDNA clone in CMV expression vector: NM_003806
Myc/DDK tagged cDNA clone in CMV expression vector: NM_003806
untagged cDNA clone in CMV expression vector: NM_003806

Primers:

Browse Quantitative PCR Central at Invitrogen for Q-PCR LUX™ Primers

OriGene genome-wide validated SYBR primer pairs: NM_003806

UniProtKB/Swiss-Prot: HRK_HUMAN, O00198

Function: Activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and

Bcl-X(L)

2 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Hrk):

cellular

nervous system

1 Gene Ontology (GO) molecular function term (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005515	protein binding	IPI	15694340 16697956

About this table

(Pathways according to Invitrogen (maps by GeneGo), Millipore, Cell Signaling Technology, Sigma-Aldrich, KEGG and/or UniProtKB,
Sets of similar genes according to GeneDecks, Proteins Network according to SABiosciences, Interactions according to ¹UniProtKB, ²MINT, and/or ³STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2009 via Entrez Gene.)
About This Section

Gene Network Central^TM Interacting Genes and Proteins Network for HRK

5/12 Interacting proteins for HRK (O00198¹ ENSP00000257572³) via UniProtKB, MINT, and/or STRING (see all 12 )

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
BCL2L1	Q07817¹, ENSP00000365230³	EBI-701322, EBI-78035 STRING (score=.999)
BCL2L2	Q92843¹, ENSP00000250405³	EBI-701322, EBI-707714 STRING (score=.853)
Bcl2a1 Bcl2a1 (xeno)	Q07440¹	EBI-701322, EBI-707754
BCL2	ENSP00000329623³	STRING (score=.998)
BCL2L7P1	ENSP00000353878³	STRING (score=.841)

About this table

3 Gene Ontology (GO) biological process terms (links to tree view):

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006917	induction of apoptosis	TAS	9130713
GO:0008634	negative regulation of survival gene product expression	TAS	9130713
GO:0042981	regulation of apoptosis	IEA	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, Sigma-Aldrich, Tocris Bioscience, and/or Novoseek and Drugs according to Enzo Life Sciences and/or PharmGKB)
About This Section

Browse drugs & compounds from Enzo Life Sciences

Browse Small Molecules at Sigma-Aldrich

Compounds for HRK available from Tocris Bioscience
1 Novoseek chemical compound relationship for HRK gene

Compound	Score	Articles	PubMed IDs for Articles with Shared Sentences (# sentences)
calcium	0.00	1	10779415 (1)

About this table

(GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 219 Homo sapiens; Jun 2 2009) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView,
non coding RNAs according to RNAdb,
ESTs according to GeneTide,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from Invitrogen, Millipore, and/or Abnova,
siRNAs from Applied Biosystems, Sigma-Aldrich,
shRNA from Sigma-Aldrich, OriGene,
Tagged/untagged cDNA clones from OriGene,
Expression Assays from Applied Biosystems)
About This Section

Inhib. RNA:		Browse Invitrogen for RNAi
		Browse for Gene Knock-down Tools from Millipore
		Browse Abnova for Chimera RNAi Products

OriGene 29mer shRNA kit in GFP-retroviral vector: NM_003806

Sigma-Aldrich siRNA and siRNA Panels for HRK

Sigma-Aldrich shRNA Panels and shRNA for HRK

Explore Sigma-Aldrich super-pooled esiRNAs

Applied Biosystems Silencer® siRNAs:

NM_003806

REFSEQ mRNAs for HRK gene:

NM_003806.1

Applied Biosystems TaqMan ® Gene Expression Assays:

NM_003806

              OriGene GFP tagged cDNA clone in CMV expression vector: NM_003806
                                 Myc/DDK tagged cDNA clone in CMV expression vector: NM_003806
                                 untagged cDNA clone in CMV expression vector: NM_003806

Additional cDNA sequence:

D83699.1 U76376.1

3 DOTS entries:

DT.308239 DT.100716408 DT.75136869

18 AceView cDNA sequences:

NM_003806 D83699 BX118100 U76376 C00709 AI083676 AA906802 AI762712

BV204371 BE674890 AA418229 BX351422 BX365952 BE165899 AI809746 BF093413

BF510077 BE247231

highest scoring ESTs for HRK:

D83699 AA418229 AA906802 AI083676 BF510077 U76376 AI809746 BE165899 BE247231 BE674890

Unigene Cluster for HRK:

Harakiri, BCL2 interacting protein (contains only BH3 domain)

Hs.87247 [show with all ESTs]

Unigene Representative Sequence: D83699

GeneLoc Exon Structure

2 Alternative Splicing Database (ASD) splice patterns (SP) for HRK

ExUns:	1	^	2	^	3	^	4	^	5
SP1:
SP2:			-		-		-

About this scheme

ECgene alternative splicing isoforms for HRK

1 Ensembl transcript including schematic representation:

ENST00000257572

(Experimental results according to ¹GeneNote and GNF BioGPS,
probe sets-to-genes annotations according to ²GeneAnnot , ³GeneTide , Sets of similar genes according to GeneDecks, Electronic Northern calculations according to data from UniGene (Build 219 Homo sapiens), SAGE tags according to CGAP, plus additional links to SOURCE, and/or GNF BioGPS, and/or EXPOLDB, and/or UniProtKB,
Expression Assays from Applied Biosystems )
About This Section

HRK expression in normal and diseased human tissues

Applied Biosystems TaqMan ® Gene Expression Assays for HRK

¹ / ² / ³

5 probe-sets matching HRK gene

Affymetrix probe-set	Array	# genes	Sensitivity	Specificity	Correlation	Length	Gb_Accession	Consensus	Uniqueness	Score	Rank
Affymetrix probe-set	Array	GeneAnnot data			GeneNote data		GeneTide data
34011_at²^{, 3}	U95-A	2	1.00	0.97	1.00	1.00	D83699	1.00	1.00	1.00	1
206865_at²^{, 3}	U133-A	1	1.00	1.00	--	--	U76376	0.80	1.00	0.91	1
206864_s_at²^{, 3}	U133-A	1	1.00	1.00	--	--	NM_003806	0.60	1.00	0.82	1
206865_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--
206864_s_at²	U133Plus2	1	1.00	1.00	--	--	--	--	--	--	--

About this table

Data from

(Publications) and GNF BioGPS
About these images
About these images

CGAP SAGE TAG: TGGCGGCGCC

SOURCE GeneReport for Unigene cluster: Hs.87247
Expression variation in blood from EXPOLDB for HRK

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD and/or ⁵MGI Jun 06 2009, with possible further links to Flybase and/or WormBase, Gene Trees according to Ensembl)
About This Section

Orthologs for HRK gene from 3 species

Organism	Gene	Locus	Description	Human Similarity	NCBI accessions
dog (Canis familiaris)	HRK¹	--	harakiri, BCL2 interacting protein (contains only BH3 more	96.7(n) 97.8(a)	612984 XM_848964.1 XP_854057.1
rat (Rattus norvegicus)	Hrk¹	--	harakiri, BCL2 interacting protein (contains only BH3 more	81.82(n) 76.14(a)	117271 NM_057130.1 NP_476471.1
mouse (Mus musculus)	Hrk^{1, 5}	5⁵	harakiri, BCL2 interacting protein (contains only BH3 more^{1, 5}	82.2(n)¹ 76.14(a)¹	12123¹ NM_007545.2¹ NP_031571.1¹ AI838259⁵ BC128022⁵ (see all 8)

About this table Species with no ortholog for HRK

ENSEMBL Gene Tree for HRK

(Paralogs according to ¹HomoloGene
and ²Ensembl, Pseudogenes according to ³Pseudogene.org)
About This Section

(According to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, and UniProtKB, Linkage Disequilibrium by HapMap, Genotyping Reagents from Applied Biosystems)
About This Section

10/107 NCBI SNPs in HRK are shown (see all 107 )
(Click for Applied Biosystems TaqMan ® Genotyping Assay) (see all 50)

AB	SNP ID	Valid	Chr 12 pos	Sequence	Recs	AA Chg	Type	More	Recs	Pop	Total sample	More
AB	Genomic Data				Transcription Data				Allele Frequencies
				--	--	--		--	--			--
	rs3809194^1,2	A,C,F,H	115804279(+)	`GGCACC/TCGCAC`	1	--	ng3¹		2	EU WA	208
--	rs7132910^1,2	A,C,F,H	115805041(+)	`aagggT/Ctcttg`	1	--	ng3¹		4	EU EA WA	412
	rs7315280^1,2	A,C,F	115805321(+)	`TCTTTA/GCAGAG`	1	--	ng3¹		4	NA EA	362
	rs884378^1,2	A,C,F,H,O	115792581(-)	`GATGAC/TGCCTA`	1	--	int¹		12	EU EA WA NA	972
	rs4766807^1,2	A,C,F,H	115785834(+)	`TAGTCA/TATGTC`	1	--	int¹		15	EU EA WA NA	1324
	rs9669553^1,2	A,C,F,H	115799732(+)	`CTTCCC/TGGGAG`	1	--	int¹		4	EU EA WA	416
	rs730512^1,2	A,C,F,H	115791685(+)	`CCAGCG/ACagat`	1	--	int¹		2	EU WA	216
	rs7972948^1,2	A,C,F,H	115796582(+)	`TTCCTC/TTTCAA`	1	--	int¹		4	EU EA WA	420
	rs11068214^1,2	C,F,H	115784744(+)	`AGGGCC/TGGGGC`	1	--	int¹		4	EU EA WA	418
	rs16947094^1,2	C,F,H	115788731(+)	`GTGGAA/GAGGAA`	1	--	int¹ trp³		11	NA EU EA WA	962

About this table

HapMap Linkage Disequilibrium images for HRK (up to first 250kb)

(in which this Gene is Involved, According to OMIM, UniProtKB, PharmGKB, Genatlas, GeneTests, Blood group antigen gene mutations by BGMUT, HGMD, GAD, HuGE Navigator, BCGD, and/or TGDB.)
About This Section

OMIM: 603447

(Possibly Related Articles in Doctor's Guide)
About This Section

(in PubMed. Associations of this gene to articles via ¹Novoseek, ²HGNC, ³Entrez Gene, ⁴UniProtKB/Swiss-Prot, ⁵UniProtKB/TrEMBL, ⁶GAD, and/or ⁷PharmGKB)
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10/30 PubMed articles for HRK gene (see all 30 ):

Harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). (PubMed id 9130713)^{2, 3, 4} Inohara N.... Nunez G. (1997)
Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells. (PubMed id 12217801)^{1, 3} Sanz C....Fernandez-Luna J.L. (2002)
Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation. (PubMed id 12606589)^{1, 3} Jurisicova A....Casper R.F. (2003)
Maternal exposure to polycyclic aromatic hydrocarbons diminishes murine ovarian reserve via induction of Harakiri. (PubMed id 18037991)^{1, 3} Jurisicova A....Casper R.F. (2007)
Interleukin 3-dependent activation of DREAM is involved in transcriptional silencing of the apoptotic Hrk gene in hematopoietic progenitor cells. (PubMed id 11331593)^{1, 3} Sanz C....Fernandez-Luna J.L. (2001)
HRK inactivation associated with promoter methylation and LOH in prostate cancer. (PubMed id 18008329)³ Higuchi T....Konishi N. (2008)
Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. (PubMed id 16697956)³ Certo M....Letai A. (2006)
Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. (PubMed id 15694340)³ Chen L....Huang D.C. (2005)
BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. (PubMed id 15721256)³ Kuwana T....Newmeyer D.D. (2005)
Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32. (PubMed id 15031724)³ Sunayama J....Kitanaka C. (2004)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, and/or H-InvDB)
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Entrez Gene: 8739	HGNC: 5185	AceView: HRK	Ensembl:ENSG00000135116	euGenes: HUgn8739
ECgene: HRK	H-InvDB: HRK

(According to HUGE)
About This Section

(According to ATLAS, HORDE, IMGT, MTDB, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
ATLAS Chromosomes in Cancer entry for HRK	Genetics and Cytogenetics in Oncology and Haematology

Licensable Technologies for HRK
(Available from WIS Yeda, Salk, Tufts)

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(Reagents available from Applied Biosystems, Antibodies and assays by Cell Signaling Technology, Abcam, Novus Biologicals,
Sigma-Aldrich, R&D Systems, Millipore, Abnova, and/or Invitrogen, Clones available from OriGene,and/or Invitrogen, Drugs and/or compounds by Sigma-Aldrich,
Enzo Life Sciences, and/or Tocris Bioscience)
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Products for HRK:

TaqMan ® Gene Expression Assays

TaqMan ® Genotyping Assays

Free SNP selection tool

Invitrogen iPath Pathways	Invitrogen BLOCK-iT™ RNAi
Invitrogen Antibodies	Invitrogen Assays
Invitrogen Clones	Invitrogen Q-PCR Products
Invitrogen Human Recombinant Kinases	Invitrogen Custom Antibody and Peptide Service
Invitrogen Proteins / Assays / Screening Services	Search Invitrogen catalog for HRK-related products

	Millipore Custom Antibody & Bulk Services
	Millipore Preclinical / Clinical Development Services
	Millipore Immunoassay Services
	Millipore Target Screening & Profiling Services

	Predesigned and custom siRNAs for HRK		Antibodies for HRK
	Explore super-pooled esiRNAs		Browse proteins at Sigma-Aldrich
	Lentivirus-delivered shRNAs for HRK		Browse small molecules at Sigma-Aldrich
	"Your Favorite Gene" Pathways		feedback

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Tocris compounds for HRK

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HRK Gene

protein-coding GIFtS: 56

Aliases &
Descriptions
for HRK

Summaries
for HRK

Genomic Location
for HRK

Proteins
for HRK

Protein Domains/
Families
for HRK

Gene Function
for HRK

Pathways & Interactions
for HRK

Drugs & Compounds
for HRK

Transcripts
for HRK

Expression
for HRK

Orthologs
for HRK

Paralogs
for HRK

SNPs/Variants
for HRK

Disorders & Mutations
for HRK

Medical News
for HRK

Publications
for HRK

Search for HRK

Genome Databases showing HRK

Other Databases showing HRK

Specialized Databases showing HRK

Licensable Technologies
for HRK

Services
for HRK

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

HRK Gene

protein-coding GIFtS: 56

Aliases & Descriptionsfor HRK

Summariesfor HRK

Genomic Locationfor HRK

Proteinsfor HRK

Protein Domains/Familiesfor HRK

Gene Functionfor HRK

Pathways & Interactionsfor HRK

Drugs & Compoundsfor HRK

Transcriptsfor HRK

Expression for HRK

Orthologsfor HRK

Paralogsfor HRK

SNPs/Variantsfor HRK

Disorders & Mutationsfor HRK

Medical Newsfor HRK

Publicationsfor HRK

Search for HRK

Genome Databases showing HRK

Other Databases showing HRK

Specialized Databases showing HRK

Licensable Technologiesfor HRK

Servicesfor HRK

Gene Index: 3 5 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

Aliases &
Descriptions
for HRK

Summaries
for HRK

Genomic Location
for HRK

Proteins
for HRK

Protein Domains/
Families
for HRK

Gene Function
for HRK

Pathways & Interactions
for HRK

Drugs & Compounds
for HRK

Transcripts
for HRK

Expression
for HRK

Orthologs
for HRK

Paralogs
for HRK

SNPs/Variants
for HRK

Disorders & Mutations
for HRK

Medical News
for HRK

Publications
for HRK

Licensable Technologies
for HRK

Services
for HRK