HRK (gene)

HRK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2L58, 2L5B
Identifiers
Aliases	HRK, DP5, HARAKIRI, harakiri, BCL2 interacting protein
External IDs	OMIM: 603447; MGI: 1201608; HomoloGene: 136405; GeneCards: HRK; OMA:HRK - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q24.22 Start 116,856,144 bp End 116,881,441 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 F Start 118,302,713 bp End 118,327,543 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell endothelial cell pancreatic ductal cell gonad testicle Brodmann area 23 hippocampus proper prefrontal cortex cingulate gyrus anterior cingulate cortex Top expressed in dentate gyrus of hippocampal formation granule cell superior frontal gyrus Rostral migratory stream trigeminal ganglion striatum of neuraxis primary visual cortex temporal lobe nucleus accumbens Region I of hippocampus proper dorsal striatum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component integral component of membrane membrane mitochondrion Biological process regulation of apoptotic process positive regulation of protein homooligomerization positive regulation of release of cytochrome c from mitochondria positive regulation of apoptotic process apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8739 12123 Ensembl ENSG00000135116 ENSMUSG00000046607 UniProt O00198 P62816 RefSeq (mRNA) NM_003806 NM_007545 RefSeq (protein) NP_003797 NP_031571 Location (UCSC) Chr 12: 116.86 – 116.88 Mb Chr 5: 118.3 – 118.33 Mb PubMed search
Wikidata
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Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.

Function

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.

Interactions

HRK (gene) has been shown to interact with:

• BCL2-like 1, and
• Bcl-2.

Further reading

• Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M (1999). "The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein". J. Biol. Chem. 274 (12): 7975–81. doi:10.1074/jbc.274.12.7975. PMID 10075695.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Sanz C, Mellstrom B, Link WA, Naranjo JR, Fernandez-Luna JL (2001). "Interleukin 3-dependent activation of DREAM is involved in transcriptional silencing of the apoptotic Hrk gene in hematopoietic progenitor cells". EMBO J. 20 (9): 2286–92. doi:10.1093/emboj/20.9.2286. PMC 125442. PMID 11331593.
• Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis. 6 (5): 319–30. doi:10.1023/A:1011319901057. PMID 11483855. S2CID 23119757.
• Wakabayashi T, Kosaka J, Hommura S (2002). "Up-regulation of Hrk, a regulator of cell death, in retinal ganglion cells of axotomized rat retina". Neurosci. Lett. 318 (2): 77–80. doi:10.1016/S0304-3940(01)02487-9. PMID 11796190. S2CID 45375137.
• Sanz C, Horita M, Fernandez-Luna JL (2004). "Fas signaling and blockade of Bcr-Abl kinase induce apoptotic Hrk protein via DREAM inhibition in human leukemia cells". Haematologica. 87 (9): 903–7. PMID 12217801.
• Jurisicova A, Antenos M, Varmuza S, Tilly JL, Casper RF (2003). "Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation". Mol. Hum. Reprod. 9 (3): 133–41. doi:10.1093/molehr/gag016. PMID 12606589.
• Whitfield J, Harada K, Bardelle C, Staddon JM (2004). "High-throughput methods to detect dimerization of Bcl-2 family proteins". Anal. Biochem. 322 (2): 170–8. doi:10.1016/j.ab.2003.07.014. PMID 14596824.
• Obata T, Toyota M, Satoh A, Sasaki Y, Ogi K, Akino K, Suzuki H, Murai M, Kikuchi T, Mita H, Itoh F, Issa JP, Tokino T, Imai K (2004). "Identification of HRK as a target of epigenetic inactivation in colorectal and gastric cancer". Clin. Cancer Res. 9 (17): 6410–8. PMID 14695142.
• Sunayama J, Ando Y, Itoh N, Tomiyama A, Sakurada K, Sugiyama A, Kang D, Tashiro F, Gotoh Y, Kuchino Y, Kitanaka C (2005). "Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32". Cell Death Differ. 11 (7): 771–81. doi:10.1038/sj.cdd.4401418. PMID 15031724.
• Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell. 17 (3): 393–403. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
• Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD (2005). "BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly". Mol. Cell. 17 (4): 525–35. doi:10.1016/j.molcel.2005.02.003. PMID 15721256.
• Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A (2006). "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members". Cancer Cell. 9 (5): 351–65. doi:10.1016/j.ccr.2006.03.027. PMID 16697956.