HRK (gene)

Harakiri, BCL2 interacting protein
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2L58​, 2L5B​
Identifiers
Symbols	HRK ; DP5; HARAKIRI
External IDs	OMIM: 603447 MGI: 1201608 HomoloGene: 136405 GeneCards: HRK Gene
Gene ontology Molecular function • protein binding Cellular component • mitochondrion • integral component of membrane Biological process • apoptotic process • positive regulation of protein homooligomerization • positive regulation of apoptotic process • positive regulation of release of cytochrome c from mitochondria Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
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: 118.17 – 118.19 Mb
PubMed search

Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.^[1][2]

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.^[2]

Interactions

HRK (gene) has been shown to interact with:

• BCL2-like 1,^[1][3][4] and
• Bcl-2.^[1][5]

References

1. Inohara N, Ding L, Chen S, Núñez G (May 1997). "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)". EMBO J 16 (7): 1686–94. doi:10.1093/emboj/16.7.1686. PMC 1169772. PMID 9130713.
2. "Entrez Gene: HRK harakiri, BCL2 interacting protein (contains only BH3 domain)".
3. Whitfield J, Harada K, Bardelle C, Staddon JM (Nov 2003). "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.
4. Imaizumi K, Morihara T, Mori Y, Katayama T, Tsuda M, Furuyama T, Wanaka A, Takeda M, Tohyama M (Mar 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.
5. Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (Feb 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.

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.
• 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.
• 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.