HRK (gene)

HRK

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2L58, 2L5B

Identifiers

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)^[1]

Band	12q24.22	Start	116,856,144 bp^[1]
Band	12q24.22	End	116,881,441 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 5 (mouse)^[2]

Band	5\|5 F	Start	118,302,713 bp^[2]
Band	5\|5 F	End	118,327,543 bp^[2]

RNA expression pattern

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


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

Species

Human

Mouse


8739


12123


ENSG00000135116


ENSMUSG00000046607


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

^[3]

^[4]

View/Edit Human

View/Edit Mouse

Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.^[5]^[6]

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.^[6]

Interactions

HRK (gene) has been shown to interact with:

BCL2-like 1,^[5]^[7]^[8] and
Bcl-2.^[5]^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000135116 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000046607 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c 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.
^ ^a ^b "Entrez Gene: HRK harakiri, BCL2 interacting protein (contains only BH3 domain)".
^ 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.
^ 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.
^ 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. 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.

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