Entry - *603289 - DEATH-ASSOCIATED PROTEIN KINASE 3; DAPK3 - OMIM
 
* 603289

DEATH-ASSOCIATED PROTEIN KINASE 3; DAPK3


Alternative titles; symbols

ZIP KINASE; ZIPK


HGNC Approved Gene Symbol: DAPK3

Cytogenetic location: 19p13.3     Genomic coordinates (GRCh38): 19:3,958,453-3,971,099 (from NCBI)


TEXT

Cloning and Expression

Saito et al. (1998) systematically screened serine/threonine protein kinases by reverse transcription-PCR with degenerated primers corresponding to the conserved regions of the protein kinase domain. One of the kinase genes identified showed a striking sequence homology to ZIP kinase reported by Kawai et al. (1998). Kawai et al. (1998) showed that human ZIPK encodes a deduced protein of 454 amino acids with a calculated molecular mass of 51.4 kD. The protein contains a kinase domain in its N terminus and a leucine zipper structure in its C terminus. The human and mouse proteins share 85% sequence identity. Northern blot analysis in mouse tissues showed ubiquitous expression. Immunostaining study showed that ZIPK localizes to the nucleus.


Gene Function

Kawai et al. (1998) showed that overexpression of ZIP kinase induced morphologic changes in apoptosis in mammalian cells, suggesting that it plays an important role in the induction of apoptosis.

Mukhopadhyay et al. (2008) noted that phosphorylation of ribosomal protein L13A (RPL13A; 619225) is essential for translational repression of inflammatory genes by the IFN-gamma (IFNG; 147570)-activated inhibitor of translation (GAIT) complex. They found that IFN-gamma activated a kinase cascade in which DAPK (DAPK1; 600831) activated ZIPK, which then phosphorylated RPL13A at ser77 in human U937 cells. RPL13A phosphorylation by DAPK-ZIPK was not only required for activation of RPL13A and subsequent release from the ribosome, but also for GAIT-mediated translational silencing. GAIT-mediated translational silencing then targeted and repressed DAPK and ZIPK expression to return RPL13A to the nonphosphorylated, inactive form. This negative-feedback circuit restored cells to the basal state, allowing subsequent renewed induction of GAIT target transcripts by repeated stimulation.


Mapping

By fluorescence in situ hybridization and by polymerase chain reaction-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, Saito et al. (1998) mapped the ZIPK gene to 19q13.3.


REFERENCES

  1. Kawai, T., Matsumoto, M., Takeda, K., Sanjo, H., Akira, S. ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Molec. Cell. Biol. 18: 1642-1651, 1998. [PubMed: 9488481, images, related citations] [Full Text]

  2. Mukhopadhyay, R., Ray, P. S., Arif, A., Brady, A. K., Kinter, M., Fox, P. L. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Molec. Cell 32: 371-382, 2008. [PubMed: 18995835, related citations] [Full Text]

  3. Saito, T., Seki, N., Ohira, M., Hayashi, A., Kozuma, S., Hattori, A., Hori, T. Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization. J. Hum. Genet. 43: 209-211, 1998. [PubMed: 9747039, related citations] [Full Text]


Contributors:
Bao Lige - updated : 03/08/2021
Creation Date:
Victor A. McKusick : 11/13/1998
mgross : 03/08/2021
carol : 09/26/2016
carol : 06/21/2012
carol : 6/21/2012
alopez : 7/15/1999
carol : 11/13/1998

* 603289

DEATH-ASSOCIATED PROTEIN KINASE 3; DAPK3


Alternative titles; symbols

ZIP KINASE; ZIPK


HGNC Approved Gene Symbol: DAPK3

Cytogenetic location: 19p13.3     Genomic coordinates (GRCh38): 19:3,958,453-3,971,099 (from NCBI)


TEXT

Cloning and Expression

Saito et al. (1998) systematically screened serine/threonine protein kinases by reverse transcription-PCR with degenerated primers corresponding to the conserved regions of the protein kinase domain. One of the kinase genes identified showed a striking sequence homology to ZIP kinase reported by Kawai et al. (1998). Kawai et al. (1998) showed that human ZIPK encodes a deduced protein of 454 amino acids with a calculated molecular mass of 51.4 kD. The protein contains a kinase domain in its N terminus and a leucine zipper structure in its C terminus. The human and mouse proteins share 85% sequence identity. Northern blot analysis in mouse tissues showed ubiquitous expression. Immunostaining study showed that ZIPK localizes to the nucleus.


Gene Function

Kawai et al. (1998) showed that overexpression of ZIP kinase induced morphologic changes in apoptosis in mammalian cells, suggesting that it plays an important role in the induction of apoptosis.

Mukhopadhyay et al. (2008) noted that phosphorylation of ribosomal protein L13A (RPL13A; 619225) is essential for translational repression of inflammatory genes by the IFN-gamma (IFNG; 147570)-activated inhibitor of translation (GAIT) complex. They found that IFN-gamma activated a kinase cascade in which DAPK (DAPK1; 600831) activated ZIPK, which then phosphorylated RPL13A at ser77 in human U937 cells. RPL13A phosphorylation by DAPK-ZIPK was not only required for activation of RPL13A and subsequent release from the ribosome, but also for GAIT-mediated translational silencing. GAIT-mediated translational silencing then targeted and repressed DAPK and ZIPK expression to return RPL13A to the nonphosphorylated, inactive form. This negative-feedback circuit restored cells to the basal state, allowing subsequent renewed induction of GAIT target transcripts by repeated stimulation.


Mapping

By fluorescence in situ hybridization and by polymerase chain reaction-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, Saito et al. (1998) mapped the ZIPK gene to 19q13.3.


REFERENCES

  1. Kawai, T., Matsumoto, M., Takeda, K., Sanjo, H., Akira, S. ZIP kinase, a novel serine/threonine kinase which mediates apoptosis. Molec. Cell. Biol. 18: 1642-1651, 1998. [PubMed: 9488481] [Full Text: https://doi.org/10.1128/MCB.18.3.1642]

  2. Mukhopadhyay, R., Ray, P. S., Arif, A., Brady, A. K., Kinter, M., Fox, P. L. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Molec. Cell 32: 371-382, 2008. [PubMed: 18995835] [Full Text: https://doi.org/10.1016/j.molcel.2008.09.019]

  3. Saito, T., Seki, N., Ohira, M., Hayashi, A., Kozuma, S., Hattori, A., Hori, T. Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization. J. Hum. Genet. 43: 209-211, 1998. [PubMed: 9747039] [Full Text: https://doi.org/10.1007/s100380050073]


Contributors:
Bao Lige - updated : 03/08/2021

Creation Date:
Victor A. McKusick : 11/13/1998

Edit History:
mgross : 03/08/2021
carol : 09/26/2016
carol : 06/21/2012
carol : 6/21/2012
alopez : 7/15/1999
carol : 11/13/1998