* 617104

PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE, TYPE II, GAMMA; PIP4K2C


Alternative titles; symbols

PIP4K2-GAMMA
PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE II, GAMMA; PIP5K2C


HGNC Approved Gene Symbol: PIP4K2C

Cytogenetic location: 12q13.3     Genomic coordinates (GRCh38): 12:57,591,192-57,603,418 (from NCBI)


TEXT

Description

PIP4K2C encodes a subunit of type-2 phosphatidylinositol-5-phosphate 4-kinase, which converts phosphatidylinositol-5-phosphate to phosphatidylinositol-4,5-bisphosphate (Shim et al., 2016).


Cloning and Expression

Using RT-PCR, Clarke et al. (2008) cloned human PIP4K2C, which they called PIP4K-gamma, from a brain cDNA library. Quantitative RT-PCR of adult mouse tissues showed that, compared with Pip4k2a (603140) and Pip4k2b (603261), Pip4k2c was highly expressed in kidney. Western blot analysis detected highest Pip4k2c expression in adult mouse kidney, brain, testis, ovary, and heart, with lower levels in liver, spleen, thymus, colon, and lung. Expression was not detected in adult mouse stomach, small intestine, adipose, blood, muscle, or pancreas. In situ hybridization of mouse kidney revealed that Pip4k2c expression was highest in cortex and outer medulla. Immunohistochemical analysis demonstrated primarily vesicular expression of Pip4k2c in epithelial cells of thick ascending limb and intercalated cells of collecting duct. PIP4K2C showed a partial Golgi localization in transfected kidney cell lines. Clarke et al. (2008) proposed that PIP4K2C may function in regulation of vesicular transport in specialized kidney epithelial cells.

Using in situ hybridization and immunohistochemistry in mouse brain, Clarke et al. (2009) found that Pip4k2c expression was restricted to neurons, particularly cerebellar Purkinje cells, hippocampal pyramidal cells, pyramidal cells in cerebral cortex, and mitral cells in olfactory bulb. Pip4k2c showed a vesicular distribution and partially colocalized with markers of cellular compartments of the endomembrane trafficking pathway. Pip4k2c expression became detectable after day 7 of postnatal development. Clarke et al. (2009) suggested that PIP4K2C may have a role in neuron function, particularly in regulation of vesicular transport, in specific brain regions.


Mapping

Gross (2016) mapped the PIP4K2C gene to chromosome 12q13.3 based on an alignment of the PIP4K2C sequence (GenBank BC028596) with the genomic sequence (GRCh38).


Gene Function

Using in vitro kinase assays, Clarke et al. (2008) found that recombinant human PIP4K2C was inactive. Immunoprecipitation experiments showed the PIP4K2C could interact with active PIP4K2A in vitro.


Animal Model

Shim et al. (2016) found that, like Pip4k2a -/- or Pip4k2b -/- mice, Pip4k2c -/- mice developed normally and had a normal life span. However, Pip4k2c -/- mice had increased inflammation and T-cell activation as they aged, resulting in autoimmunity. Pip4k2c -/- mice had increased Ifng (147570), Il12 (see 161561), and Il2 (147680) in plasma, and they had increased T-helper cell populations and decreased T-regulatory cell populations. Signaling through Mtorc1 (see 601231) was hyperactivated in several tissues of Pip4k2c -/- mice, and treatment with rapamycin reduced inflammation, plasma proinflammatory cytokines, and Mtorc1 signaling. Shim et al. (2016) concluded that PIP4K2C plays a role in regulation of the immune system via MTORC1 signaling.


REFERENCES

  1. Clarke, J. H., Emson, P. C., Irvine, R. F. Localization of phosphatidylinositol phosphate kinase II-gamma in kidney to a membrane trafficking compartment within specialized cells of the nephron. Am. J. Physiol. Renal Physiol. 295: F1422-F1430, 2008. [PubMed: 18753295, images, related citations] [Full Text]

  2. Clarke, J. H., Emson, P. C., Irvine, R. F. Distribution and neuronal expression of phosphatidylinositol phosphate kinase II-gamma in the mouse brain. J. Comp. Neurol. 517: 296-312, 2009. [PubMed: 19757494, images, related citations] [Full Text]

  3. Gross, M. B. Personal Communication. Baltimore, Md. 8/30/2016.

  4. Shim, H., Wu, C., Ramsamooj, S., Bosch, K. N., Chen, Z., Emerling, B. M., Yun, J., Liu, H., Choo-Wing, R., Yang, Z., Wulf, G. M., Kuchroo, V. K., Cantley, L. C. Deletion of the gene Pip4k2c, a novel phosphatidylinositol kinase, results in hyperactivation of the immune system. Proc. Nat. Acad. Sci. 113: 7596-7601, 2016. [PubMed: 27313209, images, related citations] [Full Text]


Contributors:
Matthew B. Gross - updated : 08/30/2016
Creation Date:
Paul J. Converse : 08/30/2016
mgross : 08/31/2016
mgross : 08/30/2016

* 617104

PHOSPHATIDYLINOSITOL 5-PHOSPHATE 4-KINASE, TYPE II, GAMMA; PIP4K2C


Alternative titles; symbols

PIP4K2-GAMMA
PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE, TYPE II, GAMMA; PIP5K2C


HGNC Approved Gene Symbol: PIP4K2C

Cytogenetic location: 12q13.3     Genomic coordinates (GRCh38): 12:57,591,192-57,603,418 (from NCBI)


TEXT

Description

PIP4K2C encodes a subunit of type-2 phosphatidylinositol-5-phosphate 4-kinase, which converts phosphatidylinositol-5-phosphate to phosphatidylinositol-4,5-bisphosphate (Shim et al., 2016).


Cloning and Expression

Using RT-PCR, Clarke et al. (2008) cloned human PIP4K2C, which they called PIP4K-gamma, from a brain cDNA library. Quantitative RT-PCR of adult mouse tissues showed that, compared with Pip4k2a (603140) and Pip4k2b (603261), Pip4k2c was highly expressed in kidney. Western blot analysis detected highest Pip4k2c expression in adult mouse kidney, brain, testis, ovary, and heart, with lower levels in liver, spleen, thymus, colon, and lung. Expression was not detected in adult mouse stomach, small intestine, adipose, blood, muscle, or pancreas. In situ hybridization of mouse kidney revealed that Pip4k2c expression was highest in cortex and outer medulla. Immunohistochemical analysis demonstrated primarily vesicular expression of Pip4k2c in epithelial cells of thick ascending limb and intercalated cells of collecting duct. PIP4K2C showed a partial Golgi localization in transfected kidney cell lines. Clarke et al. (2008) proposed that PIP4K2C may function in regulation of vesicular transport in specialized kidney epithelial cells.

Using in situ hybridization and immunohistochemistry in mouse brain, Clarke et al. (2009) found that Pip4k2c expression was restricted to neurons, particularly cerebellar Purkinje cells, hippocampal pyramidal cells, pyramidal cells in cerebral cortex, and mitral cells in olfactory bulb. Pip4k2c showed a vesicular distribution and partially colocalized with markers of cellular compartments of the endomembrane trafficking pathway. Pip4k2c expression became detectable after day 7 of postnatal development. Clarke et al. (2009) suggested that PIP4K2C may have a role in neuron function, particularly in regulation of vesicular transport, in specific brain regions.


Mapping

Gross (2016) mapped the PIP4K2C gene to chromosome 12q13.3 based on an alignment of the PIP4K2C sequence (GenBank BC028596) with the genomic sequence (GRCh38).


Gene Function

Using in vitro kinase assays, Clarke et al. (2008) found that recombinant human PIP4K2C was inactive. Immunoprecipitation experiments showed the PIP4K2C could interact with active PIP4K2A in vitro.


Animal Model

Shim et al. (2016) found that, like Pip4k2a -/- or Pip4k2b -/- mice, Pip4k2c -/- mice developed normally and had a normal life span. However, Pip4k2c -/- mice had increased inflammation and T-cell activation as they aged, resulting in autoimmunity. Pip4k2c -/- mice had increased Ifng (147570), Il12 (see 161561), and Il2 (147680) in plasma, and they had increased T-helper cell populations and decreased T-regulatory cell populations. Signaling through Mtorc1 (see 601231) was hyperactivated in several tissues of Pip4k2c -/- mice, and treatment with rapamycin reduced inflammation, plasma proinflammatory cytokines, and Mtorc1 signaling. Shim et al. (2016) concluded that PIP4K2C plays a role in regulation of the immune system via MTORC1 signaling.


REFERENCES

  1. Clarke, J. H., Emson, P. C., Irvine, R. F. Localization of phosphatidylinositol phosphate kinase II-gamma in kidney to a membrane trafficking compartment within specialized cells of the nephron. Am. J. Physiol. Renal Physiol. 295: F1422-F1430, 2008. [PubMed: 18753295] [Full Text: https://doi.org/10.1152/ajprenal.90310.2008]

  2. Clarke, J. H., Emson, P. C., Irvine, R. F. Distribution and neuronal expression of phosphatidylinositol phosphate kinase II-gamma in the mouse brain. J. Comp. Neurol. 517: 296-312, 2009. [PubMed: 19757494] [Full Text: https://doi.org/10.1002/cne.22161]

  3. Gross, M. B. Personal Communication. Baltimore, Md. 8/30/2016.

  4. Shim, H., Wu, C., Ramsamooj, S., Bosch, K. N., Chen, Z., Emerling, B. M., Yun, J., Liu, H., Choo-Wing, R., Yang, Z., Wulf, G. M., Kuchroo, V. K., Cantley, L. C. Deletion of the gene Pip4k2c, a novel phosphatidylinositol kinase, results in hyperactivation of the immune system. Proc. Nat. Acad. Sci. 113: 7596-7601, 2016. [PubMed: 27313209] [Full Text: https://doi.org/10.1073/pnas.1600934113]


Contributors:
Matthew B. Gross - updated : 08/30/2016

Creation Date:
Paul J. Converse : 08/30/2016

Edit History:
mgross : 08/31/2016
mgross : 08/30/2016