PIP4K2A

PIP4K2A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YBX
Identifiers
Aliases	PIP4K2A , PI5P4KA, PIP5K2A, PIP5KII-alpha, PIP5KIIA, PIPK, phosphatidylinositol-5-phosphate 4-kinase type 2 alpha
External IDs	OMIM: 603140; MGI: 1298206; HomoloGene: 37995; GeneCards: PIP4K2A; OMA:PIP4K2A - orthologs
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10p12.2 Start 22,534,854 bp [1] End 22,714,578 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 A3 Start 18,847,066 bp [2] End 19,002,937 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in inferior olivary nucleus internal globus pallidus inferior ganglion of vagus nerve external globus pallidus corpus callosum pars reticulata C1 segment dorsal motor nucleus of vagus nerve subthalamic nucleus Region I of hippocampus proper Top expressed in deep cerebellar nuclei anterior horn of spinal cord blood facial motor nucleus pontine nuclei thymus substantia nigra globus pallidus spleen medial vestibular nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding 1-phosphatidylinositol-4-phosphate 5-kinase activity kinase activity phosphatidylinositol phosphate kinase activity ATP binding 1-phosphatidylinositol-3-phosphate 4-kinase activity 1-phosphatidylinositol-5-phosphate 4-kinase activity protein binding Cellular component cytoplasm cytosol membrane plasma membrane autophagosome nucleus nucleoplasm Biological process megakaryocyte development phosphatidylinositol metabolic process positive regulation of autophagosome assembly phosphorylation regulation of autophagy phosphatidylinositol biosynthetic process phosphatidylinositol phosphate biosynthetic process regulation of phosphatidylinositol 3-kinase signaling phospholipid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5305 18718 Ensembl ENSG00000150867 ENSMUSG00000026737 UniProt P48426 O70172 RefSeq (mRNA) NM_005028 NM_001330062 NM_008845 NM_001355146 NM_001355147 NM_001355148 NM_001355149 RefSeq (protein) NP_001316991 NP_005019 NP_032871 NP_001342075 NP_001342076 NP_001342077 NP_001342078 Location (UCSC) Chr 10: 22.53 – 22.71 Mb Chr 2: 18.85 – 19 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Phosphatidylinositol-5-phosphate 4-kinase type-2 alpha is an enzyme that in humans is encoded by the PIP4K2A gene. ^{[5] [6] [7]}

Function

Phosphatidylinositol-4,5-bisphosphate, the precursor to second messengers of the phosphoinositide signal transduction pathways, is thought to be involved in the regulation of secretion, cell proliferation, differentiation, and motility. The protein encoded by this gene is one of a family of enzymes capable of catalyzing the phosphorylation of phosphatidylinositol-4-phosphate on the fifth hydroxyl of the myo-inositol ring to form phosphatidylinositol-4,5-bisphosphate.

The amino acid sequence of this enzyme does not show homology to other kinases, but the recombinant protein does exhibit kinase activity. This gene is a member of the phosphatidylinositol-4-phosphate 5-kinase family. ^[7]

Clinical significance

Through genome wide association studies (GWAS), some of the single nucleotide polymorphisms (SNPs) located in this gene have been noticed to be significantly associated with susceptibility of childhood acute lymphoblastic leukaemia i n ethnically diverse populations. ^{[8] [9]}

PIP4K2A Inhibitors

THZ-P1-2 ^[10] (covalent inhibitor) as well as BAY-091 and BAY-297 ^[11] (reversible inhibitors) have been reported as potent and selective PIP4K2A inhibitors. BAY-091 fulfills the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium. ^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000150867 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026737 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Boronenkov IV, Anderson RA (February 1995). "The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases". The Journal of Biological Chemistry. 270 (7): 2881–2884. doi: 10.1074/jbc.270.7.2881 . PMID   7852364.
6. Rameh LE, Tolias KF, Duckworth BC, Cantley LC (November 1997). "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate". Nature. 390 (6656): 192–196. Bibcode:1997Natur.390..192R. doi:10.1038/36621. PMID   9367159. S2CID   4403301.
7. "Entrez Gene: PIP5K2A phosphatidylinositol-4-phosphate 5-kinase, type II, alpha".
8. Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y, Cheng C, et al. (May 2013). "Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations". Journal of the National Cancer Institute. 105 (10): 733–742. doi:10.1093/jnci/djt042. PMC   3691938 . PMID   23512250.
9. Liao F, Yin D, Zhang Y, Hou Q, Zheng Z, Yang L, et al. (May 2016). "Association Between PIP4K2A Polymorphisms and Acute Lymphoblastic Leukemia Susceptibility". Medicine. 95 (18): e3542. doi:10.1097/MD.0000000000003542. PMC   4863780 . PMID   27149463.
10. Sivakumaren SC, Shim H, Zhang T, Ferguson FM, Lundquist MR, Browne CM, et al. (May 2020). "Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors". Cell Chemical Biology. 27 (5): 525–537.e6. doi:10.1016/j.chembiol.2020.02.003. PMC   7286548 . PMID   32130941.
11. Wortmann L, Bräuer N, Holton SJ, Irlbacher H, Weiske J, Lechner C, et al. (November 2021). "Discovery and Characterization of the Potent and Highly Selective 1,7-Naphthyridine-Based Inhibitors BAY-091 and BAY-297 of the Kinase PIP4K2A". Journal of Medicinal Chemistry. 64 (21): 15883–15911. doi: 10.1021/acs.jmedchem.1c01245 . PMID   34699202. S2CID   240000214.
12. "Donated Chemical Probes". 12 June 2018. Retrieved July 31, 2023.

Further reading

• Loijens JC, Boronenkov IV, Parker GJ, Anderson RA (1996). "The phosphatidylinositol 4-phosphate 5-kinase family". Advances in Enzyme Regulation. 36: 115–140. doi:10.1016/0065-2571(95)00005-4. PMID   8869744.
• Niiro H, Clark EA (November 2003). "Branches of the B cell antigen receptor pathway are directed by protein conduits Bam32 and Carma1". Immunity. 19 (5): 637–640. doi: 10.1016/S1074-7613(03)00303-0 . PMID   14614850.
• Carpenter CL (April 2004). "Btk-dependent regulation of phosphoinositide synthesis". Biochemical Society Transactions. 32 (Pt 2): 326–329. doi:10.1042/BST0320326. PMID   15046600.
• Tolias KF, Cantley LC, Carpenter CL (July 1995). "Rho family GTPases bind to phosphoinositide kinases". The Journal of Biological Chemistry. 270 (30): 17656–17659. doi: 10.1074/jbc.270.30.17656 . PMID   7629060.
• Divecha N, Truong O, Hsuan JJ, Hinchliffe KA, Irvine RF (August 1995). "The cloning and sequence of the C isoform of PtdIns4P 5-kinase". The Biochemical Journal. 309 (3): 715–9. doi:10.1042/bj3090715. PMC   1135690 . PMID   7639683.
• Rozenvayn N, Flaumenhaft R (March 2003). "Protein kinase C mediates translocation of type II phosphatidylinositol 5-phosphate 4-kinase required for platelet alpha-granule secretion". The Journal of Biological Chemistry. 278 (10): 8126–34. doi: 10.1074/jbc.M206493200 . PMID   12509423.
• Saito K, Tolias KF, Saci A, Koon HB, Humphries LA, Scharenberg A, et al. (November 2003). "BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity". Immunity. 19 (5): 669–678. doi: 10.1016/S1074-7613(03)00297-8 . PMID   14614854.
• Schwab SG, Knapp M, Sklar P, Eckstein GN, Sewekow C, Borrmann-Hassenbach M, et al. (September 2006). "Evidence for association of DNA sequence variants in the phosphatidylinositol-4-phosphate 5-kinase IIalpha gene (PIP5K2A) with schizophrenia". Molecular Psychiatry. 11 (9): 837–846. doi: 10.1038/sj.mp.4001864 . PMID   16801950.
• Bakker SC, Hoogendoorn ML, Hendriks J, Verzijlbergen K, Caron S, Verduijn W, et al. (March 2007). "The PIP5K2A and RGS4 genes are differentially associated with deficit and non-deficit schizophrenia". Genes, Brain and Behavior. 6 (2): 113–119. doi:10.1111/j.1601-183X.2006.00234.x. PMID   17410640. S2CID   32120485.
• He Z, Li Z, Shi Y, Tang W, Huang K, Ma G, et al. (August 2007). "The PIP5K2A gene and schizophrenia in the Chinese population--a case-control study". Schizophrenia Research. 94 (1–3): 359–365. doi:10.1016/j.schres.2007.04.013. PMID   17555944. S2CID   34716299.

External links

• Overview of all the structural information available in the PDB for UniProt : P48426 (Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha) at the PDBe-KB .