Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (PIP4K2B)
The protein contains 416 amino acids for an estimated molecular weight of 47378 Da.
Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate (PubMed:9038203, PubMed:26774281). Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration (PubMed:26774281). Its GTP-sensing activity is critical for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process
Autophagosome-lysosome fusion
Cell surface receptor signaling pathway
Negative regulation of 1-phosphatidylinositol-4-phosphate 5-kinase activity
Negative regulation of insulin receptor signaling pathway
Phosphatidylinositol biosynthetic process
Phospholipid metabolic process
Positive regulation of autophagosome assembly
Regulation of autophagy
Regulation of phosphatidylinositol 3-kinase signaling
Regulation of signal transduction by p53 class mediator
Cellular Component
Autophagosome
Cytosol
Endoplasmic reticulum membrane
Nucleoplasm
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 603261
Phosphatidylinositol 4-phosphate 5-kinase, type ii, beta; pip5k2b
Phosphatidylinositol 5-phosphate 4-kinase, beta; pi5p4kb
Pip4k2b
DESCRIPTION
The final step in the synthesis of the second messenger phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) is the phosphorylation of PtdIns(4)P (also known as PIP) by type I PIP kinases, or the phosphorylation of PtdIns(5)P by type II PIP kinases (EC 2.7.1.149), such as PIP5K2B (Rameh et al., 1997; Lamia, 2004).CLONING
By searching sequence databases with the PIP5K2A (603140) sequence, Castellino et al. (1997) identified a human EST encoding PIP5K2B, which they symbolized PIP5KII-beta. They screened a human fetal brain cDNA library with the PIP5K2B EST and isolated the complete PIP5K2B coding sequence. The deduced 416-amino acid protein is 78% identical to PIP5K2A. Using SDS-PAGE, the authors estimated that bacterially expressed PIP5K2B has a molecular mass of 47 kD. Northern blot analysis detected a 6.3-kb PIP5K2B transcript which was abundantly expressed in several human tissues.GENE FUNCTION
Castellino et al. (1997) found that PIP5K2B interacts specifically with the juxtamembrane region of the p55 TNF receptor (TNFR1; 191190) and that PIP5K2B activity is increased in mammalian cells by treatment with TNF-alpha (191160). By biochemical analysis of mouse PtdIns kinases, Rameh et al. (1997) concluded that type I enzymes preferentially utilize PtdIns(4)P in the production of PtdIns(4,5)P2, whereas type II enzymes preferentially utilize PtdIns(5)P. They suggested that the earlier error in characterizing the activity of type II enzymes was due to the presence of contaminating PtdIns(5)P in commercial preparations of PtdIns(4)P.BIOCHEMICAL FEATURES
Rao et al. (1998) reported the structure of type II-beta phosphatidylinositol phosphate kinase (PIPKII-beta). The structure reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to 1 superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 angstrom basic flat face that suggests an electrostatic mechanism for plasma membrane targeting. Conserved basic residues form a putative phosphatidylinositol phosphate specificity site. The substrate-binding site is open on 1 side, consistent with dual specificity for phosphatidylinositol 3- and 5-phosphates. A modeled complex with membrane-bound substrate and ATP shows how a phosphoinositide kinase can phosphorylate its substrate in situ at the membrane interface.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PIP5K2B gene to chromosome 17 (TMAP SHGC-2348).ANIMAL MODEL
Lamia et al. (2004) generated mice lacking Pip5p4kb. Homozygous mutant mice were viable at slightly less than mendelian ratios. They were small and lean compared with wildtype littermates and remained lean on a high-fat diet. Insulin signaling through protein kinase Akt (see 164730) was enhanced in skeletal muscle and liver of mutant mice. Lamia et al. (2004) concluded that PIP5P4KB plays a role in determining insulin sensitivity and adiposity. ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 603261 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).