Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (PIP5K1A)
The protein contains 562 amino acids for an estimated molecular weight of 62633 Da.
Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:8955136, PubMed:21477596, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (PubMed:19158393, PubMed:20660631). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Can also use phosphatidylinositol (PtdIns) as substrate in vitro (PubMed:22942276). Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (By similarity). Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (By similarity). Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production o (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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
Actin cytoskeleton reorganization
Activation of GTPase activity
Cell chemotaxis
Cell migration
Fibroblast migration
Focal adhesion assembly
Glycerophospholipid metabolic process
Keratinocyte differentiation
Obsolete positive regulation of glucose import in response to insulin stimulus
Phagocytosis
Phosphatidylinositol biosynthetic process
Phosphatidylinositol phosphate biosynthetic process
Phospholipid biosynthetic process
Phospholipid metabolic process
Protein localization to plasma membrane
Protein targeting to plasma membrane
Regulation of phosphatidylinositol 3-kinase signaling
Ruffle assembly
Signal transduction
Small molecule metabolic process
Cellular Component
Cytoplasm
Cytosol
Focal adhesion
Lamellipodium
Nuclear speck
Nucleoplasm
Nucleus
Plasma membrane
Ruffle membrane
Molecular Function
1-phosphatidylinositol-3-phosphate 4-kinase activity
1-phosphatidylinositol-3-phosphate 5-kinase activity
1-phosphatidylinositol-4-phosphate 5-kinase activity
1-phosphatidylinositol-5-kinase activity
ATP binding
Kinase binding
Phosphatidylinositol-3,4-bisphosphate 5-kinase activity
The reference OMIM entry for this protein is 603275
Phosphatidylinositol 4-phosphate 5-kinase, type i, alpha; pip5k1a
DESCRIPTION
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) synthesize phosphatidylinositol 4,5-bisphosphate by phosphorylating phosphatidylinositol 4-phosphate. See 603261.CLONING
By searching sequence databases with peptide sequences obtained from the 68-kD type I PIP5K purified from bovine erythrocytes, Loijens and Anderson (1996) identified a human EST encoding PIP5K1A, which they called PIP5KI-alpha. They screened a human fetal brain cDNA library and isolated full-length PIP5K1A cDNAs. The deduced 549-amino acid protein has the conserved kinase homology domain of PIP5K family members. Within this domain, PIP5K1A shows 83% and 35% amino acid identity with PIP5K1B (602745) and PIP5K2A (603140), respectively. Overall, the PIP5K1A and PIP5K1B proteins are 64% identical. Recombinant PIP5K1A expressed in bacteria had a molecular mass of approximately 66.3 kD by Western blot analysis. The authors isolated additional PIP5K1A cDNAs which they suggested represent splicing isoforms. Northern blot analysis detected a major 4.2-kb PIP5K1A transcript which had a wide tissue distribution.GENE FUNCTION
Using deletion mutant analysis, Ishihara et al. (1998) identified an approximately 380-amino acid minimal core sequence of mouse Pip5k1a that was sufficient for phosphatidylinositol 4-phosphate kinase activity. Overexpression of mouse Pip5k1a in COS-7 cells induced an increase in short actin fibers and a decrease in actin stress fibers. To determine roles for nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)), Mellman et al. (2008) set out to identify proteins that interact with the nuclear PIPK, PIPK1A. Mellman et al. (2008) found that PIPK1A colocalizes at nuclear speckles and interacts with a noncanonical poly(A) polymerase, TUT1 (610641), which they termed Star-PAP for 'nuclear speckle-targeted PIPK1A-regulated poly(A) polymerase,' and that the activity of TUT1 can be specifically regulated by PtdIns4,5P(2). TUT1 and PIPK1A function together in a complex to control the expression of select mRNAs, including the transcript encoding the key cytoprotective enzyme heme oxygenase-1 (141250) and other oxidative stress response genes, by regulating the 3-prime-end formation of their mRNAs. Mellman et al. (2008) concluded that, taken together, the data demonstrated a model by which phosphoinositide signaling works in tandem with complement pathways to regulate the activity of TUT1 (Star-PAP) and the subsequent biosynthesis of its target mRNA. Mellman et al. (2008) suggested that their results revealed a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression. By screening a human kinase small interfering RNA library, Pan et al. (2008) identified phosphatidylinositol 4-kinase type II-alpha (PI4K2A; 609763) and phosphatidylinositol 4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a (606359)-induced LRP6 (603507) phosphorylation at ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates through 'frizzled' (see 603408) and 'dishevelled' (see 601365), the latter of which directly interacted with and activated PIP5KI. In turn, phosphatidylinositol 4,5-bisphosphates regulated phosphorylation of LRP6 at thr1479 and ser1490. Pan et al. (2008) concluded that their study revealed a signaling mechanism for Wnt to regulate LRP6 ph ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603275 was added.