Phosphatidylinositol 4-kinase type 2-alpha (PI4K2A)

The protein contains 479 amino acids for an estimated molecular weight of 54022 Da.

 

Membrane-bound phosphatidylinositol-4 kinase (PI4-kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking and is required for prolonged survival of neurons. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 83%
Model score: 0
No model available.

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The reference OMIM entry for this protein is 609763

Phosphatidylinositol 4-kinase, type 2, alpha; pi4k2a
Phosphatidylinositol 4-kinase, type ii
Pi4kii
Pi4kii-alpha

DESCRIPTION

Phosphatidylinositolpolyphosphates (PtdInsPs) are centrally involved in many biologic processes, ranging from cell growth and organization of the actin cytoskeleton to endo- and exocytosis. PI4KII phosphorylates PtdIns at the D-4 position, an essential step in the biosynthesis of PtdInsPs (Barylko et al., 2001).

CLONING

Minogue et al. (2001) partially purified PI4KII from plasma membrane rafts isolated from human A431 epidermoid carcinoma cells. By peptide sequencing, database analysis, and RT-PCR of A431 total RNA, they obtained a full-length PI4KII cDNA. The deduced 479-amino acid protein has a calculated molecular mass of about 54 kD. PI4KII has a kinase domain and a leucine zipper, but no transmembrane sequence or acylation motif. Northern blot analysis detected a 6.6-kb transcript in all tissues examined. Expression was highest in kidney, brain, heart, skeletal muscle, and placenta, and was lowest in colon, thymus, and small intestine. Purified PI4KII had an apparent molecular mass of 52 kD by SDS-PAGE. Barylko et al. (2001) identified a cysteine-rich segment (CCPCC), a potential palmitoylation site, in rat and human PI4KII. By immunofluorescence localization, Wang et al. (2003) found that PI4KII localized to the Golgi in transfected COS-7 cells. Using microarray analysis, Li et al. (2010) found ubiquitous PI4K-alpha expression, with higher levels in brain, kidney, stomach, and lung, and lower levels in thyroid, dermis, breast, and fibrous tissue.

GENE FUNCTION

Minogue et al. (2001) assayed recombinant PI4KII expressed in bacteria and found that it phosphorylated PtdIns, but not PtdIns3P, PtdIns4P, or PtdIns5P. Like PI4KII purified from tissues, recombinant PI4KII was activated by detergent and inhibited by adenosine. Wang et al. (2003) found that overexpression of PI4KII in COS-7 cells increased synthesis of PtdIns4P. Some cells overexpressing PI4KII had scattered or no perinuclear Golgi. Knockdown of PI4KII by RNA interference (RNAi) did not disrupt the Golgi, and some cells showed expanded Golgi. RNAi reduced the Golgi level of PtdIns4P and blocked the association between AP1 (see 607291) and the trans-Golgi network (TGN). PI4KII RNAi had little effect on intra-Golgi trafficking, but it inhibited TGN-to-plasma membrane export by 35%. Wang et al. (2003) proposed that PI4KII generates PtdIns4P-rich domains within the Golgi that specify docking of the AP1 coat machinery. By screening a human kinase small interfering RNA library, Pan et al. (2008) identified PI4KII-alpha and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI; 603275) 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 phosphorylation. Li et al. (2010) found that PI4KII-alpha induced angiogenesis in mouse and human cells via activation of a HER2 (ERBB2; 164870)-PI3K (see PIK3CG; 601232)-ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948) signaling cascade, resulting in upregulation of HIF1-alph ... More on the omim web site

Subscribe to this protein entry history

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 609763 was added.