Protein VAC14 homolog (VAC14)
The protein contains 782 amino acids for an estimated molecular weight of 87973 Da.
The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. (updated: April 1, 2015)
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.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
Biological Process
Phosphatidylinositol biosynthetic process
Phospholipid metabolic process
Positive regulation of kinase activity
Regulation of lipid kinase activity
Signal transduction
Small molecule metabolic process
Viral process
The reference OMIM entry for this protein is 604632
Vac14, s. cerevisiae, homolog of; vac14
Associated regulator of pikfyve; arpikfyve
Tax1-binding protein 2; tax1bp2
Tax-reactive protein x; trx
DESCRIPTION
The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. VAC14 is a component of a trimolecular complex that tightly regulates the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE (609414) and the PtdIns(3,5)P2 phosphatase FIG4 (609390). VAC14 functions as an activator of PIKFYVE (Sbrissa et al., 2007).CLONING
Human T-cell lymphotropic virus type-1 (HTLV-1) encodes Tax1, a 40-kD protein that plays a key role in viral replication, transformation, and gene regulation. By screening a human Jurkat T-cell cDNA expression library with biologically active Tax1 protein to identify Tax1-binding proteins, Mireskandari et al. (1996) isolated a cDNA encoding VAC14, which they called TRX. The deduced 221-amino acid TRX protein is predominantly hydrophilic in its C-terminal region. Northern blot analysis of human tissues detected a major 3.5-kb TRX transcript in all tissues examined, namely brain, heart, lung, liver, pancreas, kidney, skeletal muscle, and placenta. However, Western blot analysis detected TRX expression only in lymphocytes and lymphocytic-derived cell lines. Sbrissa et al. (2004) obtained a full-length cDNA clone of human VAC14. The deduced protein contains 782 amino acids. Western blot analysis of human and other mammalian cell lines and of mouse tissues detected VAC14 at an apparent molecular mass of 82 kD. Fractionation and Western blot analysis of HEK293 human embryonic kidney cells revealed endogenous VAC14 in both cytosolic and membrane compartments. Immunohistochemical analysis of transfected COS cells showed that human VAC14 localized predominantly to the perinuclear region and also in more dispersed vesicles. HEAT repeats contain 2 antiparallel helices connected by a short loop and provide surfaces for protein-protein interactions. Jin et al. (2008) identified 17 HEAT repeats in mouse and human VAC14.GENE FUNCTION
Mireskandari et al. (1996) demonstrated a specific interaction between Tax1 and TRX by coimmunoprecipitation and Far Western blot analyses. Using immunohistochemical analysis, Sbrissa et al. (2004) showed that human VAC14 colocalized with mouse Pikfyve in the perinuclear region following cotransfection of COS cells. Knockdown of VAC14 expression in HEK293 cells did not alter cell morphology, but it sensitized cells to brief treatment with a weak base, which resulted in formation of cytoplasmic vacuoles and decreased production of PtsIns(3,5)P and PtdIns(5)P by PIKFYVE. Conversely, overexpression of VAC14 in HEK293 cells increased PIKFYVE protein levels and PIKFYVE activity. Reciprocal coimmunoprecipitation studies showed that endogenous Pikfyve and Vac14 interacted directly in rat PC12 cells, and the immunoprecipitates synthesized PtdIns(5)P and PtdIns(3,5)P2. Sbrissa et al. (2004) concluded that VAC14 is an activator of PIKFYVE, and thereby regulates PtdIns(3,5)P2 synthesis and intracellular membrane homeostasis. Using coimmunoprecipitation analysis, Sbrissa et al. (2007) showed that endogenous PIKFYVE, ARPIKFYVE, and SAC3 (FIG4) formed a stable ternary complex in HEK293 cells and other mammalian cell lines. Sbrissa et al. (2008) found that ARPIKFYVE interacted with both SAC3 and PIKFYVE and concluded that it is the principal organizer of the PIKFYVE-ARPIKFYVE-SAC3 (PAS) ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604632 was added.