Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (PPIP5K2)
The protein contains 1243 amino acids for an estimated molecular weight of 140407 Da.
Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at positions 1 or 3 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates at position 1 or 3 PP-InsP5, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). (updated: Oct. 16, 2019)
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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs17155115 | |
| dbSNP:rs12519525 | |
| dbSNP:rs12520040 | |
| dbSNP:rs17155138 | |
| dbSNP:rs17155147 | |
| DFNB100 |
No binding partner found
Biological Process
Inositol metabolic process
Inositol phosphate biosynthetic process
Inositol phosphate metabolic process
Sensory perception of sound
Small molecule metabolic process
Molecular Function
5-diphosphoinositol pentakisphosphate 3-kinase activity
Acid phosphatase activity
ATP binding
Diphosphoinositol-pentakisphosphate kinase activity
Inositol heptakisphosphate kinase activity
Inositol hexakisphosphate 1-kinase activity
Inositol hexakisphosphate 3-kinase activity
Inositol hexakisphosphate 5-kinase activity
Inositol hexakisphosphate kinase activity
Inositol-1,3,4,5,6-pentakisphosphate kinase activity
The reference OMIM entry for this protein is 611648
Histidine acid phosphatase domain-containing protein 1; hisppd1
Diphosphoinositol pentakisphosphate kinase 2; ppip5k2
Vip2
Kiaa0433
DESCRIPTION
Inositol phosphates (IPs) and diphosphoinositol phosphates (PP-IPs), also known as inositol pyrophosphates, act as cell signaling molecules. HISPPD1 has both IP6 kinase (EC 2.7.4.21) and PP-IP5 (also called IP7) kinase (EC 2.7.4.24) activities that produce the high-energy pyrophosphates PP-IP5 and PP2-IP4 (also called IP8), respectively (Fridy et al., 2007).CLONING
By sequencing clones obtained from a size-fractionated brain cDNA library, Ishikawa et al. (1997) cloned HISPPD1, which they designated KIAA0433. The deduced 1,243-amino acid protein had an apparent molecular mass of more than 100 kD by SDS-PAGE. RT-PCR analysis detected variable HISPPD1 expression in all tissues examined. Fridy et al. (2007) obtained full-length cDNAs encoding 2 homologs of yeast Vip1, HISPPD1 and HISPPD2A (610979), which they called VIP2 and VIP1, respectively. Like the yeast protein, both VIP1 and VIP2 have an N-terminal domain belonging to the ATP-grasp superfamily and a central domain similar to the histidine acid phosphatase family of enzymes. Fluorescence-tagged VIP2 localized primarily to the cytosol of transfected human embryonic kidney cells. By searching databases for homologs of rat Hisppd2a, or Ppip5k1, Choi et al. (2007) identified HISPPD1, which they called PPIP5K2. The deduced 1,222-amino acid PPIP5K2 protein has a calculated molecular mass of 138 kD. It shares 66% amino acid identity with rat and human PPIP5K1, with most divergence occurring in the C termini.GENE FUNCTION
Fridy et al. (2007) showed that recombinant human VIP2 exhibited robust, dose-dependent kinase activity and phosphorylated IP6 and 5-PP-IP5 to form PP-IP5 and PP2-IP4 in vitro. VIP2 had catalytic efficiencies for these substrates that were higher than those of VIP1. VIP2 also showed kinase activity in human embryonic kidney cells engineered to produce high levels of IP6 and 5-PP-IP5. Choi et al. (2007) reported that PPIP5K1 and PPIP5K2 phosphorylated PP-IP5 in vivo, but neither enzyme affected the cellular levels of any other IP. Both enzymes were more active against PP-IP5 than IP6 in vitro and in vivo, and neither showed inositol phosphate phosphatase activity, despite the presence of histidine acid phosphatase motifs. Lin et al. (2009) showed that IP8 produced by human VIP1 or VIP2 contained a pyrophosphate at position 5 of the inositol ring and another pyrophosphate at either position 1 or 3.MAPPING
By radiation hybrid analysis, Ishikawa et al. (1997) mapped the HISPPD1 gene to chromosome 5. ... More on the omim web site
Oct. 27, 2019: 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 611648 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed