Inositol monophosphatase 1 (IMPA1)
The protein contains 277 amino acids for an estimated molecular weight of 30189 Da.
Responsible for the provision of inositol required for synthesis of phosphatidylinositol and polyphosphoinositides and has been implicated as the pharmacological target for lithium action in brain. Has broad substrate specificity and can use myo-inositol monophosphates, myo-inositol 1,3-diphosphate, myo-inositol 1,4-diphosphate, scyllo-inositol-phosphate, D-galactose 1-phosphate, glucose-1-phosphate, glucose-6-phosphate, fructose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. (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.
- 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.
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| Variant | Description |
|---|---|
| dbSNP:rs204781 |
Biological Process
Inositol biosynthetic process
Inositol metabolic process
Inositol phosphate dephosphorylation
Inositol phosphate metabolic process
Phosphate-containing compound metabolic process
Phosphatidylinositol biosynthetic process
Phosphatidylinositol phosphate biosynthetic process
Signal transduction
Small molecule metabolic process
Molecular Function
Identical protein binding
Inositol monophosphate 1-phosphatase activity
Inositol monophosphate 3-phosphatase activity
Inositol monophosphate 4-phosphatase activity
Inositol monophosphate phosphatase activity
Lithium ion binding
Magnesium ion binding
Manganese ion binding
Protein homodimerization activity
The reference OMIM entry for this protein is 602064
Myo-inositol monophosphatase 1; impa1
CLONING
McAllister et al. (1992) cloned the gene encoding human enzyme IMPase (IMPA1).GENE STRUCTURE
Sjoholt et al. (1997) determined the genomic structure of the human IMPA1 gene. They found that it is composed of at least 9 exons and covers more than 20 kb of sequence on 8q21.13-q21.3. In the 3-prime untranslated part of the gene, they observed a G-to-A transition and also 2 short sequences similar to the inositol/cholin-responsive element consensus. They postulated that 2 additional IMPA-like transcripts originate from the human genome, 1 from a position close to IMPA1 itself on chromosome 8 and the other from 18p.GENE FUNCTION
Manic depressive psychosis (125480) is a serious psychiatric disorder that in many, but far from all, patients can be treated with lithium. IMPase has been postulated as a target for the mood-stabilizing effects of lithium. Variation in the 277-codon coding region of IMPA1 has not been observed in manic-depressive patients (Steen et al., 1996). Sjoholt et al. (1997) suggested that polymorphisms or mutations in the noncoding regions of this gene could influence the lithium response in psychiatric patients. In studies on the effect of lithium on Xenopus morphogenesis, Klein and Melton (1996) concluded that lithium acts through inhibition of glycogen synthase kinase beta-3 (GSK3B; 605004), and not through inhibition of IMPase. The authors suggested that their observations could provide insights into the pathogenesis and treatment of bipolar disorder.MAPPING
By PCR analysis of both CEPH megabase-insert YAC DNA pools and human/rodent somatic cell hybrid DNAs, Sjoholt et al. (1997) mapped the IMPA1 gene to 8q21.13-q21.3. ... More on the omim web site
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 602064 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed