Glucose-6-phosphate isomerase (GPI)
The protein contains 558 amino acids for an estimated molecular weight of 63147 Da.
In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:28803808). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (PubMed:11437381). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:3352745, PubMed:11004567). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:3352745, PubMed:11004567). (updated: Sept. 18, 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.
- 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.
- 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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Aldehyde catabolic process
Angiogenesis
Canonical glycolysis
Carbohydrate metabolic process
Erythrocyte homeostasis
Gluconeogenesis
Glucose 6-phosphate metabolic process
Glucose homeostasis
Glucose metabolic process
Glycolytic process
Hemostasis
Humoral immune response
In utero embryonic development
Learning or memory
Mesoderm formation
Methylglyoxal biosynthetic process
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of neuron apoptotic process
Neutrophil degranulation
Pathogenesis
Positive regulation of endothelial cell migration
Positive regulation of immunoglobulin production
Positive regulation of immunoglobulin secretion
Response to cadmium ion
Response to estradiol
Response to immobilization stress
Response to morphine
Response to muscle stretch
Response to progesterone
Response to testosterone
Small molecule metabolic process
The reference OMIM entry for this protein is 172400
Glucose-6-phosphate isomerase; gpi
Glucose phosphate isomerase
Phosphohexose isomerase; phi
Phosphoglucose isomerase; pgi
Autocrine motility factor; amf
Neuroleukin; nlk
DESCRIPTION
The GPI gene encodes glucose phosphate isomerase (GPI; EC 5.3.1.9), also known as phosphohexose isomerase (PHI; D-glucose-6-phosphate ketol-isomerase) and phosphoglucose isomerase (PGI). GPI catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, the second step of the Embden-Meyerhof glycolytic pathway. GPI is also referred to as neuroleukin (NLK) and autocrine motility factor (AMF) (Niinaka et al., 1998).CLONING
Chaput et al. (1988) cloned the gene for pig muscle phosphohexose isomerase and found 90% homology to the sequence of mouse neuroleukin. In a similar study, Faik et al. (1988) isolated a mouse phosphoglucose isomerase cDNA clone and found complete identity between 759 nucleotides at the 3-prime end of this clone and the sequence of mouse neuroleukin. Thus it seemed likely that the molecule previously described as neuroleukin was in fact glucose phosphate isomerase. Gurney (1988) found that mouse and human neuroleukin cDNAs expressed GPI enzyme activity when transfected into monkey COS cells. Neuroleukin is a lymphokine produced by lectin-stimulated T cells. It induces immunoglobulin secretion by cultured human peripheral blood mononuclear cells. Neuroleukin acts early in the in vitro response that leads to formation of antibody-secreting cells. Continued production of immunoglobulin by differentiated antibody-secreting cells is neuroleukin-independent. NLK is not directly mitogenic; however, cellular proliferation is a late component of the response to this lymphokine. Gurney et al. (1986) found that NLK had no B-cell growth factor (BCGF) or B-cell differentiation factor (BCDF) activity in defined assays. Its induction of immunoglobulin secretion was found to be both monocyte- and T-cell-dependent. Gurney et al. (1986) found NLK in mouse salivary gland. It is a 56,000-dalton growth factor which is a neurotrophic factor as well as a lymphokine. It promotes the survival in culture of a subpopulation of embryonic spinal neurons that probably includes skeletal motor neurons. It also supports the survival of cultured sensory neurons that are insensitive to nerve growth factor but it has no effect on sympathetic or parasympathetic neurons. Gurney et al. (1986) found that the amino acid sequence of NLK is partly homologous to a highly conserved region of the external envelope protein of HTLV-III-LAV, the retrovirus that causes acquired immune deficiency syndrome (AIDS). Niinaka et al. (1998) used protein microsequencing to show that the 55-kD autocrine motility factor (AMF) is NLK. Although AMF, NLK, and GPI have different assigned functions, they are the products of a single gene. Niinaka et al. (1998) cloned the human AMF cDNA. The gene encodes a 558-amino acid polypeptide. Niinaka et al. (1998) showed that the different sizes of AMF observed in normal versus cancerous cells are not the result of alternative splicing; the mRNAs are identical. Immunofluorescence studies showed that AMF is localized primarily in tubular vesicles in the cytoplasm. AMF and its receptor (AMFR; 603243) partially colocalize on the malignant cell surface.GENE STRUCTURE
Walker et al. (1995) and Xu et al. (1995) found that the GPI gene spans more than 40 kb and consists of 18 exons ranging in size from 44 to 153 bp. All splice sites conformed to the GT/AG rule.MAPPING
Ritter et al. (1971) suggested that the PGI locus may be linked to the ABO locus. However, Hamerton et al. (197 ... More on the omim web site
Sept. 22, 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 172400 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed