GPI
This gene encodes a member of the glucose phosphate isomerase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In the cytoplasm, the gene product functions as a glycolytic enzyme (glucose-6-phosphate isomerase) that interconverts glucose-6-phosphate and fructose-6-phosphate. Extracellularly, the encoded protein (also referred to as neuroleukin) functions as a neurotrophic factor that promotes survival of skeletal motor neurons and sensory neurons, and as a lymphokine that induces immunoglobulin secretion. The encoded protein is also referred to as autocrine motility factor based on an additional function as a tumor-secreted cytokine and angiogenic factor. Defects in this gene are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2016]
Full Name
Glucose-6-Phosphate Isomerase
Function
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).
Biological Process
Carbohydrate metabolic process Source: ProtInc
Erythrocyte homeostasis Source: Ensembl
Gluconeogenesis Source: GO_Central
Glucose 6-phosphate metabolic process Source: UniProtKB
Glucose homeostasis Source: Ensembl
Glycolytic process Source: GO_Central
Hemostasis Source: ProtInc
Humoral immune response Source: ProtInc
In utero embryonic development Source: Ensembl
Learning or memory Source: Ensembl
Mesoderm formation Source: Ensembl
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
Negative regulation of neuron apoptotic process Source: Ensembl
Positive regulation of endothelial cell migration Source: UniProtKB
Positive regulation of immunoglobulin production Source: CAFA
Response to cadmium ion Source: Ensembl
Response to estradiol Source: Ensembl
Response to immobilization stress Source: Ensembl
Response to morphine Source: Ensembl
Response to muscle stretch Source: Ensembl
Response to progesterone Source: Ensembl
Response to testosterone Source: Ensembl
Cellular Location
Secreted; Cytoplasm
Involvement in disease
Hemolytic anemia, non-spherocytic, due to glucose phosphate isomerase deficiency (HA-GPID):
A form of anemia in which there is no abnormal hemoglobin or spherocytosis. It is caused by glucose phosphate isomerase deficiency.
PTM
Phosphorylation at Ser-185 by CK2 has been shown to decrease enzymatic activity and may contribute to secretion by a non-classical secretory pathway.
ISGylated.
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Datasheet