GPI

Protein identityUniProt · HPA

UniProt accession

P06744

Gene

GPI

Ensembl

ENSG00000105220

Chromosome

19

Canonical length

558 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Plasma membrane,Cytosol

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

558 residues, UniProt reviewed canonical sequence.

>P06744|GPI
     1  MAALTRDPQF QKLQQWYREH RSELNLRRLF DANKDRFNHF SLTLNTNHGH ILVDYSKNLV
    61  TEDVMRMLVD LAKSRGVEAA RERMFNGEKI NYTEGRAVLH VALRNRSNTP ILVDGKDVMP
   121  EVNKVLDKMK SFCQRVRSGD WKGYTGKTIT DVINIGIGGS DLGPLMVTEA LKPYSSGGPR
   181  VWYVSNIDGT HIAKTLAQLN PESSLFIIAS KTFTTQETIT NAETAKEWFL QAAKDPSAVA
   241  KHFVALSTNT TKVKEFGIDP QNMFEFWDWV GGRYSLWSAI GLSIALHVGF DNFEQLLSGA
   301  HWMDQHFRTT PLEKNAPVLL ALLGIWYINC FGCETHAMLP YDQYLHRFAA YFQQGDMESN
   361  GKYITKSGTR VDHQTGPIVW GEPGTNGQHA FYQLIHQGTK MIPCDFLIPV QTQHPIRKGL
   421  HHKILLANFL AQTEALMRGK STEEARKELQ AAGKSPEDLE RLLPHKVFEG NRPTNSIVFT
   481  KLTPFMLGAL VAMYEHKIFV QGIIWDINSF DQWGVELGKQ LAKKIEPELD GSAQVTSHDA
   541  STNGLINFIK QQREARVQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GPI can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

391 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GPI.

Disease | AllUniProt

Conditions GPI is implicated in, by any mechanism.

• Anemia, congenital, non-spherocytic hemolytic, 4 (CNSHA4) MIM:613470

Disease | GeneticClinVar

33 pathogenic / likely-pathogenic of 279 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hemolytic anemia due to glucophosphate isomerase deficiency
• Thyroid cancer, nonmedullary, 1
• Hereditary spherocytosis
• GPI-related disorder

Disease | ImmuneIEDB

Conditions an epitope on GPI was assayed in.

• multiple sclerosis B cell
• rheumatoid arthritis B cell
• amyotrophic lateral sclerosis B cell
• neuromyelitis optica B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against GPI are reported. Each links to that disease's full target list.

• Antiphospholipid Syndrome 49
• Arthritis, Rheumatoid 44
• Thrombosis 16
• Lupus Erythematosus, Systemic 12
• Arthritis 10
• Purpura, Thrombocytopenic, Idiopathic 4
• Venous Thrombosis 4
• Abortion, Habitual 3
• Atherosclerosis 3

Showing 9 of 14 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for GPI from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.69

gnomAD pLI

0

gnomAD missense Z

1.13

DepMap mean gene effect

-0.47

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• canonical glycolysis
• carbohydrate metabolic process
• erythrocyte homeostasis
• fructose 6-phosphate metabolic process
• gluconeogenesis
• glucose 6-phosphate metabolic process
• glucose homeostasis
• glycolytic process
• hemostasis
• humoral immune response
• in utero embryonic development
• learning or memory
• mesoderm formation
• negative regulation of apoptotic process
• negative regulation of glycolytic process through fructose-6-phosphate
• positive regulation of endothelial cell migration
• positive regulation of immunoglobulin production
• response to cadmium ion
• response to estradiol
• response to immobilization stress
• response to muscle stretch
• response to progesterone
• response to testosterone

Molecular functions

• carbohydrate derivative binding
• cytokine activity
• growth factor activity
• monosaccharide binding
• racemase and epimerase activity, acting on carbohydrates and derivatives
• ubiquitin protein ligase binding
• glucose-6-phosphate isomerase activity

Cellular components

• ciliary membrane
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• membrane
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• SIS domain superfamily
• Phosphoglucose isomerase (PGI)
• Phosphoglucose isomerase, conserved site
• Phosphoglucose isomerase, C-terminal
• Phosphoglucose isomerase, SIS domain 1
• Phosphoglucose isomerase, SIS domain 2
• Phosphoglucose isomerase

KeywordsUniProt

• Acetylation
• Cytokine
• Cytoplasm
• Gluconeogenesis
• Glycolysis
• Growth factor
• Hereditary hemolytic anemia
• Hydroxylation
• Isomerase
• Phosphoprotein
• Secreted
• Ubl conjugation