Target Information

Target General Information

Target ID

T47306 (Former ID: TTDR01132)

Target Name

Glucose-6-phosphate translocase (SLC37A4)

Synonyms

Transformation-related gene 19 protein; TRG19; TRG-19; Solute carrier family 37 member 4; PRO0685; Glucose-6-phosphate exchanger SLC37A4; Glucose-5-phosphate transporter; Glucose 5-phosphate transporter; G6PT1

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Gene Name

SLC37A4

Target Type

Literature-reported target

[1]

Function

Transports cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocates inorganic phosphate into the opposite direction. Forms with glucose-6-phosphatase the complex responsible for glucose production through glycogenolysis and gluconeogenesis. Hence, it plays a central role in homeostatic regulation of blood glucose levels. Inorganic phosphate and glucose-6-phosphate antiporter of the endoplasmic reticulum.

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BioChemical Class

Major facilitator

UniProt ID

G6PT1_HUMAN

Sequence

MAAQGYGYYRTVIFSAMFGGYSLYYFNRKTFSFVMPSLVEEIPLDKDDLGFITSSQSAAY
AISKFVSGVLSDQMSARWLFSSGLLLVGLVNIFFAWSSTVPVFAALWFLNGLAQGLGWPP
CGKVLRKWFEPSQFGTWWAILSTSMNLAGGLGPILATILAQSYSWRSTLALSGALCVVVS
FLCLLLIHNEPADVGLRNLDPMPSEGKKGSLKEESTLQELLLSPYLWVLSTGYLVVFGVK
TCCTDWGQFFLIQEKGQSALVGSSYMSALEVGGLVGSIAAGYLSDRAMAKAGLSNYGNPR
HGLLLFMMAGMTVSMYLFRVTVTSDSPKLWILVLGAVFGFSSYGPIALFGVIANESAPPN
LCGTSHAIVGLMANVGGFLAGLPFSTIAKHYSWSTAFWVAEVICAASTAAFFLLRNIRTK
MGRVSKKAE

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3D Structure

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AlphaFold

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Pathway Affiliation

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Carbohydrate digestion and absorption	hsa04973	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Regulators

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Target-regulating Transcription Factors

Target-regulating Transcription Factors Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 1 KEGG Pathways

Carbohydrate digestion and absorption

Pathwhiz Pathway

[+] 2 Pathwhiz Pathways

Gluconeogenesis

Mitochondrial Electron Transport Chain

Reactome

[+] 1 Reactome Pathways

Glucose transport

WikiPathways

[+] 2 WikiPathways

Metabolism of carbohydrates

Hexose transport

References

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REF 1

Identification of protein components of the microsomal glucose 6-phosphate transporter by photoaffinity labelling. Biochem J. 1999 May 1;339 ( Pt 3):629-38.

REF 2

Chlorogenic acid and synthetic chlorogenic acid derivatives: novel inhibitors of hepatic glucose-6-phosphate translocase. J Med Chem. 1997 Jan 17;40(2):137-45.

REF 3

Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus thom DSM 11247. Isolation and structural elucidation. J Antibiot (Tokyo). 2000 Jul;53(7):677-86.

REF 4

Studies toward the total synthesis of mumbaistatin, a highly potent glucose-6-phosphate translocase inhibitor. Synthesis of a mumbaistatin analogue. J Org Chem. 2002 Dec 27;67(26):9248-56.

REF 5

The chemical structure of mumbaistatin, a novel glucose-6-phosphate translocase inhibitor produced by Streptomyces sp. DSM 11641. J Antibiot (Tokyo). 2001 Apr;54(4):354-63.

REF 6

Prolonged blood glucose reduction in mrp-2 deficient rats (GY/TR(-)) by the glucose-6-phosphate translocase inhibitor S 3025. Biochim Biophys Acta. 2002 Jan 15;1569(1-3):105-10.

REF 7

Glucose release from GLUT2-null hepatocytes: characterization of a major and a minor pathway. Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E794-801.

REF 8

Normal kinetics of intestinal glucose absorption in the absence of GLUT2: evidence for a transport pathway requiring glucose phosphorylation and tr... Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11330-5.

REF 9

Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes. Biochem J. 2001 Sep 15;358(Pt 3):665-71.

REF 10

Alterations of carbohydrate and lipid intermediary metabolism during inhibition of glucose-6-phosphatase in rats. Eur J Pharmacol. 1999 Dec 10;386(1):75-82.

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