Target Information

Target General Information

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Target ID

T14853 (Former ID: TTDI02072)

Target Name

Fibroblast growth factor-23 (FGF23)

Synonyms

Tumor-derived hypophosphatemia-inducing factor; Phosphatonin; HYPF; Fibroblast growth factor 23; FGF-23

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Gene Name

FGF23

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Vitamin/non-protein cofactor absorption/transport disorder [ICD-11: 5C63]

Function

Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.

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BioChemical Class

Growth factor

UniProt ID

FGF23_HUMAN

Sequence

MLGARLRLWVCALCSVCSMSVLRAYPNASPLLGSSWGGLIHLYTATARNSYHLQIHKNGH
VDGAPHQTIYSALMIRSEDAGFVVITGVMSRRYLCMDFRGNIFGSHYFDPENCRFQHQTL
ENGYDVYHSPQYHFLVSLGRAKRAFLPGMNPPPYSQFLSRRNEIPLIHFNTPIPRRHTRS
AEDDSERDPLNVLKPRARMTPAPASCSQELPSAEDNSPMASDPLGVVRGGRVNTHAGGTG
PEGCRPFAKFI

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3D Structure

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AlphaFold

HIT2.0 ID

T41BYM

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Burosumab

Drug Info

Approved

X-linked hypophosphataemia

[1]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 1 Modulator drugs

Burosumab

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Uridine-5'-Diphosphate

Ligand Info

Structure Description

Crystal structure of the TgGalNAc-T3 in complex with UDP, manganese and FGF23c

PDB:6S22

Method

X-ray diffraction

Resolution

1.96 Å

Mutation

[2]

PDB Sequence

NTPIPRRHTR

¹⁷⁹

Residue

Distance (Å)

ARG176

4.692

HIS177

3.112

Residue

Distance (Å)

THR178

2.698

Ligand Name: N-Acetyl-beta-D-galactosamine

Ligand Info

Structure Description

Crystal structure of the TgGalNAc-T3 in complex with UDP, manganese and FGF23c

PDB:6S22

Method

X-ray diffraction

Resolution

1.96 Å

Mutation

[2]

PDB Sequence

NTPIPRRHTR

¹⁷⁹

Residue

Distance (Å)

ASN170

4.587

THR171

1.427

PRO172

3.881

Residue

Distance (Å)

ILE173

3.837

PRO174

4.466

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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). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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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).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

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

KEGG Pathway	Pathway ID	Affiliated Target
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Regulation of actin cytoskeleton	hsa04810	Affiliated Target
Class: Cellular Processes => Cell motility	Pathway Hierarchy
Parathyroid hormone synthesis, secretion and action	hsa04928	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
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Degree	7	Degree centrality	7.52E-04	Betweenness centrality	1.07E-04
Closeness centrality	1.98E-01	Radiality	1.34E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	1.46E+01	Topological coefficient	3.14E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.

REF 2

Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3. Nat Chem Biol. 2020 Mar;16(3):351-360.

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