Target Information

Target General Information

Target ID

T57613 (Former ID: TTDR01198)

Target Name

TWIK-related acid-sensitive potassium channel 3 (TASK3)

Synonyms

Two pore potassium channel KT3.2; TWIK-related acid-sensitive K+ channel 3; KCNK9; Acid-sensitive potassium channel protein TASK-3

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Gene Name

KCNK9

Target Type

Literature-reported target

[1]

Function

pH-dependent, voltage-insensitive, background potassium channel protein.

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UniProt ID

KCNK9_HUMAN

Sequence

MKRQNVRTLSLIVCTFTYLLVGAAVFDALESDHEMREEEKLKAEEIRIKGKYNISSEDYR
QLELVILQSEPHRAGVQWKFAGSFYFAITVITTIGYGHAAPGTDAGKAFCMFYAVLGIPL
TLVMFQSLGERMNTFVRYLLKRIKKCCGMRNTDVSMENMVTVGFFSCMGTLCIGAAAFSQ
CEEWSFFHAYYYCFITLTTIGFGDYVALQTKGALQKKPLYVAFSFMYILVGLTVIGAFLN
LVVLRFLTMNSEDERRDAEERASLAGNRNSMVIHIPEEPRPSRPRYKADVPDLQSVCSCT
CYRSQDYGGRSVAPQNSFSAKLAPHYFHSISYKIEEISPSTLKNSLFPSPISSISPGLHS
FTDHQRLMKRRKSV

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3D Structure

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AlphaFold

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: L-serine-O-phosphate

Ligand Info

Structure Description

Crystal structure of human 14-3-3 sigma C38N/N166H in complex with TASK-3 peptide and stabilizer fusicoccin A

PDB:3P1S

Method

X-ray diffraction

Resolution

1.65 Å

Mutation

Yes

[2]

PDB Sequence

KRRKV

Residue

Distance (Å)

ARG370

4.675

ARG371

2.739

Residue

Distance (Å)

LYS372

1.330

VAL374

1.332

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Ligand Name: N-[(2S)-2-[(1E,3R,4S,8R,9R,10R,11S,14S)-4,9-dihydroxy-14-(methoxymethyl)-3,10-dimethyl-8-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(2-methylbut-3-en-2-yloxymethyl)oxan-2-yl]oxy-6-tricyclo[9.3.0.03,7]tetradeca-1,6-dienyl]propyl]acetamide

Ligand Info

Structure Description

14-3-3sigma in complex with a TASK3 peptide stabilized by semi-synthetic natural product FC-NAc

PDB:6GHP

Method

X-ray diffraction

Resolution

1.95 Å

Mutation

[3]

PDB Sequence

RRKV

Residue

Distance (Å)

VAL374

2.453

Residue

Distance (Å)

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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). Human Similarity Proteins Human Pathway Affiliation

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).

Human Similarity Proteins

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Voltage-gated potassium channel Kv10.2 (KCNH5)	PF00027 ; PF00520 ; PF13426 More >>	39.130 (18/46)	2.00E-03

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
Aldosterone synthesis and secretion	hsa04925	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Oncogenic potential of TASK3 (Kcnk9) depends on K+ channel function. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7803-7.

REF 2

A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface. Chem Biol. 2013 Apr 18;20(4):583-93.

REF 3

Rationally Designed Semisynthetic Natural Product Analogues for Stabilization of 14-3-3 Protein-Protein Interactions. Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13470-13474.

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