Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTH6UZY)

• DTT Name: Solute carrier family 12 member 5 (SLC12A5)
• Synonyms: hKCC2; SLC12A5; Neuronal K-Cl cotransporter; K-Cl cotransporter 2; Electroneutral potassium-chloride cotransporter 2
• Gene Name: SLC12A5
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Cation-chloride cotransporter
• UniProt ID: S12A5_HUMAN
• TTD ID: T22302
• Sequence:
  MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVKGDGNPKESSPFINSTDTEKG
  KEYDGKNMALFEEEMDTSPMVSSLLSGLANYTNLPQGSREHEEAENNEGGKKKPVQAPRM
  GTFMGVYLPCLQNIFGVILFLRLTWVVGIAGIMESFCMVFICCSCTMLTAISMSAIATNG
  VVPAGGSYYMISRSLGPEFGGAVGLCFYLGTTFAGAMYILGTIEILLAYLFPAMAIFKAE
  DASGEAAAMLNNMRVYGTCVLTCMATVVFVGVKYVNKFALVFLGCVILSILAIYAGVIKS
  AFDPPNFPICLLGNRTLSRHGFDVCAKLAWEGNETVTTRLWGLFCSSRFLNATCDEYFTR
  NNVTEIQGIPGAASGLIKENLWSSYLTKGVIVERSGMTSVGLADGTPIDMDHPYVFSDMT
  SYFTLLVGIYFPSVTGIMAGSNRSGDLRDAQKSIPTGTILAIATTSAVYISSVVLFGACI
  EGVVLRDKFGEAVNGNLVVGTLAWPSPWVIVIGSFFSTCGAGLQSLTGAPRLLQAISRDG
  IVPFLQVFGHGKANGEPTWALLLTACICEIGILIASLDEVAPILSMFFLMCYMFVNLACA
  VQTLLRTPNWRPRFRYYHWTLSFLGMSLCLALMFICSWYYALVAMLIAGLIYKYIEYRGA
  EKEWGDGIRGLSLSAARYALLRLEEGPPHTKNWRPQLLVLVRVDQDQNVVHPQLLSLTSQ
  LKAGKGLTIVGSVLEGTFLENHPQAQRAEESIRRLMEAEKVKGFCQVVISSNLRDGVSHL
  IQSGGLGGLQHNTVLVGWPRNWRQKEDHQTWRNFIELVRETTAGHLALLVTKNVSMFPGN
  PERFSEGSIDVWWIVHDGGMLMLLPFLLRHHKVWRKCKMRIFTVAQMDDNSIQMKKDLTT
  FLYHLRITAEVEVVEMHESDISAYTYEKTLVMEQRSQILKQMHLTKNEREREIQSITDES
  RGSIRRKNPANTRLRLNVPEETAGDSEEKPEEEVQLIHDQSAPSCPSSSPSPGEEPEGEG
  ETDPEKVHLTWTKDKSVAEKNKGPSPVSSEGIKDFFSMKPEWENLNQSNVRRMHTAVRLN
  EVIVKKSRDAKLVLLNMPGPPRNRNGDENYMEFLEVLTEHLDRVMLVRGGGREVITIYS
• Function: Mediates electroneutral potassium-chloride cotransportin mature neurons. Transport occurs under isotonic conditions, but is activated 20-fold by cell swelling. Important for Cl(-) homeostasis in neurons.
• KEGG Pathway: GABAergic synapse (hsa04727)
• Reactome Pathway: Cation-coupled Chloride cotransporters (R-HSA-426117)

Molecular Interaction Atlas (MIA) of This DTT

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CLP-635	DM1B0PY	Epilepsy	8A60-8A68	Investigative	[1]
DIOA	DMBKJL8	Discovery agent	N.A.	Investigative	[1]
VU0240551	DMU3YRH	Discovery agent	N.A.	Investigative	[2]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Electroneutral potassium-chloride cotransporter 2 (SLC12A5) DTP Info
• Gene Name: SLC12A5

1 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[3]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 972).
• [2] Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5383-8.
• [3] Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010 Oct;45(2):173-9.