Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXHT5FR)

• DOT Name: STE20/SPS1-related proline-alanine-rich protein kinase (STK39)
• Synonyms: Ste-20-related kinase; EC 2.7.11.1; DCHT; Serine/threonine-protein kinase 39
• Gene Name: STK39
• UniProt ID: STK39_HUMAN
• PDB ID: 7O86
• EC Number: 2.7.11.1
• Pfam ID: PF12202 ; PF00069
• Sequence:
  MAEPSGSPVHVQLPQQAAPVTAAAAAAPAAATAAPAPAAPAAPAPAPAPAAQAVGWPICR
  DAYELQEVIGSGATAVVQAALCKPRQERVAIKRINLEKCQTSMDELLKEIQAMSQCSHPN
  VVTYYTSFVVKDELWLVMKLLSGGSMLDIIKYIVNRGEHKNGVLEEAIIATILKEVLEGL
  DYLHRNGQIHRDLKAGNILLGEDGSVQIADFGVSAFLATGGDVTRNKVRKTFVGTPCWMA
  PEVMEQVRGYDFKADMWSFGITAIELATGAAPYHKYPPMKVLMLTLQNDPPTLETGVEDK
  EMMKKYGKSFRKLLSLCLQKDPSKRPTAAELLKCKFFQKAKNREYLIEKLLTRTPDIAQR
  AKKVRRVPGSSGHLHKTEDGDWEWSDDEMDEKSEEGKAAFSQEKSRRVKEENPEIAVSAS
  TIPEQIQSLSVHDSQGPPNANEDYREASSCAVNLVLRLRNSRKELNDIRFEFTPGRDTAD
  GVSQELFSAGLVDGHDVVIVAANLQKIVDDPKALKTLTFKLASGCDGSEIPDEVKLIGFA
  QLSVS
• Function: Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure. Specifically recognizes and binds proteins with a RFXV motif. Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity. Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases. Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux. Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4. Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities. Phosphorylates RELT.
• Tissue Specificity: Predominantly expressed in brain and pancreas followed by heart, lung, kidney, skeletal muscle, liver, placenta and testis.
• KEGG Pathway: Parathyroid hormone synthesis, secretion and action (hsa04928)

Molecular Interaction Atlas (MIA) of This DOT

22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[13]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[14]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[21]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[8]
Daidzein	DMRFTJX	Investigative	Daidzein decreases the expression of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[22]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of STE20/SPS1-related proline-alanine-rich protein kinase (STK39).	[20]

References

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