Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSN6YTK)

• DOT Name: G-protein coupled receptor family C group 6 member A (GPRC6A)
• Synonyms: hGPRC6A; G-protein coupled receptor GPCR33; hGPCR33
• Gene Name: GPRC6A
• UniProt ID: GPC6A_HUMAN
• Pfam ID: PF00003 ; PF01094 ; PF07562
• Sequence:
  MAFLIILITCFVIILATSQPCQTPDDFVAATSPGHIIIGGLFAIHEKMLSSEDSPRRPQI
  QECVGFEISVFLQTLAMIHSIEMINNSTLLPGVKLGYEIYDTCTEVTVAMAATLRFLSKF
  NCSRETVEFKCDYSSYMPRVKAVIGSGYSEITMAVSRMLNLQLMPQVGYESTAEILSDKI
  RFPSFLRTVPSDFHQIKAMAHLIQKSGWNWIGIITTDDDYGRLALNTFIIQAEANNVCIA
  FKEVLPAFLSDNTIEVRINRTLKKIILEAQVNVIVVFLRQFHVFDLFNKAIEMNINKMWI
  ASDNWSTATKITTIPNVKKIGKVVGFAFRRGNISSFHSFLQNLHLLPSDSHKLLHEYAMH
  LSACAYVKDTDLSQCIFNHSQRTLAYKANKAIERNFVMRNDFLWDYAEPGLIHSIQLAVF
  ALGYAIRDLCQARDCQNPNAFQPWELLGVLKNVTFTDGWNSFHFDAHGDLNTGYDVVLWK
  EINGHMTVTKMAEYDLQNDVFIIPDQETKNEFRNLKQIQSKCSKECSPGQMKKTTRSQHI
  CCYECQNCPENHYTNQTDMPHCLLCNNKTHWAPVRSTMCFEKEVEYLNWNDSLAILLLIL
  SLLGIIFVLVVGIIFTRNLNTPVVKSSGGLRVCYVILLCHFLNFASTSFFIGEPQDFTCK
  TRQTMFGVSFTLCISCILTKSLKILLAFSFDPKLQKFLKCLYRPILIIFTCTGIQVVICT
  LWLIFAAPTVEVNVSLPRVIILECEEGSILAFGTMLGYIAILAFICFIFAFKGKYENYNE
  AKFITFGMLIYFIAWITFIPIYATTFGKYVPAVEIIVILISNYGILYCTFIPKCYVIICK
  QEINTKSAFLKMIYSYSSHSVSSIALSPASLDSMSGNVTMTNPSSSGKSATWQKSKDLQA
  QAFAHICRENATSVSKTLPRKRMSSI
• Function: Receptor activated by multiple ligands, including osteocalcin (BGLAP), basic amino acids, and various cations. Activated by amino acids with a preference for basic amino acids such as L-Lys, L-Arg and L-ornithine but also by small and polar amino acids. The L-alpha amino acids respond is augmented by divalent cations Ca(2+) and Mg(2+). Seems to act through a G(q)/G(11) and G(i)-coupled pathway. Regulates testosterone production by acting as a ligand for uncarboxylated osteocalcin hormone: osteocalcin-binding at the surface of Leydig cells initiates a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Mediates the non-genomic effects of androgens in multiple tissue. May coordinate nutritional and hormonal anabolic signals through the sensing of extracellular amino acids, osteocalcin, divalent ions and its responsiveness to anabolic steroids.
• Tissue Specificity: Isoform 1 is expressed at high level in brain, skeletal muscle, testis, bone, calvaria, osteoblasts and leukocytes. Expressed at intermediate level in liver, heart, kidney and spleen. Expressed at low level in lung, pancreas, placenta and ovary. Not detected in thymus, prostate, small intestine, tongue and colon. Isoform 1 and isoform 2 are expressed in kidney at the same level. Isoform 2 is expressed at lower level than isoform 1 in the other tissues.
• KEGG Pathway: NOD-like receptor sig.ling pathway (hsa04621)
• Reactome Pathway:
  Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the methylation of G-protein coupled receptor family C group 6 member A (GPRC6A).	[1]

References

• [1] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.