Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE87WJ)

• DTT Name: Calcium-activated potassium channel KCa1.1 (KCNMA1)
• Synonyms: hSlo; Slowpoke homolog; Slo1; Slo-alpha; Slo homolog; SLO; MaxiK; Maxi K channel; KCa1.1; KCNMA; K(VCA)alpha; Calcium-activated potassium channel, subfamily M subunit alpha-1; Calcium-activated potassium channel subunit alpha-1; BKCA alpha; BK channel
• Gene Name: KCNMA1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Voltage-gated ion channel
• UniProt ID: KCMA1_HUMAN
• TTD ID: T66538
• Sequence:
  MANGGGGGGGSSGGGGGGGGSSLRMSSNIHANHLSLDASSSSSSSSSSSSSSSSSSSSSS
  VHEPKMDALIIPVTMEVPCDSRGQRMWWAFLASSMVTFFGGLFIILLWRTLKYLWTVCCH
  CGGKTKEAQKINNGSSQADGTLKPVDEKEEAVAAEVGWMTSVKDWAGVMISAQTLTGRVL
  VVLVFALSIGALVIYFIDSSNPIESCQNFYKDFTLQIDMAFNVFFLLYFGLRFIAANDKL
  WFWLEVNSVVDFFTVPPVFVSVYLNRSWLGLRFLRALRLIQFSEILQFLNILKTSNSIKL
  VNLLSIFISTWLTAAGFIHLVENSGDPWENFQNNQALTYWECVYLLMVTMSTVGYGDVYA
  KTTLGRLFMVFFILGGLAMFASYVPEIIELIGNRKKYGGSYSAVSGRKHIVVCGHITLES
  VSNFLKDFLHKDRDDVNVEIVFLHNISPNLELEALFKRHFTQVEFYQGSVLNPHDLARVK
  IESADACLILANKYCADPDAEDASNIMRVISIKNYHPKIRIITQMLQYHNKAHLLNIPSW
  NWKEGDDAICLAELKLGFIAQSCLAQGLSTMLANLFSMRSFIKIEEDTWQKYYLEGVSNE
  MYTEYLSSAFVGLSFPTVCELCFVKLKLLMIAIEYKSANRESRILINPGNHLKIQEGTLG
  FFIASDAKEVKRAFFYCKACHDDITDPKRIKKCGCKRPKMSIYKRMRRACCFDCGRSERD
  CSCMSGRVRGNVDTLERAFPLSSVSVNDCSTSFRAFEDEQPSTLSPKKKQRNGGMRNSPN
  TSPKLMRHDPLLIPGNDQIDNMDSNVKKYDSTGMFHWCAPKEIEKVILTRSEAAMTVLSG
  HVVVCIFGDVSSALIGLRNLVMPLRASNFHYHELKHIVFVGSIEYLKREWETLHNFPKVS
  ILPGTPLSRADLRAVNINLCDMCVILSANQNNIDDTSLQDKECILASLNIKSMQFDDSIG
  VLQANSQGFTPPGMDRSSPDNSPVHGMLRQPSITTGVNIPIITELVNDTNVQFLDQDDDD
  DPDTELYLTQPFACGTAFAVSVLDSLMSATYFNDNILTLIRTLVTGGATPELEALIAEEN
  ALRGGYSTPQTLANRDRCRVAQLALLDGPFADLGDGGCYGDLFCKALKTYNMLCFGIYRL
  RDAHLSTPSQCTKRYVITNPPYEFELVPTDLIFCLMQFDHNAGQSRASLSHSSHSSQSSS
  KKSSSVHSIPSTANRQNRPKSRESRDKQKYVQEERL
• Function: Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
• KEGG Pathway:
  cGMP-PKG signaling pathway (hsa04022)
  Vascular smooth muscle contraction (hsa04270)
  Insulin secretion (hsa04911)
  Salivary secretion (hsa04970)
  Pancreatic secretion (hsa04972)
• Reactome Pathway: cGMP effects (R-HSA-418457)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CROMOGLYCATE LISETIL HYDROCHLORIDE	DM129T7	Asthma	CA23	Phase 2	[2]
URO-902	DMF5794	Overactive bladder	GC50.0	Phase 2	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alopecia	EA90	Skin from scalp	4.48E-03	0.19	0.7

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Calcium-activated potassium channel subunit alpha-1 (KCNMA1) DTP Info
• Gene Name: KCNMA1

References

• [1] KCa1.1 channels regulate 1-integrin function and cell adhesion in rheumatoid arthritis fibroblast-like synoviocytes. FASEB J. 2017 Aug;31(8):3309-3320.
• [2] The significance of chloride in the inhibitory action of disodium cromoglycate on immunologically-stimulated rat peritoneal mast cells. Biochim Biophys Acta. 2011 Sep;1810(9):867-74.
• [3] Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials. Neurourol Urodyn. 2020 Feb;39(2):744-753.