1.A.1.3.10 Calcium-, magnesium- and voltage-activated K+ channel, Slo1 (Kcma1; KCNMA, KCNMA1), a BK channel, of 1236 aas and 6 N-terminal TMSs. Its activation dampens the excitatory events that elevate the cytosolic Ca2+ concentration and/or depolarize the cell membrane. It therefore
contributes to repolarization of the membrane potential, and it plays a key
role in controlling excitability in a number of systems. Ethanol and carbon monoxide-bound heme increase channel activation while heme inhibits channel activation (Tang et al. 2003). The molecular structures of the human Slo1 channel in complex with beta4 has been solved revealing four beta4 subunits, each containing two transmembrane helices, encircling Slo1, contacting it through helical interactions inside the membrane. On the extracellular side, beta4 forms a tetrameric crown over the pore. Structures with high and low Ca2+ concentrations show that identical gating conformations occur in the absence and presence of beta4, implying that beta4 serves to modulate the relative stabilities of 'pre-existing' conformations rather than creating new ones (Tao and MacKinnon 2019). BK channels show increased activities in Angelman syndrome due to genetic defects in the ubiquitin protein ligase E3A (UBE3A) gene (Sun et al. 2019). It is a large-conductance potassium (BK) channel that can be synergistically and independently activated by membrane voltage and intracellular Ca2+. The only covalent connection between the cytosolic Ca2+-sensing domain and the TM pore and voltage sensing domains is a 15-residue 'C-linker' which plays a direct role in mediating allosteric coupling between BK domains (Yazdani et al. 2020). Site specific deacylation by the alpha/beta acyl-hydrolase domain-containing protein 17A, ABHD17a (Q96GS6, 310 aas), controls BK channel splice variant activity (McClafferty et al. 2020).
|
Accession Number: | Q12791 |
Protein Name: | Calcium-activated potassium channel subunit alpha-1 |
Length: | 1236 |
Molecular Weight: | 137560.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 7 |
Location1 / Topology2 / Orientation3: |
Cell membrane1 / Multi-pass membrane protein2 |
Substrate |
potassium(1+) |
---|
1: MANGGGGGGG SSGGGGGGGG SSLRMSSNIH ANHLSLDASS SSSSSSSSSS SSSSSSSSSS
61: VHEPKMDALI IPVTMEVPCD SRGQRMWWAF LASSMVTFFG GLFIILLWRT LKYLWTVCCH
121: CGGKTKEAQK INNGSSQADG TLKPVDEKEE AVAAEVGWMT SVKDWAGVMI SAQTLTGRVL
181: VVLVFALSIG ALVIYFIDSS NPIESCQNFY KDFTLQIDMA FNVFFLLYFG LRFIAANDKL
241: WFWLEVNSVV DFFTVPPVFV SVYLNRSWLG LRFLRALRLI QFSEILQFLN ILKTSNSIKL
301: VNLLSIFIST WLTAAGFIHL VENSGDPWEN FQNNQALTYW ECVYLLMVTM STVGYGDVYA
361: KTTLGRLFMV FFILGGLAMF ASYVPEIIEL IGNRKKYGGS YSAVSGRKHI VVCGHITLES
421: VSNFLKDFLH KDRDDVNVEI VFLHNISPNL ELEALFKRHF TQVEFYQGSV LNPHDLARVK
481: IESADACLIL ANKYCADPDA EDASNIMRVI SIKNYHPKIR IITQMLQYHN KAHLLNIPSW
541: NWKEGDDAIC LAELKLGFIA QSCLAQGLST MLANLFSMRS FIKIEEDTWQ KYYLEGVSNE
601: MYTEYLSSAF VGLSFPTVCE LCFVKLKLLM IAIEYKSANR ESRILINPGN HLKIQEGTLG
661: FFIASDAKEV KRAFFYCKAC HDDITDPKRI KKCGCKRPKM SIYKRMRRAC CFDCGRSERD
721: CSCMSGRVRG NVDTLERAFP LSSVSVNDCS TSFRAFEDEQ PSTLSPKKKQ RNGGMRNSPN
781: TSPKLMRHDP LLIPGNDQID NMDSNVKKYD STGMFHWCAP KEIEKVILTR SEAAMTVLSG
841: HVVVCIFGDV SSALIGLRNL VMPLRASNFH YHELKHIVFV GSIEYLKREW ETLHNFPKVS
901: ILPGTPLSRA DLRAVNINLC DMCVILSANQ NNIDDTSLQD KECILASLNI KSMQFDDSIG
961: VLQANSQGFT PPGMDRSSPD NSPVHGMLRQ PSITTGVNIP IITELVNDTN VQFLDQDDDD
1021: DPDTELYLTQ PFACGTAFAV SVLDSLMSAT YFNDNILTLI RTLVTGGATP ELEALIAEEN
1081: ALRGGYSTPQ TLANRDRCRV AQLALLDGPF ADLGDGGCYG DLFCKALKTY NMLCFGIYRL
1141: RDAHLSTPSQ CTKRYVITNP PYEFELVPTD LIFCLMQFDH NAGQSRASLS HSSHSSQSSS
1201: KKSSSVHSIP STANRQNRPK SRESRDKQKY VQEERL