KCNN1_HUMAN
ID KCNN1_HUMAN Reviewed; 543 AA.
AC Q92952; Q5KR10; Q6DJU4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Small conductance calcium-activated potassium channel protein 1;
DE Short=SK1;
DE Short=SKCa 1;
DE Short=SKCa1;
DE AltName: Full=KCa2.1;
GN Name=KCNN1; Synonyms=SK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RC TISSUE=Hippocampus;
RX PubMed=8781233; DOI=10.1126/science.273.5282.1709;
RA Koehler M., Hirschberg B., Bond C.T., Kinzie J.M., Marrion N.V., Maylie J.,
RA Adelman J.P.;
RT "Small-conductance, calcium-activated potassium channels from mammalian
RT brain.";
RL Science 273:1709-1714(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10516439; DOI=10.1159/000015415;
RA Litt M., LaMorticella D., Bond C.T., Adelman J.P.;
RT "Gene structure and chromosome mapping of the human small-conductance
RT calcium-activated potassium channel SK1 gene (KCNN1).";
RL Cytogenet. Cell Genet. 86:70-73(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA Tagaya M., Higashioka M., Takagaki K., Ohgi T.;
RT "Molecular cloning of a small-conductance calcium-activated potassium
RT channel from human fetal brain.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-310; GLU-312; VAL-337
RP AND HIS-339.
RX PubMed=9287325; DOI=10.1074/jbc.272.37.23195;
RA Ishii T.M., Maylie J., Adelman J.P.;
RT "Determinants of apamin and d-tubocurarine block in SK potassium
RT channels.";
RL J. Biol. Chem. 272:23195-23200(1997).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-216; LYS-310; GLU-312
RP AND HIS-339.
RX PubMed=17142458; DOI=10.1074/jbc.m607213200;
RA Nolting A., Ferraro T., D'hoedt D., Stocker M.;
RT "An amino acid outside the pore region influences apamin sensitivity in
RT small conductance Ca2+-activated K+ channels.";
RL J. Biol. Chem. 282:3478-3486(2007).
CC -!- FUNCTION: Forms a voltage-independent potassium channel activated by
CC intracellular calcium (PubMed:8781233, PubMed:9287325,
CC PubMed:17142458). Activation is followed by membrane hyperpolarization
CC (By similarity). Thought to regulate neuronal excitability by
CC contributing to the slow component of synaptic afterhyperpolarization
CC (By similarity). {ECO:0000250|UniProtKB:Q9EQR3,
CC ECO:0000269|PubMed:17142458, ECO:0000269|PubMed:8781233,
CC ECO:0000269|PubMed:9287325}.
CC -!- ACTIVITY REGULATION: Inhibited by bee venom neurotoxin apamin
CC (PubMed:9287325, PubMed:17142458). Inhibited by d-tubocurarine and
CC tetraethylammonium (TEA) (PubMed:9287325, PubMed:17142458).
CC {ECO:0000269|PubMed:17142458, ECO:0000269|PubMed:9287325}.
CC -!- SUBUNIT: Heterooligomer. The complex is composed of 4 channel subunits
CC each of which binds to a calmodulin subunit which regulates the channel
CC activity through calcium-binding (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92952-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92952-2; Sequence=VSP_022501;
CC -!- SIMILARITY: Belongs to the potassium channel KCNN family. KCa2.1/KCNN1
CC subfamily. {ECO:0000305}.
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DR EMBL; U69883; AAB09562.1; -; mRNA.
DR EMBL; AF131948; AAD37507.1; -; Genomic_DNA.
DR EMBL; AF131940; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131941; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131942; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131943; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131944; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131945; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131946; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AF131947; AAD37507.1; JOINED; Genomic_DNA.
DR EMBL; AB198191; BAD86831.1; -; mRNA.
DR EMBL; BC075037; AAH75037.3; -; mRNA.
DR CCDS; CCDS67611.1; -. [Q92952-1]
DR RefSeq; NP_002239.2; NM_002248.4. [Q92952-1]
DR AlphaFoldDB; Q92952; -.
DR SMR; Q92952; -.
DR BioGRID; 109981; 5.
DR IntAct; Q92952; 3.
DR MINT; Q92952; -.
DR STRING; 9606.ENSP00000476519; -.
DR BindingDB; Q92952; -.
DR ChEMBL; CHEMBL2369; -.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB16733; Rimtuzalcap.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; Q92952; -.
DR GuidetoPHARMACOLOGY; 381; -.
DR TCDB; 1.A.1.16.6; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q92952; -.
DR PhosphoSitePlus; Q92952; -.
DR BioMuta; KCNN1; -.
DR DMDM; 124056468; -.
DR MassIVE; Q92952; -.
DR PeptideAtlas; Q92952; -.
DR PRIDE; Q92952; -.
DR Antibodypedia; 27885; 126 antibodies from 24 providers.
DR DNASU; 3780; -.
DR Ensembl; ENST00000222249.13; ENSP00000476519.1; ENSG00000105642.16. [Q92952-1]
DR Ensembl; ENST00000684775.1; ENSP00000507021.1; ENSG00000105642.16. [Q92952-1]
DR GeneID; 3780; -.
DR KEGG; hsa:3780; -.
DR MANE-Select; ENST00000684775.1; ENSP00000507021.1; NM_001386974.1; NP_001373903.1.
DR UCSC; uc002nht.4; human. [Q92952-1]
DR CTD; 3780; -.
DR DisGeNET; 3780; -.
DR GeneCards; KCNN1; -.
DR HGNC; HGNC:6290; KCNN1.
DR HPA; ENSG00000105642; Tissue enriched (brain).
DR MIM; 602982; gene.
DR neXtProt; NX_Q92952; -.
DR OpenTargets; ENSG00000105642; -.
DR PharmGKB; PA30070; -.
DR VEuPathDB; HostDB:ENSG00000105642; -.
DR eggNOG; KOG3684; Eukaryota.
DR GeneTree; ENSGT00950000182904; -.
DR HOGENOM; CLU_014617_5_0_1; -.
DR InParanoid; Q92952; -.
DR OrthoDB; 907751at2759; -.
DR PhylomeDB; Q92952; -.
DR TreeFam; TF315015; -.
DR PathwayCommons; Q92952; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR SignaLink; Q92952; -.
DR SIGNOR; Q92952; -.
DR BioGRID-ORCS; 3780; 12 hits in 1018 CRISPR screens.
DR ChiTaRS; KCNN1; human.
DR GeneWiki; KCNN1; -.
DR GenomeRNAi; 3780; -.
DR Pharos; Q92952; Tchem.
DR PRO; PR:Q92952; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q92952; protein.
DR Bgee; ENSG00000105642; Expressed in right frontal lobe and 128 other tissues.
DR ExpressionAtlas; Q92952; baseline and differential.
DR Genevisible; Q92952; HS.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; TAS:ProtInc.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0016286; F:small conductance calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0006811; P:ion transport; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR InterPro; IPR004178; CaM-bd_dom.
DR InterPro; IPR036122; CaM-bd_dom_sf.
DR InterPro; IPR015449; K_chnl_Ca-activ_SK.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR10153; PTHR10153; 1.
DR Pfam; PF02888; CaMBD; 1.
DR Pfam; PF07885; Ion_trans_2; 1.
DR Pfam; PF03530; SK_channel; 1.
DR PRINTS; PR01451; SKCHANNEL.
DR SMART; SM01053; CaMBD; 1.
DR SUPFAM; SSF81327; SSF81327; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calmodulin-binding; Ion channel; Ion transport;
KW Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..543
FT /note="Small conductance calcium-activated potassium
FT channel protein 1"
FT /id="PRO_0000155007"
FT TRANSMEM 111..131
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TRANSMEM 140..160
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..248
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TRANSMEM 277..297
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT INTRAMEM 317..337
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT REGION 1..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..463
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 505..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 505..522
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1
FT /note="M -> MPGPRAACSEPNPCTQVVM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8781233, ECO:0000303|Ref.3"
FT /id="VSP_022501"
FT MUTAGEN 216
FT /note="T->S: Significantly increased inhibition by apamin
FT (IC(50)=167 pM). No effect on inhibition by d-tubocurarine
FT and tetraethylammonium (TEA). Significant increase in
FT inhibition by apamin (IC(50)=26 pM); when associated with
FT Q-310, D-312 and N-339."
FT /evidence="ECO:0000269|PubMed:17142458"
FT MUTAGEN 310
FT /note="K->Q: Loss of inhibition by apamin. No effect on
FT inhibition by d-tubocurarine. Increased inhibition by
FT apamin; when associated with D-312. Significant increase in
FT inhibition by apamin (IC(50)=366 pM); when associated with
FT D-312 and N-339. Significant increase in inhibition by
FT apamin (IC(50)=26 pM); when associated with S-216, D-312
FT and N-339."
FT /evidence="ECO:0000269|PubMed:17142458,
FT ECO:0000269|PubMed:9287325"
FT MUTAGEN 312
FT /note="E->D: Increased inhibition by apamin or d-
FT tubocurarine (IC(50)=62.6 uM). Additive increase in
FT inhibition by apamin or d-tubocurarine (IC(50)=6.3 uM);
FT when associated with N-339. Additive increase in inhibition
FT by apamin; when associated with Q-310. Significant increase
FT in inhibition by apamin (IC(50)=366 pM); when associated
FT with Q-310 and N-339. Significant increase in inhibition by
FT apamin (IC(50)=26 pM); when associated with S-216, Q-310
FT and N-339."
FT /evidence="ECO:0000269|PubMed:17142458,
FT ECO:0000269|PubMed:9287325"
FT MUTAGEN 337
FT /note="V->Y: Increased inhibition by tetraethylammonium
FT (TEA)."
FT /evidence="ECO:0000269|PubMed:9287325"
FT MUTAGEN 339
FT /note="H->N: Increased inhibition by apamin or d-
FT tubocurarine (IC(50)=11.1 uM). Additive increase in
FT inhibition by apamin or d-tubocurarine (IC(50)=6.3 uM);
FT when associated with D-312. Significant increase in
FT inhibition by apamin (IC(50)=366 pM); when associated with
FT Q-310 and D-312. Significant increase in inhibition by
FT apamin (IC(50)=26 pM); when associated with S-216, Q-310
FT and D-312."
FT /evidence="ECO:0000269|PubMed:17142458,
FT ECO:0000269|PubMed:9287325"
FT CONFLICT 513..542
FT /note="PLPPRPGPGPQDQAARSSPCRWTPVAPSDC -> RLPRQRAGLDH (in
FT Ref. 3; BAD86831)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 543 AA; 59987 MW; 13EFF47C263BCB11 CRC64;
MNSHSYNGSV GRPLGSGPGA LGRDPPDPEA GHPPQPPHSP GLQVVVAKSE PARPSPGSPR
GQPQDQDDDE DDEEDEAGRQ RASGKPSNVG HRLGHRRALF EKRKRLSDYA LIFGMFGIVV
MVTETELSWG VYTKESLYSF ALKCLISLST AILLGLVVLY HAREIQLFMV DNGADDWRIA
MTCERVFLIS LELAVCAIHP VPGHYRFTWT ARLAFTYAPS VAEADVDVLL SIPMFLRLYL
LGRVMLLHSK IFTDASSRSI GALNKITFNT RFVMKTLMTI CPGTVLLVFS ISSWIIAAWT
VRVCERYHDK QEVTSNFLGA MWLISITFLS IGYGDMVPHT YCGKGVCLLT GIMGAGCTAL
VVAVVARKLE LTKAEKHVHN FMMDTQLTKR VKNAAANVLR ETWLIYKHTR LVKKPDQARV
RKHQRKFLQA IHQAQKLRSV KIEQGKLNDQ ANTLTDLAKT QTVMYDLVSE LHAQHEELEA
RLATLESRLD ALGASLQALP GLIAQAIRPP PPPLPPRPGP GPQDQAARSS PCRWTPVAPS
DCG
