KCNT1_RAT
ID KCNT1_RAT Reviewed; 1237 AA.
AC Q9Z258; Q5D6C6;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Potassium channel subfamily T member 1;
DE AltName: Full=Sequence like a calcium-activated potassium channel subunit;
GN Name=Kcnt1; Synonyms=Slack;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10196543; DOI=10.1038/2176;
RA Joiner W.J., Tang M.D., Wang L.-Y., Dworetzky S.I., Boissard C.G., Gan L.,
RA Gribkoff V.K., Kaczmarek L.K.;
RT "Formation of intermediate-conductance calcium-activated potassium channels
RT by interaction of Slack and Slo subunits.";
RL Nat. Neurosci. 1:462-469(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=Sprague-Dawley;
RA Bhattacharjee A., von Hehn C.A., Kaczmarek L.K.;
RT "An alternative isoform of the sodium-activated potassium channel Slack
RT exhibits fast gating kinetics.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12442315; DOI=10.1002/cne.10439;
RA Bhattacharjee A., Gan L., Kaczmarek L.K.;
RT "Localization of the Slack potassium channel in the rat central nervous
RT system.";
RL J. Comp. Neurol. 454:241-254(2002).
RN [4]
RP FUNCTION.
RX PubMed=12628167; DOI=10.1016/s0896-6273(03)00096-5;
RA Yuan A., Santi C.M., Wei A., Wang Z.W., Pollak K., Nonet M., Kaczmarek L.,
RA Crowder C.M., Salkoff L.;
RT "The sodium-activated potassium channel is encoded by a member of the Slo
RT gene family.";
RL Neuron 37:765-773(2003).
RN [5]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH CRBN.
RX PubMed=16045448; DOI=10.1111/j.1471-4159.2005.03344.x;
RA Jo S., Lee K.-H., Song S., Jung Y.-K., Park C.-S.;
RT "Identification and functional characterization of cereblon as a binding
RT protein for large-conductance calcium-activated potassium channel in rat
RT brain.";
RL J. Neurochem. 94:1212-1224(2005).
RN [6]
RP FUNCTION, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=16687497; DOI=10.1523/jneurosci.3372-05.2006;
RA Santi C.M., Ferreira G., Yang B., Gazula V.R., Butler A., Wei A.,
RA Kaczmarek L.K., Salkoff L.;
RT "Opposite regulation of Slick and Slack K+ channels by neuromodulators.";
RL J. Neurosci. 26:5059-5068(2006).
RN [7]
RP INTERACTION WITH FMR1.
RX PubMed=20512134; DOI=10.1038/nn.2563;
RA Brown M.R., Kronengold J., Gazula V.R., Chen Y., Strumbos J.G.,
RA Sigworth F.J., Navaratnam D., Kaczmarek L.K.;
RT "Fragile X mental retardation protein controls gating of the sodium-
RT activated potassium channel Slack.";
RL Nat. Neurosci. 13:819-821(2010).
RN [8]
RP MUTAGENESIS OF ARG-409 AND ALA-913.
RX PubMed=23086397; DOI=10.1038/ng.2441;
RA Barcia G., Fleming M.R., Deligniere A., Gazula V.R., Brown M.R.,
RA Langouet M., Chen H., Kronengold J., Abhyankar A., Cilio R., Nitschke P.,
RA Kaminska A., Boddaert N., Casanova J.L., Desguerre I., Munnich A.,
RA Dulac O., Kaczmarek L.K., Colleaux L., Nabbout R.;
RT "De novo gain-of-function KCNT1 channel mutations cause malignant migrating
RT partial seizures of infancy.";
RL Nat. Genet. 44:1255-1259(2012).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF ALA-945.
RX PubMed=24463883; DOI=10.1093/hmg/ddu030;
RG WGS500 Consortium;
RA Martin H.C., Kim G.E., Pagnamenta A.T., Murakami Y., Carvill G.L.,
RA Meyer E., Copley R.R., Rimmer A., Barcia G., Fleming M.R., Kronengold J.,
RA Brown M.R., Hudspith K.A., Broxholme J., Kanapin A., Cazier J.B.,
RA Kinoshita T., Nabbout R., Bentley D., McVean G., Heavin S., Zaiwalla Z.,
RA McShane T., Mefford H.C., Shears D., Stewart H., Kurian M.A.,
RA Scheffer I.E., Blair E., Donnelly P., Kaczmarek L.K., Taylor J.C.;
RT "Clinical whole-genome sequencing in severe early-onset epilepsy reveals
RT new genes and improves molecular diagnosis.";
RL Hum. Mol. Genet. 23:3200-3211(2014).
CC -!- FUNCTION: Outwardly rectifying potassium channel subunit that may
CC coassemble with other Slo-type channel subunits. Activated by high
CC intracellular sodium or chloride levels. Activated upon stimulation of
CC G-protein coupled receptors, such as CHRM1 and GRIA1. May be regulated
CC by calcium in the absence of sodium ions (in vitro).
CC {ECO:0000269|PubMed:10196543, ECO:0000269|PubMed:12628167,
CC ECO:0000269|PubMed:16687497, ECO:0000269|PubMed:24463883}.
CC -!- SUBUNIT: Interacts (via C-terminus) with FMR1; this interaction alters
CC gating properties of KCNT1 (By similarity). Interacts with CRBN via its
CC cytoplasmic C-terminus (PubMed:16045448).
CC {ECO:0000250|UniProtKB:Q5JUK3, ECO:0000269|PubMed:16045448}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12442315,
CC ECO:0000269|PubMed:16045448}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:12442315, ECO:0000269|PubMed:16045448}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Z258-1; Sequence=Displayed;
CC Name=2; Synonyms=SLACK-A;
CC IsoId=Q9Z258-2; Sequence=VSP_015472;
CC -!- TISSUE SPECIFICITY: Detected in brain and brainstem, in vestibular and
CC oculomotor nuclei, the medial nucleus of the trapezoid in the auditory
CC system, in olfactory bulb, red nucleus, and deep cerebellar nuclei.
CC Detected in thalamus, substantia nigra, and amygdala (at protein
CC level). Highly expressed in the brain and kidney.
CC {ECO:0000269|PubMed:10196543, ECO:0000269|PubMed:12442315,
CC ECO:0000269|PubMed:16687497}.
CC -!- PTM: Phosphorylated by protein kinase C. Phosphorylation of the C-
CC terminal domain increases channel activity.
CC {ECO:0000269|PubMed:16687497}.
CC -!- SIMILARITY: Belongs to the potassium channel family. Calcium-activated
CC (TC 1.A.1.3) subfamily. KCa4.1/KCNT1 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF089730; AAC83350.1; -; mRNA.
DR EMBL; AY884213; AAX16016.1; -; mRNA.
DR PIR; T46609; T46609.
DR RefSeq; NP_068625.1; NM_021853.1. [Q9Z258-1]
DR AlphaFoldDB; Q9Z258; -.
DR SMR; Q9Z258; -.
DR STRING; 10116.ENSRNOP00000023542; -.
DR BindingDB; Q9Z258; -.
DR ChEMBL; CHEMBL4739708; -.
DR DrugCentral; Q9Z258; -.
DR GuidetoPHARMACOLOGY; 385; -.
DR TCDB; 1.A.1.3.4; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q9Z258; 2 sites.
DR iPTMnet; Q9Z258; -.
DR PhosphoSitePlus; Q9Z258; -.
DR PaxDb; Q9Z258; -.
DR PRIDE; Q9Z258; -.
DR ABCD; Q9Z258; 1 sequenced antibody.
DR GeneID; 60444; -.
DR KEGG; rno:60444; -.
DR UCSC; RGD:621106; rat. [Q9Z258-1]
DR CTD; 57582; -.
DR RGD; 621106; Kcnt1.
DR eggNOG; KOG3193; Eukaryota.
DR InParanoid; Q9Z258; -.
DR OrthoDB; 858812at2759; -.
DR PhylomeDB; Q9Z258; -.
DR PRO; PR:Q9Z258; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005228; F:intracellular sodium activated potassium channel activity; IBA:GO_Central.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; IDA:RGD.
DR GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR InterPro; IPR003929; K_chnl_BK_asu.
DR InterPro; IPR013099; K_chnl_dom.
DR Pfam; PF03493; BK_channel_a; 1.
DR Pfam; PF07885; Ion_trans_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1237
FT /note="Potassium channel subfamily T member 1"
FT /id="PRO_0000054092"
FT TOPO_DOM 1..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..155
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..187
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..213
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..226
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..281
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 282..302
FT /note="Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 303..304
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..1237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 475..596
FT /note="RCK N-terminal"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 658..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1079
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1210..1237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..66
FT /note="MARAKLPRSPSEGKAGPGDTPAGSAAPEEPHGLSPLLPTRGGGSVGSDVGQR
FT LHVEDFSLDSSLSQ -> MNDLDTEVLPLPPRYRFRDLLLGDQTFPNDDR (in
FT isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_015472"
FT MUTAGEN 409
FT /note="R->Q: Generates currents that resembles wild-type in
FT terms of voltage dependence and kinetic behavior but has
FT 2- to 3-fold higher amplitude compared to wild-type. The
FT mutation shows to cause constitutive activation of the
FT channel, mimicking the effects of phosphorylation of the C-
FT terminal domain by PRKCA activation."
FT /evidence="ECO:0000269|PubMed:23086397"
FT MUTAGEN 913
FT /note="A->T: Generates currents that resembles wild-type in
FT terms of voltage dependence and kinetic behavior but has
FT 2- to 3-fold higher amplitude compared to wild-type. The
FT mutation shows to cause constitutive activation of the
FT channel, mimicking the effects of phosphorylation of the C-
FT terminal domain by PRKCA activation."
FT /evidence="ECO:0000269|PubMed:23086397"
FT MUTAGEN 945
FT /note="A->T: Increases channel activity upon positive
FT potentials. The mutation corresponds to probable disease-
FT associated variant in humans."
FT /evidence="ECO:0000269|PubMed:24463883"
SQ SEQUENCE 1237 AA; 139615 MW; E11B4A7A77EB612B CRC64;
MARAKLPRSP SEGKAGPGDT PAGSAAPEEP HGLSPLLPTR GGGSVGSDVG QRLHVEDFSL
DSSLSQVQVE FYVNENTFKE RLKLFFIKNQ RSSLRIRLFN FSLKLLTCLL YIVRVLLDNP
DQGIGCWGCT KYNYTFNGSS SEFHWAPILW VERKMALWVI QVIVATISFL ETMLLIYLSY
KGNIWEQIFH VSFVLEMINT LPFIITVFWP PLRNLFIPVF LNCWLAKHAL ENMINDFHRA
ILRTQSAMFN QVLILFCTLL CLVFTGTCGI QHLERAGGNL NLLTSFYFCI VTFSTVGFGD
VTPKIWPSQL LVVILICVTL VVLPLQFEEL VYLWMERQKS GGNYSRHRAR TEKHVVLCVS
SLKIDLLMDF LNEFYAHPRL QDYYVVILCP SEMDVQVRRV LQIPLWSQRV IYLQGSALKD
QDLMRAKMDN GEACFILSSR NEVDRTAADH QTILRAWAVK DFAPNCPLYV QILKPENKFH
VKFADHVVCE EECKYAMLAL NCICPATSTL ITLLVHTSRG QEGQESPEQW QRMYGRCSGN
EVYHIRMGDS KFFREYEGKS FTYAAFHAHK KYGVCLIGLK REENKSILLN PGPRHILAAS
DTCFYINITK EENSAFIFKQ EEKQNRRGLA GQALYEGPSR LPVHSIIASM VAMDLQNTDC
RPSQGGSGGG GGKLTLPTEN GSGSRRPSIA PVLELADSSA LLPCDLLSDQ SEDEVTPSDD
EGLSVVEYVK GYPPNSPYIG SSPTLCHLLP VKAPFCCLRL DKGCKHNSYE DAKAYGFKNK
LIIVSAETAG NGLYNFIVPL RAYYRSRREL NPIVLLLDNK PDHHFLEAIC CFPMVYYMEG
SVDNLDSLLQ CGIIYADNLV VVDKESTMSA EEDYMADAKT IVNVQTMFRL FPSLSITTEL
THPSNMRFMQ FRAKDSYSLA LSKLEKQERE NGSNLAFMFR LPFAAGRVFS ISMLDTLLYQ
SFVKDYMITI TRLLLGLDTT PGSGYLCAMK VTEDDLWIRT YGRLFQKLCS SSAEIPIGIY
RTECHVFSSE PHDLRAQSQI SVNMEDCEDT REAKGPWGTR AASGGGSTHG RHGGSADPVE
HPLLRRKSLQ WARKLSRKSS KQAGKAPMTT DWITQQRLSL YRRSERQELS ELVKNRMKHL
GLPTTGYEDV ANLTASDVMN RVNLGYLQDE MNDHHQNTLS YVLINPPPDT RLEPNDIVYL
IRSDPLAHVT SSSQSRKSSC SNKLSSCNPE TRDETQL
