KCNS1_HUMAN
ID KCNS1_HUMAN Reviewed; 526 AA.
AC Q96KK3; A2RUL9; B7ZM31; O43652; Q6DJU6;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Potassium voltage-gated channel subfamily S member 1;
DE AltName: Full=Delayed-rectifier K(+) channel alpha subunit 1;
DE AltName: Full=Voltage-gated potassium channel subunit Kv9.1;
GN Name=KCNS1;
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], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain, and Lens epithelium;
RX PubMed=10484328; DOI=10.1152/ajpcell.1999.277.3.c412;
RA Shepard A.R., Rae J.L.;
RT "Electrically silent potassium channel subunits from human lens
RT epithelium.";
RL Am. J. Physiol. 277:C412-C424(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-489.
RC TISSUE=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).
CC -!- FUNCTION: Potassium channel subunit that does not form functional
CC channels by itself. Can form functional heterotetrameric channels with
CC KCNB1 and KCNB2; modulates the delayed rectifier voltage-gated
CC potassium channel activation and deactivation rates of KCNB1 and KCNB2
CC (PubMed:10484328). {ECO:0000269|PubMed:10484328}.
CC -!- SUBUNIT: Heterotetramer with KCNB1 (PubMed:10484328). Heterotetramer
CC with KCNB2 (By similarity). Does not form homomultimers
CC (PubMed:10484328). {ECO:0000250|UniProtKB:O35173,
CC ECO:0000269|PubMed:10484328}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10484328};
CC Multi-pass membrane protein {ECO:0000305}. Note=May not reach the
CC plasma membrane but remain in an intracellular compartment in the
CC absence of KCNB1 or KCNB2 (PubMed:10484328).
CC {ECO:0000269|PubMed:10484328}.
CC -!- TISSUE SPECIFICITY: Detected in all tissues tested with the exception
CC of skeletal muscle. Highly expressed in adult and fetal brain, fetal
CC kidney and lung, and adult prostate and testis (PubMed:10484328).
CC {ECO:0000269|PubMed:10484328}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- SIMILARITY: Belongs to the potassium channel family. S (TC 1.A.1.2)
CC subfamily. Kv9.1/KCNS1 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF043473; AAC13165.2; -; mRNA.
DR EMBL; Z93016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075033; AAH75033.2; -; mRNA.
DR EMBL; BC075034; AAH75034.2; -; mRNA.
DR EMBL; BC132959; AAI32960.1; -; mRNA.
DR EMBL; BC144234; AAI44235.1; -; mRNA.
DR CCDS; CCDS13342.1; -.
DR RefSeq; NP_001309728.1; NM_001322799.1.
DR RefSeq; NP_002242.2; NM_002251.4.
DR AlphaFoldDB; Q96KK3; -.
DR SMR; Q96KK3; -.
DR STRING; 9606.ENSP00000307694; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q96KK3; -.
DR TCDB; 1.A.1.2.7; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; Q96KK3; -.
DR PhosphoSitePlus; Q96KK3; -.
DR BioMuta; KCNS1; -.
DR DMDM; 24418474; -.
DR MassIVE; Q96KK3; -.
DR PaxDb; Q96KK3; -.
DR PeptideAtlas; Q96KK3; -.
DR PRIDE; Q96KK3; -.
DR ProteomicsDB; 77080; -.
DR Antibodypedia; 27521; 60 antibodies from 20 providers.
DR DNASU; 3787; -.
DR Ensembl; ENST00000306117.5; ENSP00000307694.1; ENSG00000124134.9.
DR Ensembl; ENST00000537075.3; ENSP00000445595.1; ENSG00000124134.9.
DR GeneID; 3787; -.
DR KEGG; hsa:3787; -.
DR MANE-Select; ENST00000537075.3; ENSP00000445595.1; NM_001322799.2; NP_001309728.1.
DR UCSC; uc002xnc.4; human.
DR CTD; 3787; -.
DR DisGeNET; 3787; -.
DR GeneCards; KCNS1; -.
DR HGNC; HGNC:6300; KCNS1.
DR HPA; ENSG00000124134; Tissue enriched (brain).
DR MIM; 602905; gene.
DR neXtProt; NX_Q96KK3; -.
DR OpenTargets; ENSG00000124134; -.
DR PharmGKB; PA30078; -.
DR VEuPathDB; HostDB:ENSG00000124134; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000160096; -.
DR HOGENOM; CLU_011722_4_1_1; -.
DR InParanoid; Q96KK3; -.
DR OMA; FGQEAEY; -.
DR OrthoDB; 818306at2759; -.
DR PhylomeDB; Q96KK3; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q96KK3; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 3787; 10 hits in 1072 CRISPR screens.
DR GeneWiki; KCNS1; -.
DR GenomeRNAi; 3787; -.
DR Pharos; Q96KK3; Tclin.
DR PRO; PR:Q96KK3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q96KK3; protein.
DR Bgee; ENSG00000124134; Expressed in middle temporal gyrus and 112 other tissues.
DR ExpressionAtlas; Q96KK3; baseline and differential.
DR Genevisible; Q96KK3; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:1902259; P:regulation of delayed rectifier potassium channel activity; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003971; K_chnl_volt-dep_Kv9.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01494; KV9CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Ion channel; Ion transport; Membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..526
FT /note="Potassium voltage-gated channel subfamily S member
FT 1"
FT /id="PRO_0000054081"
FT TOPO_DOM 1..217
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 218..239
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 240..270
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 271..293
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 294..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 305..322
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 323..337
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 338..358
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 359..373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 374..395
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 396..408
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 409..420
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 421..428
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 429..435
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 436..464
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 465..526
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 493..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 421..426
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT COMPBIAS 493..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 489
FT /note="I -> V (in dbSNP:rs734784)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_020052"
FT VARIANT 508
FT /note="Q -> R (in dbSNP:rs7264544)"
FT /id="VAR_053867"
SQ SEQUENCE 526 AA; 58372 MW; 00F0E415E3A68C91 CRC64;
MLMLLVRGTH YENLRSKVVL PTPLGGRSTE TFVSEFPGPD TGIRWRRSDE ALRVNVGGVR
RQLSARALAR FPGTRLGRLQ AAASEEQARR LCDDYDEAAR EFYFDRHPGF FLSLLHFYRT
GHLHVLDELC VFAFGQEADY WGLGENALAA CCRARYLERR LTQPHAWDED SDTPSSVDPC
PDEISDVQRE LARYGAARCG RLRRRLWLTM ENPGYSLPSK LFSCVSISVV LASIAAMCIH
SLPEYQAREA AAAVAAVAAG RSPEGVRDDP VLRRLEYFCI AWFSFEVSSR LLLAPSTRNF
FCHPLNLIDI VSVLPFYLTL LAGVALGDQG GKEFGHLGKV VQVFRLMRIF RVLKLARHST
GLRSLGATLK HSYREVGILL LYLAVGVSVF SGVAYTAEKE EDVGFNTIPA CWWWGTVSMT
TVGYGDVVPV TVAGKLAASG CILGGILVVA LPITIIFNKF SHFYRRQKAL EAAVRNSNHQ
EFEDLLSSID GVSEASLETS RETSQEGQSA DLESQAPSEP PHPQMY
