ID   KCNS3_HUMAN             Reviewed;         491 AA.
AC   Q9BQ31; D6W520; O43651; Q4ZFY1; Q96B56;
DT   25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 3.
DT   24-JAN-2024, entry version 177.
DE   RecName: Full=Potassium voltage-gated channel subfamily S member 3;
DE   AltName: Full=Delayed-rectifier K(+) channel alpha subunit 3;
DE   AltName: Full=Voltage-gated potassium channel subunit Kv9.3;
GN   Name=KCNS3;
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   VARIANT ALA-450.
RC   TISSUE=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 MRNA].
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-450.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-225 AND ALA-450.
RC   TISSUE=Kidney, and Skin;
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   [6]
RP   TISSUE SPECIFICITY.
RX   PubMed=22943705; DOI=10.3109/01443615.2012.709288;
RA   Fyfe G.K., Panicker S., Jones R.L., Wareing M.;
RT   "Expression of an electrically silent voltage-gated potassium channel in
RT   the human placenta.";
RL   J. Obstet. Gynaecol. 32:624-629(2012).
CC   -!- FUNCTION: Potassium channel subunit that does not form functional
CC       channels by itself. Can form functional heterotetrameric channels with
CC       KCNB1; modulates the delayed rectifier voltage-gated potassium channel
CC       activation and deactivation rates of KCNB1 (PubMed:10484328).
CC       Heterotetrameric channel activity formed with KCNB1 show increased
CC       current amplitude with the threshold for action potential activation
CC       shifted towards more negative values in hypoxic-treated pulmonary
CC       artery smooth muscle cells (By similarity).
CC       {ECO:0000250|UniProtKB:O88759, ECO:0000269|PubMed:10484328}.
CC   -!- SUBUNIT: Heterotetramer with KCNB1 (PubMed:10484328). Does not form
CC       homomultimers (PubMed:10484328). {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 (PubMed:10484328). {ECO:0000269|PubMed:10484328}.
CC   -!- TISSUE SPECIFICITY: Detected in whole normal term placental and
CC       placental chorionic plate arteries and veins. Detected in
CC       syncytiotrophoblast and in blood vessel endothelium within intermediate
CC       villi and chorionic plate (at protein level) (PubMed:22943705).
CC       Detected in most tissues, but not in peripheral blood lymphocytes. The
CC       highest levels of expression are in lung (PubMed:10484328).
CC       {ECO:0000269|PubMed:10484328, ECO:0000269|PubMed:22943705}.
CC   -!- DOMAIN: The transmembrane segment S4 functions as a voltage-sensor and
CC       is 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. Kv9.3/KCNS3 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF043472; AAC13164.1; -; mRNA.
DR   EMBL; AK314451; BAG37059.1; -; mRNA.
DR   EMBL; AC093731; AAX88969.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00861.1; -; Genomic_DNA.
DR   EMBL; CH471053; EAX00862.1; -; Genomic_DNA.
DR   EMBL; BC004148; AAH04148.1; -; mRNA.
DR   EMBL; BC004987; AAH04987.1; -; mRNA.
DR   EMBL; BC015947; AAH15947.1; -; mRNA.
DR   CCDS; CCDS1692.1; -.
DR   RefSeq; NP_001269357.1; NM_001282428.1.
DR   RefSeq; NP_002243.3; NM_002252.4.
DR   RefSeq; XP_011531127.1; XM_011532825.1.
DR   RefSeq; XP_016859548.1; XM_017004059.1.
DR   AlphaFoldDB; Q9BQ31; -.
DR   SMR; Q9BQ31; -.
DR   BioGRID; 109991; 76.
DR   IntAct; Q9BQ31; 33.
DR   STRING; 9606.ENSP00000385968; -.
DR   ChEMBL; CHEMBL2362996; -.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB01069; Promethazine.
DR   DrugCentral; Q9BQ31; -.
DR   TCDB; 1.A.1.2.15; the voltage-gated ion channel (vic) superfamily.
DR   BioMuta; KCNS3; -.
DR   DMDM; 311033434; -.
DR   MassIVE; Q9BQ31; -.
DR   PaxDb; 9606-ENSP00000385968; -.
DR   PeptideAtlas; Q9BQ31; -.
DR   Antibodypedia; 3102; 144 antibodies from 24 providers.
DR   DNASU; 3790; -.
DR   Ensembl; ENST00000304101.9; ENSP00000305824.4; ENSG00000170745.12.
DR   Ensembl; ENST00000403915.5; ENSP00000385968.1; ENSG00000170745.12.
DR   GeneID; 3790; -.
DR   KEGG; hsa:3790; -.
DR   MANE-Select; ENST00000304101.9; ENSP00000305824.4; NM_002252.5; NP_002243.3.
DR   UCSC; uc002rcv.4; human.
DR   AGR; HGNC:6302; -.
DR   CTD; 3790; -.
DR   DisGeNET; 3790; -.
DR   GeneCards; KCNS3; -.
DR   HGNC; HGNC:6302; KCNS3.
DR   HPA; ENSG00000170745; Tissue enhanced (skeletal muscle, tongue).
DR   MIM; 603888; gene.
DR   neXtProt; NX_Q9BQ31; -.
DR   OpenTargets; ENSG00000170745; -.
DR   PharmGKB; PA30080; -.
DR   VEuPathDB; HostDB:ENSG00000170745; -.
DR   eggNOG; KOG3713; Eukaryota.
DR   GeneTree; ENSGT00940000155979; -.
DR   HOGENOM; CLU_011722_4_1_1; -.
DR   InParanoid; Q9BQ31; -.
DR   OMA; FFHRPGP; -.
DR   OrthoDB; 1478695at2759; -.
DR   PhylomeDB; Q9BQ31; -.
DR   TreeFam; TF313103; -.
DR   PathwayCommons; Q9BQ31; -.
DR   Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR   Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR   SignaLink; Q9BQ31; -.
DR   SIGNOR; Q9BQ31; -.
DR   BioGRID-ORCS; 3790; 12 hits in 1151 CRISPR screens.
DR   ChiTaRS; KCNS3; human.
DR   GeneWiki; KCNS3; -.
DR   GenomeRNAi; 3790; -.
DR   Pharos; Q9BQ31; Tclin.
DR   PRO; PR:Q9BQ31; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q9BQ31; Protein.
DR   Bgee; ENSG00000170745; Expressed in vastus lateralis and 165 other cell types or tissues.
DR   ExpressionAtlas; Q9BQ31; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IBA:GO_Central.
DR   GO; GO:0005251; F:delayed rectifier potassium channel activity; TAS:ProtInc.
DR   GO; GO:0015459; F:potassium channel regulator activity; TAS:ProtInc.
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:ProtInc.
DR   GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR   CDD; cd18428; BTB_POZ_KCNS3; 1.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 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; IPR027359; Volt_channel_dom_sf.
DR   PANTHER; PTHR11537:SF39; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY S MEMBER 3; 1.
DR   PANTHER; PTHR11537; VOLTAGE-GATED POTASSIUM CHANNEL; 1.
DR   Pfam; PF02214; BTB_2; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   PRINTS; PR00169; KCHANNEL.
DR   PRINTS; PR01494; KV9CHANNEL.
DR   PRINTS; PR01491; KVCHANNEL.
DR   SMART; SM00225; BTB; 1.
DR   SUPFAM; SSF54695; POZ domain; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   Genevisible; Q9BQ31; HS.
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..491
FT                   /note="Potassium voltage-gated channel subfamily S member
FT                   3"
FT                   /id="PRO_0000054087"
FT   TOPO_DOM        1..182
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        183..204
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        205..220
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        221..243
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        244..254
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        255..275
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        276..285
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        286..306
FT                   /note="Helical; Voltage-sensor; Name=Segment S4"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        307..321
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        322..343
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        344..357
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   INTRAMEM        358..369
FT                   /note="Helical; Name=Pore helix"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   INTRAMEM        370..377
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        378..384
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TRANSMEM        385..413
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   TOPO_DOM        414..491
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   MOTIF           370..375
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250|UniProtKB:P63142"
FT   VARIANT         225
FT                   /note="V -> L (in dbSNP:rs17856097)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_036986"
FT   VARIANT         450
FT                   /note="T -> A (in dbSNP:rs4832524)"
FT                   /evidence="ECO:0000269|PubMed:10484328,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT                   /id="VAR_014200"
FT   CONFLICT        27
FT                   /note="S -> Y (in Ref. 3; AAH15947)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   491 AA;  56001 MW;  FFE02CA3DCA50185 CRC64;
     MVFGEFFHRP GQDEELVNLN VGGFKQSVDQ STLLRFPHTR LGKLLTCHSE EAILELCDDY
     SVADKEYYFD RNPSLFRYVL NFYYTGKLHV MEELCVFSFC QEIEYWGINE LFIDSCCSNR
     YQERKEENHE KDWDQKSHDV STDSSFEESS LFEKELEKFD TLRFGQLRKK IWIRMENPAY
     CLSAKLIAIS SLSVVLASIV AMCVHSMSEF QNEDGEVDDP VLEGVEIACI AWFTGELAVR
     LAAAPCQKKF WKNPLNIIDF VSIIPFYATL AVDTKEEESE DIENMGKVVQ ILRLMRIFRI
     LKLARHSVGL RSLGATLRHS YHEVGLLLLF LSVGISIFSV LIYSVEKDDH TSSLTSIPIC
     WWWATISMTT VGYGDTHPVT LAGKLIASTC IICGILVVAL PITIIFNKFS KYYQKQKDID
     VDQCSEDAPE KCHELPYFNI RDIYAQRMHT FITSLSSVGI VVSDPDSTDA SSIEDNEDIC
     NTTSLENCTA K
//