KCNS3_HUMAN
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 03-AUG-2022, entry version 169.
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 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. Kv9.3/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; Q9BQ31; -.
DR PeptideAtlas; Q9BQ31; -.
DR PRIDE; Q9BQ31; -.
DR Antibodypedia; 3102; 122 antibodies from 23 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 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; YWGIKER; -.
DR OrthoDB; 818306at2759; -.
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 BioGRID-ORCS; 3790; 9 hits in 1071 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 164 other tissues.
DR ExpressionAtlas; Q9BQ31; baseline and differential.
DR Genevisible; Q9BQ31; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
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 GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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..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
