KCNG4_HUMAN
ID KCNG4_HUMAN Reviewed; 519 AA.
AC Q8TDN1; Q96H24;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Potassium voltage-gated channel subfamily G member 4;
DE AltName: Full=Voltage-gated potassium channel subunit Kv6.4;
GN Name=KCNG4; Synonyms=KCNG3;
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 1).
RC TISSUE=Brain;
RX PubMed=12060745; DOI=10.1073/pnas.122617999;
RA Ottschytsch N., Raes A., Van Hoorick D., Snyders D.J.;
RT "Obligatory heterotetramerization of three previously uncharacterized Kv
RT channel alpha-subunits identified in the human genome.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7986-7991(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Muscle;
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 [3]
RP FUNCTION, SUBUNIT, INTERACTION WITH KCNB1, AND SUBCELLULAR LOCATION.
RX PubMed=19074135; DOI=10.1074/jbc.m808786200;
RA Mederos y Schnitzler M., Rinne S., Skrobek L., Renigunta V.,
RA Schlichthorl G., Derst C., Gudermann T., Daut J., Preisig-Muller R.;
RT "Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1
RT disrupts heteromerization with Kv6.3 and Kv6.4.";
RL J. Biol. Chem. 284:4695-4704(2009).
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:19074135).
CC {ECO:0000269|PubMed:19074135}.
CC -!- SUBUNIT: Heterotetramer with KCNB1 (PubMed:19074135).
CC {ECO:0000269|PubMed:19074135}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19074135};
CC Multi-pass membrane protein {ECO:0000305}. Note=Has to be associated
CC with KCNB1 or possibly another partner to get inserted in the plasma
CC membrane. Colocalizes with KCNB1 at the plasma membrane. Remains
CC intracellular in the absence of KCNB1 (PubMed:19074135).
CC {ECO:0000269|PubMed:19074135}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TDN1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDN1-2; Sequence=VSP_001029, VSP_001030;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, and at lower levels in
CC liver, small intestine and colon.
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. G (TC 1.A.1.2)
CC subfamily. Kv6.4/KCNG4 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF348984; AAL83911.1; -; mRNA.
DR EMBL; BC008969; AAH08969.1; -; mRNA.
DR CCDS; CCDS10945.1; -. [Q8TDN1-1]
DR RefSeq; NP_758857.1; NM_172347.2. [Q8TDN1-1]
DR AlphaFoldDB; Q8TDN1; -.
DR SMR; Q8TDN1; -.
DR BioGRID; 125002; 19.
DR IntAct; Q8TDN1; 3.
DR STRING; 9606.ENSP00000312129; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q8TDN1; -.
DR TCDB; 1.A.1.2.26; the voltage-gated ion channel (vic) superfamily.
DR PhosphoSitePlus; Q8TDN1; -.
DR SwissPalm; Q8TDN1; -.
DR BioMuta; KCNG4; -.
DR DMDM; 26006803; -.
DR PaxDb; Q8TDN1; -.
DR PeptideAtlas; Q8TDN1; -.
DR PRIDE; Q8TDN1; -.
DR ProteomicsDB; 74307; -. [Q8TDN1-1]
DR ProteomicsDB; 74308; -. [Q8TDN1-2]
DR Antibodypedia; 30581; 109 antibodies from 25 providers.
DR DNASU; 93107; -.
DR Ensembl; ENST00000308251.6; ENSP00000312129.4; ENSG00000168418.8. [Q8TDN1-1]
DR Ensembl; ENST00000568181.1; ENSP00000457897.1; ENSG00000168418.8. [Q8TDN1-2]
DR GeneID; 93107; -.
DR KEGG; hsa:93107; -.
DR MANE-Select; ENST00000308251.6; ENSP00000312129.4; NM_172347.3; NP_758857.1.
DR UCSC; uc002fhu.1; human. [Q8TDN1-1]
DR CTD; 93107; -.
DR DisGeNET; 93107; -.
DR GeneCards; KCNG4; -.
DR HGNC; HGNC:19697; KCNG4.
DR HPA; ENSG00000168418; Group enriched (brain, retina).
DR MIM; 607603; gene.
DR neXtProt; NX_Q8TDN1; -.
DR OpenTargets; ENSG00000168418; -.
DR PharmGKB; PA134989953; -.
DR VEuPathDB; HostDB:ENSG00000168418; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000156938; -.
DR HOGENOM; CLU_011722_4_1_1; -.
DR InParanoid; Q8TDN1; -.
DR OMA; YVLPWST; -.
DR PhylomeDB; Q8TDN1; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q8TDN1; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q8TDN1; -.
DR BioGRID-ORCS; 93107; 16 hits in 1060 CRISPR screens.
DR GeneWiki; KCNG4; -.
DR GenomeRNAi; 93107; -.
DR Pharos; Q8TDN1; Tclin.
DR PRO; PR:Q8TDN1; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q8TDN1; protein.
DR Bgee; ENSG00000168418; Expressed in amygdala and 26 other tissues.
DR ExpressionAtlas; Q8TDN1; baseline and differential.
DR Genevisible; Q8TDN1; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:GO_Central.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
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; 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 SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Ion channel; Ion transport; Membrane;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..519
FT /note="Potassium voltage-gated channel subfamily G member
FT 4"
FT /id="PRO_0000054080"
FT TOPO_DOM 1..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 219..240
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 241..261
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 262..283
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 284..294
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 295..314
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 315..328
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 329..353
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 354..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 369..390
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 391..405
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 406..417
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 418..425
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 426..432
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 433..461
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 462..519
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 418..423
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT VAR_SEQ 253..256
FT /note="GECS -> VSGL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001029"
FT VAR_SEQ 257..519
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_001030"
FT VARIANT 8
FT /note="G -> W (in dbSNP:rs35379218)"
FT /id="VAR_053861"
FT VARIANT 206
FT /note="R -> W (in dbSNP:rs11646443)"
FT /id="VAR_053862"
FT VARIANT 255
FT /note="C -> Y (in dbSNP:rs17736370)"
FT /id="VAR_053863"
FT VARIANT 321
FT /note="E -> K (in dbSNP:rs4782905)"
FT /id="VAR_053864"
FT VARIANT 325
FT /note="G -> R (in dbSNP:rs7196482)"
FT /id="VAR_053865"
FT VARIANT 427
FT /note="R -> H (in dbSNP:rs35649980)"
FT /id="VAR_053866"
SQ SEQUENCE 519 AA; 58979 MW; E5BBA354931AB0A4 CRC64;
MPMPSRDGGL HPRHHHYGSH SPWSQLLSSP METPSIKGLY YRRVRKVGAL DASPVDLKKE
ILINVGGRRY LLPWSTLDRF PLSRLSKLRL CRSYEEIVQL CDDYDEDSQE FFFDRSPSAF
GVIVSFLAAG KLVLLQEMCA LSFQEELAYW GIEEAHLERC CLRKLLRKLE ELEELAKLHR
EDVLRQQRET RRPASHSSRW GLCMNRLREM VENPQSGLPG KVFACLSILF VATTAVSLCV
STMPDLRAEE DQGECSRKCY YIFIVETICV AWFSLEFCLR FVQAQDKCQF FQGPLNIIDI
LAISPYYVSL AVSEEPPEDG ERPSGSSYLE KVGLVLRVLR ALRILYVMRL ARHSLGLQTL
GLTVRRCTRE FGLLLLFLAV AITLFSPLVY VAEKESGRVL EFTSIPASYW WAIISMTTVG
YGDMVPRSVP GQMVALSSIL SGILIMAFPA TSIFHTFSHS YLELKKEQEQ LQARLRHLQN
TGPASECELL DPHVASEHEL MNDVNDLILE GPALPIMHM