ID   KCNV2_HUMAN             Reviewed;         545 AA.
AC   Q8TDN2; Q5T6X0;
DT   28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   24-JAN-2024, entry version 174.
DE   RecName: Full=Potassium voltage-gated channel subfamily V member 2;
DE   AltName: Full=Voltage-gated potassium channel subunit Kv8.2;
GN   Name=KCNV2;
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], SUBUNIT, AND TISSUE SPECIFICITY.
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 GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   VARIANTS RCD3B GLN-126; CYS-188; TRP-256; VAL-259; 339-ASP--VAL-341 DEL AND
RP   ASP-459, AND VARIANT VAL-533.
RX   PubMed=16909397; DOI=10.1086/507568;
RA   Wu H., Cowing J.A., Michaelides M., Wilkie S.E., Jeffery G., Jenkins S.A.,
RA   Mester V., Bird A.C., Robson A.G., Holder G.E., Moore A.T., Hunt D.M.,
RA   Webster A.R.;
RT   "Mutations in the gene KCNV2 encoding a voltage-gated potassium channel
RT   subunit cause 'cone dystrophy with supernormal rod electroretinogram' in
RT   humans.";
RL   Am. J. Hum. Genet. 79:574-579(2006).
RN   [5]
RP   VARIANT RCD3B PRO-244, CHARACTERIZATION OF VARIANT RCD3B PRO-244, AND
RP   INTERACTION WITH KCNB1.
RX   PubMed=34535971; DOI=10.1002/mgg3.1795;
RA   Liu M., Zhu Y., Huang L., Jiang W., Wu N., Song Y., Lu Y., Ma Y.;
RT   "Compound heterozygous KCNV2 variants contribute to cone dystrophy with
RT   supernormal rod responses in a Chinese family.";
RL   Mol. Genet. Genomic Med. 9:e1795-e1795(2021).
CC   -!- FUNCTION: Potassium channel subunit. Modulates channel activity by
CC       shifting the threshold and the half-maximal activation to more negative
CC       values.
CC   -!- SUBUNIT: Heteromultimer with KCNB1, KCNC1 and KCNF1. Does not form
CC       homomultimers. {ECO:0000269|PubMed:12060745,
CC       ECO:0000269|PubMed:34535971}.
CC   -!- INTERACTION:
CC       Q8TDN2; O15084: ANKRD28; NbExp=3; IntAct=EBI-12014650, EBI-359567;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC       Note=Has to be associated with KCNB1 or possibly another partner to get
CC       inserted in the plasma membrane. Remains intracellular in the absence
CC       of KCNB1.
CC   -!- TISSUE SPECIFICITY: Detected in lung, liver, kidney, pancreas, spleen,
CC       thymus, prostate, testis, ovary and colon.
CC       {ECO:0000269|PubMed:12060745}.
CC   -!- DOMAIN: The segment S4 is probably the voltage-sensor and is
CC       characterized by a series of positively charged amino acids at every
CC       third position.
CC   -!- DISEASE: Cone dystrophy retinal 3B (RCD3B) [MIM:610356]: A rare form of
CC       cone dystrophy associated with supernormal rod responses. The disorder
CC       is characterized by reduced visual acuity, photoaversion, night
CC       blindness, and abnormal color vision. At an early age, the retina shows
CC       subtle depigmentation at the macula and, later, more obvious areas of
CC       atrophy. {ECO:0000269|PubMed:16909397, ECO:0000269|PubMed:34535971}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the potassium channel family. V (TC 1.A.1.2)
CC       subfamily. Kv8.2/KCNV2 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF348983; AAL83910.1; -; mRNA.
DR   EMBL; AL354723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC101352; AAI01353.1; -; mRNA.
DR   EMBL; BC101353; AAI01354.1; -; mRNA.
DR   CCDS; CCDS6447.1; -.
DR   RefSeq; NP_598004.1; NM_133497.3.
DR   AlphaFoldDB; Q8TDN2; -.
DR   SMR; Q8TDN2; -.
DR   BioGRID; 127982; 16.
DR   IntAct; Q8TDN2; 4.
DR   STRING; 9606.ENSP00000371514; -.
DR   ChEMBL; CHEMBL2362996; -.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB01069; Promethazine.
DR   DrugCentral; Q8TDN2; -.
DR   TCDB; 1.A.1.2.23; the voltage-gated ion channel (vic) superfamily.
DR   TCDB; 1.A.1.2.24; the voltage-gated ion channel (vic) superfamily.
DR   GlyCosmos; Q8TDN2; 1 site, No reported glycans.
DR   GlyGen; Q8TDN2; 3 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q8TDN2; -.
DR   PhosphoSitePlus; Q8TDN2; -.
DR   BioMuta; KCNV2; -.
DR   DMDM; 26006804; -.
DR   MassIVE; Q8TDN2; -.
DR   PaxDb; 9606-ENSP00000371514; -.
DR   PeptideAtlas; Q8TDN2; -.
DR   ProteomicsDB; 74309; -.
DR   Antibodypedia; 23918; 254 antibodies from 25 providers.
DR   DNASU; 169522; -.
DR   Ensembl; ENST00000382082.4; ENSP00000371514.3; ENSG00000168263.9.
DR   GeneID; 169522; -.
DR   KEGG; hsa:169522; -.
DR   MANE-Select; ENST00000382082.4; ENSP00000371514.3; NM_133497.4; NP_598004.1.
DR   UCSC; uc003zho.3; human.
DR   AGR; HGNC:19698; -.
DR   CTD; 169522; -.
DR   DisGeNET; 169522; -.
DR   GeneCards; KCNV2; -.
DR   HGNC; HGNC:19698; KCNV2.
DR   HPA; ENSG00000168263; Tissue enriched (retina).
DR   MalaCards; KCNV2; -.
DR   MIM; 607604; gene.
DR   MIM; 610356; phenotype.
DR   neXtProt; NX_Q8TDN2; -.
DR   OpenTargets; ENSG00000168263; -.
DR   Orphanet; 209932; Cone dystrophy with supernormal rod response.
DR   PharmGKB; PA134992655; -.
DR   VEuPathDB; HostDB:ENSG00000168263; -.
DR   eggNOG; KOG3713; Eukaryota.
DR   GeneTree; ENSGT00940000157438; -.
DR   HOGENOM; CLU_011722_4_1_1; -.
DR   InParanoid; Q8TDN2; -.
DR   OMA; YQAVAIY; -.
DR   OrthoDB; 1478695at2759; -.
DR   PhylomeDB; Q8TDN2; -.
DR   TreeFam; TF313103; -.
DR   PathwayCommons; Q8TDN2; -.
DR   Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR   SignaLink; Q8TDN2; -.
DR   BioGRID-ORCS; 169522; 13 hits in 1141 CRISPR screens.
DR   ChiTaRS; KCNV2; human.
DR   GeneWiki; KCNV2; -.
DR   GenomeRNAi; 169522; -.
DR   Pharos; Q8TDN2; Tclin.
DR   PRO; PR:Q8TDN2; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q8TDN2; Protein.
DR   Bgee; ENSG00000168263; Expressed in sperm and 53 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IBA:GO_Central.
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:0051260; P:protein homooligomerization; IEA:InterPro.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 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; IPR027359; Volt_channel_dom_sf.
DR   PANTHER; PTHR11537:SF40; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY V MEMBER 2; 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   SUPFAM; SSF54695; POZ domain; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   Genevisible; Q8TDN2; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Cone-rod dystrophy; Disease variant; Glycoprotein;
KW   Ion channel; Ion transport; Membrane; Potassium; Potassium channel;
KW   Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..545
FT                   /note="Potassium voltage-gated channel subfamily V member
FT                   2"
FT                   /id="PRO_0000054094"
FT   TOPO_DOM        1..155
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        156..176
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        177..261
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        262..282
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        283..336
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        337..357
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        358..374
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        375..395
FT                   /note="Helical; Voltage-sensor; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        396..410
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        411..431
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        432..444
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        445..465
FT                   /note="Pore-forming; Name=Segment H5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        466..471
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        472..492
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        493..545
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          74..93
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           457..462
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        440
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         126
FT                   /note="L -> Q (in RCD3B; dbSNP:rs776275880)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027632"
FT   VARIANT         188
FT                   /note="W -> C (in RCD3B; dbSNP:rs772921412)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027633"
FT   VARIANT         244
FT                   /note="R -> P (in RCD3B; loss of interaction with KCNB1;
FT                   dbSNP:rs1023306854)"
FT                   /evidence="ECO:0000269|PubMed:34535971"
FT                   /id="VAR_087564"
FT   VARIANT         256
FT                   /note="S -> W (in RCD3B; dbSNP:rs104894116)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027634"
FT   VARIANT         259
FT                   /note="A -> V (in RCD3B)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027635"
FT   VARIANT         339..341
FT                   /note="Missing (in RCD3B)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027636"
FT   VARIANT         459
FT                   /note="G -> D (in RCD3B; dbSNP:rs104894115)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027637"
FT   VARIANT         533
FT                   /note="L -> V (in dbSNP:rs12352254)"
FT                   /evidence="ECO:0000269|PubMed:16909397"
FT                   /id="VAR_027638"
SQ   SEQUENCE   545 AA;  62459 MW;  72D175B4C0C6B1DA CRC64;
     MLKQSERRRS WSYRPWNTTE NEGSQHRRSI CSLGARSGSQ ASIHGWTEGN YNYYIEEDED
     GEEEDQWKDD LAEEDQQAGE VTTAKPEGPS DPPALLSTLN VNVGGHSYQL DYCELAGFPK
     TRLGRLATST SRSRQLSLCD DYEEQTDEYF FDRDPAVFQL VYNFYLSGVL LVLDGLCPRR
     FLEELGYWGV RLKYTPRCCR ICFEERRDEL SERLKIQHEL RAQAQVEEAE ELFRDMRFYG
     PQRRRLWNLM EKPFSSVAAK AIGVASSTFV LVSVVALALN TVEEMQQHSG QGEGGPDLRP
     ILEHVEMLCM GFFTLEYLLR LASTPDLRRF ARSALNLVDL VAILPLYLQL LLECFTGEGH
     QRGQTVGSVG KVGQVLRVMR LMRIFRILKL ARHSTGLRAF GFTLRQCYQQ VGCLLLFIAM
     GIFTFSAAVY SVEHDVPSTN FTTIPHSWWW AAVSISTVGY GDMYPETHLG RFFAFLCIAF
     GIILNGMPIS ILYNKFSDYY SKLKAYEYTT IRRERGEVNF MQRARKKIAE CLLGSNPQLT
     PRQEN
//