ID   KCNN3_HUMAN             Reviewed;         731 AA.
AC   Q9UGI6; B1ANX0; O43517; Q86VF9; Q8WXG7;
DT   16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT   05-DEC-2018, sequence version 2.
DT   24-JAN-2024, entry version 185.
DE   RecName: Full=Small conductance calcium-activated potassium channel protein 3;
DE            Short=SK3;
DE            Short=SKCa 3;
DE            Short=SKCa3;
DE   AltName: Full=KCa2.3;
GN   Name=KCNN3; Synonyms=K3;
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), AND POLYMORPHISM OF POLY-GLN
RP   REGION.
RX   PubMed=9491810; DOI=10.1038/sj.mp.4000353;
RA   Chandy K.G., Fantino E., Wittekindt O., Kalman K., Tong L.-L., Ho T.-H.,
RA   Gutman G.A., Crocq M.-A., Ganguli R., Nimgaonkar V., Morris-Rosendahl D.J.,
RA   Gargus J.J.;
RT   "Isolation of a novel potassium channel gene hSKCa3 containing a
RT   polymorphic CAG repeat: a candidate for schizophrenia and bipolar
RT   disorder?";
RL   Mol. Psychiatry 3:32-37(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLN-GLN-GLN-GLN-GLN-80
RP   INS.
RA   Terstappen G.C., Pula G., Chen M.X., Roncarati R.;
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA   Tomita H., Shakkottai V., Wulff H., Sun G., Potkin S.G., Bunney W.E.,
RA   Chandy G.K., Gargus J.J.;
RT   "Splice variants of small conductance calcium-activated potassium channel
RT   gene, KCNN3/ SKCa3 cause dominant-negative suppression of SKCa currents.";
RL   Am. J. Hum. Genet. 69S:569-569(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANT
RP   GLN-GLN-GLN-GLN-GLN-80 INS.
RX   PubMed=11501944; DOI=10.1007/s100380170046;
RA   Sun G., Tomita H., Shakkottai V.G., Gargus J.J.;
RT   "Genomic organization and promoter analysis of human KCNN3 gene.";
RL   J. Hum. Genet. 46:463-470(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX   PubMed=12808432; DOI=10.1038/sj.mp.4001271;
RA   Tomita H., Shakkottai V.G., Gutman G.A., Sun G., Bunney W.E., Cahalan M.D.,
RA   Chandy K.G., Gargus J.J.;
RT   "Novel truncated isoform of SK3 potassium channel is a potent dominant-
RT   negative regulator of SK currents: implications in schizophrenia.";
RL   Mol. Psychiatry 8:524-535(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lymph;
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   [9]
RP   FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-485 AND HIS-516.
RX   PubMed=20562108; DOI=10.1074/jbc.m110.110072;
RA   Lamy C., Goodchild S.J., Weatherall K.L., Jane D.E., Liegeois J.F.,
RA   Seutin V., Marrion N.V.;
RT   "Allosteric block of KCa2 channels by apamin.";
RL   J. Biol. Chem. 285:27067-27077(2010).
RN   [10]
RP   FUNCTION, ACTIVITY REGULATION, INTERACTION WITH CALM1, INVOLVEMENT IN ZLS3,
RP   VARIANTS ZLS3 GLU-269; ASP-350 AND CYS-436, CHARACTERIZATION OF VARIANTS
RP   ZLS3 GLU-269; ASP-350 AND CYS-436, AND CHARACTERIZATION OF VARIANT LEU-450.
RX   PubMed=31155282; DOI=10.1016/j.ajhg.2019.04.012;
RA   Bauer C.K., Schneeberger P.E., Kortuem F., Altmueller J.,
RA   Santos-Simarro F., Baker L., Keller-Ramey J., White S.M., Campeau P.M.,
RA   Gripp K.W., Kutsche K.;
RT   "Gain-of-function mutations in KCNN3 encoding the small-conductance Ca2+-
RT   activated K+ channel SK3 cause Zimmermann-Laband syndrome.";
RL   Am. J. Hum. Genet. 104:1139-1157(2019).
RN   [11]
RP   VARIANT LEU-450.
RX   PubMed=26658685; DOI=10.1016/j.jhep.2015.11.027;
RA   Koot B.G., Alders M., Verheij J., Beuers U., Cobben J.M.;
RT   "A de novo mutation in KCNN3 associated with autosomal dominant idiopathic
RT   non-cirrhotic portal hypertension.";
RL   J. Hepatol. 64:974-977(2016).
CC   -!- FUNCTION: Forms a voltage-independent potassium channel activated by
CC       intracellular calcium (PubMed:31155282, PubMed:20562108). Activation is
CC       followed by membrane hyperpolarization (By similarity). Thought to
CC       regulate neuronal excitability by contributing to the slow component of
CC       synaptic afterhyperpolarization (By similarity).
CC       {ECO:0000250|UniProtKB:P70605, ECO:0000269|PubMed:20562108,
CC       ECO:0000269|PubMed:31155282}.
CC   -!- ACTIVITY REGULATION: Inhibited by bee venom neurotoxin apamin.
CC       {ECO:0000269|PubMed:20562108, ECO:0000269|PubMed:31155282}.
CC   -!- SUBUNIT: Heterooligomer. The complex is composed of 4 channel subunits
CC       each of which binds to a calmodulin subunit which regulates the channel
CC       activity through calcium-binding (By similarity). Interacts with CALM1
CC       (PubMed:31155282). {ECO:0000250, ECO:0000269|PubMed:31155282}.
CC   -!- INTERACTION:
CC       Q9UGI6-2; P51798: CLCN7; NbExp=3; IntAct=EBI-17888181, EBI-4402346;
CC       Q9UGI6-2; P50402: EMD; NbExp=3; IntAct=EBI-17888181, EBI-489887;
CC       Q9UGI6-2; Q7Z2K6: ERMP1; NbExp=3; IntAct=EBI-17888181, EBI-10976398;
CC       Q9UGI6-2; Q9H115: NAPB; NbExp=3; IntAct=EBI-17888181, EBI-3921185;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q9UGI6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9UGI6-2; Sequence=VSP_039461, VSP_039462;
CC       Name=3; Synonyms=SK3-1B;
CC         IsoId=Q9UGI6-3; Sequence=VSP_047641;
CC   -!- POLYMORPHISM: The second poly-Gln region of KCNN3 is highly polymorphic
CC       and the number of Gln varies from 12 to 28 in the population.
CC       {ECO:0000269|PubMed:9491810}.
CC   -!- DISEASE: Zimmermann-Laband syndrome 3 (ZLS3) [MIM:618658]: A form of
CC       Zimmermann-Laband syndrome, a rare developmental disorder characterized
CC       by facial dysmorphism with bulbous nose and thick floppy ears, gingival
CC       enlargement, hypoplasia or aplasia of terminal phalanges and nails,
CC       hypertrichosis, joint hyperextensibility, and hepatosplenomegaly. Some
CC       patients manifest intellectual disability with or without epilepsy.
CC       ZLS3 inheritance is autosomal dominant. {ECO:0000269|PubMed:31155282}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- MISCELLANEOUS: [Isoform 3]: Do not produce functional channels, but
CC       selectively suppresses endogenous SK3 currents, in a dominant-negative
CC       fashion. This dominant inhibitory effect extends to other members of
CC       the SK subfamily. Widely distributed in human tissues and is present at
CC       20-60% of SK3 in the brain. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the potassium channel KCNN family. KCa2.3/KCNN3
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AF031815; AAC26099.1; -; mRNA.
DR   EMBL; AJ251016; CAB61331.1; -; mRNA.
DR   EMBL; AF438203; AAL40801.1; -; mRNA.
DR   EMBL; AF336797; AAK15345.1; -; Genomic_DNA.
DR   EMBL; AY138900; AAN46636.1; -; mRNA.
DR   EMBL; AL390204; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL606500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL954342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471121; EAW53180.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW53182.1; -; Genomic_DNA.
DR   EMBL; BC042147; AAH42147.1; -; mRNA.
DR   CCDS; CCDS1072.1; -. [Q9UGI6-2]
DR   CCDS; CCDS30880.1; -. [Q9UGI6-1]
DR   CCDS; CCDS91063.1; -. [Q9UGI6-3]
DR   RefSeq; NP_001191016.1; NM_001204087.1.
DR   RefSeq; NP_002240.3; NM_002249.5. [Q9UGI6-1]
DR   RefSeq; NP_740752.1; NM_170782.2. [Q9UGI6-2]
DR   AlphaFoldDB; Q9UGI6; -.
DR   SMR; Q9UGI6; -.
DR   BioGRID; 109983; 10.
DR   IntAct; Q9UGI6; 4.
DR   STRING; 9606.ENSP00000481848; -.
DR   BindingDB; Q9UGI6; -.
DR   ChEMBL; CHEMBL3381; -.
DR   DrugBank; DB02587; Colforsin.
DR   DrugBank; DB04209; Dequalinium.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB01054; Nitrendipine.
DR   DrugBank; DB00721; Procaine.
DR   DrugBank; DB16733; Rimtuzalcap.
DR   DrugBank; DB00867; Ritodrine.
DR   DrugBank; DB09089; Trimebutine.
DR   DrugCentral; Q9UGI6; -.
DR   GuidetoPHARMACOLOGY; 383; -.
DR   TCDB; 1.A.1.16.7; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; Q9UGI6; -.
DR   PhosphoSitePlus; Q9UGI6; -.
DR   BioMuta; KCNN3; -.
DR   DMDM; 17367120; -.
DR   EPD; Q9UGI6; -.
DR   jPOST; Q9UGI6; -.
DR   MassIVE; Q9UGI6; -.
DR   MaxQB; Q9UGI6; -.
DR   PaxDb; 9606-ENSP00000481848; -.
DR   PeptideAtlas; Q9UGI6; -.
DR   ProteomicsDB; 70008; -.
DR   ProteomicsDB; 84216; -. [Q9UGI6-1]
DR   ProteomicsDB; 84217; -. [Q9UGI6-2]
DR   Antibodypedia; 20402; 219 antibodies from 28 providers.
DR   DNASU; 3782; -.
DR   Ensembl; ENST00000271915.9; ENSP00000271915.3; ENSG00000143603.19. [Q9UGI6-1]
DR   Ensembl; ENST00000358505.2; ENSP00000351295.2; ENSG00000143603.19. [Q9UGI6-3]
DR   Ensembl; ENST00000361147.8; ENSP00000354764.4; ENSG00000143603.19. [Q9UGI6-2]
DR   GeneID; 3782; -.
DR   KEGG; hsa:3782; -.
DR   MANE-Select; ENST00000271915.9; ENSP00000271915.3; NM_002249.6; NP_002240.3.
DR   UCSC; uc001ffo.4; human. [Q9UGI6-1]
DR   AGR; HGNC:6292; -.
DR   CTD; 3782; -.
DR   DisGeNET; 3782; -.
DR   GeneCards; KCNN3; -.
DR   HGNC; HGNC:6292; KCNN3.
DR   HPA; ENSG00000143603; Tissue enhanced (brain).
DR   MalaCards; KCNN3; -.
DR   MIM; 602983; gene.
DR   MIM; 618658; phenotype.
DR   neXtProt; NX_Q9UGI6; -.
DR   OpenTargets; ENSG00000143603; -.
DR   Orphanet; 3473; Zimmermann-Laband syndrome.
DR   PharmGKB; PA30072; -.
DR   VEuPathDB; HostDB:ENSG00000143603; -.
DR   eggNOG; KOG3684; Eukaryota.
DR   GeneTree; ENSGT00950000182904; -.
DR   HOGENOM; CLU_014617_5_0_1; -.
DR   InParanoid; Q9UGI6; -.
DR   OrthoDB; 4200919at2759; -.
DR   PhylomeDB; Q9UGI6; -.
DR   TreeFam; TF315015; -.
DR   PathwayCommons; Q9UGI6; -.
DR   Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR   SignaLink; Q9UGI6; -.
DR   SIGNOR; Q9UGI6; -.
DR   BioGRID-ORCS; 3782; 12 hits in 1152 CRISPR screens.
DR   ChiTaRS; KCNN3; human.
DR   GeneWiki; SK3; -.
DR   GenomeRNAi; 3782; -.
DR   Pharos; Q9UGI6; Tchem.
DR   PRO; PR:Q9UGI6; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q9UGI6; Protein.
DR   Bgee; ENSG00000143603; Expressed in lateral globus pallidus and 171 other cell types or tissues.
DR   ExpressionAtlas; Q9UGI6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0016286; F:small conductance calcium-activated potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR   Gene3D; 1.10.287.70; -; 2.
DR   InterPro; IPR004178; CaM-bd_dom.
DR   InterPro; IPR036122; CaM-bd_dom_sf.
DR   InterPro; IPR015449; K_chnl_Ca-activ_SK.
DR   InterPro; IPR013099; K_chnl_dom.
DR   PANTHER; PTHR10153; SMALL CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL; 1.
DR   PANTHER; PTHR10153:SF40; SMALL CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL PROTEIN 3; 1.
DR   Pfam; PF02888; CaMBD; 1.
DR   Pfam; PF07885; Ion_trans_2; 1.
DR   Pfam; PF03530; SK_channel; 1.
DR   PRINTS; PR01451; SKCHANNEL.
DR   SMART; SM01053; CaMBD; 1.
DR   SUPFAM; SSF81327; Small-conductance potassium channel; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   Genevisible; Q9UGI6; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calmodulin-binding; Disease variant; Ion channel;
KW   Ion transport; Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..731
FT                   /note="Small conductance calcium-activated potassium
FT                   channel protein 3"
FT                   /id="PRO_0000155013"
FT   TRANSMEM        288..308
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        315..335
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        366..386
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        405..425
FT                   /note="Helical; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        454..474
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        494..514
FT                   /note="Pore-forming; Name=Segment H5"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        523..543
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
FT   REGION          1..170
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          239..258
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          561..637
FT                   /note="Calmodulin-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          709..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..16
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        25..39
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        40..61
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        62..100
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        107..153
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         167
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P58391"
FT   VAR_SEQ         1..313
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12808432"
FT                   /id="VSP_047641"
FT   VAR_SEQ         1..305
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT                   /id="VSP_039461"
FT   VAR_SEQ         306..310
FT                   /note="WGLYS -> MERPI (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT                   /id="VSP_039462"
FT   VARIANT         80
FT                   /note="Q -> QQQQQQ"
FT                   /id="VAR_081088"
FT   VARIANT         269
FT                   /note="K -> E (in ZLS3; gain-of-function variant leading to
FT                   increased channel sensitivity to calcium and faster channel
FT                   activation; does not affect interaction with CALM1;
FT                   dbSNP:rs1571353663)"
FT                   /evidence="ECO:0000269|PubMed:31155282"
FT                   /id="VAR_083434"
FT   VARIANT         350
FT                   /note="G -> D (in ZLS3; gain-of-function variant leading to
FT                   increased channel sensitivity to calcium and faster channel
FT                   activation; does not affect interaction with CALM1;
FT                   dbSNP:rs1571260285)"
FT                   /evidence="ECO:0000269|PubMed:31155282"
FT                   /id="VAR_083435"
FT   VARIANT         436
FT                   /note="S -> C (in ZLS3; gain-of-function variant leading to
FT                   increased channel sensitivity to calcium and faster channel
FT                   activation; does not affect interaction with CALM1;
FT                   dbSNP:rs1571259807)"
FT                   /evidence="ECO:0000269|PubMed:31155282"
FT                   /id="VAR_083436"
FT   VARIANT         450
FT                   /note="V -> L (found in a family with non-cirrhotic portal
FT                   hypertension; uncertain significance; gain-of-function
FT                   variant leading to constitutive activity with very low
FT                   calcium levels; does not affect interaction with CALM1)"
FT                   /evidence="ECO:0000269|PubMed:26658685,
FT                   ECO:0000269|PubMed:31155282"
FT                   /id="VAR_083437"
FT   MUTAGEN         485
FT                   /note="H->N: Reduced inhibition by apamin."
FT                   /evidence="ECO:0000269|PubMed:20562108"
FT   MUTAGEN         516
FT                   /note="H->N: No effect on inhibition by apamin."
FT                   /evidence="ECO:0000269|PubMed:20562108"
FT   CONFLICT        249
FT                   /note="T -> A (in Ref. 1; AAC26099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        276
FT                   /note="L -> P (in Ref. 1; AAC26099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        342
FT                   /note="V -> A (in Ref. 1; AAC26099)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        480
FT                   /note="V -> A (in Ref. 1; AAC26099)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   731 AA;  81385 MW;  02E5E79D7EAAAC29 CRC64;
     MDTSGHFHDS GVGDLDEDPK CPCPSSGDEQ QQQQQQQQQQ QPPPPAPPAA PQQPLGPSLQ
     PQPPQLQQQQ QQQQQQQQQQ PPHPLSQLAQ LQSQPVHPGL LHSSPTAFRA PPSSNSTAIL
     HPSSRQGSQL NLNDHLLGHS PSSTATSGPG GGSRHRQASP LVHRRDSNPF TEIAMSSCKY
     SGGVMKPLSR LSASRRNLIE AETEGQPLQL FSPSNPPEIV ISSREDNHAH QTLLHHPNAT
     HNHQHAGTTA SSTTFPKANK RKNQNIGYKL GHRRALFEKR KRLSDYALIF GMFGIVVMVI
     ETELSWGLYS KDSMFSLALK CLISLSTIIL LGLIIAYHTR EVQLFVIDNG ADDWRIAMTY
     ERILYISLEM LVCAIHPIPG EYKFFWTARL AFSYTPSRAE ADVDIILSIP MFLRLYLIAR
     VMLLHSKLFT DASSRSIGAL NKINFNTRFV MKTLMTICPG TVLLVFSISL WIIAAWTVRV
     CERYHDQQDV TSNFLGAMWL ISITFLSIGY GDMVPHTYCG KGVCLLTGIM GAGCTALVVA
     VVARKLELTK AEKHVHNFMM DTQLTKRIKN AAANVLRETW LIYKHTKLLK KIDHAKVRKH
     QRKFLQAIHQ LRSVKMEQRK LSDQANTLVD LSKMQNVMYD LITELNDRSE DLEKQIGSLE
     SKLEHLTASF NSLPLLIADT LRQQQQQLLS AIIEARGVSV AVGTTHTPIS DSPIGVSSTS
     FPTPYTSSSS C
//