LOCUS       NP_002241                427 aa            linear   PRI 21-MAY-2025
DEFINITION  intermediate conductance calcium-activated potassium channel
            protein 4 [Homo sapiens].
ACCESSION   NP_002241
VERSION     NP_002241.1
DBSOURCE    REFSEQ: accession NM_002250.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 427)
  AUTHORS   Segura,E., Zhao,J., Broszczak,M., Audet,F., Sauve,R. and Parent,L.
  TITLE     Investigating the Impact of Electrostatic Interactions on
            Calmodulin Binding and Ca2+-Dependent Activation of the
            Calcium-Gated Potassium SK4 Channel
  JOURNAL   Int J Mol Sci 25 (8), 4255 (2024)
   PUBMED   38673845
  REMARK    GeneRIF: Investigating the Impact of Electrostatic Interactions on
            Calmodulin Binding and Ca[2+]-Dependent Activation of the
            Calcium-Gated Potassium SK4 Channel.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 427)
  AUTHORS   Nikitin,E.S., Postnikova,T.Y., Proskurina,E.Y., Borodinova,A.A.,
            Ivanova,V., Roshchin,M.V., Smirnova,M.P., Kelmanson,I.,
            Belousov,V.V., Balaban,P.M. and Zaitsev,A.V.
  TITLE     Overexpression of KCNN4 channels in principal neurons produces an
            anti-seizure effect without reducing their coding ability
  JOURNAL   Gene Ther 31 (3-4), 144-153 (2024)
   PUBMED   37968509
  REMARK    GeneRIF: Overexpression of KCNN4 channels in principal neurons
            produces an anti-seizure effect without reducing their coding
            ability.
REFERENCE   3  (residues 1 to 427)
  AUTHORS   Petkova-Kirova,P., Murciano,N., Iacono,G., Jansen,J., Simionato,G.,
            Qiao,M., Van der Zwaan,C., Rotordam,M.G., John,T., Hertz,L.,
            Hoogendijk,A.J., Becker,N., Wagner,C., Von Lindern,M., Egee,S., Van
            den Akker,E. and Kaestner,L.
  TITLE     The Gardos Channel and Piezo1 Revisited: Comparison between
            Reticulocytes and Mature Red Blood Cells
  JOURNAL   Int J Mol Sci 25 (3), 1416 (2024)
   PUBMED   38338693
  REMARK    GeneRIF: The Gardos Channel and Piezo1 Revisited: Comparison
            between Reticulocytes and Mature Red Blood Cells.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 427)
  AUTHORS   Charlick,J.N., Bozadzhieva,D., Butler,A.S., Wilkinson,K.A. and
            Marrion,N.V.
  TITLE     A single coiled-coil domain mutation in hIKCa channel subunits
            disrupts preferential formation of heteromeric hSK1:hIKCa channels
  JOURNAL   Eur J Neurosci 59 (1), 3-16 (2024)
   PUBMED   38018635
  REMARK    GeneRIF: A single coiled-coil domain mutation in hIKCa channel
            subunits disrupts preferential formation of heteromeric hSK1:hIKCa
            channels.
REFERENCE   5  (residues 1 to 427)
  AUTHORS   Ran,L., Ye,T., Erbs,E., Ehl,S., Spassky,N., Sumara,I., Zhang,Z. and
            Ricci,R.
  TITLE     KCNN4 links PIEZO-dependent mechanotransduction to NLRP3
            inflammasome activation
  JOURNAL   Sci Immunol 8 (90), eadf4699 (2023)
   PUBMED   38134241
  REMARK    GeneRIF: KCNN4 links PIEZO-dependent mechanotransduction to NLRP3
            inflammasome activation.
REFERENCE   6  (residues 1 to 427)
  AUTHORS   Fanger,C.M., Ghanshani,S., Logsdon,N.J., Rauer,H., Kalman,K.,
            Zhou,J., Beckingham,K., Chandy,K.G., Cahalan,M.D. and Aiyar,J.
  TITLE     Calmodulin mediates calcium-dependent activation of the
            intermediate conductance KCa channel, IKCa1
  JOURNAL   J Biol Chem 274 (9), 5746-5754 (1999)
   PUBMED   10026195
REFERENCE   7  (residues 1 to 427)
  AUTHORS   Ghanshani,S., Coleman,M., Gustavsson,P., Wu,A.C., Gargus,J.J.,
            Gutman,G.A., Dahl,N., Mohrenweiser,H. and Chandy,K.G.
  TITLE     Human calcium-activated potassium channel gene KCNN4 maps to
            chromosome 19q13.2 in the region deleted in diamond-blackfan anemia
  JOURNAL   Genomics 51 (1), 160-161 (1998)
   PUBMED   9693050
REFERENCE   8  (residues 1 to 427)
  AUTHORS   Logsdon,N.J., Kang,J., Togo,J.A., Christian,E.P. and Aiyar,J.
  TITLE     A novel gene, hKCa4, encodes the calcium-activated potassium
            channel in human T lymphocytes
  JOURNAL   J Biol Chem 272 (52), 32723-32726 (1997)
   PUBMED   9407042
REFERENCE   9  (residues 1 to 427)
  AUTHORS   Ishii,T.M., Silvia,C., Hirschberg,B., Bond,C.T., Adelman,J.P. and
            Maylie,J.
  TITLE     A human intermediate conductance calcium-activated potassium
            channel
  JOURNAL   Proc Natl Acad Sci U S A 94 (21), 11651-11656 (1997)
   PUBMED   9326665
REFERENCE   10 (residues 1 to 427)
  AUTHORS   Joiner,W.J., Wang,L.Y., Tang,M.D. and Kaczmarek,L.K.
  TITLE     hSK4, a member of a novel subfamily of calcium-activated potassium
            channels
  JOURNAL   Proc Natl Acad Sci U S A 94 (20), 11013-11018 (1997)
   PUBMED   9380751
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF022797.1 and AF033021.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: The protein encoded by this gene is part of a potentially
            heterotetrameric voltage-independent potassium channel that is
            activated by intracellular calcium. Activation is followed by
            membrane hyperpolarization, which promotes calcium influx. The
            encoded protein may be part of the predominant calcium-activated
            potassium channel in T-lymphocytes. This gene is similar to other
            KCNN family potassium channel genes, but it differs enough to
            possibly be considered as part of a new subfamily. [provided by
            RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: DRR138512.577803.1,
                                           SRR1163657.85675.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000648319.1/ ENSP00000496939.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..427
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.31"
     Protein         1..427
                     /product="intermediate conductance calcium-activated
                     potassium channel protein 4"
                     /note="putative erythrocyte intermediate conductance
                     calcium-activated potassium Gardos channel; putative
                     Gardos channel; potassium intermediate/small conductance
                     calcium-activated channel, subfamily N, member 4; small
                     conductance calcium-activated potassium channel 4;
                     potassium channel, calcium activated intermediate/small
                     conductance subfamily N alpha, member 4;
                     intermediate-conductance Ca2+-activated K+ channel,
                     KCa3.1; gardos channel"
                     /calculated_mol_wt=47565
     Region          12..121
                     /region_name="SK_channel"
                     /note="Calcium-activated SK potassium channel; pfam03530"
                     /db_xref="CDD:460958"
     Site            29..49
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Site            59..79
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Site            108..128
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Site            143..163
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Site            207..227
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Region          <237..290
                     /region_name="Ion_trans_2"
                     /note="Ion channel; pfam07885"
                     /db_xref="CDD:462301"
     Site            265..285
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Region          286..347
                     /region_name="Calmodulin-binding"
                     /note="propagated from UniProtKB/Swiss-Prot (O15554.1)"
     Region          304..375
                     /region_name="CaMBD"
                     /note="Calmodulin binding domain; pfam02888"
                     /db_xref="CDD:460739"
     Site            358
                     /site_type="phosphorylation"
                     /note="Phosphohistidine.
                     /evidence=ECO:0000269|PubMed:17157250; propagated from
                     UniProtKB/Swiss-Prot (O15554.1)"
     CDS             1..427
                     /gene="KCNN4"
                     /gene_synonym="DHS2; hIK1; hIKCa1; hKCa4; hSK4; IK; IK1;
                     IKCA1; KCa3.1; KCA4; SK4; SKCa4"
                     /coded_by="NM_002250.3:113..1396"
                     /db_xref="CCDS:CCDS12630.1"
                     /db_xref="GeneID:3783"
                     /db_xref="HGNC:HGNC:6293"
                     /db_xref="MIM:602754"
ORIGIN      
        1 mggdlvlglg alrrrkrlle qekslagwal vlagtgiglm vlhaemlwfg gcswalylfl
       61 vkctisistf lllclivafh akevqlfmtd nglrdwrval tgrqaaqivl elvvcglhpa
      121 pvrgppcvqd lgapltspqp wpgflgqgea llslamllrl ylvpravllr sgvllnasyr
      181 sigalnqvrf rhwfvaklym nthpgrlllg ltlglwltta wvlsvaerqa vnatghlsdt
      241 lwlipitflt igygdvvpgt mwgkivclct gvmgvcctal lvavvarkle fnkaekhvhn
      301 fmmdiqytke mkesaarvlq eawmfykhtr rkeshaarrh qrkllaaina frqvrlkhrk
      361 lreqvnsmvd iskmhmilyd lqqnlssshr alekqidtla gkldaltell stalgprqlp
      421 epsqqsk
//
