LOCUS       NM_033310               1829 bp    mRNA    linear   PRI 20-SEP-2024
DEFINITION  Homo sapiens potassium two pore domain channel subfamily K member 4
            (KCNK4), transcript variant 2, mRNA.
ACCESSION   NM_033310 NM_033311
VERSION     NM_033310.3
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  (bases 1 to 1829)
  AUTHORS   Sorum,B., Docter,T., Panico,V., Rietmeijer,R.A. and Brohawn,S.G.
  TITLE     Tension activation of mechanosensitive two-pore domain K+ channels
            TRAAK, TREK-1, and TREK-2
  JOURNAL   Nat Commun 15 (1), 3142 (2024)
   PUBMED   38605031
  REMARK    Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1829)
  AUTHORS   Elhossini,R.M., Sayed,I.M., Hellal,U.S., Mahmoud,S.A.M.,
            Aglan,M.S., Hassib,N.F. and Abdel-Hamid,M.S.
  TITLE     A recurrent KCNK4 variant in a dominant pedigree with
            hypertrichosis and gingival fibromatosis syndrome: Variable
            phenotypic expressivity and insights on patients' dental management
  JOURNAL   Am J Med Genet A 194 (1), 39-45 (2024)
   PUBMED   37750049
  REMARK    GeneRIF: A recurrent KCNK4 variant in a dominant pedigree with
            hypertrichosis and gingival fibromatosis syndrome: Variable
            phenotypic expressivity and insights on patients' dental
            management.
REFERENCE   3  (bases 1 to 1829)
  AUTHORS   Rietmeijer,R.A., Sorum,B., Li,B. and Brohawn,S.G.
  TITLE     Physical basis for distinct basal and mechanically gated activity
            of the human K+ channel TRAAK
  JOURNAL   Neuron 109 (18), 2902-2913 (2021)
   PUBMED   34390650
  REMARK    GeneRIF: Physical basis for distinct basal and mechanically gated
            activity of the human K(+) channel TRAAK.
REFERENCE   4  (bases 1 to 1829)
  AUTHORS   Gripp,K.W., Smithson,S.F., Scurr,I.J., Baptista,J., Majumdar,A.,
            Pierre,G., Williams,M., Henderson,L.B., Wentzensen,I.M.,
            McLaughlin,H., Leeuwen,L., Simon,M.E.H., van Binsbergen,E.,
            Dinulos,M.B.P., Kaplan,J.D., McRae,A., Superti-Furga,A., Good,J.M.
            and Kutsche,K.
  TITLE     Syndromic disorders caused by gain-of-function variants in KCNH1,
            KCNK4, and KCNN3-a subgroup of K+ channelopathies
  JOURNAL   Eur J Hum Genet 29 (9), 1384-1395 (2021)
   PUBMED   33594261
  REMARK    GeneRIF: Syndromic disorders caused by gain-of-function variants in
            KCNH1, KCNK4, and KCNN3-a subgroup of K(+) channelopathies.
REFERENCE   5  (bases 1 to 1829)
  AUTHORS   Brohawn,S.G., del Marmol,J. and MacKinnon,R.
  TITLE     Crystal structure of the human K2P TRAAK, a lipid- and
            mechano-sensitive K+ ion channel
  JOURNAL   Science 335 (6067), 436-441 (2012)
   PUBMED   22282805
  REMARK    GeneRIF: crystal structure of TRAAK at 3.8 angstroms resolution;
            channel comprises 2 protomers that create 2-fold symmetric K(+)
            channel; extracellular surface has a helical cap; 2 diagonally
            opposed gate-forming inner helices form membrane-interacting
            structures
REFERENCE   6  (bases 1 to 1829)
  AUTHORS   Goldstein,S.A., Bockenhauer,D., O'Kelly,I. and Zilberberg,N.
  TITLE     Potassium leak channels and the KCNK family of two-P-domain
            subunits
  JOURNAL   Nat Rev Neurosci 2 (3), 175-184 (2001)
   PUBMED   11256078
  REMARK    Review article
REFERENCE   7  (bases 1 to 1829)
  AUTHORS   Meadows,H.J., Chapman,C.G., Duckworth,D.M., Kelsell,R.E.,
            Murdock,P.R., Nasir,S., Rennie,G. and Randall,A.D.
  TITLE     The neuroprotective agent sipatrigine (BW619C89) potently inhibits
            the human tandem pore-domain K(+) channels TREK-1 and TRAAK
  JOURNAL   Brain Res 892 (1), 94-101 (2001)
   PUBMED   11172753
REFERENCE   8  (bases 1 to 1829)
  AUTHORS   Chapman,C.G., Meadows,H.J., Godden,R.J., Campbell,D.A.,
            Duckworth,M., Kelsell,R.E., Murdock,P.R., Randall,A.D., Rennie,G.I.
            and Gloger,I.S.
  TITLE     Cloning, localisation and functional expression of a novel human,
            cerebellum specific, two pore domain potassium channel
  JOURNAL   Brain Res Mol Brain Res 82 (1-2), 74-83 (2000)
   PUBMED   11042359
  REMARK    GeneRIF: Human TASK-3 was cloned and expressed; protein sequence
            and activity compared to similar two pore domain potassium
            channels, including KCNK4 (TRAAK).
REFERENCE   9  (bases 1 to 1829)
  AUTHORS   Simpson,J.C., Wellenreuther,R., Poustka,A., Pepperkok,R. and
            Wiemann,S.
  TITLE     Systematic subcellular localization of novel proteins identified by
            large-scale cDNA sequencing
  JOURNAL   EMBO Rep 1 (3), 287-292 (2000)
   PUBMED   11256614
REFERENCE   10 (bases 1 to 1829)
  AUTHORS   Lesage,F., Maingret,F. and Lazdunski,M.
  TITLE     Cloning and expression of human TRAAK, a polyunsaturated fatty
            acids-activated and mechano-sensitive K(+) channel
  JOURNAL   FEBS Lett 471 (2-3), 137-140 (2000)
   PUBMED   10767409
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP001453.6, DB273064.1,
            BC067791.1, AF259500.1 and BC110327.1.
            
            On Nov 22, 2018 this sequence version replaced NM_033310.2.
            
            Summary: This gene encodes a member of the TWIK-related arachidonic
            acid-stimulated two pore potassium channel subfamily. The encoded
            protein homodimerizes and functions as an outwardly rectifying
            channel. This channel is regulated by polyunsaturated fatty acids,
            temperature and mechanical deformation of the lipid membrane. This
            protein is expressed primarily in neural tissues and may be
            involved in regulating the noxious input threshold in dorsal root
            ganglia neurons. Alternate splicing results in multiple transcript
            variants. Naturally occurring read-through transcripts also exist
            between this gene and the downstream testis expressed 40 (TEX40)
            gene, as represented in GeneID: 106780802. [provided by RefSeq, Nov
            2015].
            
            Transcript Variant: This variant (2) encodes the functional
            protein.
            
            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 :: AF259500.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2154665 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000422670.7/ ENSP00000402797.2
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-19                AP001453.6         63484-63502
            20-48               DB273064.1         1-29
            49-50               AP001453.6         63532-63533
            51-102              DB273064.1         32-83
            103-265             BC067791.1         80-242
            266-1184            AF259500.1         165-1083
            1185-1771           AP001453.6         71569-72155
            1772-1829           BC110327.1         1616-1673
FEATURES             Location/Qualifiers
     source          1..1829
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.1"
     gene            1..1829
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /note="potassium two pore domain channel subfamily K
                     member 4"
                     /db_xref="GeneID:50801"
                     /db_xref="HGNC:HGNC:6279"
                     /db_xref="MIM:605720"
     exon            1..265
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     exon            266..531
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     CDS             343..1524
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /note="two pore K+ channel KT4.1; TWIK-related arachidonic
                     acid-stimulated potassium channel protein; K2P4.1
                     potassium channel; two pore K(+) channel KT4.1; two pore
                     potassium channel KT4.1; potassium channel, subfamily K,
                     member 4; potassium channel, two pore domain subfamily K,
                     member 4"
                     /codon_start=1
                     /product="potassium channel subfamily K member 4"
                     /protein_id="NP_201567.1"
                     /db_xref="CCDS:CCDS8067.1"
                     /db_xref="GeneID:50801"
                     /db_xref="HGNC:HGNC:6279"
                     /db_xref="MIM:605720"
                     /translation="MRSTTLLALLALVLLYLVSGALVFRALEQPHEQQAQRELGEVRE
                     KFLRAHPCVSDQELGLLIKEVADALGGGADPETNSTSNSSHSAWDLGSAFFFSGTIIT
                     TIGYGNVALRTDAGRLFCIFYALVGIPLFGILLAGVGDRLGSSLRHGIGHIEAIFLKW
                     HVPPELVRVLSAMLFLLIGCLLFVLTPTFVFCYMEDWSKLEAIYFVIVTLTTVGFGDY
                     VAGADPRQDSPAYQPLVWFWILLGLAYFASVLTTIGNWLRVVSRRTRAEMGGLTAQAA
                     SWTGTVTARVTQRAGPAAPPPEKEQPLLPPPPCPAQPLGRPRSPSPPEKAQPPSPPTA
                     SALDYPSENLAFIDESSDTQSERGCPLPRAPRGRRRPNPPRKPVRPRGPGRPRDKGVP
                     V"
     exon            532..655
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     exon            656..816
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     exon            817..1003
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1004..1143
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1144..1829
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1788..1793
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /note="hexamer: AATGAA"
     polyA_site      1829
                     /gene="KCNK4"
                     /gene_synonym="FHEIG; K2p4.1; TRAAK; TRAAK1"
                     /note="major polyA site"
ORIGIN      
        1 agtgctgagc ccaagggcca ggctgtcccc aggggcggag agttgcggac ccttcccgat
       61 ccggtaatgg gcctgggaga tgccagatta gcgtggtgcc tgtccggaga gacgggccag
      121 ctgatgccca ggtcggggcc ctgccgctgg ccacactggg ctccggtcca aggctagaag
      181 gctggcccct gctgcaaccc ctctccggct cctctgccac ccacctcccg gggctggccg
      241 gctgtgggga gccaggcggc cgcagtgacg acagctcccc aggagccccc cgcccggccc
      301 ctccaggcgg gcagtggagc tggcccggcg cctgggcgcg ccatgcgcag caccacgctc
      361 ctggccctgc tggcgctggt cttgctttac ttggtgtctg gtgccctggt gttccgggcc
      421 ctggagcagc cccacgagca gcaggcccag agggagctgg gggaggtccg agagaagttc
      481 ctgagggccc atccgtgtgt gagcgaccag gagctgggcc tcctcatcaa ggaggtggct
      541 gatgccctgg gagggggtgc ggacccagaa accaactcga ccagcaacag cagccactca
      601 gcctgggacc tgggcagcgc cttctttttc tcagggacca tcatcaccac catcggctat
      661 ggcaatgtgg ccctgcgcac agatgccggg cgcctcttct gcatctttta tgcgctggtg
      721 gggattccgc tgtttgggat cctactggca ggggtcgggg accggctggg ctcctccctg
      781 cgccatggca tcggtcacat tgaagccatc ttcttgaagt ggcacgtgcc accggagcta
      841 gtaagagtgc tgtcggcgat gcttttcctg ctgatcggct gcctgctctt tgtcctcacg
      901 cccacgttcg tgttctgcta tatggaggac tggagcaagc tggaggccat ctactttgtc
      961 atagtgacgc ttaccaccgt gggctttggc gactatgtgg ccggcgcgga ccccaggcag
     1021 gactccccgg cctatcagcc gctggtgtgg ttctggatcc tgctcggcct ggcttacttc
     1081 gcctcagtgc tcaccaccat cgggaactgg ctgcgagtag tgtcccgccg cactcgggca
     1141 gagatgggcg gcctcacggc tcaggctgcc agctggactg gcacggtgac agcgcgcgtg
     1201 acccagcgag ccgggcccgc cgccccgccg ccggagaagg agcagccact gctgcctcca
     1261 ccgccctgtc cagcgcagcc gctgggcagg ccccgatccc cttcgccccc cgagaaggct
     1321 cagccgcctt ccccgcccac ggcctcggcc ctggattatc ccagcgagaa cctggccttc
     1381 atcgacgagt cctcggatac gcagagcgag cgcggctgcc cgctgccccg cgcgccgaga
     1441 ggtcgccgcc gcccaaatcc ccccaggaag cccgtgcggc cccgcggccc cgggcgtccc
     1501 cgagacaaag gcgtgccggt gtaggggcag gatccctggc cgggcctctc aagggcttcg
     1561 tttctgctct ccccggcatg cctggcttgt ttgaccaaag agccctcttt ccacgagact
     1621 gaagtctggg gaggaggcta cagttgcctc tccgcctcct ccctggcccc ggcccttccc
     1681 tcacttccat ccatctctag acccccccaa ggctttctgt gtcgctgccc cgggcgggtg
     1741 tatccctcac agcacctcac gactgtgcct caaagcctgc atcaataaat gaaaacggtc
     1801 tgcaccgctg cgggcgtgac gctcccgga
//
