KCNK1_RABIT
ID KCNK1_RABIT Reviewed; 336 AA.
AC Q5UE96; O02821;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Potassium channel subfamily K member 1;
GN Name=KCNK1 {ECO:0000312|EMBL:AAV30846.1};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000312|EMBL:AAV30846.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Corneal epithelium;
RA Rae J.L.;
RT "Ion channels in ocular epithelia.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:AAB61602.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-258, AND TISSUE SPECIFICITY.
RX PubMed=9362344; DOI=10.1152/ajprenal.1997.273.4.f663;
RA Orias M., Velazquez H., Tung F., Lee G., Desir G.V.;
RT "Cloning and localization of a double-pore K channel, KCNK1: exclusive
RT expression in distal nephron segments.";
RL Am. J. Physiol. 273:F663-F666(1997).
CC -!- FUNCTION: Ion channel that contributes to passive transmembrane
CC potassium transport and to the regulation of the resting membrane
CC potential in brain astrocytes, but also in kidney and in other tissues.
CC Forms dimeric channels through which potassium ions pass in accordance
CC with their electrochemical gradient. The channel is selective for K(+)
CC ions at physiological potassium concentrations and at neutral pH, but
CC becomes permeable to Na(+) at subphysiological K(+) levels and upon
CC acidification of the extracellular medium. The homodimer has very low
CC potassium channel activity, when expressed in heterologous systems, and
CC can function as weakly inward rectifying potassium channel (By
CC similarity). Channel activity is modulated by activation of serotonin
CC receptors (By similarity). Heterodimeric channels containing KCNK1 and
CC KCNK2 have much higher activity, and may represent the predominant form
CC in astrocytes (By similarity). Heterodimeric channels containing KCNK1
CC and KCNK3 or KCNK9 have much higher activity. Heterodimeric channels
CC formed by KCNK1 and KCNK9 may contribute to halothane-sensitive
CC currents (By similarity). Mediates outward rectifying potassium
CC currents in dentate gyrus granule cells and contributes to the
CC regulation of their resting membrane potential (By similarity).
CC Contributes to the regulation of action potential firing in dentate
CC gyrus granule cells and down-regulates their intrinsic excitability (By
CC similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2
CC is required for rapid glutamate release in response to activation of G-
CC protein coupled receptors, such as F2R and CNR1 (By similarity).
CC Required for normal ion and water transport in the kidney (By
CC similarity). Contributes to the regulation of the resting membrane
CC potential of pancreatic beta cells (By similarity). The low channel
CC activity of homodimeric KCNK1 may be due to sumoylation. The low
CC channel activity may be due to rapid internalization from the cell
CC membrane and retention in recycling endosomes (By similarity).
CC {ECO:0000250|UniProtKB:O00180, ECO:0000250|UniProtKB:O08581,
CC ECO:0000250|UniProtKB:Q9Z2T2}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Heterodimer with
CC KCNK2; disulfide-linked (By similarity). In astrocytes, forms mostly
CC heterodimeric potassium channels with KCNK2, with only a minor
CC proportion of functional channels containing homodimeric KCNK1 (By
CC similarity). Interacts with KCNK3 and KCNK9, forming functional
CC heterodimeric channels (By similarity). Interacts with GNG4 (By
CC similarity). Identified in a complex with PSD and ARF6; interacts only
CC with PSD that is bound to ARF6 (By similarity). Interacts with UBE2I
CC (By similarity). {ECO:0000250|UniProtKB:O00180,
CC ECO:0000250|UniProtKB:O08581}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O00180};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:O00180}. Recycling
CC endosome {ECO:0000250|UniProtKB:O00180}. Synaptic cell membrane
CC {ECO:0000250|UniProtKB:Q9Z2T2}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:O08581}. Perikaryon
CC {ECO:0000250|UniProtKB:O08581}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:O08581}. Cell projection
CC {ECO:0000250|UniProtKB:O08581}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O00180}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O00180}. Note=The heterodimer with KCNK2 is
CC detected at the astrocyte cell membrane. Not detected at the astrocyte
CC cell membrane when KCNK2 is absent. Detected on neuronal cell bodies,
CC and to a lesser degree on neuronal cell projections. Detected on
CC hippocampus dentate gyrus granule cell bodies and to a lesser degree on
CC proximal dendrites. Detected at the apical cell membrane in stria
CC vascularis in the cochlea. Detected at the apical cell membrane of
CC vestibular dark cells situated between the crista and the utricle in
CC the inner ear. Detected at the apical cell membrane in kidney proximal
CC tubule segment S1 and in subapical compartments in segments S1, S2 and
CC S3. Predominantly in cytoplasmic structures in kidney distal convoluted
CC tubules and collecting ducts (By similarity). Detected at the apical
CC cell membrane of bronchial epithelial cells (By similarity).
CC {ECO:0000250|UniProtKB:O00180, ECO:0000250|UniProtKB:O08581,
CC ECO:0000250|UniProtKB:Q9Z2T2}.
CC -!- TISSUE SPECIFICITY: Expressed in renal distal tubules, especially in
CC cortical collecting duct and cortical thick ascending limb, with lower
CC levels in the connecting tubule. {ECO:0000269|PubMed:9362344}.
CC -!- PTM: Sumoylation is controversial. Sumoylated by UBE2I. Not sumoylated
CC when expressed in xenopus oocytes or mammalian cells. Sumoylation
CC inactivates the channel, but does not interfere with expression at the
CC cell membrane. Sumoylation of a single subunit is sufficient to silence
CC the dimeric channel. Sumoylation of KCNK1 is sufficient to silence
CC heterodimeric channels formed by KCNK1 and KCNK3 or KCNK9. Desumoylated
CC by SENP1; this activates the channel. Desumoylated by SENP1; this
CC strongly increases halothane-mediated activation of heterodimeric
CC channels formed with KCNK9. SENP1 treatment has no effect.
CC {ECO:0000250|UniProtKB:O00180}.
CC -!- SIMILARITY: Belongs to the two pore domain potassium channel (TC
CC 1.A.1.8) family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61602.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY752982; AAV30846.1; -; mRNA.
DR EMBL; AF004695; AAB61602.1; ALT_INIT; mRNA.
DR RefSeq; NP_001075649.1; NM_001082180.1.
DR AlphaFoldDB; Q5UE96; -.
DR SMR; Q5UE96; -.
DR STRING; 9986.ENSOCUP00000013753; -.
DR Ensembl; ENSOCUT00000016002; ENSOCUP00000013753; ENSOCUG00000016003.
DR GeneID; 100008962; -.
DR KEGG; ocu:100008962; -.
DR CTD; 3775; -.
DR eggNOG; KOG1418; Eukaryota.
DR GeneTree; ENSGT00940000155293; -.
DR HOGENOM; CLU_022504_6_0_1; -.
DR InParanoid; Q5UE96; -.
DR OMA; MVAIVHA; -.
DR OrthoDB; 1211599at2759; -.
DR TreeFam; TF313947; -.
DR Proteomes; UP000001811; Chromosome 16.
DR Bgee; ENSOCUG00000016003; Expressed in prefrontal cortex and 13 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:1902937; C:inward rectifier potassium channel complex; IEA:Ensembl.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0034705; C:potassium channel complex; ISS:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0097060; C:synaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IEA:Ensembl.
DR GO; GO:0005267; F:potassium channel activity; ISS:UniProtKB.
DR GO; GO:0022841; F:potassium ion leak channel activity; ISS:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0060075; P:regulation of resting membrane potential; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR InterPro; IPR003280; 2pore_dom_K_chnl.
DR InterPro; IPR003092; 2pore_dom_K_chnl_TASK.
DR InterPro; IPR005408; 2pore_dom_K_chnl_TWIK.
DR InterPro; IPR001779; 2pore_dom_K_chnl_TWIK1.
DR InterPro; IPR013099; K_chnl_dom.
DR PANTHER; PTHR11003; PTHR11003; 1.
DR Pfam; PF07885; Ion_trans_2; 2.
DR PIRSF; PIRSF038061; K_channel_subfamily_K_type; 1.
DR PRINTS; PR01333; 2POREKCHANEL.
DR PRINTS; PR01096; TWIK1CHANNEL.
DR PRINTS; PR01586; TWIKCHANNEL.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Cytoplasmic vesicle; Disulfide bond;
KW Endosome; Glycoprotein; Ion channel; Ion transport; Isopeptide bond;
KW Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..336
FT /note="Potassium channel subfamily K member 1"
FT /id="PRO_0000299074"
FT TOPO_DOM 1..20
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 42..103
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT INTRAMEM 104..116
FT /note="Helical; Name=Pore helix 1"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT INTRAMEM 117..122
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 123..132
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TRANSMEM 133..156
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 157..181
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 203..211
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT INTRAMEM 212..224
FT /note="Helical; Name=Pore helix 2"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT INTRAMEM 225..231
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 232..243
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TRANSMEM 244..267
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT TOPO_DOM 268..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT REGION 117..122
FT /note="Selectivity filter 1"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT REGION 225..230
FT /note="Selectivity filter 2"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT REGION 293..299
FT /note="Important for intracellular retention in recycling
FT endosomes"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT REGION 315..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 118
FT /note="Important for increased permeability to Na(+) when
FT K(+) levels are subphysiological"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT SITE 146
FT /note="Part of a hydrophobic barrier that is stochastically
FT dewetted and limits ion permeability"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT SITE 261
FT /note="Part of a hydrophobic barrier that is stochastically
FT dewetted and limits ion permeability"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2T2"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT CROSSLNK 274
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:O00180"
FT CONFLICT 18..19
FT /note="RS -> T (in Ref. 2; AAB61602)"
FT /evidence="ECO:0000305"
FT CONFLICT 129
FT /note="G -> V (in Ref. 2; AAB61602)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 336 AA; 38076 MW; 00EBD13BF9178505 CRC64;
MLQSLAGSSC VRLVERHRSA WCFGFLVLGY LLYLVFGAVV FSSVELPYED LLRQELRKLK
RRFVEEHECL SEQQLEQFLG RVLEANNYGV SVRSNASGNW NWDFASALFF ASTVLSTTGY
GHTVPLSDGG KAFCIIYSVI GIPFTLLFLT AVVQRVTVHV TRRPVLYFHV RWGFSKQVVA
IVHAVLLGLI TVSCFFFIPA AVFSVLEDDW NFLESFYFCF ISLSTIGLGD YVPGEGYNQK
FRELYKIGIT CYLLLGLIAM LVVLETFCEL HELKKFRKMF YVKKDKDEDQ VHIIEHDQLS
FSSITEQAAG MKEDQKQNEP FVATPSSACA DGPANH
