KCNQ1_RABIT
ID KCNQ1_RABIT Reviewed; 661 AA.
AC Q9MYS6; G1SLX4;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 3.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Potassium voltage-gated channel subfamily KQT member 1;
DE AltName: Full=IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1 {ECO:0000250|UniProtKB:P51787};
DE AltName: Full=KQT-like 1 {ECO:0000250|UniProtKB:P51787};
DE AltName: Full=Voltage-gated potassium channel subunit Kv7.1 {ECO:0000250|UniProtKB:P51787};
GN Name=KCNQ1 {ECO:0000250|UniProtKB:P51787};
GN Synonyms=KVLQT1 {ECO:0000250|UniProtKB:P51787};
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke;
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 151-304.
RC STRAIN=New Zealand white; TISSUE=Heart;
RA Sayeed R.A., Grace A.A., Vandenberg J.I.;
RT "Patterns of ion channel expression in cardiac hypertrophy.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Potassium channel that plays an important role in a number of
CC tissues, including heart, inner ear, stomach and colon (By similarity).
CC Associates with KCNE beta subunits that modulates current kinetics (By
CC similarity). Induces a voltage-dependent by rapidly activating and
CC slowly deactivating potassium-selective outward current (By
CC similarity). Promotes also a delayed voltage activated potassium
CC current showing outward rectification characteristic (By similarity).
CC During beta-adrenergic receptor stimulation participates in cardiac
CC repolarization by associating with KCNE1 to form the I(Ks) cardiac
CC potassium current that increases the amplitude and slows down the
CC activation kinetics of outward potassium current I(Ks) (By similarity).
CC Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1
CC current (By similarity). When associated with KCNE3, forms the
CC potassium channel that is important for cyclic AMP-stimulated
CC intestinal secretion of chloride ions (By similarity). This interaction
CC with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction
CC of currents (By similarity). During conditions of increased substrate
CC load, maintains the driving force for proximal tubular and intestinal
CC sodium ions absorption, gastric acid secretion, and cAMP-induced
CC jejunal chloride ions secretion (By similarity). Allows the provision
CC of potassium ions to the luminal membrane of the secretory canaliculus
CC in the resting state as well as during stimulated acid secretion (By
CC similarity). When associated with KCNE2, forms a heterooligomer complex
CC leading to currents with an apparently instantaneous activation, a
CC rapid deactivation process and a linear current-voltage relationship
CC and decreases the amplitude of the outward current (By similarity).
CC When associated with KCNE4, inhibits voltage-gated potassium channel
CC activity (By similarity). When associated with KCNE5, this complex only
CC conducts current upon strong and continued depolarization (By
CC similarity). Also forms a heterotetramer with KCNQ5 that has a voltage-
CC gated potassium channel activity (By similarity). Binds with
CC phosphatidylinositol 4,5-bisphosphate (By similarity).
CC {ECO:0000250|UniProtKB:P51787, ECO:0000250|UniProtKB:P97414,
CC ECO:0000250|UniProtKB:Q9Z0N7}.
CC -!- SUBUNIT: Tetramer. Heterotetramer with KCNE1; targets to the membrane
CC raft. Interacts (via C-terminus) with CALM; forms a heterooctameric
CC structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent
CC manner. Interacts with AKAP9; targets protein kinase A (PKA) catalytic
CC and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-
CC KCNE1 complex, allowing PKA-mediated phosphorylation and increase of
CC delayed rectifier potassium channel activity. Interacts with KCNE2;
CC form a heterooligomer complex that targets to the membrane raft and
CC leading to currents with an apparently instantaneous activation, a
CC rapid deactivation process and a linear current-voltage relationship
CC and decreases the amplitude of the outward current. Interacts with
CC AP2M1; mediates estrogen-induced internalization via clathrin-coated
CC vesicles. Interacts with NEDD4L; promotes internalization and decreases
CC I(Ks) currents. Interacts with USP2; counteracts the NEDD4L-specific
CC down-regulation of I(Ks) and restore plasma membrane localization.
CC Heterotetramer with KCNQ5; has a voltage-gated potassium channel
CC activity. Interacts with KCNE3; alters membrane raft localization.
CC Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and
CC inhibits voltage-gated potassium channel activity. Interacts with
CC KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts
CC current upon strong and continued depolarization.
CC {ECO:0000250|UniProtKB:P51787}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P51787};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P51787}. Cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P51787}. Early endosome
CC {ECO:0000250|UniProtKB:P51787}. Membrane raft
CC {ECO:0000250|UniProtKB:P51787}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P51787}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:P51787}. Note=Colocalized with KCNE3 at the
CC plasma membrane. Upon 17beta-oestradiol treatment, colocalizes with
CC RAB5A at early endosome. Heterotetramer with KCNQ5 is highly retained
CC at the endoplasmic reticulum and is localized outside of lipid raft
CC microdomains. During the early stages of epithelial cell polarization
CC induced by the calcium switch it removed from plasma membrane to the
CC endoplasmic reticulum where it retained and it is redistributed to the
CC basolateral cell surface in a PI3K-dependent manner at a later stage.
CC {ECO:0000250|UniProtKB:P51787}.
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. {ECO:0000250|UniProtKB:P51787}.
CC -!- DOMAIN: The coiled-coil domain mediates tetramerization.
CC {ECO:0000250|UniProtKB:P51787}.
CC -!- DOMAIN: The segment S6 is involved in the inhibition of voltage-gated
CC potassium channel activity by KCNE4. {ECO:0000250|UniProtKB:P51787}.
CC -!- DOMAIN: The C-terminal assembly domain promotes self-interactiona;
CC allows functional channel. {ECO:0000250|UniProtKB:P51787}.
CC -!- DOMAIN: The C-terminal coiled-coil domain interacts with a single CALM
CC molecule via the first two membrane-proximal helical regions, with CALM
CC forming a clamp-like structure. Binding of CALM C-terminus to the first
CC helical region is calcium-independent but is essential for assembly of
CC the structure. Binding of CALM N-terminus to the second helical region
CC is calcium-dependent and regulates electrophysiological activity of the
CC channel. {ECO:0000250|UniProtKB:P51787}.
CC -!- PTM: Phosphorylation at Ser-27 by PKA; increases delayed rectifier
CC potassium channel activity of the KCNQ1-KCNE1 complex through a
CC macromolecular complex that includes PKA, PP1, and the targeting
CC protein AKAP9. {ECO:0000250|UniProtKB:P51787}.
CC -!- PTM: Ubiquitinated by NEDD4L; promotes internalization. The
CC ubiquitinylated form is internalized through a clathrin-mediated
CC endocytosis by interacting with AP2M1 and is recycled back to the cell
CC membrane via RAB4A and RAB11A. {ECO:0000250|UniProtKB:P51787}.
CC -!- PTM: Deubiquitinated by USP2; counteracts the NEDD4L-specific down-
CC regulation of I(Ks) and restores the membrane localization.
CC {ECO:0000250|UniProtKB:P51787}.
CC -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15)
CC subfamily. Kv7.1/KCNQ1 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB94848.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AAGW02076516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076517; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076518; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076519; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076521; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076525; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076529; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076531; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02076533; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; AJ291316; CAB94848.1; ALT_FRAME; mRNA.
DR BMRB; Q9MYS6; -.
DR STRING; 9986.ENSOCUP00000003879; -.
DR eggNOG; KOG1419; Eukaryota.
DR InParanoid; Q9MYS6; -.
DR OrthoDB; 1168835at2759; -.
DR TreeFam; TF315186; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0034702; C:ion channel complex; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
DR GO; GO:0086009; P:membrane repolarization; ISS:UniProtKB.
DR GO; GO:0060453; P:regulation of gastric acid secretion; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003937; K_chnl_volt-dep_KCNQ.
DR InterPro; IPR013821; K_chnl_volt-dep_KCNQ_C.
DR InterPro; IPR005827; K_chnl_volt-dep_KCQN1.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF266; PTHR11537:SF266; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03520; KCNQ_channel; 1.
DR PRINTS; PR01460; KCNQ1CHANNEL.
DR PRINTS; PR01459; KCNQCHANNEL.
PE 2: Evidence at transcript level;
KW Calmodulin-binding; Cell membrane; Coiled coil; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..661
FT /note="Potassium voltage-gated channel subfamily KQT member
FT 1"
FT /id="PRO_0000054026"
FT TOPO_DOM 1..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..146
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..216
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 217..224
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..247
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..260
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..281
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 282..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 299..319
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..326
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..347
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 348..661
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..381
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT REGION 514..528
FT /note="Interaction with CALM; calcium-dependent"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT REGION 534..571
FT /note="Interaction with KCNE1 C-terminus"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT REGION 587..615
FT /note="Interaction with AKAP9"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT REGION 588..619
FT /note="C-terminal assembly domain"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT REGION 624..661
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 584..620
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT MOTIF 311..316
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 50..81
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 27
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P51787"
FT MOD_RES 406
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97414"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97414"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 661 AA; 73636 MW; E90BB42E0D3328DB CRC64;
MAAASTPPRA ERKRXSWSRL PGAQRESAGL AKKCPFSLEL AESGPPSSAL YAPVSPPSAP
EPAPPASPAS PAPPAADQGP QPPVSLDPRV SIYSVRRPLL ARTHIQGRVY NFLERPTGWK
CFAYHFTVFL IVLVCLIFSV LSTIEQYATL ATGTLFWMEI VLVVFFGTEY VVRLWSAGCR
SKYVGLWGRL RFARKPISII DLIVVVASMV VLCVGSKGQV FATSAIRGIR FLQILRMLHV
DRQGGTWRLL GSVVFIHRQE LITTLYIGFL GLIFSSYFVY LAEKDAVNES GRVEFGSYAD
ALWWGVVTVT TIGYGDKVPQ TWVGKTIASC FSVFAISFFA LPAGILGSGF ALKVQQKQRQ
KHFNRQIPAA ASLIQTAWRC YAAENPDSAT WKIYIRKPTR GHALLSPSPK PKKSAMVKKK
KFKLDKDNGV SPGEKTLPVP QITCEPPEER RPDHFPVDSH DGSVRKSPAL LEVSTPQFLR
TNSFAEDLDL EGETLLAPIT HVSQLREHHR ATVKVIRRMQ YFVAKKKFQQ ARKPYDVRDV
IEQYSQGHLN LMVRIKELQR RLDQSIGKPS LFVPISEKSK DRGSNSIGAR LNRVEDKVTQ
LDQRLVLIAD MLQQLLALHQ GRCHGGAHPA QARDGDPADP ELFLPTYEQL TVPRRDPEEG
S
