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Database: UniProt
Entry: KCNQ1_CAVPO
LinkDB: KCNQ1_CAVPO
Original site: KCNQ1_CAVPO 
ID   KCNQ1_CAVPO             Reviewed;         671 AA.
AC   O70344; H0V4C0; Q9QYG3;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   20-JAN-2016, sequence version 3.
DT   27-SEP-2017, entry version 105.
DE   RecName: Full=Potassium voltage-gated channel subfamily KQT member 1 {ECO:0000250|UniProtKB:P51787};
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   Cavia porcellus (Guinea pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia;
OC   Hystricomorpha; Caviidae; Cavia.
OX   NCBI_TaxID=10141;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=2N;
RX   PubMed=21993624; DOI=10.1038/nature10530;
RA   Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J.,
RA   Washietl S., Kheradpour P., Ernst J., Jordan G., Mauceli E.,
RA   Ward L.D., Lowe C.B., Holloway A.K., Clamp M., Gnerre S., Alfoldi J.,
RA   Beal K., Chang J., Clawson H., Cuff J., Di Palma F., Fitzgerald S.,
RA   Flicek P., Guttman M., Hubisz M.J., Jaffe D.B., Jungreis I.,
RA   Kent W.J., Kostka D., Lara M., Martins A.L., Massingham T., Moltke I.,
RA   Raney B.J., Rasmussen M.D., Robinson J., Stark A., Vilella A.J.,
RA   Wen J., Xie X., Zody M.C., Baldwin J., Bloom T., Chin C.W., Heiman D.,
RA   Nicol R., Nusbaum C., Young S., Wilkinson J., Worley K.C., Kovar C.L.,
RA   Muzny D.M., Gibbs R.A., Cree A., Dihn H.H., Fowler G., Jhangiani S.,
RA   Joshi V., Lee S., Lewis L.R., Nazareth L.V., Okwuonu G.,
RA   Santibanez J., Warren W.C., Mardis E.R., Weinstock G.M., Wilson R.K.,
RA   Delehaunty K., Dooling D., Fronik C., Fulton L., Fulton B., Graves T.,
RA   Minx P., Sodergren E., Birney E., Margulies E.H., Herrero J.,
RA   Green E.D., Haussler D., Siepel A., Goldman N., Pollard K.S.,
RA   Pedersen J.S., Lander E.S., Kellis M.;
RT   "A high-resolution map of human evolutionary constraint using 29
RT   mammals.";
RL   Nature 478:476-482(2011).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 155-253.
RC   TISSUE=Heart;
RA   Shi H., Wang Z.;
RT   "Guinea pig cardiac KvLQT1 potassium channel mRNA.";
RL   Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 201-323.
RC   TISSUE=Heart;
RA   Ohya S., Imaizumi Y., Watanabe M.;
RT   "Guinea-pig potassium channel (KvLQT1).";
RL   Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Potassium channel that plays an important role in a
CC       number of tissues, including heart, inner ear, stomach and colon
CC       (By similarity). Associates with KCNE beta subunits that modulates
CC       current kinetics (By similarity). Induces a voltage-dependent by
CC       rapidly activating and slowly deactivating potassium-selective
CC       outward current (By similarity). Promotes also a delayed voltage
CC       activated potassium current showing outward rectification
CC       characteristic (By similarity). During beta-adrenergic receptor
CC       stimulation participates in cardiac repolarization by associating
CC       with KCNE1 to form the I(Ks) cardiac potassium current that
CC       increases the amplitude and slows down the activation kinetics of
CC       outward potassium current I(Ks) (By similarity). Muscarinic
CC       agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (By
CC       similarity). When associated with KCNE3, forms the potassium
CC       channel that is important for cyclic AMP-stimulated intestinal
CC       secretion of chloride ions (By similarity). This interaction with
CC       KCNE3 is reduced by 17beta-estradiol, resulting in the reduction
CC       of currents (By similarity). During conditions of increased
CC       substrate load, maintains the driving force for proximal tubular
CC       and intestinal sodium ions absorption, gastric acid secretion, and
CC       cAMP-induced jejunal chloride ions secretion (By similarity).
CC       Allows the provision of potassium ions to the luminal membrane of
CC       the secretory canaliculus in the resting state as well as during
CC       stimulated acid secretion (By similarity). When associated with
CC       KCNE2, forms a heterooligomer complex leading to currents with an
CC       apparently instantaneous activation, a rapid deactivation process
CC       and a linear current-voltage relationship and decreases the
CC       amplitude of the outward current (By similarity). When associated
CC       with KCNE4, inhibits voltage-gated potassium channel activity (By
CC       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
CC       voltage-gated potassium channel activity (By similarity). Binds
CC       with 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
CC       membrane raft. Interacts (via C-terminus) with CALM; forms an
CC       heterotetramer in a calcium-independent manner. Interacts with
CC       AKAP9; targets protein kinase A (PKA) catalytic and regulatory
CC       subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1
CC       complex, allowing PKA-mediated phosphorylation and increase of
CC       delayed rectifier potassium channel activity. Interacts with
CC       KCNE2; form a heterooligomer complex that targets to the membrane
CC       raft and leading to currents with an apparently instantaneous
CC       activation, a rapid deactivation process and a linear current-
CC       voltage relationship and decreases the amplitude of the outward
CC       current. Interacts with AP2M1; mediates estrogen-induced
CC       internalization via clathrin-coated vesicles. Interacts with
CC       NEDD4L; promotes internalization and decreases I(Ks) currents.
CC       Interacts with USP2; counteracts the NEDD4L-specific down-
CC       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
CC       and inhibits voltage-gated potassium channel activity. Interacts
CC       with KCNE5; impairs KCNQ1 localization in lipid rafts and only
CC       conducts current upon strong and continued depolarization.
CC       {ECO:0000250|UniProtKB:P51787}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane
CC       {ECO:0000250|UniProtKB:P51787}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P51787}. Cytoplasmic vesicle membrane
CC       {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
CC       with RAB5A at early endosome. Heterotetramer with KCNQ5 is highly
CC       retained at the endoplasmic reticulum and is localized outside of
CC       lipid raft microdomains. During the early stages of epithelial
CC       cell polarization induced by the calcium switch it removed from
CC       plasma membrane to the endoplasmic reticulum where it retained and
CC       it is redistributed to the basolateral cell surface in a PI3K-
CC       dependent manner at a later stage. {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
CC       every 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-
CC       gated potassium channel activity by KCNE4.
CC       {ECO:0000250|UniProtKB:P51787}.
CC   -!- DOMAIN: The C-terminal assembly domain promotes self-interactiona;
CC       allows functional 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
CC       cell membrane via RAB4A and RAB11A.
CC       {ECO:0000250|UniProtKB:P51787}.
CC   -!- PTM: Deubiquitinated by USP2; counteracts the NEDD4L-specific
CC       down-regulation of I(Ks) and restores the membrane localization.
CC       {ECO:0000250|UniProtKB:P51787}.
CC   -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC
CC       1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily. {ECO:0000305}.
DR   EMBL; AAKN02038603; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAKN02038605; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AAKN02038604; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF049341; AAC05498.1; -; mRNA.
DR   EMBL; AB032574; BAA88579.1; -; mRNA.
DR   ProteinModelPortal; O70344; -.
DR   STRING; 10141.ENSCPOP00000004457; -.
DR   BindingDB; O70344; -.
DR   ChEMBL; CHEMBL5135; -.
DR   Ensembl; ENSCPOT00000005005; ENSCPOP00000004457; ENSCPOG00000004952.
DR   eggNOG; KOG1419; Eukaryota.
DR   eggNOG; COG1226; LUCA.
DR   GeneTree; ENSGT00550000074513; -.
DR   InParanoid; O70344; -.
DR   OMA; ERKRWGW; -.
DR   OrthoDB; EOG091G02ZT; -.
DR   TreeFam; TF315186; -.
DR   Proteomes; UP000005447; Unassembled WGS sequence.
DR   Bgee; ENSCPOG00000004952; -.
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:0070293; P:renal absorption; ISS:UniProtKB.
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   PANTHER; PTHR11537; PTHR11537; 1.
DR   PANTHER; PTHR11537:SF189; PTHR11537:SF189; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF03520; KCNQ_channel; 1.
DR   PRINTS; PR00169; KCHANNEL.
DR   PRINTS; PR01460; KCNQ1CHANNEL.
DR   PRINTS; PR01459; KCNQCHANNEL.
PE   2: Evidence at transcript level;
KW   Calmodulin-binding; Cell membrane; Coiled coil; Complete proteome;
KW   Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Glycoprotein;
KW   Ion channel; Ion transport; Membrane; Phosphoprotein; Potassium;
KW   Potassium channel; Potassium transport; Reference proteome;
KW   Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW   Voltage-gated channel.
FT   CHAIN         1    671       Potassium voltage-gated channel subfamily
FT                                KQT member 1.
FT                                /FTId=PRO_0000054021.
FT   TOPO_DOM      1    122       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    123    143       Helical; Name=Segment S1. {ECO:0000255}.
FT   TOPO_DOM    144    148       Extracellular. {ECO:0000255}.
FT   TRANSMEM    149    169       Helical; Name=Segment S2. {ECO:0000255}.
FT   TOPO_DOM    170    196       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    197    218       Helical; Name=Segment S3. {ECO:0000255}.
FT   TOPO_DOM    219    226       Extracellular. {ECO:0000255}.
FT   TRANSMEM    227    249       Helical; Voltage-sensor; Name=Segment S4.
FT                                {ECO:0000255}.
FT   TOPO_DOM    250    262       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    263    283       Helical; Name=Segment S5. {ECO:0000255}.
FT   TOPO_DOM    284    300       Extracellular. {ECO:0000255}.
FT   INTRAMEM    301    321       Pore-forming; Name=Segment H5.
FT                                {ECO:0000255}.
FT   TOPO_DOM    322    328       Extracellular. {ECO:0000255}.
FT   TRANSMEM    329    349       Helical; Name=Segment S6. {ECO:0000255}.
FT   TOPO_DOM    350    671       Cytoplasmic. {ECO:0000255}.
FT   REGION      536    573       Interaction with KCNE1 C-terminus.
FT                                {ECO:0000250|UniProtKB:P51787}.
FT   REGION      589    617       Interaction with AKAP9.
FT                                {ECO:0000250|UniProtKB:P51787}.
FT   REGION      590    621       C-terminal assembly domain.
FT                                {ECO:0000250|UniProtKB:P51787}.
FT   COILED      586    621       {ECO:0000250|UniProtKB:P51787}.
FT   MOTIF       313    318       Selectivity filter. {ECO:0000250}.
FT   MOD_RES      27     27       Phosphoserine; by PKA.
FT                                {ECO:0000250|UniProtKB:P51787}.
FT   MOD_RES     408    408       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97414}.
FT   MOD_RES     410    410       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P97414}.
FT   CARBOHYD    290    290       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CONFLICT    236    236       I -> S (in Ref. 2; AAC05498).
FT                                {ECO:0000305}.
SQ   SEQUENCE   671 AA;  74411 MW;  68B5ABCE83313557 CRC64;
     MAAASSPPRT ERKRGGWGRL LGSRRGSASL AKKCPFSLEL AEGGPAGGTL YAPVAPPGAL
     SPGSPAPPAS PAAPPAGLEL GPRPPVSLDP RVSIYSARRP LLARTHIQGR VYNFLERPTG
     WKCFVYHFAV FLIVLACLIF SVLSTIEQYA ALATGTLFWM EIVLVVFFGT EYVVRLWSAG
     CRSKYVGIWG RLRFARKPIS IIDLIVVVAS MVVLCVGSKG QVFATSAIRG IRFLQILRML
     HVDRQGGTWR LLGSVVFIHR QELITTLYIG FLGLIFSSYF VYLAEKDAVN ESGRVEFGSY
     ADALWWGVVT VTTIGYGDKV PQTWVGKTIA SCFSVFAISF FALPAGILGS GFALKVQQKQ
     RQKHFNRQIP AAASLIQTAW RCYAAENPDS STWKIYVRKP ARSHTLLSPS PKPKKSAMVR
     KKKFKPDKDN GVSPGEKMLT VPHITCDPPE ERRPDHFSVD GYDSSVRKSP TLLEVSPTHF
     MRTNSFAEDL DLEGETLLTP ITHVSQLREH HRATIKVIRR MQYFVAKKKF QQARKPYDVR
     DVIEQYSQGH LNLMVRIKEL QRRLDQSIGK PSLFIPISEK SKDRGSNTIG ARLNRVEDKV
     TQLDQRLVVI TDMLHQLLSL HQGGPHSGGG PQMVQPCSED GSIHPELFLP SNSLPTYEQL
     TVPQRGPDEA S
//
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