HCN4_MOUSE
ID HCN4_MOUSE Reviewed; 1186 AA.
AC O70507;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4;
DE AltName: Full=Brain cyclic nucleotide-gated channel 3;
DE Short=BCNG-3;
GN Name=Hcn4; Synonyms=Bcng3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 179-684.
RC TISSUE=Brain;
RX PubMed=9630217; DOI=10.1016/s0092-8674(00)81434-8;
RA Santoro B., Liu D.T., Yao H., Bartsch D., Kandel E.R., Siegelbaum S.A.,
RA Tibbs G.R.;
RT "Identification of a gene encoding a hyperpolarization-activated
RT 'pacemaker' channel of brain.";
RL Cell 93:717-729(1998).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11675786; DOI=10.1038/35098087;
RA Stevens D.R., Seifert R., Bufe B., Mueller F., Kremmer E., Gauss R.,
RA Meyerhof W., Kaupp U.B., Lindemann B.;
RT "Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to
RT sour stimuli.";
RL Nature 413:631-635(2001).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1090 AND SER-1093, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Hyperpolarization-activated ion channel with very slow
CC activation and inactivation exhibiting weak selectivity for potassium
CC over sodium ions. Contributes to the native pacemaker currents in heart
CC (If) that regulate the rhythm of heart beat. May contribute to the
CC native pacemaker currents in neurons (Ih) (By similarity). May mediate
CC responses to sour stimuli. {ECO:0000250, ECO:0000269|PubMed:11675786}.
CC -!- ACTIVITY REGULATION: Activated by cAMP. cAMP binding causes a
CC conformation change that leads to the assembly of an active tetramer
CC and channel opening (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homotetramer. The potassium channel is composed of a homo- or
CC heterotetrameric complex of pore-forming subunits (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11675786};
CC Multi-pass membrane protein {ECO:0000269|PubMed:11675786}.
CC -!- TISSUE SPECIFICITY: Detected in a subset of elongated cells in taste
CC buds. {ECO:0000269|PubMed:11675786}.
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.
CC -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
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DR EMBL; AC110530; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF064874; AAC40126.1; -; mRNA.
DR AlphaFoldDB; O70507; -.
DR SMR; O70507; -.
DR ComplexPortal; CPX-139; HCN4 channel complex.
DR IntAct; O70507; 2.
DR STRING; 10090.ENSMUSP00000034889; -.
DR BindingDB; O70507; -.
DR ChEMBL; CHEMBL4523149; -.
DR DrugCentral; O70507; -.
DR GuidetoPHARMACOLOGY; 403; -.
DR GlyGen; O70507; 1 site.
DR iPTMnet; O70507; -.
DR PhosphoSitePlus; O70507; -.
DR SwissPalm; O70507; -.
DR MaxQB; O70507; -.
DR PaxDb; O70507; -.
DR PeptideAtlas; O70507; -.
DR PRIDE; O70507; -.
DR ProteomicsDB; 271496; -.
DR ABCD; O70507; 1 sequenced antibody.
DR MGI; MGI:1298209; Hcn4.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; O70507; -.
DR PhylomeDB; O70507; -.
DR Reactome; R-MMU-1296061; HCN channels.
DR ChiTaRS; Hcn4; mouse.
DR PRO; PR:O70507; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O70507; protein.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098855; C:HCN channel complex; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; IMP:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0086041; F:voltage-gated potassium channel activity involved in SA node cell action potential depolarization; ISO:MGI.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI.
DR GO; GO:0006812; P:cation transport; IMP:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; ISO:MGI.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0098909; P:regulation of cardiac muscle cell action potential involved in regulation of contraction; ISO:MGI.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:MGI.
DR GO; GO:2001257; P:regulation of cation channel activity; IC:ComplexPortal.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:MGI.
DR GO; GO:0002027; P:regulation of heart rate; ISS:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISO:MGI.
DR GO; GO:0003254; P:regulation of membrane depolarization; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:MGI.
DR GO; GO:0098907; P:regulation of SA node cell action potential; IC:ComplexPortal.
DR GO; GO:0086015; P:SA node cell action potential; ISO:MGI.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR013621; Ion_trans_N.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF08412; Ion_trans_N; 1.
DR PRINTS; PR01463; EAGCHANLFMLY.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW cAMP; cAMP-binding; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Nucleotide-binding;
KW Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1186
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 4"
FT /id="PRO_0000054118"
FT TOPO_DOM 1..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..293
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 315..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..368
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 421..441
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..464
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 465..486
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 487..496
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 497..517
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 518..1186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 25..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..260
FT /note="Involved in subunit assembly"
FT /evidence="ECO:0000250"
FT REGION 789..887
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 899..1186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..95
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..175
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 819..847
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 860..876
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 902..920
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1012..1026
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1040..1055
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1067..1097
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 659..662
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 669..670
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKA7"
FT MOD_RES 1090
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1093
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1186 AA; 127414 MW; B3DC16818E8697DC CRC64;
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DGEEEGAGGR QDPSRRSIRL RPLPSPSPSV
AAGCSESRGA ALGATESEGP GRSAGKSSTN GDCRRFRGSL ASLGSRGGGS GGAGGGSSLG
HLHDSAEERR LIAAEGDASP GEDRTPPGLA TEPERPATAA QPAASPPPQQ PPQPASASCE
QPSADTAIKV EGGAAAIDHI LPEAEVRLGQ SGFMQRQFGA MLQPGVNKFS LRMFGSQKAV
EREQERVKSA GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFVVDFISSI PVEYIFLIVE
TRIDSEVYKT ARAVRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIVN
LIGMMLLLCH WDGCLQFLVP MLQDFPHDCW VSINGMVNNS WGKQYSYALF KAMSHMLCIG
YGRQAPVGMS DVWLTMLSMI VGATCYAMFI GHATALIQSL DSSRRQYQEK YKQVEQYMSF
HKLPPDTRQR IHDYYEHRYQ GKMFDEESIL GELSEPLREE IINFNCRKLV ASMPLFANAD
PNFVTSMLTK LRFEVFQPGD YIIREGTIGK KMYFIQHGVV SVLTKGNKET RLADGSYFGE
ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR KKNSILLHKV QHDLNSGVFN
YQENEIIQQI VRHDREMAHC AHRVQAAASA TPTPTPVIWT PLIQAPLQAA AATTSVAIAL
THHPRLPAAI FRPPPGPGLG NLGAGQTPRH PRRLQSLIPS ALGSASPASS PSQVDTPSSS
SFHIQQLAGF SAPPGLSPLL PSSSSSPPPG ACGSPPAPTP STSTAAAAST TGFGHFHKAL
GGSLSSSDSP LLTPLQPGAR SPQAAQPPPP LPGARGGLGL LEHFLPPPPS SRSPSSSPGQ
LGQPPGELSL GLAAGPSSTP ETPPRPERPS FMAGASGGAS PVAFTPRGGL SPPGHSPGPP
RTFPSAPPRA SGSHGSLLLP PASSPPPPQV PQRRGTPPLT PGRLTQDLKL ISASQPALPQ
DGAQTLRRAS PHSSGESVAA FSLYPRAGGG SGSSGGLGPP GRPYGAIPGQ HVTLPRKTSS
GSLPPPLSLF GARAASSGGP PLTTAAPQRE PGARSEPVRS KLPSNL
