HCN4_RAT
ID HCN4_RAT Reviewed; 1198 AA.
AC Q9JKA7; Q9QZW4;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4;
GN Name=Hcn4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=11000485; DOI=10.1016/s0169-328x(00)00155-8;
RA Monteggia L.M., Eisch A.J., Tang M.D., Kaczmarek L.K., Nestler E.J.;
RT "Cloning and localization of the hyperpolarization-activated cyclic
RT nucleotide-gated channel family in rat brain.";
RL Brain Res. Mol. Brain Res. 81:129-139(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 262-428.
RC TISSUE=Heart;
RX PubMed=10400919; DOI=10.1161/01.res.85.1.e1;
RA Shi W., Wymore R., Yu H., Wu J., Wymore R.T., Pan Z., Robinson R.B.,
RA Dixon J.E., McKinnon D., Cohen I.S.;
RT "Distribution and prevalence of hyperpolarization-activated cation channel
RT (HCN) mRNA expression in cardiac tissues.";
RL Circ. Res. 85:1-6(1999).
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-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Hyperpolarization-activated ion channel with very slow
CC activation and inactivation exhibiting weak selectivity for potassium
CC over sodium ions. May contribute to the native pacemaker currents in
CC heart (If) that regulate the rhythm of heart beat. May contribute to
CC the native pacemaker currents in neurons (Ih) (By similarity). May
CC mediate responses to sour stimuli. {ECO:0000250,
CC 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: Highly expressed in pyramidal and granule layer of
CC the hippocampus, in thalamus anterior nucleus, in the supraoptic
CC nucleus in hypothalamus, in cerebellum, and in trapezoid nuclei and
CC superior olivary complex in the auditory system. Detected in a subset
CC of elongated cells in taste buds. {ECO:0000269|PubMed:11000485,
CC 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; AF247453; AAF62176.1; -; mRNA.
DR EMBL; AF155166; AAF01493.1; -; mRNA.
DR RefSeq; NP_067690.1; NM_021658.1.
DR AlphaFoldDB; Q9JKA7; -.
DR SMR; Q9JKA7; -.
DR STRING; 10116.ENSRNOP00000012644; -.
DR GlyGen; Q9JKA7; 1 site.
DR iPTMnet; Q9JKA7; -.
DR PhosphoSitePlus; Q9JKA7; -.
DR PaxDb; Q9JKA7; -.
DR PRIDE; Q9JKA7; -.
DR ABCD; Q9JKA7; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000012644; ENSRNOP00000012644; ENSRNOG00000009450.
DR GeneID; 59266; -.
DR KEGG; rno:59266; -.
DR UCSC; RGD:71065; rat.
DR CTD; 10021; -.
DR RGD; 71065; Hcn4.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000154743; -.
DR HOGENOM; CLU_005746_15_0_1; -.
DR InParanoid; Q9JKA7; -.
DR OrthoDB; 281394at2759; -.
DR PhylomeDB; Q9JKA7; -.
DR TreeFam; TF318250; -.
DR Reactome; R-RNO-1296061; HCN channels.
DR PRO; PR:Q9JKA7; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Genevisible; Q9JKA7; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0098855; C:HCN channel complex; ISO:RGD.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; TAS:RGD.
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:RGD.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:RGD.
DR GO; GO:0006812; P:cation transport; ISO:RGD.
DR GO; GO:1904045; P:cellular response to aldosterone; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; ISO:RGD.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; TAS:RGD.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:RGD.
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:RGD.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:RGD.
DR GO; GO:0002027; P:regulation of heart rate; ISS:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISO:RGD.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0003254; P:regulation of membrane depolarization; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0072718; P:response to cisplatin; IEP:RGD.
DR GO; GO:0086015; P:SA node cell action potential; ISO:RGD.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
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..1198
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 4"
FT /id="PRO_0000054120"
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..1198
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 25..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 804..1198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..137
FT /note="Basic and acidic 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 834..862
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 875..891
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 915..933
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1025..1039
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1053..1068
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1080..1110
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 BINDING 710..713
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:0007744|PubMed:22673903"
FT MOD_RES 1103
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70507"
FT MOD_RES 1106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70507"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 404
FT /note="I -> V (in Ref. 2; AAF01493)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1198 AA; 128761 MW; 6B92B8F9452F760F CRC64;
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DGEEEGAGGL QDPSRRSIRL RPLPSPSPSV
AAGCSESRGA ALGAADSEGP GRSAGKSSTN GDCRRFRGSL ASLGSRGGGS GGAGGGSSLG
HLHDSAEERR LIAAEGDASP GEDRTPPGLA TEPERPGAAA QPAASPPPQQ PPQPASASCE
QPSADTAIKV EGGAAASDQI LPEAEVRLGQ SGFMQRQFGA MLQPGVNKFS LRMFGSQKAV
EREQERVKSA GFWIIHPYSD FRFYWDLTML LLMVGNLIII PVGITFFKDE NTTPWIVFNV
VSDTFFLIDL VLNFRTGIVV EDNTEIILDP QRIKMKYLKS WFVVDFISSI PVDYIFLIVE
TRIDSEVYKT ARALRIVRFT 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 KLADGSYFGE
ICLLTRGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVALDR LDRIGKKNSI
LLHKVQHDLN SGVFNYQENE IIQQIVRHDR EMAHCAHRVQ AAASATPTPT PVIWTPLIQA
PLQAAAATTS VAIALTHHPR LPAAIFRPPP GPGLGNLGAG QTPRHPRRLQ SLIPSALGSA
SPASSPSQVD TPSSSSFHIQ QLAGFSAPPG LSPLLPSSSS SPPPGACSSP PAPTPSTSTA
ATTTGFGHFH KALGGSLSSS DSPLLTPLQP GARSPQAAQP PPPLPGARGG LGLLEHFLPP
PPSSRSPSSS PGQLGQPPGE LSPGLAAGPP STPETPPRPE RPSFMAGASG GASPVAFTPR
GGLSPPGHSP GPPRTFPSAP PRASGSHGSL LLPPASSPPP PQVPQRRGTP PLTPGRLTQD
LKLISASQPA LPQDGAQTLR RASPHSSGES MAAFSLYPRA GGGSGSSGGL GPPGRPYGAI
PGQHVTLPRK TSSGSLPPPL SLFGARAASS GGPPLTAAPQ REPGARSEPV RSKLPSNL
