HCN1_RAT
ID HCN1_RAT Reviewed; 910 AA.
AC Q9JKB0;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1;
GN Name=Hcn1;
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 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).
CC -!- FUNCTION: Hyperpolarization-activated ion channel exhibiting weak
CC selectivity for potassium over sodium ions. Contributes to the native
CC pacemaker currents in heart (If) and in neurons (Ih). May mediate
CC responses to sour stimuli. {ECO:0000269|PubMed:11675786}.
CC -!- ACTIVITY REGULATION: Activated by cAMP, and at 10-100 times higher
CC concentrations, also by cGMP. cAMP binding promotes tetramerization and
CC formation of an active channel. Compared to other family members, cAMP
CC has less stimulatory effect on HCN1 because part of the molecules
CC already contain bound cAMP and form homotetramers when cAMP levels are
CC low (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homotetramer. Heterotetramer with HCN2. The potassium channel
CC is composed of a homo- or heterotetrameric complex of pore-forming
CC subunits. Interacts with KCNE2. Interacts with the SH3 domain of CSK.
CC {ECO:0000250|UniProtKB:O88704}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11675786};
CC Multi-pass membrane protein {ECO:0000269|PubMed:11675786}.
CC -!- TISSUE SPECIFICITY: Highly expressed in cerebral cortex, cerebellum,
CC throughout the hippocampus, in medial habenula, anterior dorsal nucleus
CC in the thalamus, tenia tecta, several nuclei of the general motor
CC system and in optic nerve layer. Detected in a subset of elongated
CC 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. {ECO:0000250|UniProtKB:O60741}.
CC -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
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DR EMBL; AF247450; AAF62173.1; -; mRNA.
DR RefSeq; NP_445827.1; NM_053375.1.
DR AlphaFoldDB; Q9JKB0; -.
DR SMR; Q9JKB0; -.
DR BioGRID; 249933; 4.
DR STRING; 10116.ENSRNOP00000016142; -.
DR GlyGen; Q9JKB0; 1 site.
DR iPTMnet; Q9JKB0; -.
DR PhosphoSitePlus; Q9JKB0; -.
DR PaxDb; Q9JKB0; -.
DR PRIDE; Q9JKB0; -.
DR ABCD; Q9JKB0; 1 sequenced antibody.
DR GeneID; 84390; -.
DR KEGG; rno:84390; -.
DR CTD; 348980; -.
DR RGD; 620688; Hcn1.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; Q9JKB0; -.
DR OrthoDB; 281394at2759; -.
DR PhylomeDB; Q9JKB0; -.
DR Reactome; R-RNO-1296061; HCN channels.
DR PRO; PR:Q9JKB0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0032590; C:dendrite membrane; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; IDA:RGD.
DR GO; GO:0098855; C:HCN channel complex; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0036477; C:somatodendritic compartment; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0030552; F:cAMP binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IMP:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0022843; F:voltage-gated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0045176; P:apical protein localization; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IEP:RGD.
DR GO; GO:0006954; P:inflammatory response; IEP:RGD.
DR GO; GO:0042711; P:maternal behavior; IEP:RGD.
DR GO; GO:0045759; P:negative regulation of action potential; IMP:RGD.
DR GO; GO:0051967; P:negative regulation of synaptic transmission, glutamatergic; ISO:RGD.
DR GO; GO:2001259; P:positive regulation of cation channel activity; IDA:RGD.
DR GO; GO:1902632; P:positive regulation of membrane hyperpolarization; IMP:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0003254; P:regulation of membrane depolarization; IDA:RGD.
DR GO; GO:1902630; P:regulation of membrane hyperpolarization; IMP:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IDA:RGD.
DR GO; GO:0072718; P:response to cisplatin; IEP:RGD.
DR GO; GO:1902065; P:response to L-glutamate; IEP:RGD.
DR GO; GO:0046549; P:retinal cone cell development; 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; IPR030169; K/Na_HCN1.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR PANTHER; PTHR45689:SF3; PTHR45689:SF3; 1.
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 2: Evidence at transcript level;
KW cAMP; cAMP-binding; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Nucleotide-binding;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Sodium; Sodium channel; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..910
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 1"
FT /id="PRO_0000054110"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 132..153
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 154..162
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 163..183
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 184..204
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 205..225
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 226..249
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 250..270
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 271..284
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 285..307
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 308..333
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT INTRAMEM 334..355
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 356..360
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 361..381
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 382..910
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT REGION 1..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 634..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 740..829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 866..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 347..351
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 740..818
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 874..888
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 528..531
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT BINDING 538..539
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT BINDING 579..582
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 910 AA; 102422 MW; 11E32D2BE73F4528 CRC64;
MEGGGKPNSA SNSRDDGNSV YPSKAPATGP AAADKRLGTP PGGGAAGKEH GNSVCFKVDG
GGGEEPAGSF EDAEGPRRQY GFMQRQFTSM LQPGVNKFSL RMFGSQKAVE KEQERVKTAG
FWIIHPYSDF RFYWDLIMLI MMVGNLVIIP VGITFFTEQT TTPWIIFNVA SDTVFLLDLI
MNFRTGTVNE DSSEIILDPK VIKMNYLKSW FVVDFISSIP VDYIFLIVEK GMDSEVYKTA
RALRIVRFTK ILSLLRLLRL SRLIRYIHQW EEIFHMTYDL ASAVVRIFNL IGMMLLLCHW
DGCLQFLVPL LQDFPPDCWV SLNEMVNDSW GKQYSYALFK AMSHMLCIGY GAQAPVSMSD
LWITMLSMIV GATCYAMFVG HATALIQSLD SSRRQYQEKY KQVEQYMSFH KLPADMRQKI
HDYYEHRYQG KIFDEENILS ELNDPLREEI VNFNCRKLVA TMPLFANADP NFVTAMLSKL
RFEVFQPGDY IIREGAVGKK MYFIQHGVAG VITKSSKEMK LTDGSYFGEI CLLTKGRRTA
SVRADTYCRL YSLSVDNFNE VLEEYPMMRR AFETVAIDRL DRIGKKNSIL LQKFQKDLNT
GVFNNQENEI LKQIVKHDRE MVQAIPPINY PQMTALNCTS STTTPTSRMR TQSPPVYTAT
SLSHSNLHSP SPSTQTPQPS AILSPCSYTT AVCSPPIQSP LATRTFHYAS PTASQLSLMQ
QPQPQLQQSQ VQQTQTQTQQ QQQQQQPQPQ PQQPQQQQQQ QQQQQQQQQQ QQQQQPQTPG
SSTPKNEVHK STQALHNTHL TREVRPLSAS QPSLPHEVST MISRPHPTVG ESLASIPQPV
ATVHSTGLQA GSRSTVPQRV TLFRQMSSGA IPPNRGVPPA PPPPAAVQRE SPSVLNKDPD
AEKPRFASNL
