HCN1_RABIT
ID HCN1_RABIT Reviewed; 822 AA.
AC Q9MZS1; Q9TU38; Q9TUE2; Q9TUE3;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1;
DE AltName: Full=rbHCN1;
GN Name=HCN1;
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, AND TISSUE SPECIFICITY.
RC STRAIN=New Zealand white; TISSUE=Heart;
RX PubMed=11328811; DOI=10.1074/jbc.m100830200;
RA Moroni A., Gorza L., Beltrame M., Gravante B., Vaccari T., Bianchi M.E.,
RA Altomare C., Longhi R., Heurteaux C., Vitadello M., Malgaroli A.,
RA DiFrancesco D.;
RT "Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a
RT molecular determinant of the cardiac pacemaker current If.";
RL J. Biol. Chem. 276:29233-29241(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 95-236, AND TISSUE SPECIFICITY.
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).
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:11328811}.
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. {ECO:0000269|PubMed:11328811}.
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:11328811};
CC Multi-pass membrane protein {ECO:0000269|PubMed:11328811}.
CC -!- TISSUE SPECIFICITY: Detected in myocytes in heart sinoatrial node (SAN)
CC and in brain, in particular in the granule cell layer and in Purkinje
CC neuron bodies in the cerebellum. {ECO:0000269|PubMed:10400919,
CC ECO:0000269|PubMed:11328811}.
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}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-30 is the initiator.
CC {ECO:0000305}.
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DR EMBL; AF168122; AAF89636.2; -; mRNA.
DR EMBL; AF155167; AAF01494.1; -; mRNA.
DR RefSeq; NP_001075532.1; NM_001082063.1.
DR AlphaFoldDB; Q9MZS1; -.
DR SMR; Q9MZS1; -.
DR STRING; 9986.ENSOCUP00000014684; -.
DR PRIDE; Q9MZS1; -.
DR GeneID; 100008732; -.
DR KEGG; ocu:100008732; -.
DR CTD; 348980; -.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; Q9MZS1; -.
DR Proteomes; UP000001811; Unplaced.
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:0030552; F:cAMP binding; ISS:UniProtKB.
DR GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; ISS:UniProtKB.
DR GO; GO:0005272; F:sodium channel activity; IEA:UniProtKB-KW.
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:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
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..822
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 1"
FT /id="PRO_0000054109"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 79..100
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 101..109
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 110..130
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 131..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 152..172
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 173..196
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 197..217
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 218..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 232..254
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 255..280
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT INTRAMEM 281..302
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 303..307
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TRANSMEM 308..328
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT TOPO_DOM 329..822
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT REGION 583..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 777..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 294..298
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:O60741"
FT COMPBIAS 660..676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 691..728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 785..799
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 475..478
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT BINDING 485..486
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT BINDING 526..529
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O88704"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 822 AA; 92897 MW; 1BC67F5B35D46BD6 CRC64;
MATASSPPRR PRRARGLEDA EGPRRQYGFM QRQFTSMLQP GVNKFSLRMF GSQKAVEKEQ
ERVKTAGFWI IHPYSDFRFY WDLIMLIMMV GNLVIIPVGI TFFTEQTTTP WIIFNVASDT
VFLLDLIMNF RTGTVNEDSS EIILDPKVIK MNYLKSWFVV DFISSIPVDY IFLIVEKGMD
SEVYKTARAL RIVRFTKILS LLRLLRLSRL IRYIHQWEEI FHMTYDLASA VVRIFNLIGM
MLLLCHWDGC LQFLVPLLQD FPPDCWVSLN EMVNDSWGKQ YSYALFKAMS HMLCIGYGAQ
APVSMSDLWI TMLSMIVGAT CYAMFVGHAT ALIQSLDSSR RQYQEKYKQV EQYMSFHKLP
ADMRQKIHDY YEHRYQGKIF DEENILNELN DPLREEIVNF NCRKLVATMP LFANADPNFV
TAMLSKLRFE VFQPGDYIIR EGAVGKKMYF IQHGVAGVIT KSSKEMKLTD GSYFGEICLL
TKGRRTASVR ADTYCRLYSL SVDNFNEVLE EYPMMRRAFE TVAIDRLDRI GKKNSILLQK
FQKDLNTGVF NNQENEILKQ IVKHDREMVQ AIAPISYPQM TALNSTSSTA TPTSRMRTQS
PPVYTATSLS HSNLHSPSPS TQTPQPSAIL SPCSYTTAVC SPPVQSPLAT RTFHYASPTA
SQLSLMPQQQ QQPQAPQTQP QQPPQQPQTP GSATPKNEVH RSTQALPNTS LTREVRPLSA
SQPSLPHEVS TLISRPHPTV GESLASIPQP VAAVHSAGLQ AAGRSTVPQR VTLFRQMSSG
AIPPNRGVPP APPPPAAPLQ REASSVLNTD PEAEKPRFAS NL
