HCN4_RABIT
ID HCN4_RABIT Reviewed; 1175 AA.
AC Q9TV66; Q9TU35;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4;
DE AltName: Full=Hyperpolarization-activated cation channel 4;
DE Short=HAC-4;
GN Name=HCN4; Synonyms=HAC4;
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, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Heart atrium;
RX PubMed=10212270; DOI=10.1074/jbc.274.18.12835;
RA Ishii T.M., Takano M., Xie L.-H., Noma A., Ohmori H.;
RT "Molecular characterization of the hyperpolarization-activated cation
RT channel in rabbit heart sinoatrial node.";
RL J. Biol. Chem. 274:12835-12839(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 261-381.
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 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). May mediate responses to
CC sour stimuli. {ECO:0000269|PubMed:10212270}.
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. {ECO:0000269|PubMed:10212270}.
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:10212270};
CC Multi-pass membrane protein {ECO:0000269|PubMed:10212270}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart sinoatrial node
CC (SAN). Not detected in atrium, ventricle, forebrain or cerebellum.
CC Detected at very low levels in total brain.
CC {ECO:0000269|PubMed:10212270}.
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 -!- MISCELLANEOUS: Inhibited by extracellular cesium ions.
CC -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
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DR EMBL; AB022927; BAA77511.2; -; mRNA.
DR EMBL; AF155170; AAF01497.1; -; mRNA.
DR RefSeq; NP_001076176.1; NM_001082707.1.
DR PDB; 7NMN; EM; 3.60 A; A/B/C/D=1-1172.
DR PDB; 7NP3; EM; 3.30 A; A/B/C/D=1-1175.
DR PDB; 7NP4; EM; 3.30 A; A/B/C/D=1-1175.
DR PDBsum; 7NMN; -.
DR PDBsum; 7NP3; -.
DR PDBsum; 7NP4; -.
DR AlphaFoldDB; Q9TV66; -.
DR SMR; Q9TV66; -.
DR STRING; 9986.ENSOCUP00000006294; -.
DR PRIDE; Q9TV66; -.
DR GeneID; 100009452; -.
DR KEGG; ocu:100009452; -.
DR CTD; 10021; -.
DR eggNOG; KOG0498; Eukaryota.
DR InParanoid; Q9TV66; -.
DR OrthoDB; 281394at2759; -.
DR PRO; PR:Q9TV66; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
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: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:0002027; P:regulation of heart rate; 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; 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 3D-structure; 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..1175
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 4"
FT /id="PRO_0000054119"
FT TOPO_DOM 1..267
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 289..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..369
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 391..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..442
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..465
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 466..487
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 488..497
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 498..518
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 519..1175
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 17..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..261
FT /note="Involved in subunit assembly"
FT /evidence="ECO:0000250"
FT REGION 801..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 830..1175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..174
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 845..859
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 900..919
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1002..1020
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1036..1055
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1067..1096
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 660..663
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 670..671
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 711..714
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKA7"
FT MOD_RES 1089
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70507"
FT MOD_RES 1093
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70507"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 229..235
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 238..249
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 261..286
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 287..290
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 297..315
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 331..341
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 343..348
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 353..364
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:7NP4"
FT HELIX 373..384
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 385..390
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 392..404
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 407..410
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 415..443
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 451..454
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 462..478
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 490..519
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 523..541
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 548..560
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 569..572
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 576..593
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 602..608
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 609..611
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 613..617
FT /evidence="ECO:0007829|PDB:7NP4"
FT STRAND 622..624
FT /evidence="ECO:0007829|PDB:7NP4"
FT STRAND 632..635
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 638..644
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 653..656
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 661..663
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 673..678
FT /evidence="ECO:0007829|PDB:7NP3"
FT STRAND 683..685
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 688..696
FT /evidence="ECO:0007829|PDB:7NP3"
FT HELIX 698..703
FT /evidence="ECO:0007829|PDB:7NP3"
SQ SEQUENCE 1175 AA; 126142 MW; 35A75FA9C710BD69 CRC64;
MDKLPPSMRK RLYSLPQQVG AKAWIMDEEE DAEEEGAGGR QDPRRRSIRL RPLPSPSPSP
SAAAAAAGGA ESRGAALGGA ADGEGPARGA AKSSTNGDCR RFRGSLASLG SRGGGGGGGS
TGGGSHGHLH DSAEERRLIA EGDASPGEDR TPPGLAAEPE RPGAPAPPAA SPPQVPSSCG
EQRPADAAVK VEGGAAAGDQ ILPEAEARLG QAGFMQRQFG AMLQPGVNKF SLRMFGSQKA
VEREQERVKS AGFWIIHPYS DFRFYWDLTM LLLMVGNLII IPVGITFFKD ENTTPWIVFN
VVSDTFFLID LVLNFRTGIV VEDNTDIILD PRRIKMKYLK SWFVVDFVSS IPVDYIFLIV
ETRIDSEVYK TARALRIVRF TKILSLLRLL RLSRLIRYIH QWEEIFHMTY DLASAVVRIV
NLIGMMLLLC HWDGCLQFLV PMLQDFPDDC WVSLNNMVNN SWGKQYSYAL FKAMSHMLCI
GYGRQAPMGM SDVWLTMLSM IVGATCYAMF IGHATALIQS LDSSRRQYQE KYKQVEQYMS
FHKLPPDTRQ RIHDYYEHRY QGKMFDEESI LGELSEPLRE EIINFNCRKL VASMPLFANA
DPNFVTSMLT KLRFEVFQPG DYIIREGTIG KKMYFIQHGV VSVLTKGNKE TKLADGSYFG
EICLLTRGRR TASVRADTYC RLYSLSVDNF NEVLEEYPMM RRAFETVALD RLDRIGKKNS
ILLHKVQHDL SSGVSNYQEN AIVQRIVQHD REMAHCARRA QATTPVAPAI WTPLIQAPLQ
AAAATTSVAI ALTHHPRLPA AIFRPPPGPT TLGSLGAGQT PRHLRRLQSL APSAPSPASP
ASSPSQPDTP SSASLHVQPL PGCSTPAGLG SLLPTAGSPP APTPPTTAGA AGFSHFHRAL
GGSLSSSDSP LLTPMQSAAR SPQQPPPPPG APAGLGLLEH FLPPPARSPT SSPGQLGQPP
GELSPGLGSG PPGTPETPPR QPERLPFAAG ASAGASPVAF SPRGGPSPPG HSPGTPRTFP
SAPPRASGSH GSLLLPPASS PPPPPPPPAP QRRATPPLAP GRLSQDLKLI SASQPALPQD
GAQTLRRASP HSSSGESVAA LPPFPRAPGR PPGAGPGQHV TLTLPRKASS GSLPPPLSLF
GPRAAPAGGP RLTAAPQREP GAKSEPVRSK LPSNL
