HCN2_MOUSE
ID HCN2_MOUSE Reviewed; 863 AA.
AC O88703; O70506;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2;
DE AltName: Full=Brain cyclic nucleotide-gated channel 2;
DE Short=BCNG-2;
DE AltName: Full=Hyperpolarization-activated cation channel 1;
DE Short=HAC-1;
GN Name=Hcn2; Synonyms=Bcng2, Hac1;
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 [MRNA], AND CHARACTERIZATION.
RC STRAIN=BALB/cJ;
RX PubMed=9634236; DOI=10.1038/31255;
RA Ludwig A., Zong X., Jeglitsch M., Hofmann F., Biel M.;
RT "A family of hyperpolarization-activated cation channels.";
RL Nature 393:587-591(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 150-653, AND TISSUE SPECIFICITY.
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 MUTAGENESIS OF ASP-225; ASP-231;
RP ASP-267; ASP-275; LYS-291; ARG-294; ARG-297; ARG-300; LYS-303; SER-306;
RP ARG-309; ARG-312; ARG-315 AND ARG-318.
RX PubMed=10962006; DOI=10.1074/jbc.m007034200;
RA Chen J., Mitcheson J.S., Lin M., Sanguinetti M.C.;
RT "Functional roles of charged residues in the putative voltage sensor of the
RT HCN2 pacemaker channel.";
RL J. Biol. Chem. 275:36465-36471(2000).
RN [4]
RP INTERACTION WITH KCNE2.
RX PubMed=11420311; DOI=10.1161/hh1201.093511;
RA Yu H., Wu J., Potapova I., Wymore R.T., Holmes B., Zuckerman J., Pan Z.,
RA Wang H., Shi W., Robinson R.B., El-Maghrabi M.R., Benjamin W., Dixon J.E.,
RA McKinnon D., Cohen I.S., Wymore R.;
RT "MinK-related peptide 1: a beta subunit for the HCN ion channel subunit
RT family enhances expression and speeds activation.";
RL Circ. Res. 88:E84-E87(2001).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP HIS-321.
RX PubMed=11096117; DOI=10.1074/jbc.m010326200;
RA Zong X., Stieber J., Ludwig A., Hofmann F., Biel M.;
RT "A single histidine residue determines the pH sensitivity of the pacemaker
RT channel HCN2.";
RL J. Biol. Chem. 276:6313-6319(2001).
RN [6]
RP MUTAGENESIS OF ARG-318; GLU-324; TYR-331 AND ARG-339.
RX PubMed=11553787; DOI=10.1073/pnas.201250598;
RA Chen J., Mitcheson J.S., Tristani-Firouzi M., Lin M., Sanguinetti M.C.;
RT "The S4-S5 linker couples voltage sensing and activation of pacemaker
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11277-11282(2001).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF SER-306.
RX PubMed=11741901; DOI=10.1074/jbc.m106974200;
RA Proenza C., Angoli D., Agranovich E., Macri V., Accili E.A.;
RT "Pacemaker channels produce an instantaneous current.";
RL J. Biol. Chem. 277:5101-5109(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HCN1.
RX PubMed=12034718; DOI=10.1074/jbc.m200504200;
RA Proenza C., Tran N., Angoli D., Zahynacz K., Balcar P., Accili E.A.;
RT "Different roles for the cyclic nucleotide binding domain and amino
RT terminus in assembly and expression of hyperpolarization-activated, cyclic
RT nucleotide-gated channels.";
RL J. Biol. Chem. 277:29634-29642(2002).
RN [9]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=12193608; DOI=10.1074/jbc.m208477200;
RA Tran N., Proenza C., Macri V., Petigara F., Sloan E., Samler S.,
RA Accili E.A.;
RT "A conserved domain in the NH2 terminus important for assembly and
RT functional expression of pacemaker channels.";
RL J. Biol. Chem. 277:43588-43592(2002).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119; SER-743; SER-750;
RP SER-757; SER-840; SER-842 AND SER-847, AND IDENTIFICATION BY MASS
RP 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).
RN [11]
RP PHOSPHORYLATION AT SER-641.
RX PubMed=21347269; DOI=10.1371/journal.pone.0017078;
RA Hammelmann V., Zong X., Hofmann F., Michalakis S., Biel M.;
RT "The cGMP-dependent protein kinase II Is an inhibitory modulator of the
RT hyperpolarization-activated HCN2 channel.";
RL PLoS ONE 6:E17078-E17078(2011).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-594.
RX PubMed=23103389; DOI=10.1016/j.str.2012.09.017;
RA Xu X., Marni F., Wu S., Su Z., Musayev F., Shrestha S., Xie C., Gao W.,
RA Liu Q., Zhou L.;
RT "Local and global interpretations of a disease-causing mutation near the
RT ligand entry path in hyperpolarization-activated cAMP-gated channel.";
RL Structure 20:2116-2123(2012).
RN [13]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-728, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 443-643 IN COMPLEXES WITH CAMP AND
RP CGMP, FUNCTION, ACTIVITY REGULATION, NUCLEOTIDE-BINDING, AND SUBUNIT.
RX PubMed=12968185; DOI=10.1038/nature01922;
RA Zagotta W.N., Olivier N.B., Black K.D., Young E.C., Olson R., Gouaux E.;
RT "Structural basis for modulation and agonist specificity of HCN pacemaker
RT channels.";
RL Nature 425:200-205(2003).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 443-640, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND NUCLEOTIDE-BINDING.
RX PubMed=17562314; DOI=10.1016/j.str.2007.04.008;
RA Flynn G.E., Black K.D., Islas L.D., Sankaran B., Zagotta W.N.;
RT "Structure and rearrangements in the carboxy-terminal region of SpIH
RT channels.";
RL Structure 15:671-682(2007).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 443-640 IN COMPLEX WITH CAMP,
RP SUBUNIT, AND NUCLEOTIDE-BINDING.
RX PubMed=18367452; DOI=10.1074/jbc.m710463200;
RA Craven K.B., Olivier N.B., Zagotta W.N.;
RT "C-terminal movement during gating in cyclic nucleotide-modulated
RT channels.";
RL J. Biol. Chem. 283:14728-14738(2008).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 443-640 IN COMPLEX WITH CAMP, AND
RP NUCLEOTIDE-BINDING.
RX PubMed=19525958; DOI=10.1038/nmeth.1341;
RA Taraska J.W., Puljung M.C., Olivier N.B., Flynn G.E., Zagotta W.N.;
RT "Mapping the structure and conformational movements of proteins with
RT transition metal ion FRET.";
RL Nat. Methods 6:532-537(2009).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 857-863 IN COMPLEX WITH PEX5L, AND
RP SUBUNIT.
RX PubMed=22550182; DOI=10.1073/pnas.1201997109;
RA Bankston J.R., Camp S.S., DiMaio F., Lewis A.S., Chetkovich D.M.,
RA Zagotta W.N.;
RT "Structure and stoichiometry of an accessory subunit TRIP8b interaction
RT with hyperpolarization-activated cyclic nucleotide-gated channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7899-7904(2012).
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). Can also
CC transport ammonium in the distal nephron. Produces a large
CC instantaneous current. {ECO:0000269|PubMed:10962006,
CC ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:11741901,
CC ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12193608,
CC ECO:0000269|PubMed:12968185, ECO:0000269|PubMed:17562314,
CC ECO:0000269|PubMed:23103389}.
CC -!- ACTIVITY REGULATION: Activated by cAMP, and at 10-100 times higher
CC concentrations, also by cGMP. cAMP binding causes a conformation change
CC that leads to the assembly of an active tetramer and channel opening.
CC Channel activity is modulated by intracellular chloride ions and pH;
CC acidic pH shifts the activation to more negative voltages.
CC {ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:12968185,
CC ECO:0000269|PubMed:17562314, ECO:0000269|PubMed:23103389}.
CC -!- SUBUNIT: Homotetramer. Heterotetramer with HCN1. The potassium channel
CC is composed of a homo- or heterotetrameric complex of pore-forming
CC subunits. Forms an obligate 4:4 complex with accessory subunit PEX5L.
CC Interacts with KCNE2. {ECO:0000269|PubMed:11420311,
CC ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12193608,
CC ECO:0000269|PubMed:12968185, ECO:0000269|PubMed:17562314,
CC ECO:0000269|PubMed:18367452, ECO:0000269|PubMed:19525958,
CC ECO:0000269|PubMed:22550182}.
CC -!- INTERACTION:
CC O88703; Q8IYB4-6: PEX5L; Xeno; NbExp=18; IntAct=EBI-771231, EBI-16150786;
CC O88703; P00523: SRC; Xeno; NbExp=5; IntAct=EBI-771231, EBI-848039;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10962006,
CC ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:12034718,
CC ECO:0000269|PubMed:12193608, ECO:0000269|PubMed:17562314,
CC ECO:0000269|PubMed:23103389}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10962006, ECO:0000269|PubMed:11096117,
CC ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12193608,
CC ECO:0000269|PubMed:17562314, ECO:0000269|PubMed:23103389}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain. Detected at low levels
CC in heart, in ventricle, atrium and in sinoatrial node (SAN).
CC {ECO:0000269|PubMed:9630217}.
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 -!- PTM: Phosphorylation at Ser-641 by PRKG2 shifts the voltage-dependence
CC to more negative voltages, hence counteracting the stimulatory effect
CC of cGMP on gating. {ECO:0000269|PubMed:21347269}.
CC -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ225122; CAA12406.1; -; mRNA.
DR EMBL; AF064873; AAC40125.1; -; mRNA.
DR CCDS; CCDS23986.1; -.
DR RefSeq; NP_032252.1; NM_008226.2.
DR PDB; 1Q3E; X-ray; 1.90 A; A/B=443-645.
DR PDB; 1Q43; X-ray; 2.00 A; A/B=443-645.
DR PDB; 1Q5O; X-ray; 2.30 A; A=443-645.
DR PDB; 2Q0A; X-ray; 2.25 A; A/B=443-640.
DR PDB; 3BPZ; X-ray; 1.65 A; A/B/C/D=443-640.
DR PDB; 3ETQ; X-ray; 1.90 A; A/B=443-640.
DR PDB; 3FFQ; X-ray; 2.40 A; A/B=443-640.
DR PDB; 4EQF; X-ray; 3.00 A; B=857-863.
DR PDB; 5JON; X-ray; 2.04 A; A/B=494-640.
DR PDB; 5KHG; X-ray; 2.24 A; A=443-643.
DR PDB; 5KHH; X-ray; 1.77 A; A=443-643.
DR PDB; 5KHI; X-ray; 2.10 A; A=443-643.
DR PDB; 5KHJ; X-ray; 2.01 A; A/B=443-643.
DR PDB; 5KHK; X-ray; 2.07 A; A=443-643.
DR PDBsum; 1Q3E; -.
DR PDBsum; 1Q43; -.
DR PDBsum; 1Q5O; -.
DR PDBsum; 2Q0A; -.
DR PDBsum; 3BPZ; -.
DR PDBsum; 3ETQ; -.
DR PDBsum; 3FFQ; -.
DR PDBsum; 4EQF; -.
DR PDBsum; 5JON; -.
DR PDBsum; 5KHG; -.
DR PDBsum; 5KHH; -.
DR PDBsum; 5KHI; -.
DR PDBsum; 5KHJ; -.
DR PDBsum; 5KHK; -.
DR AlphaFoldDB; O88703; -.
DR BMRB; O88703; -.
DR SMR; O88703; -.
DR BioGRID; 200253; 8.
DR ComplexPortal; CPX-142; HCN2 channel complex.
DR DIP; DIP-29326N; -.
DR IntAct; O88703; 6.
DR MINT; O88703; -.
DR STRING; 10090.ENSMUSP00000097113; -.
DR BindingDB; O88703; -.
DR ChEMBL; CHEMBL1250408; -.
DR DrugCentral; O88703; -.
DR GuidetoPHARMACOLOGY; 401; -.
DR GlyGen; O88703; 1 site.
DR iPTMnet; O88703; -.
DR PhosphoSitePlus; O88703; -.
DR SwissPalm; O88703; -.
DR MaxQB; O88703; -.
DR PaxDb; O88703; -.
DR PRIDE; O88703; -.
DR ProteomicsDB; 269770; -.
DR ABCD; O88703; 1 sequenced antibody.
DR Antibodypedia; 22327; 227 antibodies from 32 providers.
DR DNASU; 15166; -.
DR Ensembl; ENSMUST00000020581; ENSMUSP00000020581; ENSMUSG00000020331.
DR Ensembl; ENSMUST00000099513; ENSMUSP00000097113; ENSMUSG00000020331.
DR GeneID; 15166; -.
DR KEGG; mmu:15166; -.
DR UCSC; uc007fzn.1; mouse.
DR CTD; 610; -.
DR MGI; MGI:1298210; Hcn2.
DR VEuPathDB; HostDB:ENSMUSG00000020331; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000156523; -.
DR HOGENOM; CLU_005746_15_1_1; -.
DR InParanoid; O88703; -.
DR OMA; PRMMRRF; -.
DR OrthoDB; 281394at2759; -.
DR PhylomeDB; O88703; -.
DR TreeFam; TF318250; -.
DR Reactome; R-MMU-1296061; HCN channels.
DR BioGRID-ORCS; 15166; 0 hits in 75 CRISPR screens.
DR EvolutionaryTrace; O88703; -.
DR PRO; PR:O88703; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O88703; protein.
DR Bgee; ENSMUSG00000020331; Expressed in perirhinal cortex and 105 other tissues.
DR Genevisible; O88703; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; ISO:MGI.
DR GO; GO:0098855; C:HCN channel complex; IPI:ComplexPortal.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0036477; C:somatodendritic compartment; ISO:MGI.
DR GO; GO:0045202; C:synapse; 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; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISS:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:ComplexPortal.
DR GO; GO:0071321; P:cellular response to cGMP; 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:2001257; P:regulation of cation channel activity; IC:ComplexPortal.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IC:ComplexPortal.
DR GO; GO:0003254; P:regulation of membrane depolarization; IDA:ComplexPortal.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:MGI.
DR GO; GO:0098907; P:regulation of SA node cell action potential; IC:ComplexPortal.
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 3D-structure; cAMP; cAMP-binding; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Sodium; Sodium channel;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..863
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 2"
FT /id="PRO_0000054112"
FT TOPO_DOM 1..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..213
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..234
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 235..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..290
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..311
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 312..342
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 343..363
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 364..386
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 387..408
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 409..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..863
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..131
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..182
FT /note="Involved in subunit assembly"
FT REGION 730..863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..51
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 732..759
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 581..584
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18367452,
FT ECO:0000269|PubMed:19525958"
FT BINDING 591..592
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18367452,
FT ECO:0000269|PubMed:19525958"
FT BINDING 632..635
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000269|PubMed:18367452,
FT ECO:0000269|PubMed:19525958"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKA9"
FT MOD_RES 641
FT /note="Phosphoserine; by PKG/PRKG2"
FT /evidence="ECO:0000269|PubMed:21347269"
FT MOD_RES 726
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JKA9"
FT MOD_RES 728
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 750
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 757
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 840
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 842
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 847
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 225
FT /note="D->N: Abolishes surface expression and channel
FT activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 231
FT /note="D->N: Reduces surface expression and abolishes
FT channel activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 267
FT /note="D->N: Reduces surface expression and abolishes
FT channel activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 275
FT /note="D->N: Reduces surface expression and abolishes
FT channel activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 291
FT /note="K->Q: Shifts voltage dependence of activation to
FT more negative values."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 294
FT /note="R->Q: Shifts voltage dependence of activation to
FT more negative values."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 297
FT /note="R->Q: Shifts voltage dependence of activation to
FT more negative values."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 300
FT /note="R->Q: Shifts voltage dependence of activation to
FT more negative values."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 303
FT /note="K->Q: Decreases current amplitude."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 306
FT /note="S->Q: Decreases current amplitude."
FT /evidence="ECO:0000269|PubMed:10962006,
FT ECO:0000269|PubMed:11741901"
FT MUTAGEN 309
FT /note="R->Q: Abolishes surface expression and channel
FT activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 312
FT /note="R->Q: Reduces surface expression and decreases
FT current amplitude."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 315
FT /note="R->Q: Reduces surface expression and abolishes
FT channel activity."
FT /evidence="ECO:0000269|PubMed:10962006"
FT MUTAGEN 318
FT /note="R->Q: Reduces surface expression and disrupts
FT channel closure."
FT /evidence="ECO:0000269|PubMed:10962006,
FT ECO:0000269|PubMed:11553787"
FT MUTAGEN 321
FT /note="H->E: Shifts voltage dependence of activation to
FT more positive values and abolishes pH-sensitivity."
FT /evidence="ECO:0000269|PubMed:11096117"
FT MUTAGEN 321
FT /note="H->Q: Abolishes pH-sensitivity."
FT /evidence="ECO:0000269|PubMed:11096117"
FT MUTAGEN 321
FT /note="H->R: Abolishes pH-sensitivity."
FT /evidence="ECO:0000269|PubMed:11096117"
FT MUTAGEN 324
FT /note="E->Q: Disrupts channel closure."
FT /evidence="ECO:0000269|PubMed:11553787"
FT MUTAGEN 331
FT /note="Y->A: Disrupts channel closure."
FT /evidence="ECO:0000269|PubMed:11553787"
FT MUTAGEN 331
FT /note="Y->S: Disrupts channel closure."
FT /evidence="ECO:0000269|PubMed:11553787"
FT MUTAGEN 339
FT /note="R->Q: Disrupts channel closure."
FT /evidence="ECO:0000269|PubMed:11553787"
FT MUTAGEN 594
FT /note="S->R: Shifts channel activation to more negative
FT voltage, slows channel opening and speeds up channel
FT closure. Reduces sensitivity to activation by cAMP."
FT /evidence="ECO:0000269|PubMed:23103389"
FT CONFLICT 486
FT /note="F -> S (in Ref. 2; AAC40125)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="I -> T (in Ref. 2; AAC40125)"
FT /evidence="ECO:0000305"
FT HELIX 444..462
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 467..481
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 488..494
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 497..507
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 509..513
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 516..519
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 523..532
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 534..538
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 553..559
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 561..565
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 567..569
FT /evidence="ECO:0007829|PDB:2Q0A"
FT STRAND 572..575
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:5KHK"
FT HELIX 582..587
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 588..590
FT /evidence="ECO:0007829|PDB:5KHH"
FT STRAND 592..599
FT /evidence="ECO:0007829|PDB:3BPZ"
FT STRAND 601..607
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 608..617
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 619..621
FT /evidence="ECO:0007829|PDB:3BPZ"
FT HELIX 622..635
FT /evidence="ECO:0007829|PDB:3BPZ"
SQ SEQUENCE 863 AA; 94722 MW; 17CDC4DFF07AC039 CRC64;
MDARGGGGRP GDSPGTTPAP GPPPPPPPPA PPQPQPPPAP PPNPTTPSHP ESADEPGPRA
RLCSRDSACT PGAAKGGANG ECGRGEPQCS PEGPARGPKV SFSCRGAASG PSAAEEAGSE
EAGPAGEPRG SQASFLQRQF GALLQPGVNK FSLRMFGSQK AVEREQERVK SAGAWIIHPY
SDFRFYWDFT MLLFMVGNLI IIPVGITFFK DETTAPWIVF NVVSDTFFLM DLVLNFRTGI
VIEDNTEIIL DPEKIKKKYL RTWFVVDFVS SIPVDYIFLI VEKGIDSEVY KTARALRIVR
FTKILSLLRL LRLSRLIRYI HQWEEIFHMT YDLASAVMRI CNLISMMLLL CHWDGCLQFL
VPMLQDFPSD CWVSINNMVN HSWSELYSFA LFKAMSHMLC IGYGRQAPES MTDIWLTMLS
MIVGATCYAM FIGHATALIQ SLDSSRRQYQ EKYKQVEQYM SFHKLPADFR QKIHDYYEHR
YQGKMFDEDS ILGELNGPLR EEIVNFNCRK LVASMPLFAN ADPNFVTAML TKLKFEVFQP
GDYIIREGTI GKKMYFIQHG VVSVLTKGNK EMKLSDGSYF GEICLLTRGR RTASVRADTY
CRLYSLSVDN FNEVLEEYPM MRRAFETVAI DRLDRIGKKN SILLHKVQHD LSSGVFNNQE
NAIIQEIVKY DREMVQQAEL GQRVGLFPPP PPPQVTSAIA TLQQAVAMSF CPQVARPLVG
PLALGSPRLV RRAPPGPLPP AASPGPPAAS PPAAPSSPRA PRTSPYGVPG SPATRVGPAL
PARRLSRASR PLSASQPSLP HGVPAPSPAA SARPASSSTP RLGPAPTART AAPSPDRRDS
ASPGAASGLD PLDSARSRLS SNL
