HCN3_MOUSE
ID HCN3_MOUSE Reviewed; 779 AA.
AC O88705;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3;
DE AltName: Full=Hyperpolarization-activated cation channel 3;
DE Short=HAC-3;
GN Name=Hcn3; Synonyms=Hac3;
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].
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Olfactory bulb;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY.
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15923185; DOI=10.1074/jbc.m502696200;
RA Mistrik P., Mader R., Michalakis S., Weidinger M., Pfeifer A., Biel M.;
RT "The murine HCN3 gene encodes a hyperpolarization-activated cation channel
RT with slow kinetics and unique response to cyclic nucleotides.";
RL J. Biol. Chem. 280:27056-27061(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633, AND IDENTIFICATION BY
RP MASS 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 [7]
RP INTERACTION WITH KCTD3 AND PEX5L, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=23382386; DOI=10.1074/jbc.m112.434803;
RA Cao-Ehlker X., Zong X., Hammelmann V., Gruner C., Fenske S., Michalakis S.,
RA Wahl-Schott C., Biel M.;
RT "Up-regulation of hyperpolarization-activated cyclic nucleotide-gated
RT channel 3 (HCN3) by specific interaction with K+ channel tetramerization
RT domain-containing protein 3 (KCTD3).";
RL J. Biol. Chem. 288:7580-7589(2013).
CC -!- FUNCTION: Hyperpolarization-activated potassium channel. May also
CC facilitate the permeation of sodium ions.
CC {ECO:0000269|PubMed:15923185}.
CC -!- ACTIVITY REGULATION: Inhibited by Cs(1+) and ivabradine. Is apparently
CC not activated by cAMP or cGMP. {ECO:0000269|PubMed:15923185}.
CC -!- SUBUNIT: Homotetramer. The potassium channel is probably composed of a
CC homo- or heterotetrameric complex of pore-forming subunits (By
CC similarity). Interacts with KCTD3 and PEX5L (PubMed:23382386).
CC {ECO:0000250|UniProtKB:Q9UL51, ECO:0000269|PubMed:23382386}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15923185,
CC ECO:0000269|PubMed:23382386}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15923185}.
CC -!- TISSUE SPECIFICITY: Detected in hypothalamus, amygdala, olfactory bulb,
CC hippocampus and retina (at protein level). Highly expressed in brain
CC and heart, in particular in ventricle, atrium and in sinoatrial node
CC (SAN). Detected at low levels in skeletal muscle and lung.
CC {ECO:0000269|PubMed:15923185, ECO:0000269|PubMed:23382386,
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 -!- SIMILARITY: Belongs to the potassium channel HCN family. {ECO:0000305}.
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DR EMBL; AJ225124; CAA12408.1; -; mRNA.
DR EMBL; AK032225; BAC27769.1; -; mRNA.
DR EMBL; BC039156; AAH39156.1; -; mRNA.
DR CCDS; CCDS17490.1; -.
DR RefSeq; NP_032253.1; NM_008227.1.
DR AlphaFoldDB; O88705; -.
DR SMR; O88705; -.
DR BioGRID; 200254; 4.
DR ComplexPortal; CPX-270; HCN3 channel complex.
DR IntAct; O88705; 1.
DR STRING; 10090.ENSMUSP00000029686; -.
DR GlyGen; O88705; 1 site.
DR iPTMnet; O88705; -.
DR PhosphoSitePlus; O88705; -.
DR MaxQB; O88705; -.
DR PaxDb; O88705; -.
DR PRIDE; O88705; -.
DR ProteomicsDB; 270952; -.
DR ABCD; O88705; 1 sequenced antibody.
DR Antibodypedia; 20417; 307 antibodies from 37 providers.
DR DNASU; 15168; -.
DR Ensembl; ENSMUST00000029686; ENSMUSP00000029686; ENSMUSG00000028051.
DR GeneID; 15168; -.
DR KEGG; mmu:15168; -.
DR UCSC; uc008pxr.1; mouse.
DR CTD; 57657; -.
DR MGI; MGI:1298211; Hcn3.
DR VEuPathDB; HostDB:ENSMUSG00000028051; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000162023; -.
DR HOGENOM; CLU_005746_15_1_1; -.
DR InParanoid; O88705; -.
DR OMA; VSINHMA; -.
DR OrthoDB; 281394at2759; -.
DR PhylomeDB; O88705; -.
DR TreeFam; TF318250; -.
DR Reactome; R-MMU-1296061; HCN channels.
DR BioGRID-ORCS; 15168; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Hcn3; mouse.
DR PRO; PR:O88705; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; O88705; protein.
DR Bgee; ENSMUSG00000028051; Expressed in embryonic brain and 102 other tissues.
DR ExpressionAtlas; O88705; baseline and differential.
DR Genevisible; O88705; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0044316; C:cone cell pedicle; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098855; C:HCN channel complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; IEA:Ensembl.
DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA: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; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; ISO:MGI.
DR GO; GO:0098907; P:regulation of SA node cell action potential; IC:ComplexPortal.
DR GO; GO:0072718; P:response to cisplatin; IEA:Ensembl.
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; 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; 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..779
FT /note="Potassium/sodium hyperpolarization-activated cyclic
FT nucleotide-gated channel 3"
FT /id="PRO_0000054115"
FT TOPO_DOM 1..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..123
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 171..191
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..200
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 201..221
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..296
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 297..318
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..328
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 329..349
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 350..779
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 45..90
FT /note="Involved in subunit assembly"
FT /evidence="ECO:0000250"
FT REGION 353..779
FT /note="Interaction with KCTD3"
FT /evidence="ECO:0000269|PubMed:23382386"
FT REGION 549..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 687..779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 491..494
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 501..502
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT BINDING 542..545
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 290
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 779 AA; 86641 MW; D4FF151F174DECAE CRC64;
MEEEARPAAG AGEAATPARE TPPAAPAQAR AASGGVPESA PEPKRRQLGT LLQPTVNKFS
LRVFGSHKAV EIEQERVKSA GAWIIHPYSD FRFYWDLIML LLMVGNLIVL PVGITFFKEE
NSPPWIVFNV LSDTFFLLDL VLNFRTGIVV EEGAEILLAP RAIRTRYLRT WFLVDLISSI
PVDYIFLVVE LEPRLDAEVY KTARALRIVR FTKILSLLRL LRLSRLIRYI HQWEEIFHMT
YDLASAVVRI FNLIGMMLLL CHWDGCLQFL VPMLQDFPSD CWVSMNRMVN HSWGRQYSHA
LFKAMSHMLC IGYGQQAPVG MPDVWLTMLS MIVGATCYAM FIGHATALIQ SLDSSRRQYQ
EKYKQVEQYM SFHKLPADTR QRIHEYYEHR YQGKMFDEES ILGELSEPLR EEIINFTCRG
LVAHMPLFAH ADPSFVTAVL TKLRFEVFQP GDLVVREGSV GRKMYFIQHG LLSVLARGAR
DTRLTDGSYF GEICLLTRGR RTASVRADTY CRLYSLSVDH FNAVLEEFPM MRRAFETVAM
DRLRRIGKKN SILQRKRSEP SPGSSGGVME QHLVQHDRDM ARGVRGLAPG TGARLSGKPV
LWEPLVHAPL QAAAVTSNVA IALTHQRGPL PLSPDSPATL LARSARRSAG SPASPLVPVR
AGPLLARGPW ASTSRLPAPP ARTLHASLSR TGRSQVSLLG PPPGGGARRL GPRGRPLSAS
QPSLPQRATG DGSPRRKGSG SERLPPSGLL AKPPGTVQPP RSSVPEPVTP RGPQISANM
