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Protein

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

Gene

Hcn3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.1 Publication

Enzyme regulationi

Inhibited by Cs1+ and ivabradine. Is apparently not activated by cAMP or cGMP.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi491 – 4944cAMPBy similarity
Nucleotide bindingi501 – 5022cAMPBy similarity
Nucleotide bindingi542 – 5454cAMPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Sodium transport, Transport

Keywords - Ligandi

cAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Alternative name(s):
Hyperpolarization-activated cation channel 3
Short name:
HAC-3
Gene namesi
Name:Hcn3
Synonyms:Hac3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1298211. Hcn3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 9696CytoplasmicSequence analysisAdd
BLAST
Transmembranei97 – 11721Helical; Name=Segment S1Sequence analysisAdd
BLAST
Topological domaini118 – 1236ExtracellularSequence analysis
Transmembranei124 – 14421Helical; Name=Segment S2Sequence analysisAdd
BLAST
Topological domaini145 – 17026CytoplasmicSequence analysisAdd
BLAST
Transmembranei171 – 19121Helical; Name=Segment S3Sequence analysisAdd
BLAST
Topological domaini192 – 2009ExtracellularSequence analysis
Transmembranei201 – 22121Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd
BLAST
Topological domaini222 – 25231CytoplasmicSequence analysisAdd
BLAST
Transmembranei253 – 27321Helical; Name=Segment S5Sequence analysisAdd
BLAST
Topological domaini274 – 29623ExtracellularSequence analysisAdd
BLAST
Intramembranei297 – 31822Pore-forming; Name=Segment H5Sequence analysisAdd
BLAST
Topological domaini319 – 32810ExtracellularSequence analysis
Transmembranei329 – 34921Helical; Name=Segment S6Sequence analysisAdd
BLAST
Topological domaini350 – 779430CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 779779Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3PRO_0000054115Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi290 – 2901N-linked (GlcNAc...)Sequence analysis
Modified residuei633 – 6331PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO88705.
PaxDbiO88705.
PRIDEiO88705.

PTM databases

iPTMnetiO88705.
PhosphoSiteiO88705.

Expressioni

Tissue specificityi

Detected in hypothalamus, amygdala, olfactory bulb, hippocampus and retina (at protein level). Highly expressed in brain and heart, in particular in ventricle, atrium and in sinoatrial node (SAN). Detected at low levels in skeletal muscle and lung.2 Publications

Gene expression databases

BgeeiO88705.
ExpressionAtlasiO88705. baseline and differential.
GenevisibleiO88705. MM.

Interactioni

Subunit structurei

Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits (By similarity).By similarity

Protein-protein interaction databases

BioGridi200254. 3 interactions.
MINTiMINT-4996284.
STRINGi10090.ENSMUSP00000029686.

Structurei

3D structure databases

ProteinModelPortaliO88705.
SMRiO88705. Positions 353-549.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni45 – 9046Involved in subunit assemblyBy similarityAdd
BLAST

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Sequence similaritiesi

Belongs to the potassium channel HCN family.Curated
Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88705.
KOiK04956.
OMAiMNRMVNH.
OrthoDBiEOG7VMP6X.
PhylomeDBiO88705.
TreeFamiTF318250.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O88705-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEEARPAAG AGEAATPARE TPPAAPAQAR AASGGVPESA PEPKRRQLGT
60 70 80 90 100
LLQPTVNKFS LRVFGSHKAV EIEQERVKSA GAWIIHPYSD FRFYWDLIML
110 120 130 140 150
LLMVGNLIVL PVGITFFKEE NSPPWIVFNV LSDTFFLLDL VLNFRTGIVV
160 170 180 190 200
EEGAEILLAP RAIRTRYLRT WFLVDLISSI PVDYIFLVVE LEPRLDAEVY
210 220 230 240 250
KTARALRIVR FTKILSLLRL LRLSRLIRYI HQWEEIFHMT YDLASAVVRI
260 270 280 290 300
FNLIGMMLLL CHWDGCLQFL VPMLQDFPSD CWVSMNRMVN HSWGRQYSHA
310 320 330 340 350
LFKAMSHMLC IGYGQQAPVG MPDVWLTMLS MIVGATCYAM FIGHATALIQ
360 370 380 390 400
SLDSSRRQYQ EKYKQVEQYM SFHKLPADTR QRIHEYYEHR YQGKMFDEES
410 420 430 440 450
ILGELSEPLR EEIINFTCRG LVAHMPLFAH ADPSFVTAVL TKLRFEVFQP
460 470 480 490 500
GDLVVREGSV GRKMYFIQHG LLSVLARGAR DTRLTDGSYF GEICLLTRGR
510 520 530 540 550
RTASVRADTY CRLYSLSVDH FNAVLEEFPM MRRAFETVAM DRLRRIGKKN
560 570 580 590 600
SILQRKRSEP SPGSSGGVME QHLVQHDRDM ARGVRGLAPG TGARLSGKPV
610 620 630 640 650
LWEPLVHAPL QAAAVTSNVA IALTHQRGPL PLSPDSPATL LARSARRSAG
660 670 680 690 700
SPASPLVPVR AGPLLARGPW ASTSRLPAPP ARTLHASLSR TGRSQVSLLG
710 720 730 740 750
PPPGGGARRL GPRGRPLSAS QPSLPQRATG DGSPRRKGSG SERLPPSGLL
760 770
AKPPGTVQPP RSSVPEPVTP RGPQISANM
Length:779
Mass (Da):86,641
Last modified:November 1, 1998 - v1
Checksum:iD4FF151F174DECAE
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225124 mRNA. Translation: CAA12408.1.
AK032225 mRNA. Translation: BAC27769.1.
BC039156 mRNA. Translation: AAH39156.1.
CCDSiCCDS17490.1.
RefSeqiNP_032253.1. NM_008227.1.
UniGeneiMm.389461.
Mm.489362.

Genome annotation databases

EnsembliENSMUST00000029686; ENSMUSP00000029686; ENSMUSG00000028051.
GeneIDi15168.
KEGGimmu:15168.
UCSCiuc008pxr.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ225124 mRNA. Translation: CAA12408.1.
AK032225 mRNA. Translation: BAC27769.1.
BC039156 mRNA. Translation: AAH39156.1.
CCDSiCCDS17490.1.
RefSeqiNP_032253.1. NM_008227.1.
UniGeneiMm.389461.
Mm.489362.

3D structure databases

ProteinModelPortaliO88705.
SMRiO88705. Positions 353-549.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200254. 3 interactions.
MINTiMINT-4996284.
STRINGi10090.ENSMUSP00000029686.

PTM databases

iPTMnetiO88705.
PhosphoSiteiO88705.

Proteomic databases

MaxQBiO88705.
PaxDbiO88705.
PRIDEiO88705.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029686; ENSMUSP00000029686; ENSMUSG00000028051.
GeneIDi15168.
KEGGimmu:15168.
UCSCiuc008pxr.1. mouse.

Organism-specific databases

CTDi57657.
MGIiMGI:1298211. Hcn3.

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiO88705.
KOiK04956.
OMAiMNRMVNH.
OrthoDBiEOG7VMP6X.
PhylomeDBiO88705.
TreeFamiTF318250.

Enzyme and pathway databases

ReactomeiR-MMU-1296061. HCN channels.

Miscellaneous databases

PROiO88705.
SOURCEiSearch...

Gene expression databases

BgeeiO88705.
ExpressionAtlasiO88705. baseline and differential.
GenevisibleiO88705. MM.

Family and domain databases

Gene3Di2.60.120.10. 1 hit.
InterProiIPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR005821. Ion_trans_dom.
IPR013621. Ion_trans_N.
IPR003938. K_chnl_volt-dep_EAG/ELK/ERG.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSiPR01463. EAGCHANLFMLY.
SMARTiSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A family of hyperpolarization-activated cation channels."
    Ludwig A., Zong X., Jeglitsch M., Hofmann F., Biel M.
    Nature 393:587-591(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/cJ.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Olfactory bulb.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Eye.
  4. "Identification of a gene encoding a hyperpolarization-activated 'pacemaker' channel of brain."
    Santoro B., Liu D.T., Yao H., Bartsch D., Kandel E.R., Siegelbaum S.A., Tibbs G.R.
    Cell 93:717-729(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides."
    Mistrik P., Mader R., Michalakis S., Weidinger M., Pfeifer A., Biel M.
    J. Biol. Chem. 280:27056-27061(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-633, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.

Entry informationi

Entry nameiHCN3_MOUSE
AccessioniPrimary (citable) accession number: O88705
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: November 1, 1998
Last modified: June 8, 2016
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.