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Protein

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

Gene

HCN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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

Enzyme regulationi

Inhibited by Cs1+ and ZD7288. Is apparently not activated by cAMP.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi492 – 4954cAMPBy similarity
Nucleotide bindingi502 – 5032cAMPBy similarity
Nucleotide bindingi543 – 5464cAMPBy similarity

GO - Molecular functioni

  1. cAMP binding Source: UniProtKB-KW
  2. voltage-gated potassium channel activity Source: UniProtKB
  3. voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

  1. potassium ion transmembrane transport Source: UniProtKB
  2. regulation of membrane potential Source: UniProtKB
  3. sodium ion transmembrane transport Source: UniProtKB
  4. synaptic transmission Source: Reactome
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

ReactomeiREACT_75862. HCN channels.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Gene namesi
Name:HCN3
Synonyms:KIAA1535
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componentsi: Chromosome 1, Unplaced

Organism-specific databases

HGNCiHGNC:19183. HCN3.

Subcellular locationi

Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 9797CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei98 – 11821Helical; Name=Segment S1Sequence AnalysisAdd
BLAST
Topological domaini119 – 1246ExtracellularSequence Analysis
Transmembranei125 – 14521Helical; Name=Segment S2Sequence AnalysisAdd
BLAST
Topological domaini146 – 17126CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei172 – 19221Helical; Name=Segment S3Sequence AnalysisAdd
BLAST
Topological domaini193 – 2019ExtracellularSequence Analysis
Transmembranei202 – 22221Helical; Voltage-sensor; Name=Segment S4Sequence AnalysisAdd
BLAST
Topological domaini223 – 25331CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei254 – 27421Helical; Name=Segment S5Sequence AnalysisAdd
BLAST
Topological domaini275 – 29723ExtracellularSequence AnalysisAdd
BLAST
Intramembranei298 – 31922Pore-forming; Name=Segment H5Sequence AnalysisAdd
BLAST
Topological domaini320 – 32910ExtracellularSequence Analysis
Transmembranei330 – 35021Helical; Name=Segment S6Sequence AnalysisAdd
BLAST
Topological domaini351 – 774424CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: GO_Central
  2. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA38821.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 774774Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3PRO_0000054114Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9P1Z3.
PRIDEiQ9P1Z3.

PTM databases

PhosphoSiteiQ9P1Z3.

Expressioni

Tissue specificityi

Detected in brain.1 Publication

Gene expression databases

BgeeiQ9P1Z3.
CleanExiHS_HCN3.
GenevestigatoriQ9P1Z3.

Organism-specific databases

HPAiHPA026584.

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

BioGridi121691. 3 interactions.
STRINGi9606.ENSP00000357342.

Structurei

3D structure databases

ProteinModelPortaliQ9P1Z3.
SMRiQ9P1Z3. Positions 295-550.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni46 – 9146Involved in subunit assemblyBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi696 – 76570Pro-richAdd
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

eggNOGiCOG0664.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiQ9P1Z3.
KOiK04956.
OMAiVMEQHLV.
OrthoDBiEOG7VMP6X.
PhylomeDBiQ9P1Z3.
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.

Q9P1Z3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAEQRPAAG ASEGATPGLE AVPPVAPPPA TAASGPIPKS GPEPKRRHLG
60 70 80 90 100
TLLQPTVNKF SLRVFGSHKA VEIEQERVKS AGAWIIHPYS DFRFYWDLIM
110 120 130 140 150
LLLMVGNLIV LPVGITFFKE ENSPPWIVFN VLSDTFFLLD LVLNFRTGIV
160 170 180 190 200
VEEGAEILLA PRAIRTRYLR TWFLVDLISS IPVDYIFLVV ELEPRLDAEV
210 220 230 240 250
YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM TYDLASAVVR
260 270 280 290 300
IFNLIGMMLL LCHWDGCLQF LVPMLQDFPP DCWVSINHMV NHSWGRQYSH
310 320 330 340 350
ALFKAMSHML CIGYGQQAPV GMPDVWLTML SMIVGATCYA MFIGHATALI
360 370 380 390 400
QSLDSSRRQY QEKYKQVEQY MSFHKLPADT RQRIHEYYEH RYQGKMFDEE
410 420 430 440 450
SILGELSEPL REEIINFTCR GLVAHMPLFA HADPSFVTAV LTKLRFEVFQ
460 470 480 490 500
PGDLVVREGS VGRKMYFIQH GLLSVLARGA RDTRLTDGSY FGEICLLTRG
510 520 530 540 550
RRTASVRADT YCRLYSLSVD HFNAVLEEFP MMRRAFETVA MDRLLRIGKK
560 570 580 590 600
NSILQRKRSE PSPGSSGGIM EQHLVQHDRD MARGVRGRAP STGAQLSGKP
610 620 630 640 650
VLWEPLVHAP LQAAAVTSNV AIALTHQRGP LPLSPDSPAT LLARSAWRSA
660 670 680 690 700
GSPASPLVPV RAGPWASTSR LPAPPARTLH ASLSRAGRSQ VSLLGPPPGG
710 720 730 740 750
GGRRLGPRGR PLSASQPSLP QRATGDGSPG RKGSGSERLP PSGLLAKPPR
760 770
TAQPPRPPVP EPATPRGLQL SANM
Length:774
Mass (Da):86,032
Last modified:February 28, 2003 - v2
Checksum:i37B9BC13E5E2C097
GO

Sequence cautioni

The sequence AAH28024.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti206 – 2061A → G in AAH00066 (PubMed:15489334).Curated
Sequence conflicti734 – 7341S → T in BAA96059 (PubMed:10819331).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti630 – 6301P → L.
Corresponds to variant rs35001694 [ dbSNP | Ensembl ].
VAR_048746

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL713999 Genomic DNA. Translation: CAI95100.1.
AB040968 mRNA. Translation: BAA96059.2.
CH471121 Genomic DNA. Translation: EAW53084.1.
CH471121 Genomic DNA. Translation: EAW53086.1.
BC000066 mRNA. Translation: AAH00066.1.
BC028024 mRNA. Translation: AAH28024.2. Different initiation.
CCDSiCCDS1108.1.
RefSeqiNP_065948.1. NM_020897.2.
UniGeneiHs.706960.

Genome annotation databases

EnsembliENST00000368358; ENSP00000357342; ENSG00000143630.
ENST00000575670; ENSP00000458364; ENSG00000263324.
GeneIDi57657.
KEGGihsa:57657.
UCSCiuc001fjz.2. human.

Polymorphism databases

DMDMi29840780.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL713999 Genomic DNA. Translation: CAI95100.1.
AB040968 mRNA. Translation: BAA96059.2.
CH471121 Genomic DNA. Translation: EAW53084.1.
CH471121 Genomic DNA. Translation: EAW53086.1.
BC000066 mRNA. Translation: AAH00066.1.
BC028024 mRNA. Translation: AAH28024.2. Different initiation.
CCDSiCCDS1108.1.
RefSeqiNP_065948.1. NM_020897.2.
UniGeneiHs.706960.

3D structure databases

ProteinModelPortaliQ9P1Z3.
SMRiQ9P1Z3. Positions 295-550.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121691. 3 interactions.
STRINGi9606.ENSP00000357342.

Chemistry

BindingDBiQ9P1Z3.
ChEMBLiCHEMBL1795173.
GuidetoPHARMACOLOGYi402.

PTM databases

PhosphoSiteiQ9P1Z3.

Polymorphism databases

DMDMi29840780.

Proteomic databases

PaxDbiQ9P1Z3.
PRIDEiQ9P1Z3.

Protocols and materials databases

DNASUi57657.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368358; ENSP00000357342; ENSG00000143630.
ENST00000575670; ENSP00000458364; ENSG00000263324.
GeneIDi57657.
KEGGihsa:57657.
UCSCiuc001fjz.2. human.

Organism-specific databases

CTDi57657.
GeneCardsiGC01P155247.
H-InvDBHIX0001125.
HGNCiHGNC:19183. HCN3.
HPAiHPA026584.
MIMi609973. gene.
neXtProtiNX_Q9P1Z3.
PharmGKBiPA38821.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0664.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiQ9P1Z3.
KOiK04956.
OMAiVMEQHLV.
OrthoDBiEOG7VMP6X.
PhylomeDBiQ9P1Z3.
TreeFamiTF318250.

Enzyme and pathway databases

ReactomeiREACT_75862. HCN channels.

Miscellaneous databases

ChiTaRSiHCN3. human.
GeneWikiiHCN3.
GenomeRNAii57657.
NextBioi64413.
PROiQ9P1Z3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9P1Z3.
CleanExiHS_HCN3.
GenevestigatoriQ9P1Z3.

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. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
    Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
    DNA Res. 7:143-150(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-774.
    Tissue: Brain.
  4. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-774.
    Tissue: Brain.
  5. Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION.

Entry informationi

Entry nameiHCN3_HUMAN
AccessioniPrimary (citable) accession number: Q9P1Z3
Secondary accession number(s): D3DV90
, Q4VX12, Q8N6W6, Q9BWQ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: February 28, 2003
Last modified: February 4, 2015
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.