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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)DescriptionActionsGraphical viewLength
Nucleotide bindingi492 – 495cAMPBy similarity4
Nucleotide bindingi502 – 503cAMPBy similarity2
Nucleotide bindingi543 – 546cAMPBy similarity4

GO - Molecular functioni

  • cAMP binding Source: UniProtKB-KW
  • voltage-gated potassium channel activity Source: UniProtKB
  • voltage-gated sodium channel activity Source: UniProtKB

GO - Biological processi

  • cellular response to dopamine Source: Ensembl
  • potassium ion transmembrane transport Source: UniProtKB
  • regulation of membrane potential Source: UniProtKB
  • response to cisplatin Source: Ensembl
  • sodium ion transmembrane transport Source: UniProtKB
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

BioCyciZFISH:ENSG00000143630-MONOMER.
ReactomeiR-HSA-1296061. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:19183. HCN3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 97CytoplasmicSequence analysisAdd BLAST97
Transmembranei98 – 118Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini119 – 124ExtracellularSequence analysis6
Transmembranei125 – 145Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini146 – 171CytoplasmicSequence analysisAdd BLAST26
Transmembranei172 – 192Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini193 – 201ExtracellularSequence analysis9
Transmembranei202 – 222Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST21
Topological domaini223 – 253CytoplasmicSequence analysisAdd BLAST31
Transmembranei254 – 274Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini275 – 297ExtracellularSequence analysisAdd BLAST23
Intramembranei298 – 319Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini320 – 329ExtracellularSequence analysis10
Transmembranei330 – 350Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini351 – 774CytoplasmicSequence analysisAdd BLAST424

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi57657.
OpenTargetsiENSG00000143630.
ENSG00000263324.
PharmGKBiPA38821.

Chemistry databases

ChEMBLiCHEMBL1795173.
GuidetoPHARMACOLOGYi402.

Polymorphism and mutation databases

DMDMi29840780.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000541141 – 774Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3Add BLAST774

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi291N-linked (GlcNAc...)Sequence analysis1
Modified residuei634PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9P1Z3.
PeptideAtlasiQ9P1Z3.
PRIDEiQ9P1Z3.

PTM databases

iPTMnetiQ9P1Z3.
PhosphoSitePlusiQ9P1Z3.

Expressioni

Tissue specificityi

Detected in brain.1 Publication

Gene expression databases

BgeeiENSG00000143630.
CleanExiHS_HCN3.
GenevisibleiQ9P1Z3. HS.

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 interactors.
DIPiDIP-62039N.
STRINGi9606.ENSP00000357342.

Chemistry databases

BindingDBiQ9P1Z3.

Structurei

3D structure databases

ProteinModelPortaliQ9P1Z3.
SMRiQ9P1Z3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 91Involved in subunit assemblyBy similarityAdd BLAST46

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi696 – 765Pro-richAdd BLAST70

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.
InParanoidiQ9P1Z3.
KOiK04956.
OMAiVMEQHLV.
OrthoDBiEOG091G0JQU.
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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti206A → G in AAH00066 (PubMed:15489334).Curated1
Sequence conflicti734S → T in BAA96059 (PubMed:10819331).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048746630P → L.Corresponds to variant rs35001694dbSNPEnsembl.1

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.3. human.

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121691. 3 interactors.
DIPiDIP-62039N.
STRINGi9606.ENSP00000357342.

Chemistry databases

BindingDBiQ9P1Z3.
ChEMBLiCHEMBL1795173.
GuidetoPHARMACOLOGYi402.

PTM databases

iPTMnetiQ9P1Z3.
PhosphoSitePlusiQ9P1Z3.

Polymorphism and mutation databases

DMDMi29840780.

Proteomic databases

PaxDbiQ9P1Z3.
PeptideAtlasiQ9P1Z3.
PRIDEiQ9P1Z3.

Protocols and materials databases

DNASUi57657.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368358; ENSP00000357342; ENSG00000143630.
ENST00000575670; ENSP00000458364; ENSG00000263324.
GeneIDi57657.
KEGGihsa:57657.
UCSCiuc001fjz.3. human.

Organism-specific databases

CTDi57657.
DisGeNETi57657.
GeneCardsiHCN3.
H-InvDBHIX0001125.
HGNCiHGNC:19183. HCN3.
HPAiHPA026584.
MIMi609973. gene.
neXtProtiNX_Q9P1Z3.
OpenTargetsiENSG00000143630.
ENSG00000263324.
PharmGKBiPA38821.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0498. Eukaryota.
ENOG410XPSE. LUCA.
GeneTreeiENSGT00760000118772.
HOGENOMiHOG000230717.
HOVERGENiHBG039489.
InParanoidiQ9P1Z3.
KOiK04956.
OMAiVMEQHLV.
OrthoDBiEOG091G0JQU.
PhylomeDBiQ9P1Z3.
TreeFamiTF318250.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143630-MONOMER.
ReactomeiR-HSA-1296061. HCN channels.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000143630.
CleanExiHS_HCN3.
GenevisibleiQ9P1Z3. HS.

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...

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: November 2, 2016
This is version 141 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

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.