The new UniProt website is here!
Take me to UniProt BETA
UniProtKB - Q9P1Z3 (HCN3_HUMAN)
Protein
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Gene
HCN3
Organism
Homo sapiens (Human)
Status
Functioni
Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.
1 PublicationActivity regulationi
Inhibited by Cs1+ and ZD7288. Is apparently not activated by cAMP.1 Publication
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 492 – 495 | 3',5'-cAMPBy similarity | 4 | |
Nucleotide bindingi | 502 – 503 | 3',5'-cAMPBy similarity | 2 | |
Nucleotide bindingi | 543 – 546 | 3',5'-cAMPBy similarity | 4 |
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 cAMP Source: ComplexPortal
- cellular response to dopamine Source: Ensembl
- potassium ion transmembrane transport Source: UniProtKB
- regulation of cation channel activity Source: ComplexPortal
- regulation of heart rate by cardiac conduction Source: ComplexPortal
- regulation of membrane depolarization Source: ComplexPortal
- regulation of membrane potential Source: UniProtKB
- regulation of SA node cell action potential Source: ComplexPortal
- response to cisplatin Source: Ensembl
- sodium ion transmembrane transport Source: UniProtKB
Keywordsi
Molecular function | Ion channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel |
Biological process | Ion transport, Potassium transport, Sodium transport, Transport |
Ligand | cAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q9P1Z3 |
Reactomei | R-HSA-1296061, HCN channels |
SignaLinki | Q9P1Z3 |
Names & Taxonomyi
Protein namesi | Recommended name: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 |
Gene namesi | Name:HCN3 Synonyms:KIAA1535 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:19183, HCN3 |
MIMi | 609973, gene |
neXtProti | NX_Q9P1Z3 |
VEuPathDBi | HostDB:ENSG00000143630 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma Membrane
- integral component of plasma membrane Source: Ensembl
- plasma membrane Source: UniProtKB
Other locations
- cone cell pedicle Source: Ensembl
- dendrite Source: Ensembl
- neuronal cell body Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 97 | CytoplasmicSequence analysisAdd BLAST | 97 | |
Transmembranei | 98 – 118 | Helical; Name=Segment S1Sequence analysisAdd BLAST | 21 | |
Topological domaini | 119 – 124 | ExtracellularSequence analysis | 6 | |
Transmembranei | 125 – 145 | Helical; Name=Segment S2Sequence analysisAdd BLAST | 21 | |
Topological domaini | 146 – 171 | CytoplasmicSequence analysisAdd BLAST | 26 | |
Transmembranei | 172 – 192 | Helical; Name=Segment S3Sequence analysisAdd BLAST | 21 | |
Topological domaini | 193 – 201 | ExtracellularSequence analysis | 9 | |
Transmembranei | 202 – 222 | Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST | 21 | |
Topological domaini | 223 – 253 | CytoplasmicSequence analysisAdd BLAST | 31 | |
Transmembranei | 254 – 274 | Helical; Name=Segment S5Sequence analysisAdd BLAST | 21 | |
Topological domaini | 275 – 297 | ExtracellularSequence analysisAdd BLAST | 23 | |
Intramembranei | 298 – 319 | Pore-forming; Name=Segment H5Sequence analysisAdd BLAST | 22 | |
Topological domaini | 320 – 329 | ExtracellularSequence analysis | 10 | |
Transmembranei | 330 – 350 | Helical; Name=Segment S6Sequence analysisAdd BLAST | 21 | |
Topological domaini | 351 – 774 | CytoplasmicSequence analysisAdd BLAST | 424 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 57657 |
OpenTargetsi | ENSG00000143630 |
PharmGKBi | PA38821 |
Miscellaneous databases
Pharosi | Q9P1Z3, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1795173 |
DrugCentrali | Q9P1Z3 |
GuidetoPHARMACOLOGYi | 402 |
Genetic variation databases
BioMutai | HCN3 |
DMDMi | 29840780 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054114 | 1 – 774 | Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3Add BLAST | 774 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 291 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 634 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
MassIVEi | Q9P1Z3 |
PaxDbi | Q9P1Z3 |
PeptideAtlasi | Q9P1Z3 |
PRIDEi | Q9P1Z3 |
ProteomicsDBi | 83687 |
PTM databases
GlyGeni | Q9P1Z3, 1 site |
iPTMneti | Q9P1Z3 |
PhosphoSitePlusi | Q9P1Z3 |
Expressioni
Tissue specificityi
Detected in brain.1 Publication
Gene expression databases
Bgeei | ENSG00000143630, Expressed in forebrain and 153 other tissues |
Genevisiblei | Q9P1Z3, HS |
Organism-specific databases
HPAi | ENSG00000143630, Tissue enhanced (liver) |
Interactioni
Subunit structurei
Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits.
Interacts with KCTD3 and PEX5L.
By similarityBinary interactionsi
Q9P1Z3
With | #Exp. | IntAct |
---|---|---|
Shank3 - isoform 1 [Q4ACU6-1] from Mus musculus. | 3 | EBI-11178054,EBI-16201983 |
Protein-protein interaction databases
BioGRIDi | 121691, 6 interactors |
ComplexPortali | CPX-267, HCN3 channel complex |
DIPi | DIP-62039N |
IntActi | Q9P1Z3, 2 interactors |
STRINGi | 9606.ENSP00000357342 |
Chemistry databases
BindingDBi | Q9P1Z3 |
Miscellaneous databases
RNActi | Q9P1Z3, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 48 | DisorderedSequence analysisAdd BLAST | 48 | |
Regioni | 46 – 91 | Involved in subunit assemblyBy similarityAdd BLAST | 46 | |
Regioni | 354 – 774 | Interaction with KCTD3By similarityAdd BLAST | 421 | |
Regioni | 682 – 774 | DisorderedSequence analysisAdd BLAST | 93 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 21 – 35 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 747 – 764 | Pro residuesSequence analysisAdd BLAST | 18 |
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
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0498, Eukaryota |
GeneTreei | ENSGT00940000162023 |
HOGENOMi | CLU_005746_15_1_1 |
InParanoidi | Q9P1Z3 |
OMAi | SSIPMDC |
OrthoDBi | 281394at2759 |
PhylomeDBi | Q9P1Z3 |
TreeFami | TF318250 |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit |
Gene3Di | 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, 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 |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF00520, Ion_trans, 1 hit PF08412, Ion_trans_N, 1 hit |
PRINTSi | PR01463, EAGCHANLFMLY |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit |
SUPFAMi | SSF51206, SSF51206, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9P1Z3-1 [UniParc]FASTAAdd to basket
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
Sequence cautioni
The sequence AAH28024 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 206 | A → G in AAH00066 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 734 | S → T in BAA96059 (PubMed:10819331).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_048746 | 630 | P → L. Corresponds to variant dbSNP:rs35001694Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL713999 Genomic DNA No translation available. 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. |
CCDSi | CCDS1108.1 |
RefSeqi | NP_065948.1, NM_020897.2 |
Genome annotation databases
Ensembli | ENST00000368358.4; ENSP00000357342.3; ENSG00000143630.10 ENST00000575670.1; ENSP00000458364.1; ENSG00000263324.5 |
GeneIDi | 57657 |
KEGGi | hsa:57657 |
MANE-Selecti | ENST00000368358.4; ENSP00000357342.3; NM_020897.3; NP_065948.1 |
UCSCi | uc001fjz.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL713999 Genomic DNA No translation available. 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. |
CCDSi | CCDS1108.1 |
RefSeqi | NP_065948.1, NM_020897.2 |
3D structure databases
AlphaFoldDBi | Q9P1Z3 |
SMRi | Q9P1Z3 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 121691, 6 interactors |
ComplexPortali | CPX-267, HCN3 channel complex |
DIPi | DIP-62039N |
IntActi | Q9P1Z3, 2 interactors |
STRINGi | 9606.ENSP00000357342 |
Chemistry databases
BindingDBi | Q9P1Z3 |
ChEMBLi | CHEMBL1795173 |
DrugCentrali | Q9P1Z3 |
GuidetoPHARMACOLOGYi | 402 |
PTM databases
GlyGeni | Q9P1Z3, 1 site |
iPTMneti | Q9P1Z3 |
PhosphoSitePlusi | Q9P1Z3 |
Genetic variation databases
BioMutai | HCN3 |
DMDMi | 29840780 |
Proteomic databases
MassIVEi | Q9P1Z3 |
PaxDbi | Q9P1Z3 |
PeptideAtlasi | Q9P1Z3 |
PRIDEi | Q9P1Z3 |
ProteomicsDBi | 83687 |
Protocols and materials databases
ABCDi | Q9P1Z3, 1 sequenced antibody |
Antibodypediai | 20417, 305 antibodies from 37 providers |
DNASUi | 57657 |
Genome annotation databases
Ensembli | ENST00000368358.4; ENSP00000357342.3; ENSG00000143630.10 ENST00000575670.1; ENSP00000458364.1; ENSG00000263324.5 |
GeneIDi | 57657 |
KEGGi | hsa:57657 |
MANE-Selecti | ENST00000368358.4; ENSP00000357342.3; NM_020897.3; NP_065948.1 |
UCSCi | uc001fjz.3, human |
Organism-specific databases
CTDi | 57657 |
DisGeNETi | 57657 |
GeneCardsi | HCN3 |
HGNCi | HGNC:19183, HCN3 |
HPAi | ENSG00000143630, Tissue enhanced (liver) |
MIMi | 609973, gene |
neXtProti | NX_Q9P1Z3 |
OpenTargetsi | ENSG00000143630 |
PharmGKBi | PA38821 |
VEuPathDBi | HostDB:ENSG00000143630 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0498, Eukaryota |
GeneTreei | ENSGT00940000162023 |
HOGENOMi | CLU_005746_15_1_1 |
InParanoidi | Q9P1Z3 |
OMAi | SSIPMDC |
OrthoDBi | 281394at2759 |
PhylomeDBi | Q9P1Z3 |
TreeFami | TF318250 |
Enzyme and pathway databases
PathwayCommonsi | Q9P1Z3 |
Reactomei | R-HSA-1296061, HCN channels |
SignaLinki | Q9P1Z3 |
Miscellaneous databases
BioGRID-ORCSi | 57657, 10 hits in 1071 CRISPR screens |
ChiTaRSi | HCN3, human |
GeneWikii | HCN3 |
GenomeRNAii | 57657 |
Pharosi | Q9P1Z3, Tclin |
PROi | PR:Q9P1Z3 |
RNActi | Q9P1Z3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000143630, Expressed in forebrain and 153 other tissues |
Genevisiblei | Q9P1Z3, HS |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit |
Gene3Di | 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, 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 |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF00520, Ion_trans, 1 hit PF08412, Ion_trans_N, 1 hit |
PRINTSi | PR01463, EAGCHANLFMLY |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit |
SUPFAMi | SSF51206, SSF51206, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HCN3_HUMAN | |
Accessioni | Q9P1Z3Primary (citable) accession number: Q9P1Z3 Secondary accession number(s): D3DV90 Q9BWQ2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 28, 2003 |
Last sequence update: | February 28, 2003 | |
Last modified: | May 25, 2022 | |
This is version 174 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families