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Protein

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

Gene

HCN3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

Activity 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

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Potassium channel, Sodium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Sodium transport, Transport
LigandcAMP, cAMP-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000143630.9
HGNCiHGNC:19183 HCN3
MIMi609973 gene
neXtProtiNX_Q9P1Z3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi57657
OpenTargetsiENSG00000143630
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...) asparagineSequence analysis1
Modified residuei634PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9P1Z3
PaxDbiQ9P1Z3
PeptideAtlasiQ9P1Z3
PRIDEiQ9P1Z3
ProteomicsDBi83687

PTM databases

iPTMnetiQ9P1Z3
PhosphoSitePlusiQ9P1Z3

Expressioni

Tissue specificityi

Detected in brain.1 Publication

Gene expression databases

BgeeiENSG00000143630 Expressed in 130 organ(s), highest expression level in forebrain
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. Interacts with KCTD3 and PEX5L.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Shank3Q4ACU6-13EBI-11178054,EBI-16201983From a different organism.

Protein-protein interaction databases

BioGridi121691, 3 interactors
ComplexPortaliCPX-267 HCN3 channel complex
DIPiDIP-62039N
IntActiQ9P1Z3, 2 interactors
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
Regioni354 – 774Interaction with KCTD3By similarityAdd BLAST421

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiQ9P1Z3
KOiK04956
OMAiVMEQHLV
OrthoDBiEOG091G0JQU
PhylomeDBiQ9P1Z3
TreeFamiTF318250

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di2.60.120.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS50042 CNMP_BINDING_3, 1 hit

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 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.
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 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.
CCDSiCCDS1108.1
RefSeqiNP_065948.1, NM_020897.2
UniGeneiHs.706960

3D structure databases

ProteinModelPortaliQ9P1Z3
SMRiQ9P1Z3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121691, 3 interactors
ComplexPortaliCPX-267 HCN3 channel complex
DIPiDIP-62039N
IntActiQ9P1Z3, 2 interactors
STRINGi9606.ENSP00000357342

Chemistry databases

BindingDBiQ9P1Z3
ChEMBLiCHEMBL1795173
GuidetoPHARMACOLOGYi402

PTM databases

iPTMnetiQ9P1Z3
PhosphoSitePlusiQ9P1Z3

Polymorphism and mutation databases

DMDMi29840780

Proteomic databases

EPDiQ9P1Z3
PaxDbiQ9P1Z3
PeptideAtlasiQ9P1Z3
PRIDEiQ9P1Z3
ProteomicsDBi83687

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
EuPathDBiHostDB:ENSG00000143630.9
GeneCardsiHCN3
H-InvDBiHIX0001125
HGNCiHGNC:19183 HCN3
HPAiHPA026584
MIMi609973 gene
neXtProtiNX_Q9P1Z3
OpenTargetsiENSG00000143630
PharmGKBiPA38821
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0498 Eukaryota
ENOG410XPSE LUCA
GeneTreeiENSGT00900000140801
HOGENOMiHOG000230717
HOVERGENiHBG039489
InParanoidiQ9P1Z3
KOiK04956
OMAiVMEQHLV
OrthoDBiEOG091G0JQU
PhylomeDBiQ9P1Z3
TreeFamiTF318250

Enzyme and pathway databases

ReactomeiR-HSA-1296061 HCN channels

Miscellaneous databases

ChiTaRSiHCN3 human
GeneWikiiHCN3
GenomeRNAii57657
PROiPR:Q9P1Z3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143630 Expressed in 130 organ(s), highest expression level in forebrain
CleanExiHS_HCN3
GenevisibleiQ9P1Z3 HS

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
Gene3Di2.60.120.10, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00520 Ion_trans, 1 hit
PF08412 Ion_trans_N, 1 hit
PRINTSiPR01463 EAGCHANLFMLY
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SUPFAMiSSF51206 SSF51206, 1 hit
PROSITEiView protein in PROSITE
PS50042 CNMP_BINDING_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHCN3_HUMAN
AccessioniPrimary (citable) accession number: Q9P1Z3
Secondary accession number(s): D3DV90
, Q4VX12, Q8N6W6, Q9BWQ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: February 28, 2003
Last modified: September 12, 2018
This is version 153 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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Main funding by: National Institutes of Health

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