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Q9P1Z3 (HCN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Gene names
Name:HCN3
Synonyms:KIAA1535
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length774 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions. Ref.5

Enzyme regulation

Inhibited by Cs1+ and ZD7288. Is apparently not activated by cAMP. Ref.5

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.5.

Tissue specificity

Detected in brain. Ref.5

Domain

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

Sequence similarities

Belongs to the potassium channel HCN family.

Contains 1 cyclic nucleotide-binding domain.

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 774774Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
PRO_0000054114

Regions

Topological domain1 – 9797Cytoplasmic Potential
Transmembrane98 – 11821Helical; Name=Segment S1; Potential
Topological domain119 – 1246Extracellular Potential
Transmembrane125 – 14521Helical; Name=Segment S2; Potential
Topological domain146 – 17126Cytoplasmic Potential
Transmembrane172 – 19221Helical; Name=Segment S3; Potential
Topological domain193 – 2019Extracellular Potential
Transmembrane202 – 22221Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain223 – 25331Cytoplasmic Potential
Transmembrane254 – 27421Helical; Name=Segment S5; Potential
Topological domain275 – 29723Extracellular Potential
Intramembrane298 – 31922Pore-forming; Name=Segment H5; Potential
Topological domain320 – 32910Extracellular Potential
Transmembrane330 – 35021Helical; Name=Segment S6; Potential
Topological domain351 – 774424Cytoplasmic Potential
Nucleotide binding492 – 4954cAMP By similarity
Nucleotide binding502 – 5032cAMP By similarity
Nucleotide binding543 – 5464cAMP By similarity
Region46 – 9146Involved in subunit assembly By similarity
Compositional bias696 – 76570Pro-rich

Amino acid modifications

Glycosylation2911N-linked (GlcNAc...) Potential

Natural variations

Natural variant6301P → L.
Corresponds to variant rs35001694 [ dbSNP | Ensembl ].
VAR_048746

Experimental info

Sequence conflict2061A → G in AAH00066. Ref.4
Sequence conflict7341S → T in BAA96059. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9P1Z3 [UniParc].

Last modified February 28, 2003. Version 2.
Checksum: 37B9BC13E5E2C097

FASTA77486,032
        10         20         30         40         50         60 
MEAEQRPAAG ASEGATPGLE AVPPVAPPPA TAASGPIPKS GPEPKRRHLG TLLQPTVNKF 

        70         80         90        100        110        120 
SLRVFGSHKA VEIEQERVKS AGAWIIHPYS DFRFYWDLIM LLLMVGNLIV LPVGITFFKE 

       130        140        150        160        170        180 
ENSPPWIVFN VLSDTFFLLD LVLNFRTGIV VEEGAEILLA PRAIRTRYLR TWFLVDLISS 

       190        200        210        220        230        240 
IPVDYIFLVV ELEPRLDAEV YKTARALRIV RFTKILSLLR LLRLSRLIRY IHQWEEIFHM 

       250        260        270        280        290        300 
TYDLASAVVR IFNLIGMMLL LCHWDGCLQF LVPMLQDFPP DCWVSINHMV NHSWGRQYSH 

       310        320        330        340        350        360 
ALFKAMSHML CIGYGQQAPV GMPDVWLTML SMIVGATCYA MFIGHATALI QSLDSSRRQY 

       370        380        390        400        410        420 
QEKYKQVEQY MSFHKLPADT RQRIHEYYEH RYQGKMFDEE SILGELSEPL REEIINFTCR 

       430        440        450        460        470        480 
GLVAHMPLFA HADPSFVTAV LTKLRFEVFQ PGDLVVREGS VGRKMYFIQH GLLSVLARGA 

       490        500        510        520        530        540 
RDTRLTDGSY FGEICLLTRG RRTASVRADT YCRLYSLSVD HFNAVLEEFP MMRRAFETVA 

       550        560        570        580        590        600 
MDRLLRIGKK NSILQRKRSE PSPGSSGGIM EQHLVQHDRD MARGVRGRAP STGAQLSGKP 

       610        620        630        640        650        660 
VLWEPLVHAP LQAAAVTSNV AIALTHQRGP LPLSPDSPAT LLARSAWRSA GSPASPLVPV 

       670        680        690        700        710        720 
RAGPWASTSR LPAPPARTLH ASLSRAGRSQ VSLLGPPPGG GGRRLGPRGR PLSASQPSLP 

       730        740        750        760        770 
QRATGDGSPG RKGSGSERLP PSGLLAKPPR TAQPPRPPVP EPATPRGLQL SANM 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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(2000) [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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 204-774.
Tissue: Brain.
[5]"Functional expression of the human HCN3 channel."
Stieber J., Stockl G., Herrmann S., Hassfurth B., Hofmann F.
J. Biol. Chem. 280:34635-34643(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_065948.1. NM_020897.2.
UniGeneHs.706960.

3D structure databases

ProteinModelPortalQ9P1Z3.
SMRQ9P1Z3. Positions 298-352, 354-550.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121691. 3 interactions.
STRING9606.ENSP00000357342.

Chemistry

ChEMBLCHEMBL1795173.
GuidetoPHARMACOLOGY402.

PTM databases

PhosphoSiteQ9P1Z3.

Polymorphism databases

DMDM29840780.

Proteomic databases

PaxDbQ9P1Z3.
PRIDEQ9P1Z3.

Protocols and materials databases

DNASU57657.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368358; ENSP00000357342; ENSG00000143630.
ENST00000575670; ENSP00000458364; ENSG00000263324.
GeneID57657.
KEGGhsa:57657.
UCSCuc001fjz.2. human.

Organism-specific databases

CTD57657.
GeneCardsGC01P155247.
H-InvDBHIX0001125.
HGNCHGNC:19183. HCN3.
HPAHPA026584.
MIM609973. gene.
neXtProtNX_Q9P1Z3.
PharmGKBPA38821.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0664.
HOGENOMHOG000230717.
HOVERGENHBG039489.
InParanoidQ9P1Z3.
KOK04956.
OMARMVNHSW.
OrthoDBEOG7VMP6X.
PhylomeDBQ9P1Z3.
TreeFamTF318250.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeQ9P1Z3.
CleanExHS_HCN3.
GenevestigatorQ9P1Z3.

Family and domain databases

Gene3D2.60.120.10. 1 hit.
InterProIPR018490. 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]
PfamPF00027. cNMP_binding. 1 hit.
PF00520. Ion_trans. 1 hit.
PF08412. Ion_trans_N. 1 hit.
[Graphical view]
PRINTSPR01463. EAGCHANLFMLY.
SMARTSM00100. cNMP. 1 hit.
[Graphical view]
SUPFAMSSF51206. SSF51206. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHCN3.
GenomeRNAi57657.
NextBio64413.
PROQ9P1Z3.
SOURCESearch...

Entry information

Entry nameHCN3_HUMAN
AccessionPrimary (citable) accession number: Q9P1Z3
Secondary accession number(s): D3DV90 expand/collapse secondary AC list , Q4VX12, Q8N6W6, Q9BWQ2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: February 28, 2003
Last modified: April 16, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM