Q9P1Z3 (HCN3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

Gene names

Name:	HCN3
Synonyms:	KIAA1535

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	774 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Putative hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions By similarity.
Subunit structure	The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits.
Subcellular location	Membrane; Multi-pass membrane protein.
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.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Nucleotide-binding Potassium Sodium cAMP cAMP-binding
Molecular function	Ion channel Ligand-gated ion channel Potassium channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	sodium ion transmembrane transport Inferred from electronic annotation. Source: GOC synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW sodium channel activity Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated potassium channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 774	774	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3		PRO_0000054114
Regions
	Topological domain	1 – 97	97	Cytoplasmic Potential
	Transmembrane	98 – 118	21	Helical; Name=Segment S1; Potential
	Topological domain	119 – 124	6	Extracellular Potential
	Transmembrane	125 – 145	21	Helical; Name=Segment S2; Potential
	Topological domain	146 – 171	26	Cytoplasmic Potential
	Transmembrane	172 – 192	21	Helical; Name=Segment S3; Potential
	Topological domain	193 – 201	9	Extracellular Potential
	Transmembrane	202 – 222	21	Helical; Voltage-sensor; Name=Segment S4; Potential
	Topological domain	223 – 253	31	Cytoplasmic Potential
	Transmembrane	254 – 274	21	Helical; Name=Segment S5; Potential
	Topological domain	275 – 297	23	Extracellular Potential
	Intramembrane	298 – 319	22	Pore-forming; Name=Segment H5; Potential
	Topological domain	320 – 329	10	Extracellular Potential
	Transmembrane	330 – 350	21	Helical; Name=Segment S6; Potential
	Topological domain	351 – 774	424	Cytoplasmic Potential
	Nucleotide binding	428 – 545	118	cAMP
	Region	46 – 91	46	Involved in subunit assembly By similarity
	Compositional bias	696 – 765	70	Pro-rich
Amino acid modifications
	Modified residue	634	1	Phosphoserine By similarity
	Glycosylation	291	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	630	1	P → L. Corresponds to variant rs35001694 [ dbSNP | Ensembl ].		VAR_048746
Experimental info
	Sequence conflict	206	1	A → G in AAH00066. Ref.4
	Sequence conflict	734	1	S → T in BAA96059. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9P1Z3 [UniParc]. Last modified February 28, 2003. Version 2. Checksum: 37B9BC13E5E2C097	FASTA	774	86,032
	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

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. , 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. , 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.
+	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.
IPI	IPI00163724.
RefSeq	NP_065948.1. NM_020897.2.
UniGene	Hs.706960.
3D structure databases
ProteinModelPortal	Q9P1Z3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000357342.
PTM databases
PhosphoSite	Q9P1Z3.
Polymorphism databases
DMDM	29840780.
Proteomic databases
PaxDb	Q9P1Z3.
PRIDE	Q9P1Z3.
Protocols and materials databases
DNASU	57657.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368358; ENSP00000357342; ENSG00000143630. ENST00000575670; ENSP00000458364; ENSG00000263324.
GeneID	57657.
KEGG	hsa:57657.
UCSC	uc001fjz.1. human.
Organism-specific databases
CTD	57657.
GeneCards	GC01P155247.
H-InvDB	HIX0001125.
HGNC	HGNC:19183. HCN3.
HPA	HPA026584.
MIM	609973. gene.
neXtProt	NX_Q9P1Z3.
PharmGKB	PA38821.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0664.
HOGENOM	HOG000230717.
HOVERGEN	HBG039489.
InParanoid	Q9P1Z3.
KO	K04956.
OMA	GIMEQHL.
OrthoDB	EOG46Q6S8.
PhylomeDB	Q9P1Z3.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	Q9P1Z3.
CleanEx	HS_HCN3.
Genevestigator	Q9P1Z3.
GermOnline	ENSG00000143630. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 1 hit.
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. [Graphical view]
Pfam	PF00027. cNMP_binding. 1 hit. PF00520. Ion_trans. 1 hit. PF08412. Ion_trans_N. 1 hit. [Graphical view]
PRINTS	PR01463. EAGCHANLFMLY.
SMART	SM00100. cNMP. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit.
PROSITE	PS00888. CNMP_BINDING_1. False negative. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1795173.
GenomeRNAi	57657.
NextBio	64413.
SOURCE	Search...

Entry information

Entry name

HCN3_HUMAN

Accession

Primary (citable) accession number: Q9P1Z3
Secondary accession number(s): D3DV90 , Q4VX12, Q8N6W6, Q9BWQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	February 28, 2003
Last modified:	May 1, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.