Reviewed, UniProtKB/Swiss-Prot O60741 (HCN1_HUMAN)

Names and origin

Protein names

Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1
Alternative name(s):
    Brain cyclic nucleotide-gated channel 1
      Short name=BCNG-1

Gene names

Name:	HCN1
Synonyms:	BCNG1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	890 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. May mediate responses to sour stimuli.
Subunit structure	The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits. Heteromultimer with HCN2 By similarity. Interacts with KCNE2 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Detected in brain, in particular in amygdala and hippocampus, while expression in caudate nucleus, corpus callosum, substantia nigra, subthalamic nucleus and thalamus is very low or not detectable. Detected at very low levels in muscle and pancreas. Ref.2
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 AAC39759.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Sodium transport Transport
Cellular component	Membrane
Domain	Transmembrane
Ligand	Nucleotide-binding Potassium Sodium cAMP cAMP-binding
Molecular function	Ionic channel Potassium channel Sodium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	potassium ion transport Non-traceable author statement. Source: UniProtKB sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB
Molecular function	cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW sodium channel activity Inferred from electronic annotation. Source: UniProtKB-KW sodium ion binding 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 – 890	890	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1		PRO_0000054107
Regions
	Topological domain	1 – 146	146	Cytoplasmic Potential
	Transmembrane	147 – 167	21	Segment S1 Potential
	Transmembrane	174 – 194	21	Segment S2 Potential
	Topological domain	195 – 219	25	Cytoplasmic Potential
	Transmembrane	220 – 240	21	Segment S3 Potential
	Transmembrane	249 – 269	21	Segment S4 Potential
	Topological domain	270 – 300	31	Cytoplasmic Potential
	Transmembrane	301 – 321	21	Segment S5 Potential
	Transmembrane	345 – 366	22	Segment H5 (pore-forming) Potential
	Transmembrane	372 – 392	21	Segment S6 Potential
	Topological domain	393 – 890	498	Cytoplasmic Potential
	Nucleotide binding	475 – 592	118	cAMP
	Region	89 – 140	52	Involved in subunit assembly By similarity
	Compositional bias	1 – 80	80	Gly-rich
	Compositional bias	726 – 756	31	Gln-rich
	Compositional bias	857 – 863	7	Poly-Pro
Amino acid modifications
	Modified residue	41	1	Phosphothreonine By similarity
	Glycosylation	338	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	786	1	L → F in AAC39759. Ref.2
	Sequence conflict	789	1	S → W in AAC39759. Ref.2
	Sequence conflict	841	1	L → F in AAC39759. Ref.2
	Sequence conflict	857	1	P → L in AAC39759. Ref.2
	Sequence conflict	861	1	P → L in AAC39759. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O60741-1 [UniParc]. Last modified May 5, 2009. Version 3. Checksum: A62F5E79C01257A2	FASTA	890	98,796
	10 20 30 40 50 60 MEGGGKPNSS SNSRDDGNSV FPAKASATGA GPAAAEKRLG TPPGGGGAGA KEHGNSVCFK 70 80 90 100 110 120 VDGGGGGGGG GGGGEEPAGG FEDAEGPRRQ YGFMQRQFTS MLQPGVNKFS LRMFGSQKAV 130 140 150 160 170 180 EKEQERVKTA GFWIIHPYSD FRFYWDLIML IMMVGNLVII PVGITFFTEQ TTTPWIIFNV 190 200 210 220 230 240 ASDTVFLLDL IMNFRTGTVN EDSSEIILDP KVIKMNYLKS WFVVDFISSI PVDYIFLIVE 250 260 270 280 290 300 KGMDSEVYKT ARALRIVRFT KILSLLRLLR LSRLIRYIHQ WEEIFHMTYD LASAVVRIFN 310 320 330 340 350 360 LIGMMLLLCH WDGCLQFLVP LLQDFPPDCW VSLNEMVNDS WGKQYSYALF KAMSHMLCIG 370 380 390 400 410 420 YGAQAPVSMS DLWITMLSMI VGATCYAMFV GHATALIQSL DSSRRQYQEK YKQVEQYMSF 430 440 450 460 470 480 HKLPADMRQK IHDYYEHRYQ GKIFDEENIL NELNDPLREE IVNFNCRKLV ATMPLFANAD 490 500 510 520 530 540 PNFVTAMLSK LRFEVFQPGD YIIREGAVGK KMYFIQHGVA GVITKSSKEM KLTDGSYFGE 550 560 570 580 590 600 ICLLTKGRRT ASVRADTYCR LYSLSVDNFN EVLEEYPMMR RAFETVAIDR LDRIGKKNSI 610 620 630 640 650 660 LLQKFQKDLN TGVFNNQENE ILKQIVKHDR EMVQAIAPIN YPQMTTLNST SSTTTPTSRM 670 680 690 700 710 720 RTQSPPVYTA TSLSHSNLHS PSPSTQTPQP SAILSPCSYT TAVCSPPVQS PLAARTFHYA 730 740 750 760 770 780 SPTASQLSLM QQQPQQQVQQ SQPPQTQPQQ PSPQPQTPGS STPKNEVHKS TQALHNTNLT 790 800 810 820 830 840 REVRPLSASQ PSLPHEVSTL ISRPHPTVGE SLASIPQPVT AVPGTGLQAG GRSTVPQRVT 850 860 870 880 890 LFRQMSSGAI PPNRGVPPAP PPPAAALPRE SSSVLNTDPD AEKPRFASNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Identification of a gene encoding a hyperpolarization-activated 'pacemaker' channel of brain." Santoro B., Liu D.T., Yao H., Bartsch D., Kandel E.R., Siegelbaum S.A., Tibbs G.R. Cell 93:717-729(1998) [PubMed: 9630217] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-862, TISSUE SPECIFICITY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AC099514 Genomic DNA. No translation available. AC114975 Genomic DNA. No translation available. AC117529 Genomic DNA. No translation available. AC138520 Genomic DNA. No translation available. AF064876 mRNA. Translation: AAC39759.1. Sequence problems.
IPI	IPI00031506.
RefSeq	NP_066550.2.
UniGene	Hs.650434
3D structure databases
SMR	O60741. Positions 401-601.
ModBase	Search...
PTM databases
PhosphoSite	O60741.
Proteomic databases
PRIDE	O60741.
Genome annotation databases
Ensembl	ENSG00000164588. Homo sapiens. [Contig view]
GeneID	348980.
KEGG	hsa:348980.
Organism-specific databases
GeneCards	GC05M045297.
HGNC	HGNC:4845. HCN1.
MIM	602780. gene.
PharmGKB	PA77.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O60741.
HOVERGEN	O60741.
Gene expression databases
ArrayExpress	O60741.
Bgee	O60741.
CleanEx	HS_HCN1.
GermOnline	ENSG00000164588. Homo sapiens.
Family and domain databases
InterPro	IPR000595. cNMP_bd. IPR018488. cNMP_bd_CS. IPR005821. Ion_trans. IPR013621. Ion_trans_N. IPR003938. K_chnl_volt-dep_EAG/ELK/ERG. IPR014710. RmlC-like_jellyroll. [Graphical view]
Gene3D	G3DSA:2.60.120.10. RmlC-like_jellyroll. 1 hit.
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]
PROSITE	PS00888. CNMP_BINDING_1. 1 hit. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

HCN1_HUMAN

Accession

Primary (citable) accession number: O60741

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	May 5, 2009
Last modified:	May 26, 2009
This is version 71 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)