Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

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O60741 (HCN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 105. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

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) [Reference proteome]

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.
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: Contaminating sequence. Potential poly-A sequence.

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	apical protein localization Inferred from electronic annotation. Source: Compara retinal cone cell development Inferred from electronic annotation. Source: Compara sodium ion transmembrane transport Inferred from electronic annotation. Source: GOC synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	axon Inferred from electronic annotation. Source: Compara dendrite Inferred from electronic annotation. Source: Compara integral to membrane Non-traceable author statement PubMed 9405696. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	cAMP binding Inferred from electronic annotation. Source: UniProtKB-KW potassium channel activity Non-traceable author statement PubMed 9405696. Source: UniProtKB 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 – 890

890

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

PRO_0000054107

Regions

Topological domain

1 – 146

146

Cytoplasmic Potential

Transmembrane

147 – 167

Helical; Name=Segment S1; Potential

Topological domain

168 – 173

Extracellular Potential

Transmembrane

174 – 194

Helical; Name=Segment S2; Potential

Topological domain

195 – 219

Cytoplasmic Potential

Transmembrane

220 – 240

Helical; Name=Segment S3; Potential

Topological domain

241 – 248

Extracellular Potential

Transmembrane

249 – 269

Helical; Voltage-sensor; Name=Segment S4; Potential

Topological domain

270 – 300

Cytoplasmic Potential

Transmembrane

301 – 321

Helical; Name=Segment S5; Potential

Topological domain

322 – 344

Extracellular Potential

Intramembrane

345 – 366

Pore-forming; Name=Segment H5; Potential

Topological domain

367 – 371

Extracellular Potential

Transmembrane

372 – 392

Helical; Name=Segment S6; Potential

Topological domain

393 – 890

498

Cytoplasmic Potential

Nucleotide binding

475 – 592

118

cAMP

Region

89 – 140

Involved in subunit assembly By similarity

Compositional bias

1 – 80

Gly-rich

Compositional bias

726 – 756

Gln-rich

Compositional bias

857 – 863

Poly-Pro

Amino acid modifications

Modified residue

Phosphothreonine By similarity

Glycosylation

338

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

P → S.
Corresponds to variant rs56164833 [ dbSNP | Ensembl ].

VAR_061105

Experimental info

Sequence conflict

786

L → F in AAC39759. Ref.2

Sequence conflict

789

S → W in AAC39759. Ref.2

Sequence conflict

841

L → F in AAC39759. Ref.2

Sequence conflict

857

P → L in AAC39759. Ref.2

Sequence conflict

861

P → L in AAC39759. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

O60741 [UniParc].

Last modified May 5, 2009. Version 3.
Checksum: A62F5E79C01257A2
Show »

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

« Hide

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. Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 122-862, TISSUE SPECIFICITY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_021072.3.
UniGene	Hs.353176.
3D structure databases
ProteinModelPortal	O60741.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000307342.
PTM databases
PhosphoSite	O60741.
Proteomic databases
PaxDb	O60741.
PRIDE	O60741.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303230; ENSP00000307342; ENSG00000164588.
GeneID	348980.
KEGG	hsa:348980.
UCSC	uc003jok.3. human.
Organism-specific databases
CTD	348980.
GeneCards	GC05M045260.
H-InvDB	HIX0004850.
HGNC	HGNC:4845. HCN1.
HPA	HPA019195.
MIM	602780. gene.
neXtProt	NX_O60741.
PharmGKB	PA77.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0664.
HOGENOM	HOG000230717.
HOVERGEN	HBG039489.
InParanoid	O60741.
KO	K04954.
OMA	PINYPQM.
OrthoDB	EOG46Q6S8.
PhylomeDB	O60741.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	O60741.
CleanEx	HS_HCN1.
Genevestigator	O60741.
GermOnline	ENSG00000164588. Homo sapiens.
Family and domain databases
Gene3D	2.60.120.10. 1 hit.
InterPro	IPR018490. cNMP-bd-like. IPR018488. cNMP-bd_CS. 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. 1 hit. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1795171.
GenomeRNAi	348980.
NextBio	99467.
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 1, 2013
This is version 105 of the entry and version 3 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.

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents