HCN2
entrez
610
canonical
uniprot
Q9UL51
canonical
ensembl
ENSG00000099822
resolver
ensp
ENSP00000251287
resolver
enst
ENST00000251287
resolver
genesymbol
HCN2
resolver
genesymbol_syn
BCNG2
resolver
hgnc
HGNC:4846
resolver
uniprot
O60742
resolver
uniprot
O60743
resolver
uniprot
O75267
resolver
uniprot
Q9UBS2
resolver
uniprot_entry
HCN2_HUMAN
resolver
uniprot_sec
O60742
resolver
uniprot_sec
O60743
resolver
uniprot_sec
O75267
resolver
uniprot_sec
Q9UBS2
resolver
activity_regulation
ACTIVITY REGULATION: Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP (PubMed:10228147, PubMed:22006928). cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Binding of cAMP removes a tonic inhibition conferred by cyclic nucleotide-binding domain (CNBD) on channel opening (PubMed:22006928). Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity). Inhibited by extracellular cesium ions (PubMed:10228147). {ECO:0000250|UniProtKB:O88703, ECO:0000269|PubMed:10228147, ECO:0000269|PubMed:22006928}.
uniprot
proteins
amino_acid_sequence
MDARGGGGRPGESPGATPAPGPPPPPPPAPPQQQPPPPPPPAPPPGPGPAPPQHPPRAEALPPEAADEGGPRGRLRSRDSSCGRPGTPGAASTAKGSPNGECGRGEPQCSPAGPEGPARGPKVSFSCRGAASGPAPGPGPAEEAGSEEAGPAGEPRGSQASFMQRQFGALLQPGVNKFSLRMFGSQKAVEREQERVKSAGAWIIHPYSDFRFYWDFTMLLFMVGNLIIIPVGITFFKDETTAPWIVFNVVSDTFFLMDLVLNFRTGIVIEDNTEIILDPEKIKKKYLRTWFVVDFVSSIPVDYIFLIVEKGIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVMRICNLISMMLLLCHWDGCLQFLVPMLQDFPRNCWVSINGMVNHSWSELYSFALFKAMSHMLCIGYGRQAPESMTDIWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADFRQKIHDYYEHRYQGKMFDEDSILGELNGPLREEIVNFNCRKLVASMPLFANADPNFVTAMLTKLKFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKEMKLSDGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVAIDRLDRIGKKNSILLHKVQHDLNSGVFNNQENAIIQEIVKYDREMVQQAELGQRVGLFPPPPPPPQVTSAIATLQQAAAMSFCPQVARPLVGPLALGSPRLVRRPPPGPAPAAASPGPPPPASPPGAPASPRAPRTSPYGGLPAAPLAGPALPARRLSRASRPLSASQPSLPHGAPGPAASTRPASSSTPRLGPTPAARAAAPSPDRRDSASPGAAGGLDPQDSARSRLSSNL
uniprot
proteins
disease_involvement
DISEASE: Epilepsy, idiopathic generalized 17 (EIG17) [MIM:602477]: A form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. Both autosomal dominant and autosomal recessive EIG17 inheritance have been reported. {ECO:0000269|PubMed:22131395, ECO:0000269|PubMed:29064616}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Febrile seizures, familial, 2 (FEB2) [MIM:602477]: Seizures associated with febrile episodes in childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures (generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex febrile seizures are associated with a moderately increased incidence of epilepsy. FEB2 transmission pattern is consistent with autosomal dominant inheritance. {ECO:0000269|PubMed:24324597}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Hyperpolarization-activated ion channel that is permeable to sodium and potassium ions. Displays lower selectivity for K(+) over Na(+) ions (PubMed:10228147, PubMed:22006928). Contributes to the native pacemaker currents in heart (If) and in neurons (Ih) (PubMed:10228147, PubMed:10524219). Can also transport ammonium in the distal nephron (By similarity). Involved in the initiation of neuropathic pain in sensory neurons (By similarity). {ECO:0000250|UniProtKB:Q9JKA9, ECO:0000269|PubMed:10228147, ECO:0000269|PubMed:10524219, ECO:0000269|PubMed:22006928}.
uniprot
proteins
mass_dalton
96950
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating. {ECO:0000250|UniProtKB:O88703}.; PTM: S-palmitoylated. {ECO:0000269|PubMed:26546007}.; PTM: N-glycosylated; required for cell surface trafficking of HCN2. {ECO:0000250|UniProtKB:O88703}.
uniprot
proteins
protein_family
Potassium channel HCN family
uniprot
proteins
pubmed
10228147
uniprot
proteins
pubmed
10524219
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
22006928
uniprot
proteins
pubmed
22131395
uniprot
proteins
pubmed
24324597
uniprot
proteins
pubmed
25197093
uniprot
proteins
pubmed
26546007
uniprot
proteins
pubmed
29064616
uniprot
proteins
pubmed
29463886
uniprot
proteins
pubmed
9630217
uniprot
proteins
sequence_length
889
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10228147, ECO:0000269|PubMed:10524219}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 216..236; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 241..261; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 289..309; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 318..338; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 370..390; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 441..461; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:O60741
uniprot
proteins