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Details on Person UniProt:Q9UL51 HCN2

Class:IdReferenceGeneProduct:56398
_chainChangeLogchain:1-889 added on Fri February 6 2015
_displayNameUniProt:Q9UL51 HCN2
_timestamp2024-11-03 20:14:40
chainchain:1-889
checksum4B263E0C06C2A47D
commentFUNCTION 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).CATALYTIC ACTIVITY Na(+)(in) = Na(+)(out)CATALYTIC ACTIVITY K(+)(in) = K(+)(out)CATALYTIC ACTIVITY NH4(+)(in) = NH4(+)(out)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).SUBUNIT Homotetramer (PubMed:22006928). The channel is composed of a homo- or heterotetrameric complex of pore-forming subunits (PubMed:22006928). Heterotetramer with HCN1 (By similarity). Forms an obligate 4:4 complex with accessory subunit PEX5L (By similarity). Interacts with KCNE2 (By similarity).INTERACTION Highly expressed throughout the brain. Detected at low levels in heart.DOMAIN The segment S4 is the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. The ion-conducting pore region is between segment S5 and S6.DOMAIN The cytosolic C-terminal domain contains the cyclic nucleotide-binding domain (CNBD), which mediates modulation by cyclic nucleotides.PTM Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.PTM S-palmitoylated.PTM N-glycosylated; required for cell surface trafficking of HCN2.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the potassium channel HCN family.
descriptionrecommendedName: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 alternativeName: Brain cyclic nucleotide-gated channel 2 shortName: BCNG-2
geneNameHCN2
BCNG2
identifierQ9UL51
isSequenceChangedFALSE
keyword3D-structure
Ammonia transport
cAMP
cAMP-binding
Cell membrane
Disease variant
Epilepsy
Glycoprotein
Ion channel
Ion transport
Ligand-gated ion channel
Lipoprotein
Membrane
Methylation
Nucleotide-binding
Palmitate
Phosphoprotein
Potassium
Potassium channel
Potassium transport
Proteomics identification
Reference proteome
Sodium
Sodium channel
Sodium transport
Transmembrane
Transmembrane helix
Transport
Voltage-gated channel
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
nameHCN2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8999547] ENSEMBL:ENSG00000099822 HCN2 [Homo sapiens]
secondaryIdentifierHCN2_HUMAN
O60742
O60743
O75267
Q9UBS2
sequenceLength889
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:977502] HCN2 [plasma membrane] [Homo sapiens]
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