Hcn2
entrez
15166
canonical
uniprot
O88703
canonical
ensembl
ENSMUSG00000020331
resolver
ensp
ENSMUSP00000097113
resolver
enst
ENSMUST00000099513
resolver
genesymbol
Hcn2
resolver
genesymbol_syn
Bcng2
resolver
genesymbol_syn
Hac1
resolver
uniprot
O70506
resolver
uniprot_entry
HCN2_MOUSE
resolver
uniprot_sec
O70506
resolver
activity_regulation
ACTIVITY REGULATION: Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP (PubMed:12968185, PubMed:17562314, PubMed:23103389, PubMed:27568927). cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening (PubMed:12968185, PubMed:27568927). In the absence of cAMP, the C-terminal region is thought to exert a tonic inhibition on the pore when HCN2 is in a non-tetrameric form (By similarity). Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (PubMed:11096117). Phosphatidylinositol-4,5- bisphosphate (PIP(2)) acts as a ligand that allosterically opens HCN2 by shifting voltage-dependent channel activation toward depolarized potentials (PubMed:17178405). Inhibited by extracellular cesium ions (By similarity). {ECO:0000250|UniProtKB:Q9UL51, ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:12968185, ECO:0000269|PubMed:17178405, ECO:0000269|PubMed:17562314, ECO:0000269|PubMed:23103389, ECO:0000269|PubMed:27568927}.
uniprot
proteins
amino_acid_sequence
MDARGGGGRPGDSPGTTPAPGPPPPPPPPAPPQPQPPPAPPPNPTTPSHPESADEPGPRARLCSRDSACTPGAAKGGANGECGRGEPQCSPEGPARGPKVSFSCRGAASGPSAAEEAGSEEAGPAGEPRGSQASFLQRQFGALLQPGVNKFSLRMFGSQKAVEREQERVKSAGAWIIHPYSDFRFYWDFTMLLFMVGNLIIIPVGITFFKDETTAPWIVFNVVSDTFFLMDLVLNFRTGIVIEDNTEIILDPEKIKKKYLRTWFVVDFVSSIPVDYIFLIVEKGIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVMRICNLISMMLLLCHWDGCLQFLVPMLQDFPSDCWVSINNMVNHSWSELYSFALFKAMSHMLCIGYGRQAPESMTDIWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADFRQKIHDYYEHRYQGKMFDEDSILGELNGPLREEIVNFNCRKLVASMPLFANADPNFVTAMLTKLKFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKEMKLSDGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDNFNEVLEEYPMMRRAFETVAIDRLDRIGKKNSILLHKVQHDLSSGVFNNQENAIIQEIVKYDREMVQQAELGQRVGLFPPPPPPQVTSAIATLQQAVAMSFCPQVARPLVGPLALGSPRLVRRAPPGPLPPAASPGPPAASPPAAPSSPRAPRTSPYGVPGSPATRVGPALPARRLSRASRPLSASQPSLPHGVPAPSPAASARPASSSTPRLGPAPTARTAAPSPDRRDSASPGAASGLDPLDSARSRLSSNL
uniprot
proteins
function
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) (PubMed:10962006, PubMed:11096117, PubMed:11459060, PubMed:11741901, PubMed:12034718, PubMed:12193608, PubMed:12968185, PubMed:17562314, PubMed:21347269, PubMed:21903816, PubMed:23103389). Can also transport ammonium in the distal nephron (By similarity). Involved in the initiation of neuropathic pain in sensory neurons (PubMed:21903816). {ECO:0000250|UniProtKB:Q9JKA9, ECO:0000269|PubMed:10962006, ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:11459060, ECO:0000269|PubMed:11741901, ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12193608, ECO:0000269|PubMed:12968185, ECO:0000269|PubMed:17562314, ECO:0000269|PubMed:21347269, ECO:0000269|PubMed:21903816, ECO:0000269|PubMed:23103389}.
uniprot
proteins
mass_dalton
94722
uniprot
proteins
mutagenesis
MUTAGEN 225; /note="D->N: Abolishes surface expression and channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 231; /note="D->N: Reduces surface expression and abolishes channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 267; /note="D->N: Reduces surface expression and abolishes channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 275; /note="D->N: Reduces surface expression and abolishes channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 291; /note="K->Q: Shifts voltage dependence of activation to more negative values."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 294; /note="R->Q: Shifts voltage dependence of activation to more negative values."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 297; /note="R->Q: Shifts voltage dependence of activation to more negative values."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 300; /note="R->Q: Shifts voltage dependence of activation to more negative values."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 303; /note="K->Q: Decreases current amplitude."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 306; /note="S->Q: Decreases current amplitude."; /evidence="ECO:0000269|PubMed:10962006, ECO:0000269|PubMed:11741901"; MUTAGEN 309; /note="R->Q: Abolishes surface expression and channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 312; /note="R->Q: Reduces surface expression and decreases current amplitude."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 315; /note="R->Q: Reduces surface expression and abolishes channel activity."; /evidence="ECO:0000269|PubMed:10962006"; MUTAGEN 318; /note="R->Q: Reduces surface expression and disrupts channel closure."; /evidence="ECO:0000269|PubMed:10962006, ECO:0000269|PubMed:11553787"; MUTAGEN 321; /note="H->E: Shifts voltage dependence of activation to more positive values and abolishes pH-sensitivity."; /evidence="ECO:0000269|PubMed:11096117"; MUTAGEN 321; /note="H->Q: Abolishes pH-sensitivity."; /evidence="ECO:0000269|PubMed:11096117"; MUTAGEN 321; /note="H->R: Abolishes pH-sensitivity."; /evidence="ECO:0000269|PubMed:11096117"; MUTAGEN 324; /note="E->Q: Disrupts channel closure."; /evidence="ECO:0000269|PubMed:11553787"; MUTAGEN 331; /note="Y->A: Disrupts channel closure."; /evidence="ECO:0000269|PubMed:11553787"; MUTAGEN 331; /note="Y->S: Disrupts channel closure."; /evidence="ECO:0000269|PubMed:11553787"; MUTAGEN 339; /note="R->Q: Disrupts channel closure."; /evidence="ECO:0000269|PubMed:11553787"; MUTAGEN 380; /note="N->Q: Abolishes cell membrane localization."; /evidence="ECO:0000269|PubMed:12928435"; MUTAGEN 594; /note="S->R: Shifts channel activation to more negative voltage, slows channel opening and speeds up channel closure. Reduces sensitivity to activation by cAMP."; /evidence="ECO:0000269|PubMed:23103389"; MUTAGEN 671; /note="D->A: Reduced the response to cAMP."; /evidence="ECO:0000269|PubMed:38287019
uniprot
proteins
post_translational_modification
PTM: S-palmitoylated. {ECO:0000250|UniProtKB:Q9UL51}.; PTM: N-glycosylated; required for cell surface trafficking of HCN2. {ECO:0000269|PubMed:12928435}.; PTM: Phosphorylation at Ser-641 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating. {ECO:0000269|PubMed:21347269}.
uniprot
proteins
protein_family
Potassium channel HCN family
uniprot
proteins
pubmed
10962006
uniprot
proteins
pubmed
11096117
uniprot
proteins
pubmed
11420311
uniprot
proteins
pubmed
11459060
uniprot
proteins
pubmed
11553787
uniprot
proteins
pubmed
11741901
uniprot
proteins
pubmed
12034718
uniprot
proteins
pubmed
12193608
uniprot
proteins
pubmed
12514127
uniprot
proteins
pubmed
12928435
uniprot
proteins
pubmed
12968185
uniprot
proteins
pubmed
17178405
uniprot
proteins
pubmed
17562314
uniprot
proteins
pubmed
18367452
uniprot
proteins
pubmed
19525958
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21347269
uniprot
proteins
pubmed
21903816
uniprot
proteins
pubmed
22550182
uniprot
proteins
pubmed
23103389
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
27568927
uniprot
proteins
pubmed
38287019
uniprot
proteins
pubmed
9630217
uniprot
proteins
pubmed
9634236
uniprot
proteins
sequence_length
863
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10962006, ECO:0000269|PubMed:11096117, ECO:0000269|PubMed:12034718, ECO:0000269|PubMed:12193608, ECO:0000269|PubMed:12928435, ECO:0000269|PubMed:17562314, ECO:0000269|PubMed:23103389}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 189..209; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 214..234; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 262..282; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 291..311; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 343..363; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:O60741"; TRANSMEM 414..434; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:O60741
uniprot
proteins