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Identification
HMDB Protein ID HMDBP09053
Secondary Accession Numbers
  • 14795
Name Amiloride-sensitive cation channel 2, neuronal
Synonyms
  1. ASIC1
  2. Acid-sensing ion channel 1
  3. BNaC2
  4. Brain sodium channel 2
Gene Name ACCN2
Protein Type Unknown
Biological Properties
General Function Involved in ligand-gated sodium channel activity
Specific Function Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
sodium channel activity
amiloride-sensitive sodium channel activity
transporter activity
ion channel activity
cation channel activity
Process
sodium ion transport
establishment of localization
transport
monovalent inorganic cation transport
ion transport
cation transport
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 12q12
SNPs ACCN2
Gene Sequence
>1587 bp
ATGGAACTGAAGGCCGAGGAGGAGGAGGTGGGTGGCGTCCAGCCGGTGAGCATCCAGGCC
TTCGCCAGCAGCTCCACACTGCACGGCCTGGCCCACATCTTCTCCTACGAGCGGCTGTCT
CTGAAGCGGGCACTGTGGGCCCTGTGCTTCCTGGGCTCGCTGGCTGTGCTGCTGTGTGTG
TGCACGGAGCGTGTGCAGTACTACTTCCACTACCACCATGTCACCAAGCTCGACGAGGTG
GCTGCCTCTCAGCTTACCTTCCCTGCTGTCACGCTGTGCAACCTCAACGAGTTCCGCTTT
AGCCAAGTCTCCAAGAATGACCTGTATCATGCTGGGGAGCTGCTGGCCCTGCTCAACAAC
AGGTATGAGATACCAGACACACAGATGGCAGATGAAAAGCAGCTGGAGATACTGCAGGAC
AAAGCCAACTTCCGCAGCTTCAAACCCAAACCCTTCAACATGCGTGAGTTCTACGACCGA
GCTGGGCACGACATTCGAGACATGCTGCTCTCCTGCCACTTCCGGGGGGAGGTCTGCAGC
GCTGAAGACTTCAAGGTGGTCTTCACACGCTATGGAAAGTGCTACACGTTCAACTCGGGC
CGAGATGGGCGGCCGCGGCTGAAGACCATGAAGGGTGGGACGGGCAATGGGCTGGAAATC
ATGCTGGACATCCAGCAGGACGAGTACCTGCCTGTGTGGGGGGAGACTGACGAGACGTCC
TTCGAAGCAGGCATCAAAGTGCAGATCCATAGTCAGGATGAACCTCCTTTCATCGACCAG
CTGGGCTTTGGCGTGGCCCCAGGCTTCCAGACCTTTGTGGCCTGCCAGGAGCAGCGGCTC
ATCTACCTGCCCCCACCCTGGGGCACCTGCAAAGCTGTTACCATGGACTCGGATTTGGAT
TTCTTCGACTCCTACAGCATCACTGCCTGCCGCATCGACTGTGAGACGCGCTACCTGGTG
GAGAACTGCAACTGCCGCATGGTGCACATGCCAGGGGATGCCCCATACTGTACTCCAGAG
CAGTACAAGGAGTGTGCAGATCCTGCTCTGGACTTCCTGGTGGAGAAGGACCAGGAGTAC
TGCGTGTGTGAAATGCCTTGCAACCTGACCCGCTATGGCAAAGAGCTGTCCATGGTCAAG
ATCCCCAGCAAAGCCTCAGCCAAGTACCTGGCCAAGAAGTTCAACAAATCTGAGCAATAC
ATAGGGGAGAACATCCTGGTGCTGGACATTTTCTTTGAAGTCCTCAACTATGAGACCATT
GAACAGAAGAAGGCCTATGAGATTGCAGGGCTCCTGGGTGACATCGGGGGCCAGATGGGG
CTGTTCATCGGGGCCAGCATCCTCACGGTGCTGGAGCTCTTTGACTACGCCTACGAGGTC
ATTAAGCACAAGCTGTGCCGACGAGGAAAATGCCAGAAGGAGGCCAAAAGGAGCAGTGCG
GACAAGGGCGTGGCCCTCAGCCTGGACGACGTCAAAAGACACAACCCGTGCGAGAGCCTT
CGGGGCCACCCTGCCGGGATGACATACGCTGCCAACATCCTACCTCACCATCCGGCCCGA
GGCACGTTCGAGGACTTTACCTGCTGA
Protein Properties
Number of Residues 528
Molecular Weight 59908.9
Theoretical pI 5.5
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 45-65
  • 428-448
Protein Sequence
>Amiloride-sensitive cation channel 2, neuronal
MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCV
CTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNN
RYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCS
AEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETS
FEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLD
FFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEY
CVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETI
EQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSA
DKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC
GenBank ID Protein 21536349
UniProtKB/Swiss-Prot ID P78348
UniProtKB/Swiss-Prot Entry Name ACCN2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001095.2
GeneCard ID ACCN2
GenAtlas ID ACCN2
HGNC ID HGNC:100
References
General References
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  3. Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ: Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). Biochem J. 2002 Feb 1;361(Pt 3):443-50. [PubMed:11802773 ]
  4. Garcia-Anoveros J, Derfler B, Neville-Golden J, Hyman BT, Corey DP: BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1459-64. [PubMed:9037075 ]
  5. Askwith CC, Cheng C, Ikuma M, Benson C, Price MP, Welsh MJ: Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels. Neuron. 2000 Apr;26(1):133-41. [PubMed:10798398 ]
  6. Berdiev BK, Xia J, Jovov B, Markert JM, Mapstone TB, Gillespie GY, Fuller CM, Bubien JK, Benos DJ: Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function. J Biol Chem. 2002 Nov 29;277(48):45734-40. Epub 2002 Sep 19. [PubMed:12244121 ]
  7. Leonard AS, Yermolaieva O, Hruska-Hageman A, Askwith CC, Price MP, Wemmie JA, Welsh MJ: cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2029-34. Epub 2003 Feb 10. [PubMed:12578970 ]
  8. Poirot O, Vukicevic M, Boesch A, Kellenberger S: Selective regulation of acid-sensing ion channel 1 by serine proteases. J Biol Chem. 2004 Sep 10;279(37):38448-57. Epub 2004 Jul 6. [PubMed:15247234 ]