Reviewed, UniProtKB/Swiss-Prot P78348 (ACCN2_HUMAN)

Names and origin

Protein names

Recommended name:
    Amiloride-sensitive cation channel 2, neuronal
Alternative name(s):
    Acid-sensing ion channel 1
      Short name=ASIC1
    Brain sodium channel 2
    BNaC2

Gene names

Name:	ACCN2
Synonyms:	ASIC1, BNAC2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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 By similarity.
Subunit structure	Homotetramer or heterotetramer with other ASIC proteins Probable. Interacts with STOM and ACCN1 By similarity. Interacts with PRKCABP.
Subcellular location	Cell membrane; Multi-pass membrane proteinBy similarity. Note= Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 By similarity.
Tissue specificity	Expressed in most or all neurons.
Post-translational modification	Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel.
Miscellaneous	Potentiated by Ca(2+), Mg(2+), Ba(2+) and multivalent cations. Inhibited by anti-inflammatory drugs like salicylic acid By similarity. Potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases.
Sequence similarities	Belongs to the amiloride-sensitive sodium channel family.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Ligand	Calcium Sodium
Molecular function	Ionic channel Sodium channel
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	response to pH Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc sodium ion transport Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	amiloride-sensitive sodium channel activity Non-traceable author statement. Source: UniProtKB protein binding Ref.4 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PICK1	Q9NRD5	1	EBI-79189,EBI-79165

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Notes: The splice variant from ASIC1a described in mouse and rat, which gives rise to an isoform with different N-termini (Asic1b), does not seem to exist in human.

Isoform 2 (identifier: P78348-2)

Also known as: Asic1a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P78348-1)

The sequence of this isoform differs from the canonical sequence as follows:
     433-433: G → GELLMTPVPFSCHGHGVAPYHPKAGCSLLSHEGPPPQRPFPKPCCLG

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 528	528	Amiloride-sensitive cation channel 2, neuronal
Regions
	Topological domain	1 – 44	44	Cytoplasmic Potential
	Transmembrane	45 – 65	21	Potential
	Topological domain	66 – 427	362	Extracellular Potential
	Transmembrane	428 – 448	21	Potential
	Topological domain	449 – 528	80	Cytoplasmic Potential
Amino acid modifications
	Modified residue	479	1	Phosphoserine; by PKA
	Glycosylation	368	1	N-linked (GlcNAc...) Potential
	Glycosylation	395	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	433	1	G → GELLMTPVPFSCHGHGVAPY HPKAGCSLLSHEGPPPQRPF PKPCCLG in isoform 1.
Experimental info
	Mutagenesis	478	1	S → A: No effect on phosphorylation
	Mutagenesis	479	1	S → A: Loss of phosphorylation

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Asic1a) [UniParc]. Last modified September 13, 2005. Version 2. Checksum: 22AA007002F04B50	FASTA	528	59,967
	10 20 30 40 50 60 MELKAEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV 70 80 90 100 110 120 CTERVQYYFH YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN 130 140 150 160 170 180 RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEVCS 190 200 210 220 230 240 AEDFKVVFTR YGKCYTFNSG RDGRPRLKTM KDGTGNGLEI MLDIQQDEYL PVWGETDETS 250 260 270 280 290 300 FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVACQEQRL IYLPPPWGTC KAVTMDSDLD 310 320 330 340 350 360 FFDSYSITAC RIDCETRYLV ENCNCRMVHM PGDAPYCTPE QYKECADPAL DFLVEKDQEY 370 380 390 400 410 420 CVCEMPCNLT RYGKELSMVK IPSKASAKYL AKKFNKSEQY IGENILVLDI FFEVLNYETI 430 440 450 460 470 480 EQKKAYEIAG LLGDIGGQMG LFIGASILTV LELFDYAYEV IKHKLCRRGK CQKEAKRSSA 490 500 510 520 DKGVALSLDD VKRHNPCESL RGHPAGMTYA ANILPHHPAR GTFEDFTC
	Isoform 1 [UniParc]. Checksum: 8A981A8B1488CD3A		574	64,841
	10 20 30 40 50 60 MELKAEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV 70 80 90 100 110 120 CTERVQYYFH YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN 130 140 150 160 170 180 RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEVCS 190 200 210 220 230 240 AEDFKVVFTR YGKCYTFNSG RDGRPRLKTM KDGTGNGLEI MLDIQQDEYL PVWGETDETS 250 260 270 280 290 300 FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVACQEQRL IYLPPPWGTC KAVTMDSDLD 310 320 330 340 350 360 FFDSYSITAC RIDCETRYLV ENCNCRMVHM PGDAPYCTPE QYKECADPAL DFLVEKDQEY 370 380 390 400 410 420 CVCEMPCNLT RYGKELSMVK IPSKASAKYL AKKFNKSEQY IGENILVLDI FFEVLNYETI 430 440 450 460 470 480 EQKKAYEIAG LLGELLMTPV PFSCHGHGVA PYHPKAGCSL LSHEGPPPQR PFPKPCCLGD 490 500 510 520 530 540 IGGQMGLFIG ASILTVLELF DYAYEVIKHK LCRRGKCQKE AKRSSADKGV ALSLDDVKRH 550 560 570 NPCESLRGHP AGMTYAANIL PHHPARGTFE DFTC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels." Garcia-Anoveros J., Derfler B.H., Neville-Golden J., Hyman B.T., Corey D.P. Proc. Natl. Acad. Sci. U.S.A. 94:1459-1464(1997) [PubMed: 9037075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-528 (ISOFORM 1). Tissue: Ovary.
[3]	"Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels." Askwith C.C., Cheng C., Ikuma M., Benson C., Price M.P., Welsh M.J. Neuron 26:133-141(2000) [PubMed: 10798398] [Abstract] Cited for: REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
[4]	"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)." Hruska-Hageman A.M., Wemmie J.A., Price M.P., Welsh M.J. Biochem. J. 361:443-450(2002) [PubMed: 11802773] [Abstract] Cited for: INTERACTION WITH PRKCABP.
[5]	"Protein kinase C isoform antagonism controls BNaC2 (ASIC1) function." Berdiev B.K., Xia J., Jovov B., Markert J.M., Mapstone T.B., Gillespie G.Y., Fuller C.M., Bubien J.K., Benos D.J. J. Biol. Chem. 277:45734-45740(2002) [PubMed: 12244121] [Abstract] Cited for: PHOSPHORYLATION BY PKC.
[6]	"cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1." Leonard A.S., Yermolaieva O., Hruska-Hageman A., Askwith C.C., Price M.P., Wemmie J.A., Welsh M.J. Proc. Natl. Acad. Sci. U.S.A. 100:2029-2034(2003) [PubMed: 12578970] [Abstract] Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-478 AND SER-479, PHOSPHORYLATION AT SER-479, INTERACTION WITH PRKCABP, SUBCELLULAR LOCATION.
[7]	"Selective regulation of acid-sensing ion channel 1 by serine proteases." Poirot O., Vukicevic M., Boesch A., Kellenberger S. J. Biol. Chem. 279:38448-38457(2004) [PubMed: 15247234] [Abstract] Cited for: REGULATION BY SERINE PROTEASES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U78180 mRNA. Translation: AAB48980.1. U78181 mRNA. Translation: AAB48981.1. BC013891 mRNA. Translation: AAH13891.2.
RefSeq	NP_001086.2. NP_064423.2.
UniGene	Hs.274361 Hs.647113
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P78348.
Genome annotation databases
Ensembl	ENSG00000110881. Homo sapiens. [Contig view]
GeneID	41.
KEGG	hsa:41.
Organism-specific databases
H-InvDB	HIX0036785.
HGNC	HGNC:100. ACCN2.
MIM	602866. gene.
PharmGKB	PA24434.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	P78348.
Gene expression databases
CleanEx	HS_ACCN2.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. [Graphical view]
PANTHER	PTHR11690. Na+channel_ASC. 1 hit.
Pfam	PF00858. ASC. 1 hit. [Graphical view]
PRINTS	PR01078. AMINACHANNEL.
TIGRFAMs	TIGR00859. ENaC. 1 hit.
PROSITE	PS01206. ASC. 1 hit. [Graphical view]
ProDom	P78348. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
DrugBank	DB00594. Amiloride.
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

ACCN2_HUMAN

Accession

Primary (citable) accession number: P78348
Secondary accession number(s): P78349, Q96CV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	September 13, 2005
Last modified:	July 22, 2008
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)