P78348 (ASIC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acid-sensing ion channel 1
Short name=ASIC1

Alternative name(s):
Amiloride-sensitive cation channel 2, neuronal
Brain sodium channel 2
Short name=BNaC2

Gene names

Name:	ASIC1
Synonyms:	ACCN2, BNAC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	528 AA.
Sequence status	Complete.
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 Ca2+, Li+ and K+. Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca2+ entry into neurons upon acidosis. This Ca2+ 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 Ca2+ 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	Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM and ASIC2 By similarity. Interacts with PRKCABP. Ref.8 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Note: Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 By similarity. Ref.10
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 Ca2+, Mg2+, Ba2+ 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 (TC 1.A.6) family. ASIC1 subfamily. [View classification]

Ontologies

Keywords
Biological process	Calcium transport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Calcium Sodium
Molecular function	Ion channel Sodium channel
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	associative learning Inferred from electronic annotation. Source: Compara calcium ion transmembrane transport Inferred from electronic annotation. Source: Compara memory Inferred from electronic annotation. Source: Compara negative regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara regulation of membrane potential Inferred from electronic annotation. Source: Compara response to acid Inferred from electronic annotation. Source: Compara response to pH Traceable author statement PubMed 9062189. Source: ProtInc signal transduction Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc synapse Inferred from electronic annotation. Source: Compara
Molecular_function	ligand-gated sodium channel activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PICK1	Q9NRD5	3	EBI-79189,EBI-79165

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: 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

Isoform 3 (identifier: P78348-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: MELKAEEEEV...GEVCSAEDFK → MPIQIFCSMS...GGPCGPHNFS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 528	528	Acid-sensing ion channel 1		PRO_0000181294
Regions
	Topological domain	1 – 45	45	Cytoplasmic By similarity
	Transmembrane	46 – 69	24	Helical; By similarity
	Topological domain	70 – 427	358	Extracellular By similarity
	Transmembrane	428 – 454	27	Helical; By similarity
	Topological domain	455 – 528	74	Cytoplasmic By similarity
Amino acid modifications
	Modified residue	479	1	Phosphoserine; by PKA Ref.10
	Glycosylation	368	1	N-linked (GlcNAc...) Potential
	Glycosylation	395	1	N-linked (GlcNAc...) Potential
	Disulfide bond	93 ↔ 194		By similarity
	Disulfide bond	172 ↔ 179		By similarity
	Disulfide bond	290 ↔ 367		By similarity
	Disulfide bond	310 ↔ 363		By similarity
	Disulfide bond	314 ↔ 361		By similarity
	Disulfide bond	323 ↔ 345		By similarity
	Disulfide bond	325 ↔ 337		By similarity
Natural variations
	Alternative sequence	1 – 185	185	MELKA…AEDFK → MPIQIFCSMSFSSGEEAPGP LGDIWGPHHHQQQQDISESE EEEEEKEKEAVRKEASEGHS PMDLVAFANSCTLHGTNHIF VEGGPGPRQVLWAVAFVLAL GAFLCQVGDRVAYYLSYPHV TLLNEVATTELAFPAVTLCN TNAVRLSQLSYPDLLYLAPM LGLDESDDPGVPLAPPGPEA FSGEPFNLHRFYNRSCHRLE DMLLYCSYQGGPCGPHNFS in isoform 3.		VSP_045298
	Alternative sequence	433	1	G → GELLMTPVPFSCHGHGVAPY HPKAGCSLLSHEGPPPQRPF PKPCCLG in isoform 1.		VSP_015596
Experimental info
	Mutagenesis	478	1	S → A: No effect on phosphorylation. Ref.10
	Mutagenesis	479	1	S → A: Loss of phosphorylation. Ref.10
	Sequence conflict	212	1	G → D in AAB48980. Ref.1
	Sequence conflict	212	1	G → D in AAB48981. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (Asic1a) [UniParc]. Last modified May 18, 2010. Version 3. Checksum: 9E998F711C208450	FASTA	528	59,909
	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 KGGTGNGLEI 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: 04B7E51DF15F90BF	FASTA	574	64,783
	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 KGGTGNGLEI 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
	Isoform 3 [UniParc]. Checksum: 0EC8183120C02EC4	FASTA	562	62,700
	10 20 30 40 50 60 MPIQIFCSMS FSSGEEAPGP LGDIWGPHHH QQQQDISESE EEEEEKEKEA VRKEASEGHS 70 80 90 100 110 120 PMDLVAFANS CTLHGTNHIF VEGGPGPRQV LWAVAFVLAL GAFLCQVGDR VAYYLSYPHV 130 140 150 160 170 180 TLLNEVATTE LAFPAVTLCN TNAVRLSQLS YPDLLYLAPM LGLDESDDPG VPLAPPGPEA 190 200 210 220 230 240 FSGEPFNLHR FYNRSCHRLE DMLLYCSYQG GPCGPHNFSV VFTRYGKCYT FNSGRDGRPR 250 260 270 280 290 300 LKTMKGGTGN GLEIMLDIQQ DEYLPVWGET DETSFEAGIK VQIHSQDEPP FIDQLGFGVA 310 320 330 340 350 360 PGFQTFVACQ EQRLIYLPPP WGTCKAVTMD SDLDFFDSYS ITACRIDCET RYLVENCNCR 370 380 390 400 410 420 MVHMPGDAPY CTPEQYKECA DPALDFLVEK DQEYCVCEMP CNLTRYGKEL SMVKIPSKAS 430 440 450 460 470 480 AKYLAKKFNK SEQYIGENIL VLDIFFEVLN YETIEQKKAY EIAGLLGDIG GQMGLFIGAS 490 500 510 520 530 540 ILTVLELFDY AYEVIKHKLC RRGKCQKEAK RSSADKGVAL SLDDVKRHNP CESLRGHPAG 550 560 MTYAANILPH HPARGTFEDF TC

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[2]	"Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant." Hoagland E.N., Sherwood T.W., Lee K.G., Walker C.J., Askwith C.C. J. Biol. Chem. 285:41852-41862(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Spinal ganglion.
[3]	"Acid sensing ion channels in human taste tissue." Huque T., Cao J., Lischka F.W., Spielman A.I., Feldman R.S., Cowart B.J., Wise P.M., Pribitkin E.A., Mackler S.A., Brand J.G. Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 231-528 (ISOFORM 1). Tissue: Ovary.
[7]	"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] [Europe PMC] [Abstract] Cited for: REGULATION BY FMRFAMIDE-RELATED PEPTIDES.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCABP.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY PKC.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-478 AND SER-479, PHOSPHORYLATION AT SER-479, INTERACTION WITH PRKCABP, SUBCELLULAR LOCATION.
[11]	"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] [Europe PMC] [Abstract] Cited for: REGULATION BY SERINE PROTEASES.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U78180 mRNA. Translation: AAB48980.1. U78181 mRNA. Translation: AAB48981.1. HM991481 mRNA. Translation: ADP44689.1. EU078959 mRNA. Translation: ABU48925.1. AC025154 Genomic DNA. No translation available. CH471111 Genomic DNA. Translation: EAW58118.1. BC013891 mRNA. Translation: AAH13891.2. BC133707 mRNA. Translation: AAI33708.1.
IPI	IPI00293398. IPI00293399.
RefSeq	NP_001086.2. NM_001095.3. NP_001243759.1. NM_001256830.1. NP_064423.2. NM_020039.3.
UniGene	Hs.274361.
3D structure databases
ProteinModelPortal	P78348.
SMR	P78348. Positions 40-462.
ModBase	Search...
Protein-protein interaction databases
IntAct	P78348. 1 interaction.
STRING	9606.ENSP00000228468.
Polymorphism databases
DMDM	296439456.
Proteomic databases
PaxDb	P78348.
PRIDE	P78348.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000228468; ENSP00000228468; ENSG00000110881. ENST00000447966; ENSP00000400228; ENSG00000110881. ENST00000552438; ENSP00000450247; ENSG00000110881.
GeneID	41.
KEGG	hsa:41.
UCSC	uc001rvv.3. human. uc001rvw.3. human.
Organism-specific databases
CTD	41.
GeneCards	GC12P050452.
HGNC	HGNC:100. ASIC1.
MIM	602866. gene.
neXtProt	NX_P78348.
PharmGKB	PA24434.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG262945.
HOGENOM	HOG000247010.
HOVERGEN	HBG004150.
KO	K04829.
OMA	PVPFPCH.
Gene expression databases
ArrayExpress	P78348.
Bgee	P78348.
CleanEx	HS_ACCN2.
Genevestigator	P78348.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. IPR020903. Na+channel_ASC_CS. [Graphical view]
PANTHER	PTHR11690. PTHR11690. 1 hit.
Pfam	PF00858. ASC. 1 hit. [Graphical view]
PRINTS	PR01078. AMINACHANNEL.
TIGRFAMs	TIGR00859. ENaC. 1 hit.
PROSITE	PS01206. ASC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P78348.
ChEMBL	CHEMBL1628477.
DrugBank	DB00594. Amiloride.
GenomeRNAi	41.
NextBio	167.
SOURCE	Search...

Entry information

Entry name

ASIC1_HUMAN

Accession

Primary (citable) accession number: P78348
Secondary accession number(s): A3KN86 , E5KBL7, P78349, Q96CV2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	May 18, 2010
Last modified:	April 3, 2013
This is version 117 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.