Q16515 (ASIC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acid-sensing ion channel 2
Short name=ASIC2

Alternative name(s):
Amiloride-sensitive brain sodium channel
Amiloride-sensitive cation channel 1, neuronal
Amiloride-sensitive cation channel neuronal 1
Brain sodium channel 1
Short name=BNC1
Short name=BNaC1
Mammalian degenerin homolog

Gene names

Name:	ASIC2
Synonyms:	ACCN, ACCN1, BNAC1, MDEG

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	512 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 Li+ and K+. Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.
Subunit structure	Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM By similarity. Interacts with PRKCABP and ASIC3. Ref.6 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein By similarity. Note: Localized at the plasma membrane of neurons, in the soma and punctated peripheral processes By similarity.
Tissue specificity	Brain and spinal cord. Isoform 1 is also detected in testis, liver, colon and ovary. Ref.2 Ref.6
Miscellaneous	Inhibited by anti-inflammatory drugs like salicylic acid By similarity. Regulated by Zn2+.
Sequence similarities	Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC2 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Traceable author statement Ref.1. Source: ProtInc peripheral nervous system development Traceable author statement Ref.1. Source: ProtInc synaptic transmission Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ligand-gated sodium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PICK1	Q9NRD5	3	EBI-79149,EBI-79165

Alternative products

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

Isoform 1 (identifier: Q16515-1)

Also known as: Asic2a;

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 2 (identifier: Q16515-2)

Also known as: Asic2b; MDEG2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-184: Missing.
     185-185: T → MSRIGGAGLP...ELCGPHNFSS

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 512	512	Acid-sensing ion channel 2		PRO_0000181290
Regions
	Topological domain	1 – 37	37	Cytoplasmic By similarity
	Transmembrane	38 – 58	21	Helical; Potential
	Topological domain	59 – 427	369	Extracellular By similarity
	Transmembrane	428 – 448	21	Helical; Potential
	Topological domain	449 – 512	64	Cytoplasmic By similarity
Amino acid modifications
	Glycosylation	365	1	N-linked (GlcNAc...) By similarity
	Glycosylation	392	1	N-linked (GlcNAc...) By similarity
	Disulfide bond	92 ↔ 193		By similarity
	Disulfide bond	171 ↔ 178		By similarity
	Disulfide bond	289 ↔ 364		By similarity
	Disulfide bond	307 ↔ 360		By similarity
	Disulfide bond	311 ↔ 358		By similarity
	Disulfide bond	320 ↔ 342		By similarity
	Disulfide bond	322 ↔ 334		By similarity
Natural variations
	Alternative sequence	1 – 184	184	Missing in isoform 2.		VSP_015590
	Alternative sequence	185	1	T → MSRIGGAGLPAAALTGPGRF RMAREEPAPAALAAAGQPGG GRGGERALQGPGVARRGRPS LSRAKLRGLRHMCAGRTAAG GSFQRRALWVLAFCTSFGLL LSWSSNRLLYWLSFPSHTRV HREWSRQLPFPAVTVCNNNP LRFPRLSKGDLYYAGHWLGL LLPNRTARPLVSELLRGDEP RRQWFRKLADFRLFLPPRHF EGISAAFMDRLGHQLEDMLL SCKYRGELCGPHNFSS in isoform 2.		VSP_015591
	Natural variant	354	1	D → G. Corresponds to variant rs16967895 [ dbSNP | Ensembl ].		VAR_052036
Experimental info
	Sequence conflict	495	1	T → A in AAC50432. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Asic2a) [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 7C95B0B32EFF2814	FASTA	512	57,709
	10 20 30 40 50 60 MDLKESPSEG SLQPSSIQIF ANTSTLHGIR HIFVYGPLTI RRVLWAVAFV GSLGLLLVES 70 80 90 100 110 120 SERVSYYFSY QHVTKVDEVV AQSLVFPAVT LCNLNGFRFS RLTTNDLYHA GELLALLDVN 130 140 150 160 170 180 LQIPDPHLAD PSVLEALRQK ANFKHYKPKQ FSMLEFLHRV GHDLKDMMLY CKFKGQECGH 190 200 210 220 230 240 QDFTTVFTKY GKCYMFNSGE DGKPLLTTVK GGTGNGLEIM LDIQQDEYLP IWGETEETTF 250 260 270 280 290 300 EAGVKVQIHS QSEPPFIQEL GFGVAPGFQT FVATQEQRLT YLPPPWGECR SSEMGLDFFP 310 320 330 340 350 360 VYSITACRID CETRYIVENC NCRMVHMPGD APFCTPEQHK ECAEPALGLL AEKDSNYCLC 370 380 390 400 410 420 RTPCNLTRYN KELSMVKIPS KTSAKYLEKK FNKSEKYISE NILVLDIFFE ALNYETIEQK 430 440 450 460 470 480 KAYEVAALLG DIGGQMGLFI GASILTILEL FDYIYELIKE KLLDLLGKEE DEGSHDENVS 490 500 510 TCDTMPNHSE TISHTVNVPL QTTLGTLEEI AC
	Isoform 2 (Asic2b) (MDEG2) [UniParc]. Checksum: 95F4576891C1C4A4	FASTA	563	62,906
	10 20 30 40 50 60 MSRIGGAGLP AAALTGPGRF RMAREEPAPA ALAAAGQPGG GRGGERALQG PGVARRGRPS 70 80 90 100 110 120 LSRAKLRGLR HMCAGRTAAG GSFQRRALWV LAFCTSFGLL LSWSSNRLLY WLSFPSHTRV 130 140 150 160 170 180 HREWSRQLPF PAVTVCNNNP LRFPRLSKGD LYYAGHWLGL LLPNRTARPL VSELLRGDEP 190 200 210 220 230 240 RRQWFRKLAD FRLFLPPRHF EGISAAFMDR LGHQLEDMLL SCKYRGELCG PHNFSSVFTK 250 260 270 280 290 300 YGKCYMFNSG EDGKPLLTTV KGGTGNGLEI MLDIQQDEYL PIWGETEETT FEAGVKVQIH 310 320 330 340 350 360 SQSEPPFIQE LGFGVAPGFQ TFVATQEQRL TYLPPPWGEC RSSEMGLDFF PVYSITACRI 370 380 390 400 410 420 DCETRYIVEN CNCRMVHMPG DAPFCTPEQH KECAEPALGL LAEKDSNYCL CRTPCNLTRY 430 440 450 460 470 480 NKELSMVKIP SKTSAKYLEK KFNKSEKYIS ENILVLDIFF EALNYETIEQ KKAYEVAALL 490 500 510 520 530 540 GDIGGQMGLF IGASILTILE LFDYIYELIK EKLLDLLGKE EDEGSHDENV STCDTMPNHS 550 560 ETISHTVNVP LQTTLGTLEE IAC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of a novel human brain Na+ channel." Price M.P., Snyder P.M., Welsh M.J. J. Biol. Chem. 271:7879-7882(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans." Waldmann R., Champigny G., Voilley N., Lauritzen I., Lazdunski M. J. Biol. Chem. 271:10433-10436(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Brain.
[3]	"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] (ISOFORM 1). Tissue: Frontal cortex.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Amygdala.
[5]	"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] (ISOFORM 1). Tissue: Brain.
[6]	"Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+." Babinski K., Catarsi S., Biagini G., Seguela P. J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASIC3, TISSUE SPECIFICITY.
[7]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U50352 mRNA. Translation: AAC50432.1. U53212 mRNA. Translation: AAC50498.1. U57352 mRNA. Translation: AAB49182.1. AL834182 mRNA. Translation: CAD38879.1. BC075042 mRNA. Translation: AAH75042.1. BC075043 mRNA. Translation: AAH75043.1.
IPI	IPI00002807. IPI00333823.
RefSeq	NP_001085.2. NM_001094.4. NP_899233.1. NM_183377.1.
UniGene	Hs.368417.
3D structure databases
ProteinModelPortal	Q16515.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16515. 1 interaction.
MINT	MINT-223746.
STRING	9606.ENSP00000225823.
PTM databases
PhosphoSite	Q16515.
Polymorphism databases
DMDM	2500840.
Proteomic databases
PaxDb	Q16515.
PRIDE	Q16515.
Protocols and materials databases
DNASU	40.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359872; ENSP00000352934; ENSG00000108684.
GeneID	40.
KEGG	hsa:40.
UCSC	uc002hhu.3. human.
Organism-specific databases
CTD	40.
GeneCards	GC17M031341.
HGNC	HGNC:99. ASIC2.
HPA	HPA052112.
MIM	601784. gene.
neXtProt	NX_Q16515.
PharmGKB	PA24433.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG262945.
HOGENOM	HOG000247010.
HOVERGEN	HBG004150.
KO	K04828.
OMA	LCNNNPL.
Gene expression databases
ArrayExpress	Q16515.
Bgee	Q16515.
CleanEx	HS_ACCN1.
Genevestigator	Q16515.
GermOnline	ENSG00000108684. Homo sapiens.
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
ChEMBL	CHEMBL1628467.
DrugBank	DB00594. Amiloride.
GenomeRNAi	40.
NextBio	157.
SOURCE	Search...

Entry information

Entry name

ASIC2_HUMAN

Accession

Primary (citable) accession number: Q16515
Secondary accession number(s): Q13553, Q6DJU1, Q8N3E2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 122 of the entry and version 1 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.