ID   ASI1A_DANRE             Reviewed;         501 AA.
AC   Q708S7;
DT   13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 117.
DE   RecName: Full=Acid-sensing ion channel 1A;
DE            Short=ASIC1-A;
DE   AltName: Full=Acid-sensing ion channel 1.2-A;
DE   AltName: Full=Amiloride-sensitive cation channel 2-B, neuronal-A;
DE   AltName: Full=ZASIC1.2;
GN   Name=asic1a; Synonyms=accn2b;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   INTERACTION WITH ASIC1, FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP   REGULATION.
RX   PubMed=14970195; DOI=10.1074/jbc.m401477200;
RA   Paukert M., Sidi S., Russell C., Siba M., Wilson S.W., Nicolson T.,
RA   Gruender S.;
RT   "A family of acid-sensing ion channels (ASICs) from the zebrafish:
RT   widespread e xpression in the central nervous system suggests a conserved
RT   role in neuronal communication.";
RL   J. Biol. Chem. 279:18783-18791(2004).
CC   -!- FUNCTION: Proton-gated sodium channel; it is activated by a drop of the
CC       extracellular pH and then becomes rapidly desensitized. Generates a
CC       biphasic current with a fast inactivating and a slow sustained phase.
CC       Has high selectivity for sodium ions and can also transport lithium
CC       ions with high efficiency. Can also transport potassium ions, but with
CC       lower efficiency. It is nearly impermeable to the larger rubidium and
CC       cesium ions. {ECO:0000269|PubMed:14970195}.
CC   -!- ACTIVITY REGULATION: Inhibited by the diuretic amiloride.
CC       {ECO:0000269|PubMed:14970195}.
CC   -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins (By
CC       similarity). Interacts with asic1/accn2c. {ECO:0000250,
CC       ECO:0000269|PubMed:14970195}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14970195};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:14970195}.
CC   -!- TISSUE SPECIFICITY: Expressed in central nervous system. Faintly
CC       expressed in the trunk, presumably in dorsal root ganglia.
CC       {ECO:0000269|PubMed:14970195}.
CC   -!- DEVELOPMENTAL STAGE: First detected 48 hours post-fertilization (hpf)
CC       in the ventral thalamus, ventral midbrain, ventral cerebellum, ventral
CC       hindbrain, dorsal thalamus, hypothalamus, telencephalon, along the
CC       tract of the anterior commissure. Weakly expressed in the dorsal
CC       midbrain and olfactory bulb. Expression increases by 96 hpf and is
CC       detected in the tectum and trunk. {ECO:0000269|PubMed:14970195}.
CC   -!- DOMAIN: Channel opening involves a conformation change that affects
CC       primarily the extracellular domain and the second transmembrane helix
CC       and its orientation in the membrane. In the open state, the second
CC       transmembrane helix is nearly perpendicular to the plane of the
CC       membrane; in the desensitized state it is strongly tilted. Besides, the
CC       second transmembrane domain is discontinuously helical in the open
CC       state. The GAS motif of the selectivity filter is in an extended
CC       conformation, giving rise to a distinct kink in the polypeptide chain.
CC       A domain swap between subunits gives rise to a full-length
CC       transmembrane helix (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC       1.A.6) family. ASIC1 subfamily. {ECO:0000305}.
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DR   EMBL; AJ609616; CAE81919.1; -; mRNA.
DR   RefSeq; NP_999955.1; NM_214790.2.
DR   RefSeq; XP_009302015.1; XM_009303740.2.
DR   AlphaFoldDB; Q708S7; -.
DR   SMR; Q708S7; -.
DR   STRING; 7955.ENSDARP00000096318; -.
DR   PaxDb; Q708S7; -.
DR   Ensembl; ENSDART00000004588; ENSDARP00000011782; ENSDARG00000008329.
DR   GeneID; 791696; -.
DR   KEGG; dre:791696; -.
DR   CTD; 791696; -.
DR   ZFIN; ZDB-GENE-040513-2; asic1a.
DR   eggNOG; KOG4294; Eukaryota.
DR   GeneTree; ENSGT00940000158414; -.
DR   HOGENOM; CLU_020415_1_2_1; -.
DR   OMA; RNCSHLF; -.
DR   OrthoDB; 686369at2759; -.
DR   PhylomeDB; Q708S7; -.
DR   TreeFam; TF330663; -.
DR   Reactome; R-DRE-2672351; Stimuli-sensing channels.
DR   PRO; PR:Q708S7; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 8.
DR   Bgee; ENSDARG00000008329; Expressed in brain and 4 other tissues.
DR   ExpressionAtlas; Q708S7; baseline.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:ZFIN.
DR   GO; GO:0044736; F:acid-sensing ion channel activity; ISS:UniProtKB.
DR   GO; GO:0005261; F:cation channel activity; IGI:ZFIN.
DR   GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:ZFIN.
DR   GO; GO:0071467; P:cellular response to pH; ISS:UniProtKB.
DR   GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   InterPro; IPR001873; ENaC.
DR   InterPro; IPR004724; ENaC_chordates.
DR   InterPro; IPR020903; ENaC_CS.
DR   PANTHER; PTHR11690; PTHR11690; 1.
DR   Pfam; PF00858; ASC; 1.
DR   PRINTS; PR01078; AMINACHANNEL.
DR   TIGRFAMs; TIGR00859; ENaC; 1.
DR   PROSITE; PS01206; ASC; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW   Membrane; Reference proteome; Sodium; Sodium channel; Sodium transport;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..501
FT                   /note="Acid-sensing ion channel 1A"
FT                   /id="PRO_0000181297"
FT   TOPO_DOM        1..50
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        51..74
FT                   /note="Helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        75..429
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        430..456
FT                   /note="Discontinuously helical"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        457..501
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   MOTIF           446..448
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000305"
FT   SITE            76
FT                   /note="Important for channel gating"
FT                   /evidence="ECO:0000250"
FT   SITE            84
FT                   /note="Important for channel desensitizing"
FT                   /evidence="ECO:0000250"
FT   SITE            291
FT                   /note="Important for channel gating"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        164
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        370
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        98..199
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        177..184
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        294..369
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        312..365
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        316..363
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        325..347
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
FT   DISULFID        327..339
FT                   /evidence="ECO:0000250|UniProtKB:Q1XA76"
SQ   SEQUENCE   501 AA;  57419 MW;  5CF87EC031A87CF3 CRC64;
     MKTSVMDLKV EPMDIDFDQP PPLQVFAHTS TLHGISHIFS YEKITAKCCL WVVFFLSSLT
     FLMYVCIDRI QFYLEYPHVT KLDEITTPVM VFPAVTICNL NSIRFSRITR NDLYHAGELL
     ALLNSRHEVR EAHLVEESVM EVLKSKTDFR SFKPRHFNMW EFYNRTGHDI KDMLLSCQFR
     GSPCRPEDFS VVFTRYGKCY TFNSGETGPP RVSVKGGMGN GLEIMLDIQQ DEYLPVWGES
     DESSFEAGIK VQIHSQDEPP FIDQLGFGVA PGFQTFVSCQ EQRLVYLPAP WGSCKSTPPS
     SDYFRAYSIS ACRTDCETRY LVENCNCRMV HMPGDAPYCT PVLYKECAHP ALDFLVETDS
     DYCSCETPCN ITRYSKELSF VKIPSKASVK YLAKKYSKSE KYITENVMVL DVFFEALNYE
     TIEQRKAYEV AGLLGDIGGQ MGLFIGASIL TILELFDYLY EVMKYRLCRC SNKKHHNNNN
     NTDHNAVFSL DDVNCHVSKF H