ID   ASIC4_HUMAN             Reviewed;         539 AA.
AC   Q96FT7; Q53SB7; Q6GMS1; Q6PIN9; Q9NQA4;
DT   13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 3.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Acid-sensing ion channel 4;
DE            Short=ASIC4;
DE   AltName: Full=Amiloride-sensitive cation channel 4;
DE   AltName: Full=Amiloride-sensitive cation channel 4, pituitary;
GN   Name=ASIC4; Synonyms=ACCN4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), TISSUE SPECIFICITY,
RP   MUTAGENESIS OF GLY-441, FUNCTION, AND VARIANTS LEU-508 AND ALA-511.
RC   TISSUE=Pituitary;
RX   PubMed=10852210; DOI=10.1097/00001756-200006050-00003;
RA   Gruender S., Geisler H.-S., Baessler E.-L., Ruppersberg J.P.;
RT   "A new member of acid-sensing ion channels from pituitary gland.";
RL   NeuroReport 11:1607-1611(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP   LEU-508 AND ALA-511.
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 3), AND VARIANTS LEU-508 AND
RP   ALA-511.
RX   PubMed=11571555; DOI=10.1038/sj.ejhg.5200699;
RA   Gruender S., Geisler H.-S., Rainier S., Fink J.K.;
RT   "Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic
RT   organisation, and evaluation as a candidate for paroxysmal dystonia.";
RL   Eur. J. Hum. Genet. 9:672-676(2001).
CC   -!- FUNCTION: Probable cation channel with high affinity for sodium. In
CC       vitro, has no proton-gated channel activity.
CC       {ECO:0000269|PubMed:10852210}.
CC   -!- SUBUNIT: Homotrimer or heterotrimer with other ASIC proteins.
CC       {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q96FT7; P32243-2: OTX2; NbExp=3; IntAct=EBI-9116154, EBI-9087860;
CC       Q96FT7-2; O76024: WFS1; NbExp=3; IntAct=EBI-25898949, EBI-720609;
CC       Q96FT7-4; Q92870-2: APBB2; NbExp=3; IntAct=EBI-9089489, EBI-21535880;
CC       Q96FT7-4; P54253: ATXN1; NbExp=6; IntAct=EBI-9089489, EBI-930964;
CC       Q96FT7-4; P54252: ATXN3; NbExp=3; IntAct=EBI-9089489, EBI-946046;
CC       Q96FT7-4; P46379-2: BAG6; NbExp=3; IntAct=EBI-9089489, EBI-10988864;
CC       Q96FT7-4; O14645: DNALI1; NbExp=3; IntAct=EBI-9089489, EBI-395638;
CC       Q96FT7-4; P50570-2: DNM2; NbExp=3; IntAct=EBI-9089489, EBI-10968534;
CC       Q96FT7-4; P41091: EIF2S3; NbExp=3; IntAct=EBI-9089489, EBI-1054228;
CC       Q96FT7-4; O75460-2: ERN1; NbExp=3; IntAct=EBI-9089489, EBI-25852368;
CC       Q96FT7-4; P22607: FGFR3; NbExp=3; IntAct=EBI-9089489, EBI-348399;
CC       Q96FT7-4; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-9089489, EBI-10226858;
CC       Q96FT7-4; P14136: GFAP; NbExp=3; IntAct=EBI-9089489, EBI-744302;
CC       Q96FT7-4; Q14957: GRIN2C; NbExp=3; IntAct=EBI-9089489, EBI-8285963;
CC       Q96FT7-4; P28799: GRN; NbExp=3; IntAct=EBI-9089489, EBI-747754;
CC       Q96FT7-4; P06396: GSN; NbExp=3; IntAct=EBI-9089489, EBI-351506;
CC       Q96FT7-4; P54652: HSPA2; NbExp=3; IntAct=EBI-9089489, EBI-356991;
CC       Q96FT7-4; P04792: HSPB1; NbExp=3; IntAct=EBI-9089489, EBI-352682;
CC       Q96FT7-4; O43464: HTRA2; NbExp=3; IntAct=EBI-9089489, EBI-517086;
CC       Q96FT7-4; P42858: HTT; NbExp=3; IntAct=EBI-9089489, EBI-466029;
CC       Q96FT7-4; O60333-2: KIF1B; NbExp=3; IntAct=EBI-9089489, EBI-10975473;
CC       Q96FT7-4; O14901: KLF11; NbExp=3; IntAct=EBI-9089489, EBI-948266;
CC       Q96FT7-4; P19404: NDUFV2; NbExp=3; IntAct=EBI-9089489, EBI-713665;
CC       Q96FT7-4; P29474: NOS3; NbExp=3; IntAct=EBI-9089489, EBI-1391623;
CC       Q96FT7-4; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-9089489, EBI-2811583;
CC       Q96FT7-4; O14832: PHYH; NbExp=3; IntAct=EBI-9089489, EBI-721853;
CC       Q96FT7-4; D3DTS7: PMP22; NbExp=3; IntAct=EBI-9089489, EBI-25882629;
CC       Q96FT7-4; P60891: PRPS1; NbExp=3; IntAct=EBI-9089489, EBI-749195;
CC       Q96FT7-4; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-9089489, EBI-396669;
CC       Q96FT7-4; P49591: SARS1; NbExp=3; IntAct=EBI-9089489, EBI-1053431;
CC       Q96FT7-4; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-9089489, EBI-5235340;
CC       Q96FT7-4; Q13148: TARDBP; NbExp=6; IntAct=EBI-9089489, EBI-372899;
CC       Q96FT7-4; O14656: TOR1A; NbExp=3; IntAct=EBI-9089489, EBI-524257;
CC       Q96FT7-4; O76024: WFS1; NbExp=3; IntAct=EBI-9089489, EBI-720609;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=3;
CC         IsoId=Q96FT7-4; Sequence=Displayed;
CC       Name=1;
CC         IsoId=Q96FT7-1; Sequence=VSP_061445;
CC       Name=2;
CC         IsoId=Q96FT7-2; Sequence=VSP_061443, VSP_061444;
CC   -!- TISSUE SPECIFICITY: Expressed in pituitary gland. Weakly expressed in
CC       brain, vestibular system and organ of Corti.
CC       {ECO:0000269|PubMed:10852210}.
CC   -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel
CC       (TC 1.A.6) family. ASIC4 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH10439.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAH31812.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AJ271643; CAB93980.1; -; Genomic_DNA.
DR   EMBL; AC009955; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC053503; AAY15054.1; -; Genomic_DNA.
DR   EMBL; AC139723; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC010439; AAH10439.1; ALT_INIT; mRNA.
DR   EMBL; BC031812; AAH31812.1; ALT_INIT; mRNA.
DR   EMBL; AJ408881; CAC51338.1; -; Genomic_DNA.
DR   EMBL; AJ408882; CAC51338.1; JOINED; Genomic_DNA.
DR   EMBL; AJ408883; CAC51338.1; JOINED; Genomic_DNA.
DR   EMBL; AJ408884; CAC51338.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS2442.2; -. [Q96FT7-1]
DR   CCDS; CCDS33384.2; -. [Q96FT7-4]
DR   RefSeq; NP_878267.2; NM_182847.2. [Q96FT7-1]
DR   AlphaFoldDB; Q96FT7; -.
DR   SMR; Q96FT7; -.
DR   BioGRID; 120693; 179.
DR   IntAct; Q96FT7; 75.
DR   MINT; Q96FT7; -.
DR   STRING; 9606.ENSP00000350786; -.
DR   GlyCosmos; Q96FT7; 3 sites, No reported glycans.
DR   GlyGen; Q96FT7; 3 sites.
DR   iPTMnet; Q96FT7; -.
DR   PhosphoSitePlus; Q96FT7; -.
DR   BioMuta; ASIC4; -.
DR   DMDM; 296434387; -.
DR   MassIVE; Q96FT7; -.
DR   PaxDb; 9606-ENSP00000326627; -.
DR   PeptideAtlas; Q96FT7; -.
DR   ProteomicsDB; 76552; -. [Q96FT7-1]
DR   ProteomicsDB; 76553; -. [Q96FT7-2]
DR   ProteomicsDB; 76554; -. [Q96FT7-4]
DR   Antibodypedia; 20142; 159 antibodies from 24 providers.
DR   DNASU; 55515; -.
DR   Ensembl; ENST00000347842.8; ENSP00000326627.4; ENSG00000072182.14. [Q96FT7-1]
DR   Ensembl; ENST00000358078.5; ENSP00000350786.5; ENSG00000072182.14. [Q96FT7-4]
DR   GeneID; 55515; -.
DR   KEGG; hsa:55515; -.
DR   MANE-Select; ENST00000358078.5; ENSP00000350786.5; NM_018674.6; NP_061144.4.
DR   UCSC; uc002vma.4; human. [Q96FT7-4]
DR   AGR; HGNC:21263; -.
DR   CTD; 55515; -.
DR   DisGeNET; 55515; -.
DR   GeneCards; ASIC4; -.
DR   HGNC; HGNC:21263; ASIC4.
DR   HPA; ENSG00000072182; Group enriched (brain, pituitary gland, retina).
DR   MIM; 606715; gene.
DR   neXtProt; NX_Q96FT7; -.
DR   OpenTargets; ENSG00000072182; -.
DR   PharmGKB; PA134956731; -.
DR   VEuPathDB; HostDB:ENSG00000072182; -.
DR   eggNOG; KOG4294; Eukaryota.
DR   GeneTree; ENSGT00940000159052; -.
DR   HOGENOM; CLU_020415_1_2_1; -.
DR   InParanoid; Q96FT7; -.
DR   OMA; IHEYCDY; -.
DR   OrthoDB; 3415680at2759; -.
DR   PhylomeDB; Q96FT7; -.
DR   TreeFam; TF330663; -.
DR   PathwayCommons; Q96FT7; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; Q96FT7; -.
DR   BioGRID-ORCS; 55515; 5 hits in 1150 CRISPR screens.
DR   ChiTaRS; ASIC4; human.
DR   GeneWiki; ACCN4; -.
DR   GenomeRNAi; 55515; -.
DR   Pharos; Q96FT7; Tbio.
DR   PRO; PR:Q96FT7; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q96FT7; Protein.
DR   Bgee; ENSG00000072182; Expressed in pituitary gland and 123 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR   GO; GO:0015280; F:ligand-gated sodium channel activity; IBA:GO_Central.
DR   GO; GO:0005216; F:monoatomic ion channel activity; TAS:ProtInc.
DR   GO; GO:0015081; F:sodium ion transmembrane transporter activity; TAS:ProtInc.
DR   GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR   GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR   Gene3D; 2.60.470.10; Acid-sensing ion channels like domains; 1.
DR   Gene3D; 1.10.287.770; YojJ-like; 1.
DR   InterPro; IPR001873; ENaC.
DR   InterPro; IPR020903; ENaC_CS.
DR   PANTHER; PTHR11690:SF13; ACID-SENSING ION CHANNEL 4; 1.
DR   PANTHER; PTHR11690; AMILORIDE-SENSITIVE SODIUM CHANNEL-RELATED; 1.
DR   Pfam; PF00858; ASC; 1.
DR   PRINTS; PR01078; AMINACHANNEL.
DR   PROSITE; PS01206; ASC; 1.
DR   Genevisible; Q96FT7; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Membrane; Reference proteome; Sodium; Sodium channel;
KW   Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..539
FT                   /note="Acid-sensing ion channel 4"
FT                   /id="PRO_0000181304"
FT   TOPO_DOM        1..68
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        69..89
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        90..438
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        439..459
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        460..539
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          501..531
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        243
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        376
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        118..202
FT                   /evidence="ECO:0000250"
FT   DISULFID        180..187
FT                   /evidence="ECO:0000250"
FT   DISULFID        296..375
FT                   /evidence="ECO:0000250"
FT   DISULFID        318..371
FT                   /evidence="ECO:0000250"
FT   DISULFID        322..369
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         286..290
FT                   /note="LTYLP -> VSISC (in isoform 2)"
FT                   /id="VSP_061443"
FT   VAR_SEQ         291..539
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_061444"
FT   VAR_SEQ         340..358
FT                   /note="Missing (in isoform 1)"
FT                   /id="VSP_061445"
FT   VARIANT         506
FT                   /note="P -> Q (in dbSNP:rs6436153)"
FT                   /id="VAR_052038"
FT   VARIANT         508
FT                   /note="R -> L (in dbSNP:rs11689281)"
FT                   /evidence="ECO:0000269|PubMed:10852210,
FT                   ECO:0000269|PubMed:11571555, ECO:0000269|PubMed:15489334"
FT                   /id="VAR_052039"
FT   VARIANT         511
FT                   /note="V -> A (in dbSNP:rs11695248)"
FT                   /evidence="ECO:0000269|PubMed:10852210,
FT                   ECO:0000269|PubMed:11571555, ECO:0000269|PubMed:15489334"
FT                   /id="VAR_059806"
FT   MUTAGEN         441
FT                   /note="G->A: No effect on channel function."
FT                   /evidence="ECO:0000269|PubMed:10852210"
SQ   SEQUENCE   539 AA;  59278 MW;  1F5BEF0DE39D70F6 CRC64;
     MPIEIVCKIK FAEEDAKPKE KEAGDEQSLL GAVAPGAAPR DLATFASTST LHGLGRACGP
     GPHGLRRTLW ALALLTSLAA FLYQAAGLAR GYLTRPHLVA MDPAAPAPVA GFPAVTLCNI
     NRFRHSALSD ADIFHLANLT GLPPKDRDGH RAAGLRYPEP DMVDILNRTG HQLADMLKSC
     NFSGHHCSAS NFSVVYTRYG KCYTFNADPR SSLPSRAGGM GSGLEIMLDI QQEEYLPIWR
     ETNETSFEAG IRVQIHSQEE PPYIHQLGFG VSPGFQTFVS CQEQRLTYLP QPWGNCRAES
     ELREPELQGY SAYSVSACRL RCEKEAVLQR CHCRMVHMPG NETICPPNIY IECADHTLDS
     LGGGPEGPCF CPTPCNLTRY GKEISMVRIP NRGSARYLAR KYNRNETYIR ENFLVLDVFF
     EALTSEAMEQ RAAYGLSALL GDLGGQMGLF IGASILTLLE ILDYIYEVSW DRLKRVWRRP
     KTPLRTSTGG ISTLGLQELK EQSPCPSRGR VEGGGVSSLL PNHHHPHGPP GGLFEDFAC
//