ASIC4_HUMAN
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 03-AUG-2022, entry version 153.
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 (TC
CC 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};
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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; CCDS2442.1; -. [Q96FT7-1]
DR CCDS; CCDS33384.1; -. [Q96FT7-4]
DR RefSeq; NP_061144.3; NM_018674.5.
DR RefSeq; NP_878267.2; NM_182847.2.
DR AlphaFoldDB; Q96FT7; -.
DR BioGRID; 120693; 178.
DR IntAct; Q96FT7; 74.
DR STRING; 9606.ENSP00000326627; -.
DR GlyGen; Q96FT7; 3 sites.
DR iPTMnet; Q96FT7; -.
DR PhosphoSitePlus; Q96FT7; -.
DR BioMuta; ASIC4; -.
DR DMDM; 296434387; -.
DR MassIVE; Q96FT7; -.
DR PaxDb; Q96FT7; -.
DR PeptideAtlas; Q96FT7; -.
DR PRIDE; Q96FT7; -.
DR ProteomicsDB; 76552; -. [Q96FT7-1]
DR ProteomicsDB; 76553; -. [Q96FT7-2]
DR ProteomicsDB; 76554; -. [Q96FT7-4]
DR Antibodypedia; 20142; 141 antibodies from 23 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 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 OrthoDB; 686369at2759; -.
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 1070 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 122 other tissues.
DR Genevisible; Q96FT7; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005216; F:ion channel activity; TAS:ProtInc.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IBA:GO_Central.
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 InterPro; IPR001873; ENaC.
DR InterPro; IPR020903; ENaC_CS.
DR PANTHER; PTHR11690; PTHR11690; 1.
DR Pfam; PF00858; ASC; 1.
DR PRINTS; PR01078; AMINACHANNEL.
DR PROSITE; PS01206; ASC; 1.
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
