LOCUS ZACN_HUMAN 412 aa linear PRI 27-NOV-2024
DEFINITION RecName: Full=Ligand-gated cation channel ZACN; AltName:
Full=Ligand-gated ion channel zinc-activated 1; AltName:
Full=Ligand-gated ion-channel receptor L2; AltName:
Full=Zinc-activated channel; Flags: Precursor.
ACCESSION Q401N2
VERSION Q401N2.2
DBSOURCE UniProtKB: locus ZACN_HUMAN, accession Q401N2;
class: standard.
extra accessions:Q2TB29,Q6ZWK3,Q86YW4
created: Feb 5, 2008.
sequence updated: Feb 5, 2008.
annotation updated: Nov 27, 2024.
xrefs: AF512521.1, AAO20969.1, AB223030.1, BAE19924.1, AK122638.1,
AC018665.9, CH471099.1, EAW89365.1, EAW89366.1, BC110596.1,
BC110597.1, AAI10598.1, NP_851321.2
xrefs (non-sequence databases): CCDS:CCDS11740.2,
AlphaFoldDB:Q401N2, SMR:Q401N2, BioGRID:131658, IntAct:Q401N2,
STRING:9606.ENSP00000334854, DrugCentral:Q401N2,
GuidetoPHARMACOLOGY:587, TCDB:1.A.9.2.4, GlyCosmos:Q401N2,
GlyGen:Q401N2, iPTMnet:Q401N2, BioMuta:ZACN, DMDM:166991030,
MassIVE:Q401N2, PaxDb:9606-ENSP00000334854, PeptideAtlas:Q401N2,
ProteomicsDB:61925, ProteomicsDB:61926, TopDownProteomics:Q401N2-3,
Antibodypedia:46125, DNASU:353174, Ensembl:ENST00000334586.10,
Ensembl:ENSP00000334854.5, Ensembl:ENSG00000186919.13,
Ensembl:ENST00000421794.1, Ensembl:ENSP00000391936.1,
Ensembl:ENST00000425015.5, Ensembl:ENSP00000397489.1,
GeneID:353174, KEGG:hsa:353174, MANE-Select:ENST00000334586.10,
UCSC:uc002jqn.3, AGR:HGNC:29504, CTD:353174, DisGeNET:353174,
GeneCards:ZACN, HGNC:29504, HPA:ENSG00000186919, MIM 610935,
neXtProt:NX_Q401N2, OpenTargets:ENSG00000186919,
PharmGKB:PA162409377, VEuPathDB:HostDB:ENSG00000186919,
eggNOG:KOG3645, GeneTree:ENSGT00920000149199,
HOGENOM:CLU_672608_0_0_1, InParanoid:Q401N2, OMA:TWPLVHG,
OrthoDB:4630813at2759, PhylomeDB:Q401N2, TreeFam:TF315605,
PathwayCommons:Q401N2, SignaLink:Q401N2, BioGRID-ORCS:353174,
ChiTaRS:ZACN, GeneWiki:Zinc-activated_ion_channel,
GenomeRNAi:353174, Pharos:Q401N2, PRO:PR:Q401N2,
Proteomes:UP000005640, RNAct:Q401N2, Bgee:ENSG00000186919,
GO:0005886, GO:1902495, GO:0005230, GO:0099094, GO:0015276,
GO:0160128, GO:0004888, GO:0008270, GO:0034220, GO:0010043,
CDD:cd18994, FunFam:1.20.58.390:FF:000068,
FunFam:2.70.170.10:FF:000037, Gene3D:2.70.170.10,
Gene3D:1.20.58.390, InterPro:IPR006202, InterPro:IPR036734,
InterPro:IPR006201, InterPro:IPR036719, InterPro:IPR038050,
InterPro:IPR018000, PANTHER:PTHR18945, PANTHER:PTHR18945:SF912,
Pfam:PF02931, SUPFAM:SSF90112, SUPFAM:SSF63712, PROSITE:PS00236
KEYWORDS Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
Receptor; Reference proteome; Signal; Transmembrane; Transmembrane
helix; Transport; Zinc.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 412)
AUTHORS Davies,P.A., Wang,W., Hales,T.G. and Kirkness,E.F.
TITLE A novel class of ligand-gated ion channel is activated by Zn2+
JOURNAL J Biol Chem 278 (2), 712-717 (2003)
PUBMED 12381728
REMARK NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE
SPECIFICITY, AND VARIANT THR-152.
REFERENCE 2 (residues 1 to 412)
AUTHORS Houtani,T., Munemoto,Y., Kase,M., Sakuma,S., Tsutsumi,T. and
Sugimoto,T.
TITLE Cloning and expression of ligand-gated ion-channel receptor L2 in
central nervous system
JOURNAL Biochem Biophys Res Commun 335 (2), 277-285 (2005)
PUBMED 16083862
REMARK NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION,
TISSUE SPECIFICITY, AND GLYCOSYLATION.;
TISSUE=Brain
REFERENCE 3 (residues 1 to 412)
AUTHORS Ota,T., Suzuki,Y., Nishikawa,T., Otsuki,T., Sugiyama,T., Irie,R.,
Wakamatsu,A., Hayashi,K., Sato,H., Nagai,K., Kimura,K., Makita,H.,
Sekine,M., Obayashi,M., Nishi,T., Shibahara,T., Tanaka,T.,
Ishii,S., Yamamoto,J., Saito,K., Kawai,Y., Isono,Y., Nakamura,Y.,
Nagahari,K., Murakami,K., Yasuda,T., Iwayanagi,T., Wagatsuma,M.,
Shiratori,A., Sudo,H., Hosoiri,T., Kaku,Y., Kodaira,H., Kondo,H.,
Sugawara,M., Takahashi,M., Kanda,K., Yokoi,T., Furuya,T.,
Kikkawa,E., Omura,Y., Abe,K., Kamihara,K., Katsuta,N., Sato,K.,
Tanikawa,M., Yamazaki,M., Ninomiya,K., Ishibashi,T., Yamashita,H.,
Murakawa,K., Fujimori,K., Tanai,H., Kimata,M., Watanabe,M.,
Hiraoka,S., Chiba,Y., Ishida,S., Ono,Y., Takiguchi,S., Watanabe,S.,
Yosida,M., Hotuta,T., Kusano,J., Kanehori,K., Takahashi-Fujii,A.,
Hara,H., Tanase,T.O., Nomura,Y., Togiya,S., Komai,F., Hara,R.,
Takeuchi,K., Arita,M., Imose,N., Musashino,K., Yuuki,H., Oshima,A.,
Sasaki,N., Aotsuka,S., Yoshikawa,Y., Matsunawa,H., Ichihara,T.,
Shiohata,N., Sano,S., Moriya,S., Momiyama,H., Satoh,N., Takami,S.,
Terashima,Y., Suzuki,O., Nakagawa,S., Senoh,A., Mizoguchi,H.,
Goto,Y., Shimizu,F., Wakebe,H., Hishigaki,H., Watanabe,T.,
Sugiyama,A., Takemoto,M., Kawakami,B., Yamazaki,M., Watanabe,K.,
Kumagai,A., Itakura,S., Fukuzumi,Y., Fujimori,Y., Komiyama,M.,
Tashiro,H., Tanigami,A., Fujiwara,T., Ono,T., Yamada,K., Fujii,Y.,
Ozaki,K., Hirao,M., Ohmori,Y., Kawabata,A., Hikiji,T., Kobatake,N.,
Inagaki,H., Ikema,Y., Okamoto,S., Okitani,R., Kawakami,T.,
Noguchi,S., Itoh,T., Shigeta,K., Senba,T., Matsumura,K.,
Nakajima,Y., Mizuno,T., Morinaga,M., Sasaki,M., Togashi,T.,
Oyama,M., Hata,H., Watanabe,M., Komatsu,T., Mizushima-Sugano,J.,
Satoh,T., Shirai,Y., Takahashi,Y., Nakagawa,K., Okumura,K.,
Nagase,T., Nomura,N., Kikuchi,H., Masuho,Y., Yamashita,R.,
Nakai,K., Yada,T., Nakamura,Y., Ohara,O., Isogai,T. and Sugano,S.
TITLE Complete sequencing and characterization of 21,243 full-length
human cDNAs
JOURNAL Nat Genet 36 (1), 40-45 (2004)
PUBMED 14702039
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
THR-152.;
TISSUE=Thymus
REFERENCE 4 (residues 1 to 412)
AUTHORS Zody,M.C., Garber,M., Adams,D.J., Sharpe,T., Harrow,J.,
Lupski,J.R., Nicholson,C., Searle,S.M., Wilming,L., Young,S.K.,
Abouelleil,A., Allen,N.R., Bi,W., Bloom,T., Borowsky,M.L.,
Bugalter,B.E., Butler,J., Chang,J.L., Chen,C.K., Cook,A., Corum,B.,
Cuomo,C.A., de Jong,P.J., DeCaprio,D., Dewar,K., FitzGerald,M.,
Gilbert,J., Gibson,R., Gnerre,S., Goldstein,S., Grafham,D.V.,
Grocock,R., Hafez,N., Hagopian,D.S., Hart,E., Norman,C.H.,
Humphray,S., Jaffe,D.B., Jones,M., Kamal,M., Khodiyar,V.K.,
LaButti,K., Laird,G., Lehoczky,J., Liu,X., Lokyitsang,T.,
Loveland,J., Lui,A., Macdonald,P., Major,J.E., Matthews,L.,
Mauceli,E., McCarroll,S.A., Mihalev,A.H., Mudge,J., Nguyen,C.,
Nicol,R., O'Leary,S.B., Osoegawa,K., Schwartz,D.C., Shaw-Smith,C.,
Stankiewicz,P., Steward,C., Swarbreck,D., Venkataraman,V.,
Whittaker,C.A., Yang,X., Zimmer,A.R., Bradley,A., Hubbard,T.,
Birren,B.W., Rogers,J., Lander,E.S. and Nusbaum,C.
TITLE DNA sequence of human chromosome 17 and analysis of rearrangement
in the human lineage
JOURNAL Nature 440 (7087), 1045-1049 (2006)
PUBMED 16625196
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
REFERENCE 5 (residues 1 to 412)
AUTHORS 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. and Venter,J.C.
TITLE Direct Submission
JOURNAL Submitted (??-JUL-2005) to the EMBL/GenBank/DDBJ databases
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
REFERENCE 6 (residues 1 to 412)
AUTHORS Gerhard,D.S., Wagner,L., Feingold,E.A., Shenmen,C.M., Grouse,L.H.,
Schuler,G., Klein,S.L., Old,S., Rasooly,R., Good,P., Guyer,M.,
Peck,A.M., Derge,J.G., Lipman,D., Collins,F.S., Jang,W., Sherry,S.,
Feolo,M., Misquitta,L., Lee,E., Rotmistrovsky,K., Greenhut,S.F.,
Schaefer,C.F., Buetow,K., Bonner,T.I., Haussler,D., Kent,J.,
Kiekhaus,M., Furey,T., Brent,M., Prange,C., Schreiber,K.,
Shapiro,N., Bhat,N.K., Hopkins,R.F., Hsie,F., Driscoll,T.,
Soares,M.B., Casavant,T.L., Scheetz,T.E., Brown-stein,M.J.,
Usdin,T.B., Toshiyuki,S., Carninci,P., Piao,Y., Dudekula,D.B.,
Ko,M.S., Kawakami,K., Suzuki,Y., Sugano,S., Gruber,C.E.,
Smith,M.R., Simmons,B., Moore,T., Waterman,R., Johnson,S.L.,
Ruan,Y., Wei,C.L., Mathavan,S., Gunaratne,P.H., Wu,J., Garcia,A.M.,
Hulyk,S.W., Fuh,E., Yuan,Y., Sneed,A., Kowis,C., Hodgson,A.,
Muzny,D.M., McPherson,J., Gibbs,R.A., Fahey,J., Helton,E.,
Ketteman,M., Madan,A., Rodrigues,S., Sanchez,A., Whiting,M.,
Madari,A., Young,A.C., Wetherby,K.D., Granite,S.J., Kwong,P.N.,
Brinkley,C.P., Pearson,R.L., Bouffard,G.G., Blakesly,R.W.,
Green,E.D., Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J.,
Myers,R.M., Butterfield,Y.S., Griffith,M., Griffith,O.L.,
Krzywinski,M.I., Liao,N., Morin,R., Palmquist,D., Petrescu,A.S.,
Skalska,U., Smailus,D.E., Stott,J.M., Schnerch,A., Schein,J.E.,
Jones,S.J., Holt,R.A., Baross,A., Marra,M.A., Clifton,S.,
Makowski,K.A., Bosak,S. and Malek,J.
CONSRTM MGC Project Team
TITLE The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC)
JOURNAL Genome Res 14 (10B), 2121-2127 (2004)
PUBMED 15489334
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Erratum:[Genome Res. 2006 Jun;16(6):804. Morrin, Ryan [corrected to
Morin, Ryan]]
REFERENCE 7 (residues 1 to 412)
AUTHORS Trattnig,S.M., Gasiorek,A., Deeb,T.Z., Ortiz,E.J., Moss,S.J.,
Jensen,A.A. and Davies,P.A.
TITLE Copper and protons directly activate the zinc-activated channel
JOURNAL Biochem Pharmacol 103, 109-117 (2016)
PUBMED 26872532
REMARK FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND
SUBCELLULAR LOCATION.
COMMENT On or before Feb 5, 2008 this sequence version replaced
gi:121941806, gi:74749715, gi:74723572, gi:121945913.
[FUNCTION] Ligand-gated cation channel that allows the movement of
sodium and potassium monoatomic cations across cell membranes when
activated by zinc (Zn2+), copper (Cu2+), and changes in pH
(PubMed:26872532). Could also transport cesium (PubMed:26872532).
{ECO:0000269|PubMed:26872532}.
[CATALYTIC ACTIVITY] Reaction=Na(+)(in) = Na(+)(out);
Xref=Rhea:RHEA:34963, ChEBI:CHEBI:29101;
Evidence={ECO:0000269|PubMed:26872532}.
[CATALYTIC ACTIVITY] Reaction=K(+)(in) = K(+)(out);
Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103;
Evidence={ECO:0000269|PubMed:26872532}.
ACTIVITY REGULATION: Inhibited by the divalent cations magnesium
and calcium. {ECO:0000269|PubMed:26872532}.
[SUBCELLULAR LOCATION] Cell membrane {ECO:0000269|PubMed:16083862,
ECO:0000269|PubMed:26872532}; Multi-pass membrane protein
{ECO:0000255}.
[ALTERNATIVE PRODUCTS] Event=Alternative splicing; Named
isoforms=3; Name=1; IsoId=Q401N2-1; Sequence=Displayed; Name=2;
IsoId=Q401N2-2; Sequence=VSP_030911, VSP_030912; Name=3;
IsoId=Q401N2-3; Sequence=VSP_030909, VSP_030910.
[TISSUE SPECIFICITY] Detected in pancreas, brain, liver, placenta,
trachea, kidney, spinal cord, stomach and fetal brain. In the adult
brain region expression is detected in the hippocampus, striatum,
amygdala and thalamus. {ECO:0000269|PubMed:12381728,
ECO:0000269|PubMed:16083862}.
[PTM] Glycosylated. {ECO:0000269|PubMed:16083862}.
[MISCELLANEOUS] [Isoform 3]: May be produced at very low levels due
to a premature stop codon in the mRNA, leading to nonsense-mediated
mRNA decay. {ECO:0000305}.
[SIMILARITY] Belongs to the ligand-gated ion channel (TC 1.A.9)
family. {ECO:0000305}.
[CAUTION] It is uncertain whether Met-1 or Met-2 is the initiator.
{ECO:0000305}.
[SEQUENCE CAUTION] Sequence=AAI10598.1; Type=Erroneous initiation;
Note=Truncated N-terminus.; Evidence={ECO:0000305};
Sequence=AAO20969.1; Type=Erroneous initiation; Note=Truncated
N-terminus.; Evidence={ECO:0000305}; Sequence=EAW89365.1;
Type=Erroneous initiation; Note=Truncated N-terminus.;
Evidence={ECO:0000305}.
FEATURES Location/Qualifiers
source 1..412
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene 1..412
/gene="ZACN"
/gene_synonym="L2"
/gene_synonym="LGICZ"
/gene_synonym="LGICZ1"
/gene_synonym="ZAC"
Protein 1..412
/product="Ligand-gated cation channel ZACN"
/note="Ligand-gated ion channel zinc-activated 1;
Ligand-gated ion-channel receptor L2; Zinc-activated
channel"
/UniProtKB_evidence="Evidence at protein level"
Region 1..25
/region_name="Signal"
/note="/evidence=ECO:0000255."
Region 26..412
/region_name="Mature chain"
/note="Ligand-gated cation channel ZACN.
/id=PRO_0000317165."
Region 26..233
/region_name="Topological domain"
/note="Extracellular. /evidence=ECO:0000255."
Site 41
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255."
Site 55
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255."
Region 60..229
/region_name="LGIC_ECD_ZAC"
/note="extracellular domain of zinc-activated ligand-gated
ion channel; cd18994"
/db_xref="CDD:349795"
Region 75..126
/region_name="Splicing variant"
/note="DILRYTMSSMLLLRLSWLDTRLAWNTSAHPRHAITLPWESLWTPRLTILEA
L -> SSVLPRATALHSHGDCSGSAPCSKARGSGCHGLTPGNHLKVQPPCINPSGDI
(in isoform 3). /evidence=ECO:0000303|PubMed:15489334.
/id=VSP_030909."
Site 99
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255."
Region 127..412
/region_name="Splicing variant"
/note="Missing (in isoform 3).
/evidence=ECO:0000303|PubMed:15489334. /id=VSP_030910."
Region 152
/region_name="Variant"
/note="A -> T (in dbSNP:rs2257020).
/evidence=ECO:0000269|PubMed:12381728,
ECO:0000269|PubMed:14702039. /id=VAR_038483."
Region 157..171
/region_name="Cys-loop"
/note="Cys-loop [structural motif]"
/db_xref="CDD:349795"
Bond bond(157,171)
/bond_type="disulfide"
/note="/evidence=ECO:0000250."
Site 170
/site_type="glycosylation"
/note="N-linked (GlcNAc...) asparagine.
/evidence=ECO:0000255."
Region 182..266
/region_name="Splicing variant"
/note="AMELEFQAHVVNEIVSVKREYVVYDLKTQVPPQQLVPCFQVTLRLKNTALK
SIIALLVPAEALLLADVCGGLLPLRAIERIGYKV ->
GADRAGAAGLRRGGGRWGRGTPRSVVQGQGAGQGEGAKADRRRTPRSVFRAVYPRLRR
AAPALPLRPPLEWQPISVLSGSLRAPL (in isoform 2).
/evidence=ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334. /id=VSP_030911."
Region 231..407
/region_name="LGIC_TM"
/note="transmembrane domain of Cys-loop
neurotransmitter-gated ion channels; cl38911"
/db_xref="CDD:476813"
Region 234..254
/region_name="Transmembrane region"
/note="Helical; Name=1. /evidence=ECO:0000255."
Site order(235..236,243..244,246..247,250,253..255,263..264,
266..268,270..271,274..275,281..282,284,305,309,312,316,
371)
/site_type="other"
/note="pentamer interface [polypeptide binding]"
/db_xref="CDD:349850"
Region 235..255
/region_name="TM1 helix"
/note="TM1 helix [structural motif]"
/db_xref="CDD:349850"
Region 255..265
/region_name="Topological domain"
/note="Cytoplasmic. /evidence=ECO:0000255."
Region 263..284
/region_name="TM2 helix"
/note="TM2 helix [structural motif]"
/db_xref="CDD:349850"
Region 266..286
/region_name="Transmembrane region"
/note="Helical; Name=2. /evidence=ECO:0000255."
Region 267..412
/region_name="Splicing variant"
/note="Missing (in isoform 2).
/evidence=ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334. /id=VSP_030912."
Region 287..298
/region_name="Topological domain"
/note="Extracellular. /evidence=ECO:0000255."
Region 295..317
/region_name="TM3 helix"
/note="TM3 helix [structural motif]"
/db_xref="CDD:349850"
Region 299..319
/region_name="Transmembrane region"
/note="Helical; Name=3. /evidence=ECO:0000255."
Region 320..368
/region_name="Topological domain"
/note="Cytoplasmic. /evidence=ECO:0000255."
Region 328..360
/region_name="Region of interest in the sequence"
/note="Disordered. /evidence=ECO:0000256|SAM:MobiDB-lite."
Region 365..386
/region_name="TM4 helix"
/note="TM4 helix [structural motif]"
/db_xref="CDD:349850"
Region 369..389
/region_name="Transmembrane region"
/note="Helical; Name=4. /evidence=ECO:0000255."
Region 390..412
/region_name="Topological domain"
/note="Extracellular. /evidence=ECO:0000255."
ORIGIN
1 mmalwsllhl tflgfsitll lvhgqgfqgt aaiwpslfnv nlskkvqesi qipnngsapl
61 lvdvrvfvsn vfnvdilryt mssmlllrls wldtrlawnt sahprhaitl pweslwtprl
121 tilealwvdw rdqspqarvd qdghvklnla latetncnfe llhfprdhsn cslsfyalsn
181 tamelefqah vvneivsvkr eyvvydlktq vppqqlvpcf qvtlrlknta lksiiallvp
241 aeallladvc ggllplraie rigykvtlll sylvlhsslv qalpsssscn plliyyftil
301 llllflstie tvllagllar gnlgaksgps paprgeqreh gnpgphpaee psrgvkgsqr
361 swpetadrif flvyvvgvlc tqfvfagiwm waacksdaap geaaphgrrp rl
//