ZACN_HUMAN
ID ZACN_HUMAN Reviewed; 412 AA.
AC Q401N2; Q2TB29; Q6ZWK3; Q86YW4;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Zinc-activated ligand-gated ion channel;
DE AltName: Full=Ligand-gated ion channel zinc-activated 1;
DE AltName: Full=Ligand-gated ion-channel receptor L2;
DE Flags: Precursor;
GN Name=ZACN; Synonyms=L2, LGICZ, LGICZ1, ZAC;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, AND
RP VARIANT THR-152.
RX PubMed=12381728; DOI=10.1074/jbc.m208814200;
RA Davies P.A., Wang W., Hales T.G., Kirkness E.F.;
RT "A novel class of ligand-gated ion channel is activated by Zn2+.";
RL J. Biol. Chem. 278:712-717(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND GLYCOSYLATION.
RC TISSUE=Brain;
RX PubMed=16083862; DOI=10.1016/j.bbrc.2005.07.079;
RA Houtani T., Munemoto Y., Kase M., Sakuma S., Tsutsumi T., Sugimoto T.;
RT "Cloning and expression of ligand-gated ion-channel receptor L2 in central
RT nervous system.";
RL Biochem. Biophys. Res. Commun. 335:277-285(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-152.
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
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).
CC -!- FUNCTION: Zinc-activated ligand-gated ion channel.
CC {ECO:0000269|PubMed:12381728}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16083862};
CC Multi-pass membrane protein {ECO:0000269|PubMed:16083862}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q401N2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q401N2-2; Sequence=VSP_030911, VSP_030912;
CC Name=3;
CC IsoId=Q401N2-3; Sequence=VSP_030909, VSP_030910;
CC -!- TISSUE SPECIFICITY: Detected in pancreas, brain, liver, placenta,
CC trachea, kidney, spinal cord, stomach and fetal brain. In the adult
CC brain region expression is detected in the hippocampus, striatum,
CC amygdala and thalamus. {ECO:0000269|PubMed:12381728,
CC ECO:0000269|PubMed:16083862}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:16083862}.
CC -!- MISCELLANEOUS: The mouse and rat orthologous proteins do not exist.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI10598.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAO20969.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW89365.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF512521; AAO20969.1; ALT_INIT; mRNA.
DR EMBL; AB223030; BAE19924.1; -; mRNA.
DR EMBL; AK122638; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC018665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89365.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471099; EAW89366.1; -; Genomic_DNA.
DR EMBL; BC110596; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC110597; AAI10598.1; ALT_INIT; mRNA.
DR CCDS; CCDS11740.2; -. [Q401N2-1]
DR RefSeq; NP_851321.2; NM_180990.3. [Q401N2-1]
DR AlphaFoldDB; Q401N2; -.
DR SMR; Q401N2; -.
DR BioGRID; 131658; 99.
DR IntAct; Q401N2; 42.
DR STRING; 9606.ENSP00000334854; -.
DR DrugCentral; Q401N2; -.
DR GuidetoPHARMACOLOGY; 587; -.
DR TCDB; 1.A.9.2.4; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; Q401N2; 4 sites.
DR iPTMnet; Q401N2; -.
DR BioMuta; ZACN; -.
DR DMDM; 166991030; -.
DR MassIVE; Q401N2; -.
DR PaxDb; Q401N2; -.
DR PeptideAtlas; Q401N2; -.
DR PRIDE; Q401N2; -.
DR ProteomicsDB; 61925; -. [Q401N2-1]
DR ProteomicsDB; 61926; -. [Q401N2-2]
DR TopDownProteomics; Q401N2-3; -. [Q401N2-3]
DR Antibodypedia; 46125; 78 antibodies from 14 providers.
DR DNASU; 353174; -.
DR Ensembl; ENST00000334586.10; ENSP00000334854.5; ENSG00000186919.13. [Q401N2-1]
DR Ensembl; ENST00000421794.1; ENSP00000391936.1; ENSG00000186919.13. [Q401N2-3]
DR Ensembl; ENST00000425015.5; ENSP00000397489.1; ENSG00000186919.13. [Q401N2-2]
DR GeneID; 353174; -.
DR KEGG; hsa:353174; -.
DR MANE-Select; ENST00000334586.10; ENSP00000334854.5; NM_180990.4; NP_851321.2.
DR UCSC; uc002jqn.3; human. [Q401N2-1]
DR CTD; 353174; -.
DR DisGeNET; 353174; -.
DR GeneCards; ZACN; -.
DR HGNC; HGNC:29504; ZACN.
DR HPA; ENSG00000186919; Not detected.
DR MIM; 610935; gene.
DR neXtProt; NX_Q401N2; -.
DR OpenTargets; ENSG00000186919; -.
DR PharmGKB; PA162409377; -.
DR VEuPathDB; HostDB:ENSG00000186919; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00920000149199; -.
DR HOGENOM; CLU_672608_0_0_1; -.
DR InParanoid; Q401N2; -.
DR OMA; WATCKSD; -.
DR OrthoDB; 1001614at2759; -.
DR PhylomeDB; Q401N2; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; Q401N2; -.
DR SignaLink; Q401N2; -.
DR BioGRID-ORCS; 353174; 31 hits in 1060 CRISPR screens.
DR ChiTaRS; ZACN; human.
DR GeneWiki; Zinc-activated_ion_channel; -.
DR GenomeRNAi; 353174; -.
DR Pharos; Q401N2; Tchem.
DR PRO; PR:Q401N2; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q401N2; protein.
DR Bgee; ENSG00000186919; Expressed in right hemisphere of cerebellum and 92 other tissues.
DR Genevisible; Q401N2; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IDA:BHF-UCL.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0010043; P:response to zinc ion; IDA:HGNC-UCL.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport;
KW Zinc.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..412
FT /note="Zinc-activated ligand-gated ion channel"
FT /id="PRO_0000317165"
FT TOPO_DOM 26..233
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..286
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 287..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..368
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 369..389
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 390..412
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 328..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT /id="PRO_5000052473"
FT DISULFID 157..171
FT /evidence="ECO:0000250"
FT VAR_SEQ 75..126
FT /note="DILRYTMSSMLLLRLSWLDTRLAWNTSAHPRHAITLPWESLWTPRLTILEAL
FT -> SSVLPRATALHSHGDCSGSAPCSKARGSGCHGLTPGNHLKVQPPCINPSGDI (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030909"
FT VAR_SEQ 127..412
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_030910"
FT VAR_SEQ 182..266
FT /note="AMELEFQAHVVNEIVSVKREYVVYDLKTQVPPQQLVPCFQVTLRLKNTALKS
FT IIALLVPAEALLLADVCGGLLPLRAIERIGYKV -> GADRAGAAGLRRGGGRWGRGTP
FT RSVVQGQGAGQGEGAKADRRRTPRSVFRAVYPRLRRAAPALPLRPPLEWQPISVLSGSL
FT RAPL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030911"
FT VAR_SEQ 267..412
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030912"
FT VARIANT 152
FT /note="A -> T (in dbSNP:rs2257020)"
FT /evidence="ECO:0000269|PubMed:12381728,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_038483"
SQ SEQUENCE 412 AA; 45816 MW; B894A28F5163723F CRC64;
MMALWSLLHL TFLGFSITLL LVHGQGFQGT AAIWPSLFNV NLSKKVQESI QIPNNGSAPL
LVDVRVFVSN VFNVDILRYT MSSMLLLRLS WLDTRLAWNT SAHPRHAITL PWESLWTPRL
TILEALWVDW RDQSPQARVD QDGHVKLNLA LATETNCNFE LLHFPRDHSN CSLSFYALSN
TAMELEFQAH VVNEIVSVKR EYVVYDLKTQ VPPQQLVPCF QVTLRLKNTA LKSIIALLVP
AEALLLADVC GGLLPLRAIE RIGYKVTLLL SYLVLHSSLV QALPSSSSCN PLLIYYFTIL
LLLLFLSTIE TVLLAGLLAR GNLGAKSGPS PAPRGEQREH GNPGPHPAEE PSRGVKGSQR
SWPETADRIF FLVYVVGVLC TQFVFAGIWM WAACKSDAAP GEAAPHGRRP RL
