MCLN3_HUMAN
ID MCLN3_HUMAN Reviewed; 553 AA.
AC Q8TDD5; Q5T4H5; Q5T4H6; Q9NV09;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Mucolipin-3 {ECO:0000303|PubMed:19497048};
DE AltName: Full=Transient receptor potential channel mucolipin 3;
DE Short=TRPML3 {ECO:0000303|PubMed:18369318};
GN Name=MCOLN3;
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).
RA Falardeau J.L., Kennedy J.C., Acierno J.S. Jr., Slaugenhaupt S.A.;
RT "Cloning of the MCOLN3 gene.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-252; HIS-273; HIS-283
RP AND ALA-419.
RX PubMed=18369318; DOI=10.1038/emboj.2008.56;
RA Kim H.J., Li Q., Tjon-Kon-Sang S., So I., Kiselyov K., Soyombo A.A.,
RA Muallem S.;
RT "A novel mode of TRPML3 regulation by extracytosolic pH absent in the
RT varitint-waddler phenotype.";
RL EMBO J. 27:1197-1205(2008).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19497048; DOI=10.1111/j.1600-0854.2009.00935.x;
RA Martina J.A., Lelouvier B., Puertollano R.;
RT "The calcium channel mucolipin-3 is a novel regulator of trafficking along
RT the endosomal pathway.";
RL Traffic 10:1143-1156(2009).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF ASP-458
RP AND 458-ASP-ASP-459.
RX PubMed=19522758; DOI=10.1111/j.1600-0854.2009.00924.x;
RA Kim H.J., Soyombo A.A., Tjon-Kon-Sang S., So I., Muallem S.;
RT "The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy.";
RL Traffic 10:1157-1167(2009).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-283; ALA-419; GLU-449
RP AND ASP-459.
RX PubMed=20378547; DOI=10.1074/jbc.m109.078204;
RA Kim H.J., Yamaguchi S., Li Q., So I., Muallem S.;
RT "Properties of the TRPML3 channel pore and its stable expansion by the
RT Varitint-Waddler-causing mutation.";
RL J. Biol. Chem. 285:16513-16520(2010).
RN [8]
RP SUBUNIT, AND FUNCTION.
RX PubMed=19885840; DOI=10.1002/jcp.21956;
RA Curcio-Morelli C., Zhang P., Venugopal B., Charles F.A., Browning M.F.,
RA Cantiello H.F., Slaugenhaupt S.A.;
RT "Functional multimerization of mucolipin channel proteins.";
RL J. Cell. Physiol. 222:328-335(2010).
RN [9]
RP FUNCTION.
RX PubMed=21245134; DOI=10.1074/jbc.m110.169185;
RA Lelouvier B., Puertollano R.;
RT "Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion
RT in the endosomal pathway.";
RL J. Biol. Chem. 286:9826-9832(2011).
RN [10]
RP FUNCTION, AND SUBUNIT.
RX PubMed=23469151; DOI=10.1371/journal.pone.0058174;
RA Guo Z., Grimm C., Becker L., Ricci A.J., Heller S.;
RT "A novel ion channel formed by interaction of TRPML3 with TRPV5.";
RL PLoS ONE 8:E58174-E58174(2013).
RN [11]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.62 ANGSTROMS), FUNCTION, ACTIVITY
RP REGULATION, SUBCELLULAR LOCATION, TOPOLOGY, SUBUNIT, GLYCOSYLATION AT
RP ASN-138 AND ASN-172, AND MUTAGENESIS OF ASP-108; ASP-111; ASP-112; TYR-423
RP AND PHE-497.
RX PubMed=29106414; DOI=10.1038/nsmb.3502;
RA Zhou X., Li M., Su D., Jia Q., Li H., Li X., Yang J.;
RT "Cryo-EM structures of the human endolysosomal TRPML3 channel in three
RT distinct states.";
RL Nat. Struct. Mol. Biol. 24:1146-1154(2017).
CC -!- FUNCTION: Nonselective ligand-gated cation channel probably playing a
CC role in the regulation of membrane trafficking events. Acts as Ca(2+)-
CC permeable cation channel with inwardly rectifying activity
CC (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840,
CC PubMed:29106414). Mediates release of Ca(2+) from endosomes to the
CC cytoplasm, contributes to endosomal acidification and is involved in
CC the regulation of membrane trafficking and fusion in the endosomal
CC pathway (PubMed:21245134). Does not seem to act as mechanosensory
CC transduction channel in inner ear sensory hair cells. Proposed to play
CC a critical role at the cochlear stereocilia ankle-link region during
CC hair-bundle growth (By similarity). Involved in the regulation of
CC autophagy (PubMed:19522758). Through association with GABARAPL2 may be
CC involved in autophagosome formation possibly providing Ca(2+) for the
CC fusion process (By similarity). Through a possible and probably tissue-
CC specific heteromerization with MCOLN1 may be at least in part involved
CC in many lysosome-dependent cellular events (PubMed:19885840). Possible
CC heteromeric ion channel assemblies with TRPV5 show pharmacological
CC similarity with TRPML3 (PubMed:23469151).
CC {ECO:0000250|UniProtKB:Q8R4F0, ECO:0000269|PubMed:18369318,
CC ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758,
CC ECO:0000269|PubMed:19885840, ECO:0000269|PubMed:20378547,
CC ECO:0000269|PubMed:21245134, ECO:0000269|PubMed:23469151,
CC ECO:0000269|PubMed:29106414, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by lumenal H(+) and Na(+)
CC (PubMed:18369318, PubMed:29106414). The channel pore shows dynamic
CC behavior and undergoes spontaneous, Ca(2+)-dependent modulation when
CC conducting Ca(2+) (PubMed:20378547). {ECO:0000269|PubMed:18369318,
CC ECO:0000269|PubMed:20378547, ECO:0000269|PubMed:29106414}.
CC -!- SUBUNIT: Homotetramer (PubMed:29106414). Can heterooligomerize with
CC MCOLN1; heteromeric assemblies have different channel properties as
CC compared to the respective homooligomers and may be tissue-specific
CC (PubMed:19885840). May heterooligomerize with TRPV5 to form a
CC functional distinct ion channel (PubMed:23469151). Interacts with
CC GABARAPL2 (By similarity). {ECO:0000250|UniProtKB:Q8R4F0,
CC ECO:0000269|PubMed:19885840, ECO:0000269|PubMed:29106414,
CC ECO:0000305|PubMed:23469151}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19522758,
CC ECO:0000269|PubMed:29106414}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29106414}. Early endosome membrane
CC {ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:29106414}. Late endosome membrane
CC {ECO:0000269|PubMed:19497048, ECO:0000269|PubMed:19522758}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:29106414}. Lysosome membrane
CC {ECO:0000269|PubMed:19522758}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29106414}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000269|PubMed:19522758}. Note=Recycles between the
CC plasma membrane and intracellular compartments by a dynamin-dependent
CC endocytic pathway (PubMed:19522758). Under normal conditions, only a
CC very minor proportion is present at the cell membrane
CC (PubMed:19522758). In the cochlea located at the base of stereocilia
CC near the position of the ankle links (By similarity).
CC {ECO:0000250|UniProtKB:Q8R4F0, ECO:0000269|PubMed:19522758}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TDD5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TDD5-2; Sequence=VSP_010823;
CC -!- DOMAIN: The most N-terminal extracellular/lumenal domain (referred to
CC as I-II linker or polycystin-mucolipin domain) contributes to a
CC structure with a four-fold rotational symmetry in a tetrameric
CC assembly; the structure contains a central highly electronegative pore
CC with a 14 A diameter. The pore is critical for Ca(2+) and pH
CC regulation. The protruding structure formed by the I-II linkers may
CC contain all the interaction sites with lipids and proteins in the
CC endolysosomal lumen. {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19885840}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC Polycystin subfamily. MCOLN3 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF475085; AAL84622.1; -; mRNA.
DR EMBL; AK001868; BAA91951.1; -; mRNA.
DR EMBL; AL358789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS58009.1; -. [Q8TDD5-2]
DR CCDS; CCDS701.1; -. [Q8TDD5-1]
DR RefSeq; NP_001240622.1; NM_001253693.1. [Q8TDD5-2]
DR RefSeq; NP_060768.8; NM_018298.10. [Q8TDD5-1]
DR RefSeq; XP_005271060.1; XM_005271003.1. [Q8TDD5-1]
DR RefSeq; XP_006710813.1; XM_006710750.1. [Q8TDD5-1]
DR PDB; 6AYE; EM; 4.06 A; A/B/C/D=1-553.
DR PDB; 6AYF; EM; 3.62 A; A/B/C/D=1-553.
DR PDB; 6AYG; EM; 4.65 A; A/B/C/D=1-553.
DR PDBsum; 6AYE; -.
DR PDBsum; 6AYF; -.
DR PDBsum; 6AYG; -.
DR AlphaFoldDB; Q8TDD5; -.
DR SMR; Q8TDD5; -.
DR BioGRID; 120571; 67.
DR IntAct; Q8TDD5; 40.
DR STRING; 9606.ENSP00000359621; -.
DR BindingDB; Q8TDD5; -.
DR ChEMBL; CHEMBL1293243; -.
DR GuidetoPHARMACOLOGY; 503; -.
DR TCDB; 1.A.5.3.4; the polycystin cation channel (pcc) family.
DR GlyConnect; 1522; 2 N-Linked glycans (1 site).
DR GlyGen; Q8TDD5; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q8TDD5; -.
DR PhosphoSitePlus; Q8TDD5; -.
DR SwissPalm; Q8TDD5; -.
DR BioMuta; MCOLN3; -.
DR DMDM; 50401084; -.
DR EPD; Q8TDD5; -.
DR jPOST; Q8TDD5; -.
DR MassIVE; Q8TDD5; -.
DR MaxQB; Q8TDD5; -.
DR PaxDb; Q8TDD5; -.
DR PeptideAtlas; Q8TDD5; -.
DR PRIDE; Q8TDD5; -.
DR ProteomicsDB; 74270; -. [Q8TDD5-1]
DR ProteomicsDB; 74271; -. [Q8TDD5-2]
DR ABCD; Q8TDD5; 1 sequenced antibody.
DR Antibodypedia; 19787; 151 antibodies from 28 providers.
DR DNASU; 55283; -.
DR Ensembl; ENST00000341115.8; ENSP00000342698.3; ENSG00000055732.13. [Q8TDD5-2]
DR Ensembl; ENST00000370589.7; ENSP00000359621.1; ENSG00000055732.13. [Q8TDD5-1]
DR GeneID; 55283; -.
DR KEGG; hsa:55283; -.
DR MANE-Select; ENST00000370589.7; ENSP00000359621.1; NM_018298.11; NP_060768.8.
DR UCSC; uc001dkp.4; human. [Q8TDD5-1]
DR CTD; 55283; -.
DR DisGeNET; 55283; -.
DR GeneCards; MCOLN3; -.
DR HGNC; HGNC:13358; MCOLN3.
DR HPA; ENSG00000055732; Group enriched (adrenal gland, epididymis, parathyroid gland).
DR MIM; 607400; gene.
DR neXtProt; NX_Q8TDD5; -.
DR OpenTargets; ENSG00000055732; -.
DR PharmGKB; PA134947324; -.
DR VEuPathDB; HostDB:ENSG00000055732; -.
DR eggNOG; KOG3733; Eukaryota.
DR GeneTree; ENSGT00950000183036; -.
DR HOGENOM; CLU_020945_1_1_1; -.
DR InParanoid; Q8TDD5; -.
DR OMA; WQARRKF; -.
DR OrthoDB; 1379516at2759; -.
DR PhylomeDB; Q8TDD5; -.
DR TreeFam; TF317783; -.
DR PathwayCommons; Q8TDD5; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SignaLink; Q8TDD5; -.
DR BioGRID-ORCS; 55283; 15 hits in 1067 CRISPR screens.
DR ChiTaRS; MCOLN3; human.
DR GeneWiki; MCOLN3; -.
DR GenomeRNAi; 55283; -.
DR Pharos; Q8TDD5; Tchem.
DR PRO; PR:Q8TDD5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TDD5; protein.
DR Bgee; ENSG00000055732; Expressed in right adrenal gland cortex and 145 other tissues.
DR ExpressionAtlas; Q8TDD5; baseline and differential.
DR Genevisible; Q8TDD5; HS.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0072345; F:NAADP-sensitive calcium-release channel activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; TAS:Reactome.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR InterPro; IPR039031; Mucolipin.
DR InterPro; IPR013122; PKD1_2_channel.
DR PANTHER; PTHR12127; PTHR12127; 1.
DR Pfam; PF08016; PKD_channel; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasmic vesicle;
KW Disulfide bond; Endosome; Glycoprotein; Ion channel; Ion transport;
KW Lipid-binding; Lysosome; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..553
FT /note="Mucolipin-3"
FT /id="PRO_0000215367"
FT TOPO_DOM 1..62
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 84..283
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 284..304
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 305..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 363..371
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 372..392
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 393..414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 436..443
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29106414"
FT INTRAMEM 444..464
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 465..475
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TRANSMEM 476..497
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29106414"
FT TOPO_DOM 498..553
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29106414"
FT REGION 52..62
FT /note="Interaction with phosphoinositides"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT REGION 104..118
FT /note="Extracellular/lumenal pore loop"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT MOTIF 456..459
FT /note="Selectivity filter"
FT /evidence="ECO:0000269|PubMed:29106414"
FT SITE 305
FT /note="Interaction with phosphoinositides"
FT /evidence="ECO:0000250|UniProtKB:F6RG56"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29106414"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29106414"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 159..185
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT DISULFID 238..269
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT VAR_SEQ 77..132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_010823"
FT MUTAGEN 108
FT /note="D->N: Abolishes basal channel activity without
FT affecting channel activation by a synthetic agonist; when
FT associated with N-111 and N-112."
FT /evidence="ECO:0000269|PubMed:29106414"
FT MUTAGEN 111
FT /note="D->N: Abolishes basal channel activity without
FT affecting channel activation by a synthetic agonist; when
FT associated with N-108 and N-112."
FT /evidence="ECO:0000269|PubMed:29106414"
FT MUTAGEN 112
FT /note="D->N: Abolishes basal channel activity without
FT affecting channel activation by a synthetic agonist; when
FT associated with N-108 and N-111."
FT /evidence="ECO:0000269|PubMed:29106414"
FT MUTAGEN 252
FT /note="H->A: Increases inhibition by lumenal H(+).
FT Decreases inhibition by lumenal H(+); when associated with
FT A-283."
FT /evidence="ECO:0000269|PubMed:18369318"
FT MUTAGEN 273
FT /note="H->A: Increases inhibition by lumenal H(+).
FT Decreases inhibition by lumenal H(+); when associated with
FT A-283."
FT /evidence="ECO:0000269|PubMed:18369318"
FT MUTAGEN 283
FT /note="H->A: Constitutive active channel; abolishes
FT inhibition by lumenal H(+); retains the Ca(2+)-dependent
FT inactivation of the Ca(2+) current. Decreases inhibition by
FT lumenal H(+); when associated with A-252. Decreases
FT inhibition by lumenal H(+); when associated with A-273."
FT /evidence="ECO:0000269|PubMed:18369318"
FT MUTAGEN 283
FT /note="H->R: Increases inhibition by lumenal H(+)."
FT /evidence="ECO:0000269|PubMed:18369318"
FT MUTAGEN 419
FT /note="A->P: Constitutive active channel; abolishes
FT inhibition by lumenal H(+); increases the pore diameter."
FT /evidence="ECO:0000269|PubMed:18369318,
FT ECO:0000269|PubMed:20378547"
FT MUTAGEN 423
FT /note="Y->A: Nearly abolishes channel activation by a
FT synthetic agonist."
FT /evidence="ECO:0000269|PubMed:29106414"
FT MUTAGEN 449
FT /note="E->A: Constitutive active channel; greatly impairs
FT inhibition by lumenal Na(+)."
FT /evidence="ECO:0000269|PubMed:20378547"
FT MUTAGEN 449
FT /note="E->K: Abolishes channel activity."
FT /evidence="ECO:0000269|PubMed:20378547"
FT MUTAGEN 458..459
FT /note="DD->KK: Enhances endocytosis."
FT /evidence="ECO:0000269|PubMed:19522758"
FT MUTAGEN 458
FT /note="D->K: Nearly abolishes channel activity; inhibits
FT starvation-induced autophagy."
FT /evidence="ECO:0000269|PubMed:19522758"
FT MUTAGEN 459
FT /note="D->A: Decreases in Ca(2+) permeability and
FT selectivity; decreases channel pore dynamic behavior."
FT /evidence="ECO:0000269|PubMed:20378547"
FT MUTAGEN 497
FT /note="F->A: Nearly abolishes channel activation by a
FT synthetic agonist."
FT /evidence="ECO:0000269|PubMed:29106414"
FT CONFLICT 9
FT /note="S -> C (in Ref. 2; BAA91951)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 553 AA; 64248 MW; 2E63DA196379F9E3 CRC64;
MADPEVVVSS CSSHEEENRC NFNQQTSPSE ELLLEDQMRR KLKFFFMNPC EKFWARGRKP
WKLAIQILKI AMVTIQLVLF GLSNQMVVAF KEENTIAFKH LFLKGYMDRM DDTYAVYTQS
DVYDQLIFAV NQYLQLYNVS VGNHAYENKG TKQSAMAICQ HFYKRGNIYP GNDTFDIDPE
IETECFFVEP DEPFHIGTPA ENKLNLTLDF HRLLTVELQF KLKAINLQTV RHQELPDCYD
FTLTITFDNK AHSGRIKISL DNDISIRECK DWHVSGSIQK NTHYMMIFDA FVILTCLVSL
ILCIRSVIRG LQLQQEFVNF FLLHYKKEVS VSDQMEFVNG WYIMIIISDI LTIIGSILKM
EIQAKSLTSY DVCSILLGTS TMLVWLGVIR YLGFFAKYNL LILTLQAALP NVIRFCCCAA
MIYLGYCFCG WIVLGPYHDK FRSLNMVSEC LFSLINGDDM FATFAKMQQK SYLVWLFSRI
YLYSFISLFI YMILSLFIAL ITDTYETIKQ YQQDGFPETE LRTFISECKD LPNSGKYRLE
DDPPVSLFCC CKK
