MCLN1_MOUSE
ID MCLN1_MOUSE Reviewed; 580 AA.
AC Q99J21;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Mucolipin-1 {ECO:0000305};
DE AltName: Full=Mucolipidin;
DE AltName: Full=Transient receptor potential-mucolipin 1;
DE Short=TRPML1 {ECO:0000303|PubMed:27623384};
GN Name=Mcoln1 {ECO:0000312|MGI:MGI:1890498};
GN Synonyms=Trpml1 {ECO:0000303|PubMed:27623384};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RX PubMed=11897010; DOI=10.1186/1471-2164-3-3;
RA Falardeau J.L., Kennedy J.C., Acierno J.S. Jr., Sun M., Stahl S.,
RA Goldin E., Slaugenhaupt S.A.;
RT "Cloning and characterization of the mouse Mcoln1 gene reveals an
RT alternatively spliced transcript not seen in humans.";
RL BMC Genomics 3:3-3(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Diencephalon, Extraembryonic tissue, Placenta, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP FUNCTION.
RX PubMed=17050035; DOI=10.1016/j.ejcb.2006.08.004;
RA Song Y., Dayalu R., Matthews S.A., Scharenberg A.M.;
RT "TRPML cation channels regulate the specialized lysosomal compartment of
RT vertebrate B-lymphocytes.";
RL Eur. J. Cell Biol. 85:1253-1264(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23993788; DOI=10.1016/j.devcel.2013.08.003;
RA Samie M., Wang X., Zhang X., Goschka A., Li X., Cheng X., Gregg E.,
RA Azar M., Zhuo Y., Garrity A.G., Gao Q., Slaugenhaupt S., Pickel J.,
RA Zolov S.N., Weisman L.S., Lenk G.M., Titus S., Bryant-Genevier M.,
RA Southall N., Juan M., Ferrer M., Xu H.;
RT "A TRP channel in the lysosome regulates large particle phagocytosis via
RT focal exocytosis.";
RL Dev. Cell 26:511-524(2013).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=25733853; DOI=10.1073/pnas.1419669112;
RA Wang W., Gao Q., Yang M., Zhang X., Yu L., Lawas M., Li X.,
RA Bryant-Genevier M., Southall N.T., Marugan J., Ferrer M., Xu H.;
RT "Up-regulation of lysosomal TRPML1 channels is essential for lysosomal
RT adaptation to nutrient starvation.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1373-E1381(2015).
RN [11]
RP FUNCTION.
RX PubMed=27623384; DOI=10.1016/j.devcel.2016.08.001;
RA Krishna S., Palm W., Lee Y., Yang W., Bandyopadhyay U., Xu H., Florey O.,
RA Thompson C.B., Overholtzer M.;
RT "PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following
RT Engulfment.";
RL Dev. Cell 38:536-547(2016).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.59 ANGSTROMS), FUNCTION, ACTIVITY
RP REGULATION, TOPOLOGY, SUBUNIT, GLYCOSYLATION AT ASN-230, AND MUTAGENESIS OF
RP VAL-432.
RX PubMed=29019981; DOI=10.1038/nature24035;
RA Chen Q., She J., Zeng W., Guo J., Xu H., Bai X.C., Jiang Y.;
RT "Structure of mammalian endolysosomal TRPML1 channel in nanodiscs.";
RL Nature 550:415-418(2017).
RN [13]
RP STRUCTURE BY ELECTRON MICROSCOPY (5.4 ANGSTROMS), SUBUNIT, TOPOLOGY, AND
RP GLYCOSYLATION AT ASN-230.
RX PubMed=28936784; DOI=10.1007/s13238-017-0476-5;
RA Zhang S., Li N., Zeng W., Gao N., Yang M.;
RT "Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel
RT elucidate the combined regulation mechanism.";
RL Protein Cell 8:834-847(2017).
CC -!- FUNCTION: Nonselective cation channel probably playing a role in the
CC regulation of membrane trafficking events and of metal homeostasis
CC (PubMed:29019981). Proposed to play a major role in Ca(2+) release from
CC late endosome and lysosome vesicles to the cytoplasm, which is
CC important for many lysosome-dependent cellular events, including the
CC fusion and trafficking of these organelles, exocytosis and autophagy.
CC Required for efficient uptake of large particles in macrophages in
CC which Ca(2+) release from the lysosomes triggers lysosomal exocytosis.
CC May also play a role in phagosome-lysosome fusion (PubMed:23993788,
CC PubMed:27623384). Involved in lactosylceramide trafficking indicative
CC for a role in the regulation of late endocytic membrane fusion/fission
CC events. By mediating lysosomal Ca(2+) release is involved in regulation
CC of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to
CC environmental cues such as nutrient levels (PubMed:25733853). Seems to
CC act as lysosomal active oxygen species (ROS) sensor involved in ROS-
CC induced TFEB activation and autophagy (By similarity). Functions as a
CC Fe(2+) permeable channel in late endosomes and lysosomes. Proposed to
CC play a role in zinc homeostasis probably implicating its association
CC with TMEM163 (By similarity). In adaptive immunity, TRPML2 and TRPML1
CC may play redundant roles in the function of the specialized lysosomes
CC of B cells (PubMed:17050035). {ECO:0000250|UniProtKB:Q9GZU1,
CC ECO:0000269|PubMed:17050035, ECO:0000269|PubMed:23993788,
CC ECO:0000269|PubMed:25733853, ECO:0000269|PubMed:27623384,
CC ECO:0000269|PubMed:29019981}.
CC -!- FUNCTION: May contribute to cellular lipase activity within the late
CC endosomal pathway or at the cell surface which may be involved in
CC processes of membrane reshaping and vesiculation, especially the growth
CC of tubular structures. However, it is not known, whether it conveys the
CC enzymatic activity directly, or merely facilitates the activity of an
CC associated phospholipase. {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- ACTIVITY REGULATION: Channel activity is controlled by multiple
CC regulatory mechanisms in different subcellular compartments (By
CC similarity). Channel function is transiently modulated by changes in
CC Ca(2+), and inhibited by a reduction of pH; pH changes modify the
CC aggregation state of unitary channels; a negative cooperativity between
CC extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:29019981).
CC Regulated by phosphoinositides in a compartment-specific manner: in
CC lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-
CC bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2
CC (Phosphatidylinositol 4,5-bisphosphate) (PubMed:29019981).
CC {ECO:0000250|UniProtKB:Q9GZU1, ECO:0000269|PubMed:29019981}.
CC -!- SUBUNIT: Homotetramer (PubMed:29019981). Homooligomer. Can
CC heterooligomerize with MCOLN2 or MCOLN3; heteromeric assemblies have
CC different channel properties as compared to the respective
CC homooligomers and may be tissue-specific. Interacts with PDCD6.
CC Interacts with TMEM163. Interacts with LAPTM4B (By similarity).
CC {ECO:0000250|UniProtKB:Q9GZU1, ECO:0000269|PubMed:29019981}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29019981}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29019981}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29019981}. Cell projection, phagocytic cup
CC {ECO:0000269|PubMed:23993788}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000269|PubMed:23993788}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29019981}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9GZU1}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29019981}. Note=Delivery from the trans-Golgi to
CC lysosomes seems to occur mainly in a direct intracellular manner
CC without intermediate delivery to the plasma membrane (By similarity).
CC Under normal conditions, restricted to intracellular compartments so
CC that only a very minor proportion is present at the cell membrane
CC (PubMed:29019981). {ECO:0000250|UniProtKB:Q9GZU1,
CC ECO:0000269|PubMed:29019981}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99J21-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99J21-2; Sequence=VSP_010821;
CC -!- TISSUE SPECIFICITY: Widely expressed, with the highest expression in
CC brain, liver and kidney. {ECO:0000269|PubMed:11897010}.
CC -!- INDUCTION: Up-regulated by nutrient starvation.
CC {ECO:0000269|PubMed:25733853}.
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: Palmitoylated; involved in association with membranes.
CC {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- PTM: Phosphorylation by PKA inhibits channel activity.
CC Dephosphorylation increases activity. {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- PTM: Proteolytically cleaved probably involving multiple lysosomal
CC proteases including cathepsin B; inhibits lysosomal channel activity.
CC {ECO:0000250|UniProtKB:Q9GZU1}.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family.
CC Polycystin subfamily. MCOLN1 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF302009; AAL58667.1; -; mRNA.
DR EMBL; AK028385; BAC25922.1; -; mRNA.
DR EMBL; AK034471; BAC28719.1; -; mRNA.
DR EMBL; AK049606; BAC33838.1; -; mRNA.
DR EMBL; BC005651; AAH05651.1; -; mRNA.
DR CCDS; CCDS22063.1; -. [Q99J21-1]
DR RefSeq; NP_444407.1; NM_053177.1. [Q99J21-1]
DR PDB; 5WPQ; EM; 3.64 A; A/B/C/D=1-580.
DR PDB; 5WPT; EM; 3.75 A; A/B/C/D=1-580.
DR PDB; 5WPV; EM; 3.59 A; A/B/C/D=1-580.
DR PDB; 5YDZ; EM; 5.80 A; A/B/C/D=1-580.
DR PDB; 5YE1; EM; 5.80 A; A/B/C/D=1-580.
DR PDB; 5YE2; EM; 5.80 A; A/B/C/D=1-580.
DR PDB; 5YE5; EM; 5.80 A; A/B/C/D=1-580.
DR PDB; 7SQ6; EM; 2.32 A; A/B/C/D=1-580.
DR PDB; 7SQ7; EM; 2.41 A; A/B/C/D=1-580.
DR PDB; 7SQ8; EM; 2.60 A; A/B/C/D=1-580.
DR PDB; 7SQ9; EM; 2.11 A; A/B/C/D=1-580.
DR PDBsum; 5WPQ; -.
DR PDBsum; 5WPT; -.
DR PDBsum; 5WPV; -.
DR PDBsum; 5YDZ; -.
DR PDBsum; 5YE1; -.
DR PDBsum; 5YE2; -.
DR PDBsum; 5YE5; -.
DR PDBsum; 7SQ6; -.
DR PDBsum; 7SQ7; -.
DR PDBsum; 7SQ8; -.
DR PDBsum; 7SQ9; -.
DR AlphaFoldDB; Q99J21; -.
DR SMR; Q99J21; -.
DR STRING; 10090.ENSMUSP00000004683; -.
DR GlyConnect; 2514; 2 N-Linked glycans (1 site).
DR GlyGen; Q99J21; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q99J21; -.
DR PhosphoSitePlus; Q99J21; -.
DR SwissPalm; Q99J21; -.
DR EPD; Q99J21; -.
DR jPOST; Q99J21; -.
DR MaxQB; Q99J21; -.
DR PaxDb; Q99J21; -.
DR PeptideAtlas; Q99J21; -.
DR PRIDE; Q99J21; -.
DR ProteomicsDB; 252749; -. [Q99J21-1]
DR ProteomicsDB; 252750; -. [Q99J21-2]
DR Antibodypedia; 12053; 167 antibodies from 22 providers.
DR DNASU; 94178; -.
DR Ensembl; ENSMUST00000004683; ENSMUSP00000004683; ENSMUSG00000004567. [Q99J21-1]
DR GeneID; 94178; -.
DR KEGG; mmu:94178; -.
DR UCSC; uc009krq.1; mouse. [Q99J21-1]
DR CTD; 57192; -.
DR MGI; MGI:1890498; Mcoln1.
DR VEuPathDB; HostDB:ENSMUSG00000004567; -.
DR eggNOG; KOG3733; Eukaryota.
DR GeneTree; ENSGT00950000183036; -.
DR HOGENOM; CLU_020945_1_1_1; -.
DR InParanoid; Q99J21; -.
DR OMA; DKYLAIP; -.
DR OrthoDB; 1379516at2759; -.
DR PhylomeDB; Q99J21; -.
DR TreeFam; TF317783; -.
DR Reactome; R-MMU-3295583; TRP channels.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR BioGRID-ORCS; 94178; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Mcoln1; mouse.
DR PRO; PR:Q99J21; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99J21; protein.
DR Bgee; ENSMUSG00000004567; Expressed in retinal neural layer and 203 other tissues.
DR ExpressionAtlas; Q99J21; baseline and differential.
DR Genevisible; Q99J21; MM.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0097708; C:intracellular vesicle; EXP:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0005261; F:cation channel activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0097682; F:intracellular phosphatidylinositol-3,5-bisphosphate-sensitive cation channel activity; IDA:UniProtKB.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; ISO:MGI.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0072345; F:NAADP-sensitive calcium-release channel activity; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0097352; P:autophagosome maturation; IMP:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0098655; P:cation transmembrane transport; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB.
DR GO; GO:0071467; P:cellular response to pH; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; ISO:MGI.
DR GO; GO:0090382; P:phagosome maturation; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISO:MGI.
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; Adaptive immunity; Alternative splicing; Calcium;
KW Calcium transport; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Disulfide bond; Endosome; Glycoprotein; Immunity; Ion channel;
KW Ion transport; Lipid-binding; Lysosome; Membrane; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..580
FT /note="Mucolipin-1"
FT /id="PRO_0000215364"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 66..86
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 87..298
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 299..321
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 322..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 351..371
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 372..382
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 383..405
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 406..427
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 428..448
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 449..456
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29019981"
FT INTRAMEM 457..477
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 478..491
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TRANSMEM 492..513
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|PubMed:29019981"
FT TOPO_DOM 514..580
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29019981"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..62
FT /note="Interaction with phosphoinositides"
FT /evidence="ECO:0000269|PubMed:29019981"
FT REGION 107..121
FT /note="Extracellular/lumenal pore loop"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT REGION 565..567
FT /note="Required for palmitoylation and association with
FT membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT MOTIF 11..16
FT /note="Dileucine motif; mediates targeting to lysosomes"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT MOTIF 469..474
FT /note="Selectivity filter"
FT /evidence="ECO:0000269|PubMed:29019981"
FT MOTIF 573..578
FT /note="Dileucine internalization motif; mediates AP2
FT complex-dependent internalization"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT COMPBIAS 17..35
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939,
FT ECO:0007744|PubMed:19144319"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 559
FT /note="Phosphoserine; by PAK"
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 230
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28936784,
FT ECO:0000269|PubMed:29019981"
FT DISULFID 166..192
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT DISULFID 253..284
FT /evidence="ECO:0000250|UniProtKB:Q9GZU1"
FT VAR_SEQ 526..580
FT /note="HPGGTGTEKSELQAYIEQCQDSPTSGKFRRGSGSACSLFCCCGRDSPEDHSL
FT LVN -> RTNHRNWFSSFTVWIIDLNTSYQLCSKCLYLPHHLTGFLPLSYHLLLKTIYL
FT FRGERRLCTAQCVWKLETTCGNQLSSSTMWSHQV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11897010"
FT /id="VSP_010821"
FT MUTAGEN 432
FT /note="V->P: Constitutively active channel that is targeted
FT to the cell membrane."
FT /evidence="ECO:0000269|PubMed:29019981"
SQ SEQUENCE 580 AA; 65506 MW; F64D2E6C5D4C041C CRC64;
MATPAGRRAS ETERLLTPNP GYGTQVGTSP APTTPTEEED LRRRLKYFFM SPCDKFRAKG
RKPCKLMLQV VKILVVTVQL ILFGLSNQLV VTFREENTIA FRHLFLLGYS DGSDDTFAAY
TQEQLYQAIF YAVDQYLILP EISLGRYAYV RGGGGPWANG SALALCQRYY HRGHVDPAND
TFDIDPRVVT DCIQVDPPDR PPDIPSEDLD FLDGSASYKN LTLKFHKLIN VTIHFQLKTI
NLQSLINNEI PDCYTFSILI TFDNKAHSGR IPIRLETKTH IQECKHPSVS RHGDNSFRLL
FDVVVILTCS LSFLLCARSL LRGFLLQNEF VVFMWRRRGR EISLWERLEF VNGWYILLVT
SDVLTISGTV MKIGIEAKNL ASYDVCSILL GTSTLLVWVG VIRYLTFFHK YNILIATLRV
ALPSVMRFCC CVAVIYLGYC FCGWIVLGPY HVKFRSLSMV SECLFSLING DDMFVTFAAM
QAQQGHSSLV WLFSQLYLYS FISLFIYMVL SLFIALITGA YDTIKHPGGT GTEKSELQAY
IEQCQDSPTS GKFRRGSGSA CSLFCCCGRD SPEDHSLLVN
