ID MLC1_HUMAN Reviewed; 377 AA. AC Q15049; B3KW61; B7Z659; Q5JZ83; Q8TAG4; Q96RP5; Q9UGY8; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 5. DT 27-MAR-2024, entry version 193. DE RecName: Full=Membrane protein MLC1; GN Name=MLC1; Synonyms=KIAA0027, WKL1; 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 / MRNA] (ISOFORM 1), TISSUE SPECIFICITY, RP AND VARIANT MET-309. RC TISSUE=Hippocampus; RX PubMed=11326298; DOI=10.1038/sj.mp.4000869; RA Meyer J., Huberth A., Ortega G., Syagailo Y.V., Jatzke S., Moessner R., RA Strom T.M., Ulzheimer-Teuber I., Stoeber G., Schmitt A., Lesch K.P.; RT "A missense mutation in a novel gene encoding a putative cation channel is RT associated with catatonic schizophrenia in a large pedigree."; RL Mol. Psychiatry 6:302-306(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=7584026; DOI=10.1093/dnares/1.1.27; RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., RA Nagase T., Seki N., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. I. The RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of RT randomly sampled cDNA clones from human immature myeloid cell line KG-1."; RL DNA Res. 1:27-35(1994). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Kidney; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [9] RP PROTEIN SEQUENCE OF 2-14. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH ATP1B1, AND RP CHARACTERIZATION OF VARIANTS MLC1 ARG-125; ARG-246 AND LEU-280. RX PubMed=22328087; DOI=10.1093/hmg/dds032; RA Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., RA Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., Ambrosini E.; RT "Megalencephalic leukoencephalopathy with subcortical cysts protein 1 RT functionally cooperates with the TRPV4 cation channel to activate the RT response of astrocytes to osmotic stress: dysregulation by pathological RT mutations."; RL Hum. Mol. Genet. 21:2166-2180(2012). RN [11] RP VARIANTS MLC1 LEU-93; ARG-118; ARG-212 AND LEU-280. RX PubMed=11254442; DOI=10.1086/319519; RA Leegwater P.A.J., Yuan B.Q., van der Steen J., Mulders J., Koenst A.A.M., RA Ilja Boor P.K., Mejaski-Bosnjak V., van der Maarel S.M., Frants R.R., RA Oudejans C.B.M., Schutgens R.B.H., Pronk J.C., van der Knapp M.S.; RT "Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause RT megalencephalic leukoencephalopathy with subcortical cysts."; RL Am. J. Hum. Genet. 68:831-838(2001). RN [12] RP VARIANTS MLC1 SER-92; ARG-125; LYS-141; SER-141 AND ARG-246. RX PubMed=11935341; DOI=10.1007/s00439-002-0682-x; RA Leegwater P.A.J., Boor P.K.I., Yuan B.Q., van der Steen J., Visser A., RA Konst A.A.M., Oudejans C.B.M., Schutgens R.B.H., Pronk J.C., RA van der Knaap M.S.; RT "Identification of novel mutations in MLC1 responsible for megalencephalic RT leukoencephalopathy with subcortical cysts."; RL Hum. Genet. 110:279-283(2002). RN [13] RP VARIANT MLC1 GLU-59. RX PubMed=12189496; DOI=10.1007/s00439-002-0770-y; RA Ben-Zeev B., Levy-Nissenbaum E., Lahat H., Anikster Y., Shinar Y., RA Brand N., Gross-Tzur V., MacGregor D., Sidi R., Kleta R., Frydman M., RA Pras E.; RT "Megalencephalic leukoencephalopathy with subcortical cysts; a founder RT effect in Israeli patients and a higher than expected carrier rate among RT Libyan Jews."; RL Hum. Genet. 111:214-218(2002). RN [14] RP VARIANTS MLC1 LEU-69; ILE-80; CYS-84; PRO-245 AND LYS-320. RX PubMed=16652334; DOI=10.1002/humu.20332; RA Ilja Boor P.K., de Groot K., Mejaski-Bosnjak V., Brenner C., RA van der Knaap M.S., Scheper G.C., Pronk J.C.; RT "Megalencephalic leukoencephalopathy with subcortical cysts: an update and RT extended mutation analysis of MLC1."; RL Hum. Mutat. 27:505-512(2006). CC -!- FUNCTION: Regulates the response of astrocytes to hypo-osmosis by CC promoting calcium influx. {ECO:0000269|PubMed:22328087}. CC -!- SUBUNIT: Interacts with ATP1B1. Part of a complex containing ATP1B1, CC TRPV4, AQP4 and HEPACAM. {ECO:0000269|PubMed:22328087}. CC -!- INTERACTION: CC Q15049; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-8475277, EBI-702390; CC Q15049; Q01658: DR1; NbExp=3; IntAct=EBI-8475277, EBI-750300; CC Q15049; P14136: GFAP; NbExp=3; IntAct=EBI-8475277, EBI-744302; CC Q15049; Q00403: GTF2B; NbExp=3; IntAct=EBI-8475277, EBI-389564; CC Q15049; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-8475277, EBI-1054873; CC Q15049; P04792: HSPB1; NbExp=3; IntAct=EBI-8475277, EBI-352682; CC Q15049; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-8475277, EBI-1055254; CC Q15049; O60333-2: KIF1B; NbExp=3; IntAct=EBI-8475277, EBI-10975473; CC Q15049; P07196: NEFL; NbExp=3; IntAct=EBI-8475277, EBI-475646; CC Q15049; P60891: PRPS1; NbExp=3; IntAct=EBI-8475277, EBI-749195; CC Q15049; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-8475277, EBI-396669; CC Q15049; Q13148: TARDBP; NbExp=6; IntAct=EBI-8475277, EBI-372899; CC Q15049; O76024: WFS1; NbExp=3; IntAct=EBI-8475277, EBI-720609; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane CC protein {ECO:0000305}. Cell membrane {ECO:0000269|PubMed:22328087}. CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:22328087}. CC Endoplasmic reticulum {ECO:0000269|PubMed:22328087}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15049-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15049-2; Sequence=VSP_055494; CC -!- TISSUE SPECIFICITY: Expressed in the brain, with highest levels found CC in the amygdala, nucleus caudatus, thalamus and hippocampus. CC {ECO:0000269|PubMed:11326298}. CC -!- DISEASE: Megalencephalic leukoencephalopathy with subcortical cysts 1 CC (MLC1) [MIM:604004]: A syndrome of cerebral leukoencephalopathy and CC megalencephaly characterized by ataxia, spasticity, seizures, delay in CC motor development and mild intellectual disability. The brain appears CC swollen on magnetic resonance imaging, with diffuse white-matter CC abnormalities and the invariable presence of subcortical cysts in CC frontal and temporal lobes. {ECO:0000269|PubMed:11254442, CC ECO:0000269|PubMed:11935341, ECO:0000269|PubMed:12189496, CC ECO:0000269|PubMed:16652334, ECO:0000269|PubMed:22328087}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA04947.3; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mendelian genes megalencephalic leukoencephalopathy CC with subcortical cysts 1 (MLC1); Note=Leiden Open Variation Database CC (LOVD); CC URL="https://databases.lovd.nl/shared/genes/MLC1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF319633; AAK60119.1; -; mRNA. DR EMBL; D25217; BAA04947.3; ALT_INIT; mRNA. DR EMBL; CR456460; CAG30346.1; -; mRNA. DR EMBL; AK124264; BAG54023.1; -; mRNA. DR EMBL; AK299841; BAH13145.1; -; mRNA. DR EMBL; AL022327; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471138; EAW73490.1; -; Genomic_DNA. DR EMBL; BC028425; AAH28425.1; -; mRNA. DR CCDS; CCDS14083.1; -. [Q15049-1] DR RefSeq; NP_055981.1; NM_015166.3. [Q15049-1] DR RefSeq; NP_631941.1; NM_139202.2. [Q15049-1] DR RefSeq; XP_016884160.1; XM_017028671.1. DR AlphaFoldDB; Q15049; -. DR BioGRID; 116816; 25. DR CORUM; Q15049; -. DR IntAct; Q15049; 18. DR MINT; Q15049; -. DR STRING; 9606.ENSP00000310375; -. DR ChEMBL; CHEMBL4523299; -. DR TCDB; 9.B.129.1.1; the membrane protein mlc1 (mlc1) family. DR iPTMnet; Q15049; -. DR PhosphoSitePlus; Q15049; -. DR BioMuta; MLC1; -. DR DMDM; 20141590; -. DR EPD; Q15049; -. DR MassIVE; Q15049; -. DR PaxDb; 9606-ENSP00000310375; -. DR PeptideAtlas; Q15049; -. DR ProteomicsDB; 60401; -. [Q15049-1] DR ProteomicsDB; 6749; -. DR Antibodypedia; 297; 183 antibodies from 28 providers. DR DNASU; 23209; -. DR Ensembl; ENST00000311597.10; ENSP00000310375.6; ENSG00000100427.16. [Q15049-1] DR Ensembl; ENST00000395876.6; ENSP00000379216.2; ENSG00000100427.16. [Q15049-1] DR GeneID; 23209; -. DR KEGG; hsa:23209; -. DR MANE-Select; ENST00000311597.10; ENSP00000310375.6; NM_015166.4; NP_055981.1. DR UCSC; uc003bjg.2; human. [Q15049-1] DR AGR; HGNC:17082; -. DR CTD; 23209; -. DR DisGeNET; 23209; -. DR GeneCards; MLC1; -. DR GeneReviews; MLC1; -. DR HGNC; HGNC:17082; MLC1. DR HPA; ENSG00000100427; Tissue enriched (brain). DR MalaCards; MLC1; -. DR MIM; 604004; phenotype. DR MIM; 605908; gene. DR neXtProt; NX_Q15049; -. DR OpenTargets; ENSG00000100427; -. DR Orphanet; 2478; Megalencephalic leukoencephalopathy with subcortical cysts. DR PharmGKB; PA38199; -. DR VEuPathDB; HostDB:ENSG00000100427; -. DR eggNOG; ENOG502QUF1; Eukaryota. DR GeneTree; ENSGT00390000015442; -. DR InParanoid; Q15049; -. DR OMA; KAWRAVM; -. DR OrthoDB; 4165706at2759; -. DR PhylomeDB; Q15049; -. DR TreeFam; TF333109; -. DR PathwayCommons; Q15049; -. DR SignaLink; Q15049; -. DR BioGRID-ORCS; 23209; 13 hits in 1147 CRISPR screens. DR ChiTaRS; MLC1; human. DR GeneWiki; MLC1; -. DR GenomeRNAi; 23209; -. DR Pharos; Q15049; Tbio. DR PRO; PR:Q15049; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q15049; Protein. DR Bgee; ENSG00000100427; Expressed in nucleus accumbens and 120 other cell types or tissues. DR ExpressionAtlas; Q15049; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0005901; C:caveola; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005769; C:early endosome; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0072584; P:caveolin-mediated endocytosis; ISS:UniProtKB. DR GO; GO:0071397; P:cellular response to cholesterol; ISS:UniProtKB. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; IEA:UniProtKB-KW. DR GO; GO:0032388; P:positive regulation of intracellular transport; IDA:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:Ensembl. DR GO; GO:0047484; P:regulation of response to osmotic stress; IMP:UniProtKB. DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB. DR InterPro; IPR033280; Membrane_MLC1. DR PANTHER; PTHR17597; MEMBRANE PROTEIN MLC1; 1. DR PANTHER; PTHR17597:SF0; MEMBRANE PROTEIN MLC1; 1. DR Genevisible; Q15049; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasm; Direct protein sequencing; KW Disease variant; Endoplasmic reticulum; Ion channel; Ion transport; KW Membrane; Phosphoprotein; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801" FT CHAIN 2..377 FT /note="Membrane protein MLC1" FT /id="PRO_0000096496" FT TRANSMEM 52..72 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 82..100 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 111..131 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 144..164 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 199..219 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 230..250 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 257..277 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 304..324 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 1..36 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..20 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 177 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHK5" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VHK5" FT VAR_SEQ 60..89 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055494" FT VARIANT 59 FT /note="G -> E (in MLC1; dbSNP:rs80358242)" FT /evidence="ECO:0000269|PubMed:12189496" FT /id="VAR_017438" FT VARIANT 69 FT /note="S -> L (in MLC1; dbSNP:rs281875309)" FT /evidence="ECO:0000269|PubMed:16652334" FT /id="VAR_067762" FT VARIANT 80 FT /note="M -> I (in MLC1; dbSNP:rs281875310)" FT /evidence="ECO:0000269|PubMed:16652334" FT /id="VAR_067763" FT VARIANT 84 FT /note="R -> C (in MLC1; dbSNP:rs281875311)" FT /evidence="ECO:0000269|PubMed:16652334" FT /id="VAR_067764" FT VARIANT 92 FT /note="P -> S (in MLC1; dbSNP:rs121908345)" FT /evidence="ECO:0000269|PubMed:11935341" FT /id="VAR_017439" FT VARIANT 93 FT /note="S -> L (in MLC1; dbSNP:rs80358245)" FT /evidence="ECO:0000269|PubMed:11254442" FT /id="VAR_011699" FT VARIANT 118 FT /note="T -> R (in MLC1; dbSNP:rs281875316)" FT /evidence="ECO:0000269|PubMed:11254442" FT /id="VAR_011700" FT VARIANT 125 FT /note="C -> R (in MLC1; accumulates in the cytoplasmic FT perinuclear region and endoplasmic reticulum; affects FT interaction with ATP1B1; dbSNP:rs281875314)" FT /evidence="ECO:0000269|PubMed:11935341, FT ECO:0000269|PubMed:22328087" FT /id="VAR_067765" FT VARIANT 141 FT /note="N -> K (in MLC1; dbSNP:rs121908343)" FT /evidence="ECO:0000269|PubMed:11935341" FT /id="VAR_017440" FT VARIANT 141 FT /note="N -> S (in MLC1; dbSNP:rs121908344)" FT /evidence="ECO:0000269|PubMed:11935341" FT /id="VAR_017441" FT VARIANT 171 FT /note="C -> F (in dbSNP:rs6010260)" FT /id="VAR_051186" FT VARIANT 212 FT /note="G -> R (in MLC1; dbSNP:rs281875317)" FT /evidence="ECO:0000269|PubMed:11254442" FT /id="VAR_011701" FT VARIANT 245 FT /note="A -> P (in MLC1; dbSNP:rs281875312)" FT /evidence="ECO:0000269|PubMed:16652334" FT /id="VAR_067766" FT VARIANT 246 FT /note="S -> R (in MLC1; does not affect subcellular FT location; dbSNP:rs281875315)" FT /evidence="ECO:0000269|PubMed:11935341, FT ECO:0000269|PubMed:22328087" FT /id="VAR_067767" FT VARIANT 280 FT /note="S -> L (in MLC1; accumulates in the cytoplasmic FT perinuclear region and endoplasmic reticulum; affects the FT interaction with ATP1B1, TRPV4, AQP4 and HEPACAM; FT dbSNP:rs121908341)" FT /evidence="ECO:0000269|PubMed:11254442, FT ECO:0000269|PubMed:22328087" FT /id="VAR_011702" FT VARIANT 309 FT /note="L -> M (in a pedigree affected by schizophrenia; FT dbSNP:rs80358240)" FT /evidence="ECO:0000269|PubMed:11326298" FT /id="VAR_012731" FT VARIANT 320 FT /note="T -> K (in MLC1; dbSNP:rs281875313)" FT /evidence="ECO:0000269|PubMed:16652334" FT /id="VAR_067768" FT VARIANT 344 FT /note="N -> S (in dbSNP:rs11568188)" FT /id="VAR_051187" FT CONFLICT 25 FT /note="P -> H (in Ref. 8; AAH28425)" FT /evidence="ECO:0000305" SQ SEQUENCE 377 AA; 41141 MW; 9AF70B87D979F459 CRC64; MTQEPFREEL AYDRMPTLER GRQDPASYAP DAKPSDLQLS KRLPPCFSHK TWVFSVLMGS CLLVTSGFSL YLGNVFPAEM DYLRCAAGSC IPSAIVSFTV SRRNANVIPN FQILFVSTFA VTTTCLIWFG CKLVLNPSAI NINFNLILLL LLELLMAATV IIAARSSEED CKKKKGSMSD SANILDEVPF PARVLKSYSV VEVIAGISAV LGGIIALNVD DSVSGPHLSV TFFWILVACF PSAIASHVAA ECPSKCLVEV LIAISSLTSP LLFTASGYLS FSIMRIVEMF KDYPPAIKPS YDVLLLLLLL VLLLQAGLNT GTAIQCVRFK VSARLQGASW DTQNGPQERL AGEVARSPLK EFDKEKAWRA VVVQMAQ //