ID CLN3_HUMAN Reviewed; 438 AA. AC Q13286; B2R7J1; B4DXL3; O00668; O95089; Q549S9; Q9UP09; Q9UP11; Q9UP12; AC Q9UP13; Q9UP14; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 24-JAN-2024, entry version 205. DE RecName: Full=Battenin {ECO:0000305}; DE AltName: Full=Batten disease protein; DE AltName: Full=Protein CLN3; DE Flags: Precursor; GN Name=CLN3 {ECO:0000312|HGNC:HGNC:2074}; Synonyms=BTS; 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). RC TISSUE=Brain; RX PubMed=7553855; DOI=10.1016/0092-8674(95)90274-0; RA Lerner T.J., Boustany R.-M.N., Anderson J.W., D'Arigo K.L., Schlumpf K., RA Buckler A.J., Gusella J.F., Haines J.L., Kremmidiotis G., Lensink I.L., RA Sutherland G.R., Callen D.F., Taschner P.E.M., de Vos N., van Ommen G.B., RA Breuning M.H., Doggett N.A., Meincke L.J., Liu Z., Goodwin L.A., RA Tesmer J.G., Mitchison H.M., O'Rawe A.M., Munroe P.B., Jarvela I.E., RA Gardiner M.R., Mole S.E.; RT "Isolation of a novel gene underlying Batten disease, CLN3."; RL Cell 82:949-957(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9119403; DOI=10.1006/geno.1996.4576; RA Mitchison H.M., Munroe P.B., O'Rawe A.M., Taschner P.E.M., de Vos N., RA Kremmidiotis G., Lensink I., Munk A.C., D'Arigo K.L., Anderson J.W., RA Lerner T.J., Moyzis R.K., Callen D.F., Breuning M.H., Doggett N.A., RA Gardiner R.M., Mole S.E.; RT "Genomic structure and complete nucleotide sequence of the Batten disease RT gene, CLN3."; RL Genomics 40:346-350(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 6). RA LaFauci G., Papini M., Pullarkat R., Rubenstein R.; RT "Unique alternative spliced transcripts associated with the 56 chromosome RT haplotype allele of the Batten disease gene, CLN3."; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). RA LaFauci G., Kaczmarski W., Papini M., Pullarkat R.K., Wisniewski K.E., RA Zhong N., Rubenstein R.; RT "Characterization of alternatively spliced transcripts of the Batten RT disease CLN3 gene in human lymphoblastoid cell lines."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 7). RC TISSUE=Cerebellum, and Testis; 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=10493829; DOI=10.1006/geno.1999.5927; RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., RA Adams M.D.; RT "Genome duplications and other features in 12 Mb of DNA sequence from human RT chromosome 16p and 16q."; RL Genomics 60:295-308(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [10] RP PHOSPHORYLATION. RX PubMed=9878558; DOI=10.1006/bbrc.1998.9210; RA Michalewski M.P., Kaczmarski W., Golabek A.A., Kida E., Kaczmarski A., RA Wisniewski K.E.; RT "Evidence for phosphorylation of CLN3 protein associated with Batten RT disease."; RL Biochem. Biophys. Res. Commun. 253:458-462(1998). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=9949212; DOI=10.1093/hmg/8.3.523; RA Kremmidiotis G., Lensink I.L., Bilton R.L., Woollatt E., Chataway T.K., RA Sutherland G.R., Callen D.F.; RT "The Batten disease gene product (CLN3p) is a Golgi integral membrane RT protein."; RL Hum. Mol. Genet. 8:523-531(1999). RN [12] RP CHARACTERIZATION OF VARIANT CLN3 LYS-295, AND SUBCELLULAR LOCATION. RX PubMed=10332042; DOI=10.1093/hmg/8.6.1091; RA Jaervelae I., Lehtovirta M., Tikkanen R., Kyttaelae A., Jalanko A.; RT "Defective intracellular transport of CLN3 is the molecular basis of Batten RT disease (JNCL)."; RL Hum. Mol. Genet. 8:1091-1098(1999). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=10191115; DOI=10.1006/mgme.1999.2836; RA Golabek A.A., Kaczmarski W., Kida E., Kaczmarski A., Michalewski M.P., RA Wisniewski K.E.; RT "Expression studies of CLN3 protein (battenin) in fusion with the green RT fluorescent protein in mammalian cells in vitro."; RL Mol. Genet. Metab. 66:277-282(1999). RN [14] RP TISSUE SPECIFICITY. RX PubMed=10191116; DOI=10.1006/mgme.1999.2830; RA Margraf L.R., Boriack R.L., Routheut A.A., Cuppen I., Alhilali L., RA Bennett C.J., Bennett M.J.; RT "Tissue expression and subcellular localization of CLN3, the Batten disease RT protein."; RL Mol. Genet. Metab. 66:283-289(1999). RN [15] RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND CHARACTERIZATION OF VARIANT CLN3 RP CYS-334. RX PubMed=10924275; DOI=10.1006/mgme.2000.3006; RA Golabek A.A., Kida E., Walus M., Kaczmarski W., Michalewski M., RA Wisniewski K.E.; RT "CLN3 protein regulates lysosomal pH and alters intracellular processing of RT Alzheimer's amyloid-beta protein precursor and cathepsin D in human RT cells."; RL Mol. Genet. Metab. 70:203-213(2000). RN [16] RP MUTAGENESIS OF ASN-310, GLYCOSYLATION, AND TOPOLOGY. RX PubMed=12706816; DOI=10.1016/s0014-5793(03)00284-9; RA Mao Q., Foster B.J., Xia H., Davidson B.L.; RT "Membrane topology of CLN3, the protein underlying Batten disease."; RL FEBS Lett. 541:40-46(2003). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=14644441; DOI=10.1016/s0014-5793(03)01274-2; RA Mao Q., Xia H., Davidson B.L.; RT "Intracellular trafficking of CLN3, the protein underlying the childhood RT neurodegenerative disease, Batten disease."; RL FEBS Lett. 555:351-357(2003). RN [18] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [19] RP INTERACTION WITH HOOK1, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=15471887; DOI=10.1093/hmg/ddh321; RA Luiro K., Yliannala K., Ahtiainen L., Maunu H., Jaervelae I., Kyttaelae A., RA Jalanko A.; RT "Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to RT defects in the endocytic pathway."; RL Hum. Mol. Genet. 13:3017-3027(2004). RN [20] RP MUTAGENESIS OF 242-GLU--GLU-244; GLU-246 AND 253-LEU-ILE-254, AND MOTIF. RX PubMed=15469932; DOI=10.1074/jbc.m410930200; RA Storch S., Pohl S., Braulke T.; RT "A dileucine motif and a cluster of acidic amino acids in the second RT cytoplasmic domain of the batten disease-related CLN3 protein are required RT for efficient lysosomal targeting."; RL J. Biol. Chem. 279:53625-53634(2004). RN [21] RP SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF 242-GLU--GLU-244; LEU-253; RP ILE-254; MET-409 AND GLY-419, CHARACTERIZATION OF VARIANT CLN3 GLU-399 DEL, RP IDENTIFICATION OF LYSOSOMAL TARGETING MOTIF, AND INTERACTION WITH CLN5. RX PubMed=14699076; DOI=10.1091/mbc.e03-02-0120; RA Kyttaelae A., Ihrke G., Vesa J., Schell M.J., Luzio J.P.; RT "Two motifs target Batten disease protein CLN3 to lysosomes in transfected RT nonneuronal and neuronal cells."; RL Mol. Biol. Cell 15:1313-1323(2004). RN [22] RP SUBCELLULAR LOCATION. RX PubMed=15240864; DOI=10.1203/01.pdr.0000136152.54638.95; RA Persaud-Sawin D.A., McNamara J.O. II, Rylova S., Vandongen A., RA Boustany R.M.; RT "A galactosylceramide binding domain is involved in trafficking of CLN3 RT from Golgi to rafts via recycling endosomes."; RL Pediatr. Res. 56:449-463(2004). RN [23] RP SUBCELLULAR LOCATION, MUTAGENESIS OF 253-LEU-ILE-254; MET-409 AND GLY-419, RP INTERACTION WITH AP3D1; AP1G1 AND AP2A2, AND DOMAIN. RX PubMed=15598649; DOI=10.1074/jbc.m411862200; RA Kyttaelae A., Yliannala K., Schu P., Jalanko A., Luzio J.P.; RT "AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein RT CLN3 via its dileucine motif."; RL J. Biol. Chem. 280:10277-10283(2005). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [25] RP FUNCTION, AND CHARACTERIZATION OF VARIANT CLN3 PRO-170. RX PubMed=17482562; DOI=10.1016/j.bbrc.2007.04.064; RA Hobert J.A., Dawson G.; RT "A novel role of the Batten disease gene CLN3: association with BMP RT synthesis."; RL Biochem. Biophys. Res. Commun. 358:111-116(2007). RN [26] RP INTERACTION WITH KCNIP3, SUBCELLULAR LOCATION, AND DOMAIN. RX PubMed=17189291; DOI=10.1093/hmg/ddl466; RA Chang J.W., Choi H., Kim H.J., Jo D.G., Jeon Y.J., Noh J.Y., Park W.J., RA Jung Y.K.; RT "Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is RT mediated by calsenilin."; RL Hum. Mol. Genet. 16:317-326(2007). RN [27] RP INTERACTION WITH TPP1; CLN6 AND CLN8. RX PubMed=17237713; DOI=10.1203/pdr.0b013e31802d8a4a; RA Persaud-Sawin D.A., Mousallem T., Wang C., Zucker A., Kominami E., RA Boustany R.M.; RT "Neuronal ceroid lipofuscinosis: a common pathway?"; RL Pediatr. Res. 61:146-152(2007). RN [28] RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-71 AND ASN-85, AND RP ISOPRENYLATION AT CYS-435. RX PubMed=17286803; DOI=10.1111/j.1600-0854.2007.00537.x; RA Storch S., Pohl S., Quitsch A., Falley K., Braulke T.; RT "C-terminal prenylation of the CLN3 membrane glycoprotein is required for RT efficient endosomal sorting to lysosomes."; RL Traffic 8:431-444(2007). RN [29] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Placenta; RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x; RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., RA Elsaesser H.-P., Mann M., Hasilik A.; RT "Integral and associated lysosomal membrane proteins."; RL Traffic 8:1676-1686(2007). RN [30] RP INTERACTION WITH SPTAN1; HSPA5 AND ATP1A1. RX PubMed=18621045; DOI=10.1016/j.yexcr.2008.06.016; RA Uusi-Rauva K., Luiro K., Tanhuanpaeae K., Kopra O., Martin-Vasallo P., RA Kyttaelae A., Jalanko A.; RT "Novel interactions of CLN3 protein link Batten disease to dysregulation of RT fodrin-Na+, K+ ATPase complex."; RL Exp. Cell Res. 314:2895-2905(2008). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [32] RP FUNCTION. RX PubMed=18317235; DOI=10.1203/pdr.0b013e31816fdc17; RA Rusyn E., Mousallem T., Persaud-Sawin D.A., Miller S., Boustany R.M.; RT "CLN3p impacts galactosylceramide transport, raft morphology, and lipid RT content."; RL Pediatr. Res. 63:625-631(2008). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [34] RP FUNCTION. RX PubMed=18817525; DOI=10.1111/j.1600-0854.2008.00807.x; RA Metcalf D.J., Calvi A.A., Seaman M.N.J., Mitchison H.M., Cutler D.F.; RT "Loss of the Batten disease gene CLN3 prevents exit from the TGN of the RT mannose 6-phosphate receptor."; RL Traffic 9:1905-1914(2008). RN [35] RP INTERACTION WITH CLN5, AND SUBCELLULAR LOCATION. RX PubMed=19941651; DOI=10.1186/1471-2121-10-83; RA Lyly A., von Schantz C., Heine C., Schmiedt M.L., Sipilae T., Jalanko A., RA Kyttaelae A.; RT "Novel interactions of CLN5 support molecular networking between neuronal RT ceroid lipofuscinosis proteins."; RL BMC Cell Biol. 10:83-83(2009). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [37] RP INTERACTION WITH SBDS. RX PubMed=20015955; DOI=10.1093/hmg/ddp560; RA Vitiello S.P., Benedict J.W., Padilla-Lopez S., Pearce D.A.; RT "Interaction between Sdo1p and Btn1p in the Saccharomyces cerevisiae model RT for Batten disease."; RL Hum. Mol. Genet. 19:931-942(2010). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [39] RP FUNCTION, AND INTERACTION WITH MYH10. RX PubMed=20850431; DOI=10.1016/j.yexcr.2010.09.007; RA Getty A.L., Benedict J.W., Pearce D.A.; RT "A novel interaction of CLN3 with nonmuscle myosin-IIB and defects in cell RT motility of Cln3(-/-) cells."; RL Exp. Cell Res. 317:51-69(2011). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [41] RP FUNCTION IN ANTEROGRADE TRANSPORT OF LATE ENDOSOMES AND LYSOSOMES, RP SUBCELLULAR LOCATION, INTERACTION WITH DCTN1; KIF3A; RAB7A AND RILP, AND RP CHARACTERIZATION OF VARIANT CLN3 LYS-295. RX PubMed=22261744; DOI=10.1007/s00018-011-0913-1; RA Uusi-Rauva K., Kyttala A., van der Kant R., Vesa J., Tanhuanpaa K., RA Neefjes J., Olkkonen V.M., Jalanko A.; RT "Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins RT and modifies location of late endosomal compartments."; RL Cell. Mol. Life Sci. 69:2075-2089(2012). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [43] RP INDUCTION BY OSMOTIC STRESS, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=23840424; DOI=10.1371/journal.pone.0066203; RA Getty A., Kovacs A.D., Lengyel-Nelson T., Cardillo A., Hof C., Chan C.H., RA Pearce D.A.; RT "Osmotic stress changes the expression and subcellular localization of the RT Batten disease protein CLN3."; RL PLoS ONE 8:E66203-E66203(2013). RN [44] RP TOPOLOGY. RX PubMed=25051496; DOI=10.1371/journal.pone.0102593; RA Ratajczak E., Petcherski A., Ramos-Moreno J., Ruonala M.O.; RT "FRET-assisted determination of CLN3 membrane topology."; RL PLoS ONE 9:E102593-E102593(2014). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [46] RP FUNCTION. RX PubMed=28390177; DOI=10.1002/jcb.26039; RA Carcel-Trullols J., Kovacs A.D., Pearce D.A.; RT "Role of the Lysosomal Membrane Protein, CLN3, in the Regulation of RT Cathepsin D Activity."; RL J. Cell. Biochem. 118:3883-3890(2017). RN [47] RP VARIANTS CLN3 PRO-101; PRO-170; LYS-295; PHE-330; CYS-334 AND HIS-334. RX PubMed=9311735; DOI=10.1086/514846; RA Munroe P.B., Mitchison H.M., O'Rawe A.M., Anderson J.W., Boustany R.-M.N., RA Lerner T.J., Taschner P.E.M., de Vos N., Breuning M.H., Gardiner R.M., RA Mole S.E.; RT "Spectrum of mutations in the Batten disease gene, CLN3."; RL Am. J. Hum. Genet. 61:310-316(1997). RN [48] RP VARIANT CLN3 LYS-295. RX PubMed=9490299; DOI=10.1007/s004390050654; RA Zhong N., Wisniewski K.E., Kaczmarski A.L., Ju W., Xu W.M., Xu W.W., RA McLendon L., Liu B., Kaczmarski W., Brooks S.S., Brown W.T.; RT "Molecular screening of Batten disease: identification of a missense RT mutation (E295K) in the CLN3 gene."; RL Hum. Genet. 102:57-62(1998). RN [49] RP VARIANTS CLN3 PRO-101; ARG-134; PRO-170; ALA-187; ARG-189; LYS-295 AND RP HIS-334. RX PubMed=21990111; DOI=10.1002/humu.21624; RA Kousi M., Lehesjoki A.E., Mole S.E.; RT "Update of the mutation spectrum and clinical correlations of over 360 RT mutations in eight genes that underlie the neuronal ceroid RT lipofuscinoses."; RL Hum. Mutat. 33:42-63(2012). CC -!- FUNCTION: Mediates microtubule-dependent, anterograde transport CC connecting the Golgi network, endosomes, autophagosomes, lysosomes and CC plasma membrane, and participates in several cellular processes such as CC regulation of lysosomal pH, lysosome protein degradation, receptor- CC mediated endocytosis, autophagy, transport of proteins and lipids from CC the TGN, apoptosis and synaptic transmission (PubMed:10924275, CC PubMed:18817525, PubMed:18317235, PubMed:22261744, PubMed:15471887, CC PubMed:20850431). Facilitates the proteins transport from trans-Golgi CC network (TGN)-to other membrane compartments such as transport of CC microdomain-associated proteins to the plasma membrane, IGF2R transport CC to the lysosome where it regulates the CTSD release leading to CC regulation of CTSD maturation and thereby APP intracellular processing CC (PubMed:10924275, PubMed:18817525). Moreover regulates CTSD activity in CC response to osmotic stress (PubMed:23840424, PubMed:28390177). Also CC binds galactosylceramide and transports it from the trans Golgi to the CC rafts, which may have immediate and downstream effects on cell survival CC by modulating ceramide synthesis (PubMed:18317235). At the plasma CC membrane, regulates actin-dependent events including filopodia CC formation, cell migration, and pinocytosis through ARF1-CDC42 pathway CC and also the cytoskeleton organization through interaction with MYH10 CC and fodrin leading to the regulation of the plasma membrane association CC of Na+, K+ ATPase complex (PubMed:20850431). Regulates synaptic CC transmission in the amygdala, hippocampus, and cerebellum through CC regulation of synaptic vesicles density and their proximity to active CC zones leading to modulation of short-term plasticity and age-dependent CC anxious behavior, learning and memory (By similarity). Regulates CC autophagic vacuoles (AVs) maturation by modulating the trafficking CC between endocytic and autophagolysosomal/lysosomal compartments, which CC involves vesicle fusion leading to regulation of degradation process CC (By similarity). Participates also in cellular homeostasis of compounds CC such as, water, ions, amino acids, proteins and lipids in several CC tissue namely in brain and kidney through regulation of their transport CC and synthesis (PubMed:17482562). {ECO:0000250|UniProtKB:Q61124, CC ECO:0000269|PubMed:10924275, ECO:0000269|PubMed:15471887, CC ECO:0000269|PubMed:17482562, ECO:0000269|PubMed:18317235, CC ECO:0000269|PubMed:18817525, ECO:0000269|PubMed:20850431, CC ECO:0000269|PubMed:22261744, ECO:0000269|PubMed:23840424, CC ECO:0000269|PubMed:28390177}. CC -!- SUBUNIT: Homooligomer (By similarity). Interacts with DCTN1, KIF3A, CC RAB7A and RILP (PubMed:22261744). Interacts with CLN5 (PubMed:19941651, CC PubMed:14699076). May interact with HOOK1 (PubMed:15471887). Interacts CC with KCNIP3; this interaction is disrupted by intracellular increase of CC calcium level (PubMed:17189291). Interacts with TPP1, CLN6 and CLN8 CC (PubMed:17237713). Interacts with MYH10; this interaction may play a CC role in regulation of cytoskeleton organization (PubMed:20850431). CC Interacts with SBDS (PubMed:20015955). Interacts with sodium/potassium- CC transporting ATPase complex (via ATP1A1) and fodrin heteromer (via CC SPTAN1); this interaction regulates their localization at the plasma CC membrane (Probable). Interacts with HSPA5 (Probable). Interacts (via CC dileucine motif) with AP3D1 and AP1G1; this interaction facilitates CC lysosomal targeting (PubMed:15598649). Interacts (via dileucine motif) CC with AP2A2 (PubMed:15598649). {ECO:0000250|UniProtKB:Q61124, CC ECO:0000269|PubMed:14699076, ECO:0000269|PubMed:15471887, CC ECO:0000269|PubMed:15598649, ECO:0000269|PubMed:17189291, CC ECO:0000269|PubMed:17237713, ECO:0000269|PubMed:19941651, CC ECO:0000269|PubMed:20015955, ECO:0000269|PubMed:20850431, CC ECO:0000269|PubMed:22261744, ECO:0000305|PubMed:18621045}. CC -!- INTERACTION: CC Q13286; Q6ZTQ4: CDHR3; NbExp=3; IntAct=EBI-3248760, EBI-12143631; CC Q13286; O75503: CLN5; NbExp=2; IntAct=EBI-3248760, EBI-1043514; CC Q13286; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-3248760, EBI-9091197; CC Q13286; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-3248760, EBI-6447163; CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:10332042, CC ECO:0000269|PubMed:14644441, ECO:0000269|PubMed:15471887, CC ECO:0000269|PubMed:15598649, ECO:0000269|PubMed:17286803, CC ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:23840424}; Multi-pass CC membrane protein {ECO:0000269|PubMed:17286803, CC ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:9949212}. Late endosome CC {ECO:0000269|PubMed:10332042, ECO:0000269|PubMed:15471887, CC ECO:0000269|PubMed:17286803, ECO:0000269|PubMed:23840424}. Lysosome CC {ECO:0000269|PubMed:10332042, ECO:0000269|PubMed:10924275, CC ECO:0000269|PubMed:14699076, ECO:0000269|PubMed:19941651, CC ECO:0000269|PubMed:9949212}. Golgi apparatus CC {ECO:0000269|PubMed:10332042, ECO:0000269|PubMed:15240864, CC ECO:0000269|PubMed:23840424}. Golgi apparatus membrane CC {ECO:0000269|PubMed:9949212}. Golgi apparatus, Golgi stack CC {ECO:0000269|PubMed:15240864}. Golgi apparatus, trans-Golgi network CC {ECO:0000269|PubMed:10332042, ECO:0000269|PubMed:15240864}. Cell CC membrane {ECO:0000269|PubMed:14644441, ECO:0000269|PubMed:15240864}. CC Recycling endosome {ECO:0000269|PubMed:15240864}. Membrane raft CC {ECO:0000269|PubMed:15240864, ECO:0000269|PubMed:23840424}. Membrane, CC caveola {ECO:0000269|PubMed:23840424}. Early endosome membrane CC {ECO:0000269|PubMed:23840424}. Synapse, synaptosome CC {ECO:0000250|UniProtKB:Q61124}. Late endosome membrane CC {ECO:0000250|UniProtKB:Q61124}. Cytoplasmic vesicle, autophagosome CC {ECO:0000250|UniProtKB:Q61124}. Note=CLN3 is not present in late CC endosomes/lysosomes in fibroblasts and neurons (PubMed:15240864). CC Trafficks from cell membrane to Golgi via endosomes (PubMed:15240864). CC Osmotic stress changes the subcellular localization of CLN3 CC (PubMed:23840424). Trafficks to intracellular compartments via the CC plasma membranet through AP3M1-dependent mechanisms (PubMed:14644441). CC Excluded from the synaptic vesicles (By similarity). CC {ECO:0000250|UniProtKB:Q61124, ECO:0000269|PubMed:14644441, CC ECO:0000269|PubMed:15240864, ECO:0000269|PubMed:23840424}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q13286-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13286-2; Sequence=VSP_004166; CC Name=3; CC IsoId=Q13286-3; Sequence=VSP_004167; CC Name=4; CC IsoId=Q13286-4; Sequence=VSP_004168; CC Name=5; CC IsoId=Q13286-5; Sequence=VSP_004169, VSP_004170; CC Name=6; CC IsoId=Q13286-6; Sequence=VSP_047631, VSP_047632; CC Name=7; CC IsoId=Q13286-7; Sequence=VSP_057347; CC -!- TISSUE SPECIFICITY: Expressed in the cortical brain, pancreas, spleen, CC and testis with weaker expression in the peripheral nerve (at protein CC level). Highly expressed in gray matter (at protein level). CC {ECO:0000269|PubMed:10191116}. CC -!- INDUCTION: Increased by osmotic stress. {ECO:0000269|PubMed:23840424}. CC -!- DOMAIN: The C-terminal (153-438) mediates KCNIP3 interaction and the CC cytoprotective activity (PubMed:17189291). the dileucine motif mediates CC AP1G1 and AP3D1 interaction (PubMed:15598649). CC {ECO:0000269|PubMed:15598649, ECO:0000269|PubMed:17189291}. CC -!- PTM: Highly glycosylated. {ECO:0000269|PubMed:10924275, CC ECO:0000269|PubMed:12706816, ECO:0000269|PubMed:17286803}. CC -!- PTM: Farnesylation is important for trafficking to lysosomes. CC {ECO:0000269|PubMed:17286803}. CC -!- PTM: Phosphorylated on both serine and threonine residues by PKA, PKG CC and CK2. {ECO:0000269|PubMed:9878558}. CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 3 (CLN3) [MIM:204200]: A form CC of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are CC progressive neurodegenerative, lysosomal storage diseases characterized CC by intracellular accumulation of autofluorescent liposomal material, CC and clinically by seizures, dementia, visual loss, and/or cerebral CC atrophy. The hallmark of CLN3 is the ultrastructural pattern of CC lipopigment with a fingerprint profile, which can have 3 different CC appearances: pure within a lysosomal residual body; in conjunction with CC curvilinear or rectilinear profiles; and as a small component within CC large membrane-bound lysosomal vacuoles. The combination of fingerprint CC profiles within lysosomal vacuoles is a regular feature of blood CC lymphocytes from patients with neuronal ceroid lipofuscinosis type 3. CC {ECO:0000269|PubMed:10332042, ECO:0000269|PubMed:10924275, CC ECO:0000269|PubMed:14699076, ECO:0000269|PubMed:17482562, CC ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22261744, CC ECO:0000269|PubMed:9311735, ECO:0000269|PubMed:9490299}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 4]: 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 -!- MISCELLANEOUS: [Isoform 5]: 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 battenin family. {ECO:0000305}. CC -!- CAUTION: Mao et al suggest that CLN3 has five transmembranes with a CC long lumenal N-terminus because their antibody does not CC immunoprecipitate the N-terminus in the presence of microsomes. CC {ECO:0000269|PubMed:12706816}. CC -!- WEB RESOURCE: Name=NCL CLN3; Note=Neural Ceroid Lipofuscinoses mutation CC db; CC URL="https://www.ucl.ac.uk/ncl/cln3.shtml"; CC -!- WEB RESOURCE: Name=Mutations of the CLN3 gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/cln3mut.htm"; 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; U32680; AAB51075.1; -; mRNA. DR EMBL; X99832; CAA68148.1; -; Genomic_DNA. DR EMBL; AF015593; AAD01555.1; -; mRNA. DR EMBL; AF015598; AAD01560.1; -; mRNA. DR EMBL; AF077956; AAD51478.1; -; mRNA. DR EMBL; AF077957; AAD51479.1; -; mRNA. DR EMBL; AF077958; AAD51480.1; -; mRNA. DR EMBL; AF077959; AAD51481.1; -; mRNA. DR EMBL; AF077961; AAD51483.1; -; mRNA. DR EMBL; AF077962; AAD51484.1; -; mRNA. DR EMBL; AF077966; AAD51488.1; -; mRNA. DR EMBL; AF077960; AAD51482.1; -; mRNA. DR EMBL; AF077963; AAD51485.1; -; mRNA. DR EMBL; AF077965; AAD51487.1; -; mRNA. DR EMBL; AF077971; AAD51493.1; -; mRNA. DR EMBL; AF077972; AAD51494.1; -; mRNA. DR EMBL; AF078169; AAD48543.1; -; mRNA. DR EMBL; AK302027; BAG63425.1; -; mRNA. DR EMBL; AK313002; BAG35838.1; -; mRNA. DR EMBL; AC002425; AAC05337.1; -; Genomic_DNA. DR EMBL; AC002544; AAC27430.1; -; Genomic_DNA. DR EMBL; AC138894; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471279; EAW52281.1; -; Genomic_DNA. DR EMBL; CH471279; EAW52286.1; -; Genomic_DNA. DR EMBL; BC002394; AAH02394.1; -; mRNA. DR EMBL; BC004433; AAH04433.1; -; mRNA. DR CCDS; CCDS10632.1; -. [Q13286-1] DR CCDS; CCDS73855.1; -. [Q13286-7] DR PIR; A57219; A57219. DR RefSeq; NP_000077.1; NM_000086.2. [Q13286-1] DR RefSeq; NP_001035897.1; NM_001042432.1. [Q13286-1] DR RefSeq; NP_001273033.1; NM_001286104.1. [Q13286-7] DR RefSeq; NP_001273034.1; NM_001286105.1. DR AlphaFoldDB; Q13286; -. DR BioGRID; 107612; 116. DR IntAct; Q13286; 43. DR MINT; Q13286; -. DR STRING; 9606.ENSP00000454229; -. DR TCDB; 2.A.57.5.8; the equilibrative nucleoside transporter (ent) family. DR GlyCosmos; Q13286; 3 sites, No reported glycans. DR GlyGen; Q13286; 5 sites, 2 O-linked glycans (2 sites). DR iPTMnet; Q13286; -. DR PhosphoSitePlus; Q13286; -. DR SwissPalm; Q13286; -. DR BioMuta; CLN3; -. DR DMDM; 2498243; -. DR EPD; Q13286; -. DR jPOST; Q13286; -. DR MassIVE; Q13286; -. DR MaxQB; Q13286; -. DR PaxDb; 9606-ENSP00000454229; -. DR PeptideAtlas; Q13286; -. DR ProteomicsDB; 50650; -. DR ProteomicsDB; 5449; -. DR ProteomicsDB; 59277; -. [Q13286-1] DR ProteomicsDB; 59278; -. [Q13286-2] DR ProteomicsDB; 59279; -. [Q13286-3] DR ProteomicsDB; 59280; -. [Q13286-4] DR ProteomicsDB; 59281; -. [Q13286-5] DR Pumba; Q13286; -. DR ABCD; Q13286; 1 sequenced antibody. DR Antibodypedia; 26372; 202 antibodies from 29 providers. DR DNASU; 1201; -. DR Ensembl; ENST00000333496.14; ENSP00000329171.9; ENSG00000188603.22. [Q13286-7] DR Ensembl; ENST00000355477.10; ENSP00000347660.7; ENSG00000188603.22. [Q13286-2] DR Ensembl; ENST00000357806.11; ENSP00000350457.7; ENSG00000188603.22. [Q13286-6] DR Ensembl; ENST00000359984.12; ENSP00000353073.9; ENSG00000188603.22. [Q13286-1] DR Ensembl; ENST00000360019.8; ENSP00000353116.3; ENSG00000188603.22. [Q13286-7] DR Ensembl; ENST00000565316.6; ENSP00000456117.1; ENSG00000188603.22. [Q13286-3] DR Ensembl; ENST00000569030.5; ENSP00000454680.1; ENSG00000188603.22. [Q13286-5] DR Ensembl; ENST00000569430.7; ENSP00000454229.1; ENSG00000188603.22. [Q13286-1] DR Ensembl; ENST00000636147.2; ENSP00000490105.1; ENSG00000188603.22. [Q13286-1] DR GeneID; 1201; -. DR KEGG; hsa:1201; -. DR MANE-Select; ENST00000636147.2; ENSP00000490105.1; NM_001042432.2; NP_001035897.1. DR UCSC; uc002dpo.4; human. [Q13286-1] DR AGR; HGNC:2074; -. DR CTD; 1201; -. DR DisGeNET; 1201; -. DR GeneCards; CLN3; -. DR HGNC; HGNC:2074; CLN3. DR HPA; ENSG00000188603; Low tissue specificity. DR MalaCards; CLN3; -. DR MIM; 204200; phenotype. DR MIM; 607042; gene. DR neXtProt; NX_Q13286; -. DR OpenTargets; ENSG00000188603; -. DR OpenTargets; ENSG00000261832; -. DR Orphanet; 79264; Juvenile neuronal ceroid lipofuscinosis. DR PharmGKB; PA26601; -. DR VEuPathDB; HostDB:ENSG00000188603; -. DR eggNOG; KOG3880; Eukaryota. DR GeneTree; ENSGT00390000003249; -. DR HOGENOM; CLU_1098212_0_0_1; -. DR InParanoid; Q13286; -. DR OMA; WLCNWQV; -. DR OrthoDB; 2912995at2759; -. DR PhylomeDB; Q13286; -. DR TreeFam; TF314055; -. DR PathwayCommons; Q13286; -. DR SignaLink; Q13286; -. DR BioGRID-ORCS; 1201; 14 hits in 1170 CRISPR screens. DR ChiTaRS; CLN3; human. DR GeneWiki; CLN3; -. DR GenomeRNAi; 1201; -. DR Pharos; Q13286; Tbio. DR PRO; PR:Q13286; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q13286; Protein. DR Bgee; ENSG00000188603; Expressed in mucosa of transverse colon and 98 other cell types or tissues. DR ExpressionAtlas; Q13286; baseline and differential. DR GO; GO:0044754; C:autolysosome; ISS:UniProtKB. DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB. DR GO; GO:0005901; C:caveola; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IMP:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IDA:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB. DR GO; GO:0048306; F:calcium-dependent protein binding; IEA:Ensembl. DR GO; GO:0051861; F:glycolipid binding; IDA:UniProtKB. DR GO; GO:0120146; F:sulfatide binding; IDA:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl. DR GO; GO:0001508; P:action potential; ISS:UniProtKB. DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IDA:UniProtKB. DR GO; GO:0008306; P:associative learning; ISS:UniProtKB. DR GO; GO:0097352; P:autophagosome maturation; ISS:UniProtKB. DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB. DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEA:Ensembl. DR GO; GO:0046474; P:glycerophospholipid biosynthetic process; IMP:UniProtKB. DR GO; GO:0046836; P:glycolipid transport; IMP:UniProtKB. DR GO; GO:0090160; P:Golgi to lysosome transport; IMP:UniProtKB. DR GO; GO:0009992; P:intracellular water homeostasis; ISS:UniProtKB. DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB. DR GO; GO:1903826; P:L-arginine transmembrane transport; IDA:UniProtKB. DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB. DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB. DR GO; GO:0035752; P:lysosomal lumen pH elevation; IDA:UniProtKB. DR GO; GO:1905146; P:lysosomal protein catabolic process; ISS:UniProtKB. DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB. DR GO; GO:0061024; P:membrane organization; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0045861; P:negative regulation of proteolysis; ISS:UniProtKB. DR GO; GO:0050885; P:neuromuscular process controlling balance; ISS:UniProtKB. DR GO; GO:0090384; P:phagosome-lysosome docking; ISS:UniProtKB. DR GO; GO:0090385; P:phagosome-lysosome fusion; ISS:UniProtKB. DR GO; GO:0044857; P:plasma membrane raft organization; ISS:UniProtKB. DR GO; GO:2001288; P:positive regulation of caveolin-mediated endocytosis; ISS:UniProtKB. DR GO; GO:0042998; P:positive regulation of Golgi to plasma membrane protein transport; ISS:UniProtKB. DR GO; GO:0048549; P:positive regulation of pinocytosis; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0016485; P:protein processing; ISS:UniProtKB. DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:UniProtKB. DR GO; GO:1900079; P:regulation of arginine biosynthetic process; ISS:UniProtKB. DR GO; GO:1901096; P:regulation of autophagosome maturation; ISS:UniProtKB. DR GO; GO:0016243; P:regulation of autophagosome size; IEA:Ensembl. DR GO; GO:0106049; P:regulation of cellular response to osmotic stress; IMP:UniProtKB. DR GO; GO:0051493; P:regulation of cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:UniProtKB. DR GO; GO:0010762; P:regulation of fibroblast migration; IMP:UniProtKB. DR GO; GO:0051489; P:regulation of filopodium assembly; IEA:Ensembl. DR GO; GO:1905244; P:regulation of modification of synaptic structure; ISS:UniProtKB. DR GO; GO:1905162; P:regulation of phagosome maturation; ISS:UniProtKB. DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:0070613; P:regulation of protein processing; IMP:UniProtKB. DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; ISS:UniProtKB. DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; ISS:UniProtKB. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:UniProtKB. DR GO; GO:0036359; P:renal potassium excretion; ISS:UniProtKB. DR GO; GO:0047496; P:vesicle transport along microtubule; IMP:UniProtKB. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR003492; Battenin_disease_Cln3. DR InterPro; IPR018460; Battenin_disease_Cln3_subgr. DR InterPro; IPR036259; MFS_trans_sf. DR PANTHER; PTHR10981; BATTENIN; 1. DR PANTHER; PTHR10981:SF0; BATTENIN; 1. DR Pfam; PF02487; CLN3; 1. DR PIRSF; PIRSF015974; CLN3_BTN1; 1. DR PRINTS; PR01315; BATTENIN. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR Genevisible; Q13286; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cytoplasmic vesicle; Disease variant; KW Endosome; Glycoprotein; Golgi apparatus; Lipoprotein; Lysosome; Membrane; KW Methylation; Neurodegeneration; Neuronal ceroid lipofuscinosis; KW Phosphoprotein; Prenylation; Reference proteome; Synapse; Synaptosome; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..435 FT /note="Battenin" FT /id="PRO_0000089857" FT PROPEP 436..438 FT /note="Removed in mature form" FT /evidence="ECO:0000305" FT /id="PRO_0000422290" FT TOPO_DOM 1..37 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:14699076" FT TRANSMEM 38..58 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 59..127 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 128..148 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 149..151 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 152..172 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 173..182 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 183..203 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 204..277 FT /note="Cytoplasmic" FT /evidence="ECO:0000255, ECO:0000305|PubMed:12706816, FT ECO:0000305|PubMed:14699076" FT TRANSMEM 278..298 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 299..346 FT /note="Lumenal" FT /evidence="ECO:0000255, ECO:0000305|PubMed:12706816" FT TRANSMEM 347..367 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 368..438 FT /note="Cytoplasmic" FT /evidence="ECO:0000255, ECO:0000305|PubMed:12706816, FT ECO:0000305|PubMed:14699076" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 237..268 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 242..244 FT /note="Lysosomal targeting motif" FT /evidence="ECO:0000269|PubMed:15469932" FT MOTIF 253..254 FT /note="Lysosomal targeting motif. Required for AP1G1, AP2A2 FT and AP3D1 interaction" FT /evidence="ECO:0000269|PubMed:14699076, FT ECO:0000269|PubMed:15469932, ECO:0000269|PubMed:15598649" FT MOTIF 409..419 FT /note="Lysosomal targeting motif" FT /evidence="ECO:0000269|PubMed:14699076" FT COMPBIAS 10..24 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 14 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 435 FT /note="Cysteine methyl ester" FT /evidence="ECO:0000305" FT LIPID 435 FT /note="S-farnesyl cysteine" FT /evidence="ECO:0000269|PubMed:17286803" FT CARBOHYD 71 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17286803" FT CARBOHYD 85 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17286803" FT CARBOHYD 310 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 75..98 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057347" FT VAR_SEQ 99..127 FT /note="AVLLADILPTLVIKLLAPLGLHLLPYSPR -> PPGSRQWDLCCWKLRPGCL FT FSFCGDQPVC (in isoform 6)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_047631" FT VAR_SEQ 128..226 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_047632" FT VAR_SEQ 155..264 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_004169" FT VAR_SEQ 178..225 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_004166" FT VAR_SEQ 280..302 FT /note="GLLWYIVPLVVVYFAEYFINQGL -> VRMMAG (in isoform 3)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_004167" FT VAR_SEQ 322..438 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_004168" FT VAR_SEQ 353..438 FT /note="CLNLVFLLADVWFGFLPSIYLVFLIILYEGLLGGAAYVNTFHNIALETSDEH FT REFAMAATCISDTLGISLSGLLALPLHDFLCQLS -> MESRSVAQAGM (in FT isoform 5)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_004170" FT VARIANT 101 FT /note="L -> P (in CLN3; dbSNP:rs386833714)" FT /evidence="ECO:0000269|PubMed:21990111, FT ECO:0000269|PubMed:9311735" FT /id="VAR_005131" FT VARIANT 134 FT /note="C -> R (in CLN3; dbSNP:rs386833719)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066892" FT VARIANT 170 FT /note="L -> P (in CLN3; Decreases synthesis of FT bis(monoacylglycerol)phosphate.; dbSNP:rs386833727)" FT /evidence="ECO:0000269|PubMed:17482562, FT ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:9311735" FT /id="VAR_005132" FT VARIANT 187 FT /note="G -> A (in CLN3; dbSNP:rs386833730)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066893" FT VARIANT 189 FT /note="G -> R (in CLN3; dbSNP:rs386833731)" FT /evidence="ECO:0000269|PubMed:21990111" FT /id="VAR_066894" FT VARIANT 295 FT /note="E -> K (in CLN3; the mutant is located to vesicles FT clustered in a perinuclear region. Does not affect protein FT synthesis and maturation. Does not affect lysosomal FT localization.; dbSNP:rs121434286)" FT /evidence="ECO:0000269|PubMed:10332042, FT ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:22261744, FT ECO:0000269|PubMed:9311735, ECO:0000269|PubMed:9490299" FT /id="VAR_005133" FT VARIANT 330 FT /note="V -> F (in CLN3; dbSNP:rs386833744)" FT /evidence="ECO:0000269|PubMed:9311735" FT /id="VAR_005134" FT VARIANT 334 FT /note="R -> C (in CLN3; Does not affect lysosomal FT localization. Does not affect lysosomal protein catabolic FT process. Does not affect lysosomal pH; dbSNP:rs386833694)" FT /evidence="ECO:0000269|PubMed:10924275, FT ECO:0000269|PubMed:9311735" FT /id="VAR_005135" FT VARIANT 334 FT /note="R -> H (in CLN3; dbSNP:rs386833695)" FT /evidence="ECO:0000269|PubMed:21990111, FT ECO:0000269|PubMed:9311735" FT /id="VAR_005136" FT VARIANT 399 FT /note="Missing (in CLN3; Loss of lysosomal localization)" FT /evidence="ECO:0000269|PubMed:14699076" FT /id="VAR_083168" FT MUTAGEN 242..244 FT /note="EEE->AAA: Loss of lysosomal targeting; when FT associated with A-409 and A-419. Loss of lysosomal FT localization; when associated with A-246." FT /evidence="ECO:0000269|PubMed:14699076, FT ECO:0000269|PubMed:15469932" FT MUTAGEN 246 FT /note="E->A: Loss of lysosomal localization; when FT associated with 242-A--A-244." FT /evidence="ECO:0000269|PubMed:15469932" FT MUTAGEN 253..254 FT /note="LI->AA: Does not affect lysosomal localization in FT AP3D1 or AP2A2 or AP1G1 deficient cells. Abolishes the FT interaction of AP3D1, AP2A2 and AP1G1. Loss of lysosomal FT localization." FT /evidence="ECO:0000269|PubMed:15469932, FT ECO:0000269|PubMed:15598649" FT MUTAGEN 253 FT /note="L->A: Loss of lysosomal targeting; when associated FT with A-254. Does not affect interaction with CLN5; when FT associated with A-254. Does not affect interaction with FT CLN5; when associated with A-254; A-409 and A-419. Loss of FT lysosomal targeting; when associated with A-254; A-409 and FT A-409." FT /evidence="ECO:0000269|PubMed:14699076" FT MUTAGEN 254 FT /note="I->A: Loss of lysosomal targeting. Does not affect FT interaction with CLN5; when associated with A-253. Does not FT affect interaction with CLN5; when associated with A-253; FT A-409 and A-419. Loss of lysosomal targeting; when FT associated with A-253; A-409 and A-409." FT /evidence="ECO:0000269|PubMed:14699076" FT MUTAGEN 310 FT /note="N->Q: Does not affect glycosylation." FT /evidence="ECO:0000269|PubMed:12706816" FT MUTAGEN 409 FT /note="M->A: Does not affect lysosomal targeting; when FT associated with A-419. Loss of lysosomal targeting; when FT associated with A-253 and A-254. Loss of lysosomal FT targeting; when associated with 242-A--A-244 and A-419. FT Does not affect interaction with CLN5; when associated with FT A-419. Does not affect interaction with CLN5; when FT associated with A-253; A-254 and A-419. Loss of lysosomal FT targeting; when associated with A-253; A-254 and A-419. FT Loss of lysosomal localization in AP3D1 or AP1G1 deficient FT cells; when associated with A-419." FT /evidence="ECO:0000269|PubMed:14699076, FT ECO:0000269|PubMed:15598649" FT MUTAGEN 419 FT /note="G->A: Does not affect lysosomal targeting; when FT associated with A-409. Loss of lysosomal targeting; when FT associated with A-253 and A-254. Loss of lysosomal FT targeting; when associated with 242-A--A-244 and A-409. FT Does not affect interaction with CLN5; when associated with FT A-409. Does not affect interaction with CLN5; when FT associated with A-253; A-254 and A-409. Loss of lysosomal FT targeting; when associated with A-253; A-254 and A-409. FT Loss of lysosomal localization in AP3D1 or AP1G1 deficient FT cells; when associated with A-409." FT /evidence="ECO:0000269|PubMed:14699076, FT ECO:0000269|PubMed:15598649" FT CONFLICT 259 FT /note="P -> L (in Ref. 5; BAG35838)" FT /evidence="ECO:0000305" SQ SEQUENCE 438 AA; 47623 MW; BE25E973CEEC4FD5 CRC64; MGGCAGSRRR FSDSEGEETV PEPRLPLLDH QGAHWKNAVG FWLLGLCNNF SYVVMLSAAH DILSHKRTSG NQSHVDPGPT PIPHNSSSRF DCNSVSTAAV LLADILPTLV IKLLAPLGLH LLPYSPRVLV SGICAAGSFV LVAFSHSVGT SLCGVVFASI SSGLGEVTFL SLTAFYPRAV ISWWSSGTGG AGLLGALSYL GLTQAGLSPQ QTLLSMLGIP ALLLASYFLL LTSPEAQDPG GEEEAESAAR QPLIRTEAPE SKPGSSSSLS LRERWTVFKG LLWYIVPLVV VYFAEYFINQ GLFELLFFWN TSLSHAQQYR WYQMLYQAGV FASRSSLRCC RIRFTWALAL LQCLNLVFLL ADVWFGFLPS IYLVFLIILY EGLLGGAAYV NTFHNIALET SDEHREFAMA ATCISDTLGI SLSGLLALPL HDFLCQLS //