CLN3_HUMAN
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 03-AUG-2022, entry version 197.
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 ---------------------------------------------------------------------------
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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; 115.
DR IntAct; Q13286; 42.
DR MINT; Q13286; -.
DR STRING; 9606.ENSP00000454229; -.
DR TCDB; 2.A.57.5.8; the equilibrative nucleoside transporter (ent) family.
DR GlyGen; Q13286; 3 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; Q13286; -.
DR PeptideAtlas; Q13286; -.
DR PRIDE; 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 ABCD; Q13286; 1 sequenced antibody.
DR Antibodypedia; 26372; 190 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 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; 228346; CLN3 disease.
DR PharmGKB; PA26601; -.
DR VEuPathDB; HostDB:ENSG00000188603; -.
DR eggNOG; KOG3880; Eukaryota.
DR GeneTree; ENSGT00390000003249; -.
DR GeneTree; ENSGT00540000072033; -.
DR HOGENOM; CLU_1098212_0_0_1; -.
DR InParanoid; Q13286; -.
DR OMA; WLCNWQV; -.
DR PhylomeDB; Q13286; -.
DR TreeFam; TF314055; -.
DR PathwayCommons; Q13286; -.
DR SignaLink; Q13286; -.
DR BioGRID-ORCS; 1201; 13 hits in 1089 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 97 other tissues.
DR ExpressionAtlas; Q13286; baseline and differential.
DR Genevisible; Q13286; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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: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:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; 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: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:0005773; C:vacuole; IBA:GO_Central.
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:0009992; P:cellular water homeostasis; ISS:UniProtKB.
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: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:0043086; P:negative regulation of catalytic activity; ISS: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:0042133; P:neurotransmitter metabolic process; 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:0006468; P:protein phosphorylation; 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:0051453; P:regulation of intracellular pH; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR003492; Battenin_disease_Cln3.
DR InterPro; IPR018460; Battenin_disease_Cln3_subgr.
DR InterPro; IPR036259; MFS_trans_sf.
DR PANTHER; PTHR10981; PTHR10981; 1.
DR Pfam; PF02487; CLN3; 1.
DR PIRSF; PIRSF015974; CLN3_BTN1; 1.
DR PRINTS; PR01315; BATTENIN.
DR SUPFAM; SSF103473; SSF103473; 1.
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
