ID GNPTA_HUMAN Reviewed; 1256 AA. AC Q3T906; A2RRQ9; Q3ZQK2; Q6IPW5; Q86TQ2; Q96N13; Q9ULL2; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2005, sequence version 1. DT 27-MAR-2024, entry version 160. DE RecName: Full=N-acetylglucosamine-1-phosphotransferase subunits alpha/beta; DE EC=2.7.8.17 {ECO:0000269|PubMed:19955174}; DE AltName: Full=GlcNAc-1-phosphotransferase subunits alpha/beta; DE AltName: Full=Stealth protein GNPTAB; DE AltName: Full=UDP-N-acetylglucosamine-1-phosphotransferase subunits alpha/beta; DE Contains: DE RecName: Full=N-acetylglucosamine-1-phosphotransferase subunit alpha; DE Contains: DE RecName: Full=N-acetylglucosamine-1-phosphotransferase subunit beta; DE Flags: Precursor; GN Name=GNPTAB; Synonyms=GNPTA, KIAA1208; 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), SUBCELLULAR LOCATION, AND RP INVOLVEMENT IN MLII. RX PubMed=16200072; DOI=10.1038/nm1305; RA Tiede S., Storch S., Luebke T., Henrissat B., Bargal R., RA Raas-Rothschild A., Braulke T.; RT "Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta RT GlcNAc-1-phosphotransferase."; RL Nat. Med. 11:1109-1112(2005). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RX PubMed=16120602; DOI=10.1074/jbc.m509008200; RA Kudo M., Bao M., D'Souza A., Ying F., Pan H., Roe B.A., Canfield W.M.; RT "The alpha- and beta-subunits of the human UDP-N- RT acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase RT are encoded by a single cDNA."; RL J. Biol. Chem. 280:36141-36149(2005). RN [3] RP ERRATUM OF PUBMED:16120602. RA Kudo M., Bao M., D'Souza A., Ying F., Pan H., Roe B.A., Canfield W.M.; RL J. Biol. Chem. 280:42476-42476(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Liver; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-847 (ISOFORM 1). 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 MRNA] OF 307-1256 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10574462; DOI=10.1093/dnares/6.5.337; RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XV. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:337-345(1999). RN [7] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [8] RP IDENTIFICATION AS A STEALTH PROTEIN, AND PUTATIVE FUNCTION. RX PubMed=16299590; DOI=10.1371/journal.pcbi.0010063; RA Sperisen P., Schmid C.D., Bucher P., Zilian O.; RT "Stealth proteins: in silico identification of a novel protein family RT rendering bacterial pathogens invisible to host immune defense."; RL PLoS Comput. Biol. 1:492-499(2005). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-699. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=19955174; DOI=10.1074/jbc.m109.068650; RA Qian Y., Lee I., Lee W.S., Qian M., Kudo M., Canfield W.M., Lobel P., RA Kornfeld S.; RT "Functions of the alpha, beta, and gamma subunits of UDP-GlcNAc:lysosomal RT enzyme N-acetylglucosamine-1-phosphotransferase."; RL J. Biol. Chem. 285:3360-3370(2010). RN [11] RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, GLYCOSYLATION, AND RP MUTAGENESIS OF ARG-925; LEU-927 AND LYS-928. RX PubMed=21719679; DOI=10.1126/science.1205677; RA Marschner K., Kollmann K., Schweizer M., Braulke T., Pohl S.; RT "A key enzyme in the biogenesis of lysosomes is a protease that regulates RT cholesterol metabolism."; RL Science 333:87-90(2011). RN [12] RP INVOLVEMENT IN MLII. RX PubMed=23773965; DOI=10.1016/j.ygeno.2013.06.001; RA Yang Y., Wu J., Liu H., Chen X., Wang Y., Zhao M., He X.; RT "Two homozygous nonsense mutations of GNPTAB gene in two Chinese families RT with mucolipidosis II alpha/beta using targeted next-generation RT sequencing."; RL Genomics 102:169-173(2013). RN [13] RP INTERACTION WITH LYSET. RX PubMed=36074821; DOI=10.1126/science.abn5648; RA Richards C.M., Jabs S., Qiao W., Varanese L.D., Schweizer M., Mosen P.R., RA Riley N.M., Kluessendorf M., Zengel J.R., Flynn R.A., Rustagi A., RA Widen J.C., Peters C.E., Ooi Y.S., Xie X., Shi P.Y., Bartenschlager R., RA Puschnik A.S., Bogyo M., Bertozzi C.R., Blish C.A., Winter D., RA Nagamine C.M., Braulke T., Carette J.E.; RT "The human disease gene LYSET is essential for lysosomal enzyme transport RT and viral infection."; RL Science 2022:eabn5648-eabn5648(2022). RN [14] RP CHARACTERIZATION OF VARIANTS MLIIIA GLN-4 AND TYR-15. RX PubMed=24550498; DOI=10.1073/pnas.1401417111; RA van Meel E., Qian Y., Kornfeld S.A.; RT "Mislocalization of phosphotransferase as a cause of mucolipidosis III RT alphabeta."; RL Proc. Natl. Acad. Sci. U.S.A. 111:3532-3537(2014). RN [15] RP CHARACTERIZATION OF VARIANTS MLII LEU-81; ASP-182; PRO-205; LEU-334; RP LEU-348; LEU-374; ASN-732; ARG-928; VAL-955; CYS-986; PRO-1001; VAL-1054 RP AND MET-1236, CHARACTERIZATION OF VARIANTS MLIIIA GLN-4; TYR-15; VAL-190; RP GLN-334; PHE-399; THR-403; ALA-407; TYR-442; GLY-461; SER-468; TYR-505; RP PRO-587; PRO-926; TYR-956; GLY-1018 AND SER-1153, AND CHARACTERIZATION OF RP VARIANTS ARG-523; THR-592 AND TRP-785. RX PubMed=25505245; DOI=10.1074/jbc.m114.612507; RA Qian Y., van Meel E., Flanagan-Steet H., Yox A., Steet R., Kornfeld S.; RT "Analysis of mucolipidosis II/III GNPTAB missense mutations identifies RT domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved RT in catalytic function and lysosomal enzyme recognition."; RL J. Biol. Chem. 290:3045-3056(2015). RN [16] RP VARIANT MLIIIA ALA-407, AND VARIANT GLY-662. RX PubMed=16094673; DOI=10.1002/ajmg.a.30868; RA Tiede S., Muschol N., Reutter G., Cantz M., Ullrich K., Braulke T.; RT "Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta RT subunit gene in a patient with mucolipidosis III and a mild clinical RT phenotype."; RL Am. J. Med. Genet. A 137:235-240(2005). RN [17] RP VARIANT MLIIIA GLN-4. RX PubMed=16465621; DOI=10.1086/500849; RA Kudo M., Brem M.S., Canfield W.M.; RT "Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical RT pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc- RT phosphotransferase alpha/beta-subunits precursor gene."; RL Am. J. Hum. Genet. 78:451-463(2006). RN [18] RP VARIANT MLII MET-1236. RX PubMed=16835905; DOI=10.1002/humu.9443; RA Tiede S., Cantz M., Spranger J., Braulke T.; RT "Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene RT (GNPTA) in a patient with mucolipidosis II induces changes in the size and RT cellular distribution of GNPTG."; RL Hum. Mutat. 27:830-831(2006). RN [19] RP VARIANT MLIIIA PHE-399. RX PubMed=16630736; DOI=10.1016/j.ymgme.2006.03.003; RA Bargal R., Zeigler M., Abu-Libdeh B., Zuri V., Mandel H., Ben Neriah Z., RA Stewart F., Elcioglu N., Hindi T., Le Merrer M., Bach G., RA Raas-Rothschild A.; RT "When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 RT patients."; RL Mol. Genet. Metab. 88:359-363(2006). RN [20] RP VARIANT MLIIIA PRO-587. RX PubMed=17034777; DOI=10.1016/j.cca.2006.09.004; RA Lam C.W., Yan M.S., Li C.K., Lau K.C., Tong S.F., Tang H.Y.; RT "DNA-based diagnosis of mucolipidosis type IIIA and mucopolysacchariodisis RT type VI in a Chinese family: a chance of 1 in 7.6 trillion."; RL Clin. Chim. Acta 376:250-252(2007). RN [21] RP VARIANTS MLII ASP-182; PRO-205; ASN-732; ARG-928; VAL-955 AND VAL-1054, RP VARIANT MLIIIA GLN-4, AND CHARACTERIZATION OF VARIANT MLIIIA GLN-4. RX PubMed=19938078; DOI=10.1002/ajmg.a.33134; RA Zarghooni M., Dittakavi S.S.; RT "Molecular analysis of cell lines from patients with mucolipidosis II and RT mucolipidosis III."; RL Am. J. Med. Genet. A 149A:2753-2761(2009). RN [22] RP VARIANTS MLIIIA THR-403; TYR-442; GLY-461 AND PRO-926, AND VARIANT MLII RP PRO-1001. RX PubMed=19634183; DOI=10.1002/humu.21099; RA Tappino B., Chuzhanova N.A., Regis S., Dardis A., Corsolini F., RA Stroppiano M., Tonoli E., Beccari T., Rosano C., Mucha J., Blanco M., RA Szlago M., Di Rocco M., Cooper D.N., Filocamo M.; RT "Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate RT transferase alpha- and beta-subunit (GNPTAB) gene mutations causing RT mucolipidosis types IIalpha/beta and IIIalpha/beta in 46 patients."; RL Hum. Mutat. 30:E956-E973(2009). RN [23] RP VARIANTS MLII LEU-334 AND LEU-374, AND VARIANTS MLIIIA LEU-374; TYR-956 AND RP SER-1153. RX PubMed=19197337; DOI=10.1038/jhg.2009.3; RA Otomo T., Muramatsu T., Yorifuji T., Okuyama T., Nakabayashi H., Fukao T., RA Ohura T., Yoshino M., Tanaka A., Okamoto N., Inui K., Ozono K., Sakai N.; RT "Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese RT patients showed genotype-phenotype correlation."; RL J. Hum. Genet. 54:145-151(2009). RN [24] RP VARIANTS MLIIIA GLN-4; TYR-15; VAL-190; GLN-334; PHE-399; SER-468; TYR-505; RP ARG-956 AND GLY-1018, AND VARIANT MLII LEU-348. RX PubMed=19617216; DOI=10.1136/jmg.2009.067736; RA Cathey S.S., Leroy J.G., Wood T., Eaves K., Simensen R.J., Kudo M., RA Stevenson R.E., Friez M.J.; RT "Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of RT 61 probands."; RL J. Med. Genet. 47:38-48(2010). RN [25] RP VARIANTS SER-455; LEU-625 AND LYS-1200, AND POSSIBLE INVOLVEMENT IN RP PERSISTENT STUTTERING. RX PubMed=20147709; DOI=10.1056/nejmoa0902630; RA Kang C., Riazuddin S., Mundorff J., Krasnewich D., Friedman P., RA Mullikin J.C., Drayna D.; RT "Mutations in the lysosomal enzyme-targeting pathway and persistent RT stuttering."; RL N. Engl. J. Med. 362:677-685(2010). RN [26] RP VARIANT MLII CYS-986. RX PubMed=22495880; DOI=10.1002/ajmg.a.35295; RA Coutinho M.F., Santos L.S., Girisha K.M., Satyamoorthy K., Lacerda L., RA Prata M.J., Alves S.; RT "Mucolipidosis type II alpha/beta with a homozygous missense mutation in RT the GNPTAB gene."; RL Am. J. Med. Genet. A 158A:1225-1228(2012). RN [27] RP VARIANT MLIIIA GLN-4, AND CHARACTERIZATION OF VARIANT MLIIIA GLN-4. RX PubMed=24045841; DOI=10.1038/ejhg.2013.207; RA Leroy J.G., Sillence D., Wood T., Barnes J., Lebel R.R., Friez M.J., RA Stevenson R.E., Steet R., Cathey S.S.; RT "A novel intermediate mucolipidosis II/IIIalphabeta caused by GNPTAB RT mutation in the cytosolic N-terminal domain."; RL Eur. J. Hum. Genet. 22:594-601(2014). RN [28] RP VARIANT MLII LEU-81, AND VARIANTS MLIIIA PHE-399; THR-403 AND TYR-505. RX PubMed=23566849; DOI=10.1016/j.gene.2013.03.105; RA Cury G.K., Matte U., Artigalas O., Alegra T., Velho R.V., Sperb F., RA Burin M.G., Ribeiro E.M., Lourenco C.M., Kim C.A., Valadares E.R., RA Galera M.F., Acosta A.X., Schwartz I.V.; RT "Mucolipidosis II and III alpha/beta in Brazil: analysis of the GNPTAB RT gene."; RL Gene 524:59-64(2013). RN [29] RP VARIANTS MLII LEU-81; CYS-986 AND MET-1236, VARIANT MLIIIA PHE-399, RP CHARACTERIZATION OF VARIANTS MLII LEU-81; CYS-986 AND MET-1236, RP CHARACTERIZATION OF VARIANT MLIIIA PHE-399, SUBCELLULAR LOCATION, RP PROTEOLYTIC PROCESSING, AND GLYCOSYLATION. RX PubMed=24375680; DOI=10.1002/humu.22502; RA De Pace R., Coutinho M.F., Koch-Nolte F., Haag F., Prata M.J., Alves S., RA Braulke T., Pohl S.; RT "Mucolipidosis II-related mutations inhibit the exit from the endoplasmic RT reticulum and proteolytic cleavage of GlcNAc-1-phosphotransferase precursor RT protein (GNPTAB)."; RL Hum. Mutat. 35:368-376(2014). RN [30] RP VARIANT MLII ASN-732, CHARACTERIZATION OF VARIANT MLII ASN-732, FUNCTION, RP AND SUBCELLULAR LOCATION. RX PubMed=23733939; DOI=10.1073/pnas.1308453110; RA Qian Y., Flanagan-Steet H., van Meel E., Steet R., Kornfeld S.A.; RT "The DMAP interaction domain of UDP-GlcNAc:lysosomal enzyme N- RT acetylglucosamine-1-phosphotransferase is a substrate recognition module."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10246-10251(2013). RN [31] RP VARIANTS THR-592 AND TRP-785. RX PubMed=24767253; DOI=10.1186/1750-1172-9-59; RA Fernandez-Marmiesse A., Morey M., Pineda M., Eiris J., Couce M.L., RA Castro-Gago M., Fraga J.M., Lacerda L., Gouveia S., Perez-Poyato M.S., RA Armstrong J., Castineiras D., Cocho J.A.; RT "Assessment of a targeted resequencing assay as a support tool in the RT diagnosis of lysosomal storage disorders."; RL Orphanet J. Rare Dis. 9:59-59(2014). RN [32] RP VARIANTS MLIIIA MET-644 AND THR-1223 DEL, CHARACTERIZATION OF VARIANTS RP MLIIIA PHE-399; THR-403; TYR-505; ARG-575; MET-644 AND THR-1223 DEL, RP CHARACTERIZATION OF VARIANT MLII 937-TYR--MET-972 DEL, MUTAGENESIS OF RP ILE-346 AND TRP-357, SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=25788519; DOI=10.1093/hmg/ddv100; RA Velho R.V., De Pace R., Kluender S., Sperb-Ludwig F., Lourenco C.M., RA Schwartz I.V., Braulke T., Pohl S.; RT "Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1- RT phosphotransferase interaction domain and an alternative site-1 protease RT cleavage site."; RL Hum. Mol. Genet. 24:3497-3505(2015). RN [33] RP VARIANT MLII CYS-986, AND VARIANT ARG-523. RX PubMed=24798265; DOI=10.1007/8904_2014_308; RA Cobos P.N., Steglich C., Santer R., Lukacs Z., Gal A.; RT "Dried blood spots allow targeted screening to diagnose RT mucopolysaccharidosis and mucolipidosis."; RL JIMD Rep. 15:123-132(2015). RN [34] RP VARIANT LYS-1200. RX PubMed=27535533; DOI=10.1038/nature19057; RG Exome Aggregation Consortium; RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T., RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T., RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J., RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M., RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N., RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P., RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A., RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G., RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M., RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C., RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M., RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M., RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P., RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G., RA Daly M.J., MacArthur D.G.; RT "Analysis of protein-coding genetic variation in 60,706 humans."; RL Nature 536:285-291(2016). RN [35] RP VARIANTS MLII GLY-76; LEU-81; LEU-385 AND 1111-TYR--VAL-1256 DEL, RP CHARACTERIZATION OF VARIANTS MLII GLY-76 AND LEU-385, VARIANTS MLIIIA RP LEU-81; 278-GLN--VAL-1256 DEL; THR-403 AND TYR-505, FUNCTION, SUBCELLULAR RP LOCATION, AND PROTEOLYTIC PROCESSING. RX PubMed=28918368; DOI=10.1016/j.biocel.2017.09.006; RA Ludwig N.F., Velho R.V., Sperb-Ludwig F., Acosta A.X., Ribeiro E.M., RA Kim C.A., Gandelman Horovitz D.D., Boy R., Rodovalho-Doriqui M.J., RA Lourenco C.M., Santos E.S., Braulke T., Pohl S., Schwartz I.V.D.; RT "GNPTAB missense mutations cause loss of GlcNAc-1-phosphotransferase RT activity in mucolipidosis type II through distinct mechanisms."; RL Int. J. Biochem. Cell Biol. 92:90-94(2017). CC -!- FUNCTION: Catalyzes the formation of mannose 6-phosphate (M6P) markers CC on high mannose type oligosaccharides in the Golgi apparatus. M6P CC residues are required to bind to the M6P receptors (MPR), which mediate CC the vesicular transport of lysosomal enzymes to the CC endosomal/prelysosomal compartment. {ECO:0000269|PubMed:19955174, CC ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:28918368}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(4)-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(glycan)]-L- CC asparaginyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = H(+) + CC N(4)-[6-(N-acetyl-alpha-D-glucosaminyl-1-phospho)-alpha-D-mannosyl- CC (1->2)-alpha-D-mannosyl-(glycan)]-L-asparaginyl-[protein] + UMP; CC Xref=Rhea:RHEA:13581, Rhea:RHEA-COMP:14507, Rhea:RHEA-COMP:14508, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:57865, CC ChEBI:CHEBI:140357, ChEBI:CHEBI:140369; EC=2.7.8.17; CC Evidence={ECO:0000269|PubMed:19955174}; CC -!- SUBUNIT: Hexamer of two alpha, two beta and two gamma (GNPTG) subunits; CC disulfide-linked. The alpha and/or the beta subunits of the enzyme CC constitute the catalytic subunits (PubMed:19955174). Interacts with CC LYSET; facilitates proper localization of GNPTAB (PubMed:36074821). CC {ECO:0000269|PubMed:19955174, ECO:0000269|PubMed:36074821}. CC -!- INTERACTION: CC Q3T906; Q8WTP8: AEN; NbExp=3; IntAct=EBI-1104907, EBI-8637627; CC Q3T906; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-1104907, EBI-6658203; CC Q3T906; Q9UJJ9: GNPTG; NbExp=6; IntAct=EBI-1104907, EBI-372067; CC Q3T906; P25786: PSMA1; NbExp=3; IntAct=EBI-1104907, EBI-359352; CC Q3T906; Q96FJ0: STAMBPL1; NbExp=3; IntAct=EBI-1104907, EBI-745021; CC Q3T906; P15622-3: ZNF250; NbExp=3; IntAct=EBI-1104907, EBI-10177272; CC -!- SUBCELLULAR LOCATION: [N-acetylglucosamine-1-phosphotransferase subunit CC alpha]: Golgi apparatus membrane {ECO:0000269|PubMed:16120602, CC ECO:0000269|PubMed:16200072, ECO:0000269|PubMed:21719679, CC ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:24375680, CC ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368}; Single-pass CC type I membrane protein {ECO:0000305}. CC -!- SUBCELLULAR LOCATION: [N-acetylglucosamine-1-phosphotransferase subunit CC beta]: Golgi apparatus membrane {ECO:0000269|PubMed:16120602, CC ECO:0000269|PubMed:16200072, ECO:0000269|PubMed:21719679, CC ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:24375680, CC ECO:0000269|PubMed:28918368}; Single-pass type II membrane protein CC {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q3T906-1; Sequence=Displayed; CC Name=2; CC IsoId=Q3T906-2; Sequence=VSP_017338, VSP_017339; CC -!- TISSUE SPECIFICITY: Expressed in the heart, whole brain, placenta, CC lung, liver, skeletal muscle, kidney and pancreas. CC {ECO:0000269|PubMed:16120602}. CC -!- DOMAIN: The DMAP1-binding domain mediates substrate recognition. It CC specifically recognizes a conformation-dependent protein determinant CC present in acid hydrolases (PubMed:23733939). CC {ECO:0000269|PubMed:23733939}. CC -!- PTM: The alpha- and beta-subunits are generated by a proteolytic CC cleavage by MBTPS1 protease at the Lys-928-Asp-929 bond. CC {ECO:0000269|PubMed:21719679, ECO:0000269|PubMed:24375680, CC ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368}. CC -!- DISEASE: Mucolipidosis type II (MLII) [MIM:252500]: Fatal, autosomal CC recessive, lysosomal storage disorder characterized by severe clinical CC and radiologic features, peculiar fibroblast inclusions, and no CC excessive mucopolysacchariduria. Congenital dislocation of the hip, CC thoracic deformities, hernia, and hyperplastic gums are evident soon CC after birth. {ECO:0000269|PubMed:16200072, ECO:0000269|PubMed:16835905, CC ECO:0000269|PubMed:19197337, ECO:0000269|PubMed:19617216, CC ECO:0000269|PubMed:19634183, ECO:0000269|PubMed:19938078, CC ECO:0000269|PubMed:22495880, ECO:0000269|PubMed:23566849, CC ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:23773965, CC ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24798265, CC ECO:0000269|PubMed:25505245, ECO:0000269|PubMed:25788519, CC ECO:0000269|PubMed:28918368}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mucolipidosis type III complementation group A (MLIIIA) CC [MIM:252600]: Autosomal recessive disease of lysosomal enzyme CC targeting. Clinically MLIII is characterized by restricted joint CC mobility, skeletal dysplasia, and short stature. Mildly coarsened CC facial features and thickening of the skin have been described. Cardiac CC valvular disease and corneal clouding may also occur. Half of the CC reported patients show learning disabilities or intellectual CC disability. {ECO:0000269|PubMed:16094673, ECO:0000269|PubMed:16465621, CC ECO:0000269|PubMed:16630736, ECO:0000269|PubMed:17034777, CC ECO:0000269|PubMed:19197337, ECO:0000269|PubMed:19617216, CC ECO:0000269|PubMed:19634183, ECO:0000269|PubMed:19938078, CC ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:24045841, CC ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24550498, CC ECO:0000269|PubMed:25505245, ECO:0000269|PubMed:25788519, CC ECO:0000269|PubMed:28918368}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Genetic variations in GNPTAB have been suggested to play CC a role in susceptibility to persistent stuttering. Stuttering is a CC common speech disorder characterized by repetitions, prolongations, and CC interruptions in the flow of speech. {ECO:0000269|PubMed:20147709}. CC -!- MISCELLANEOUS: Due to the low pH in the endosomal/prelysosomal CC compartment, the lysosomal enzyme-MPR complex dissociates and then the CC enzyme is delivered to the lysosome. Between 5% and 20% of newly CC synthesized lysosomal enzymes escape the binding to the MPR in the CC Golgi apparatus and are secreted. CC -!- MISCELLANEOUS: Stealth proteins are part of a protein family that is CC conserved from bacteria to higher eukaryotes. Family members were first CC identified in microbes as proteins that help pathogens to elude the CC host innate immune system. Microbial stealth proteins are most likely CC involved in the biosynthesis of exopolysaccharides. Stealth proteins CC are predicted to function as hexose-1-phosphoryltransferases. CC -!- SIMILARITY: Belongs to the stealth family. {ECO:0000305}. 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; AM085438; CAJ30014.1; -; mRNA. DR EMBL; AY687932; AAV98624.1; -; mRNA. DR EMBL; BC071687; AAH71687.1; -; mRNA. DR EMBL; BC042615; AAH42615.1; -; mRNA. DR EMBL; BC131787; AAI31788.1; -; mRNA. DR EMBL; AK056137; BAB71102.1; -; mRNA. DR EMBL; AB033034; BAA86522.2; -; mRNA. DR CCDS; CCDS9088.1; -. [Q3T906-1] DR RefSeq; NP_077288.2; NM_024312.4. [Q3T906-1] DR PDB; 2N6D; NMR; -; A=135-305. DR PDB; 7S05; EM; 3.10 A; A/B=44-1209. DR PDB; 7S06; EM; 3.30 A; A/B=44-1209. DR PDBsum; 2N6D; -. DR PDBsum; 7S05; -. DR PDBsum; 7S06; -. DR AlphaFoldDB; Q3T906; -. DR BMRB; Q3T906; -. DR EMDB; EMD-24784; -. DR EMDB; EMD-24785; -. DR SMR; Q3T906; -. DR BioGRID; 122576; 48. DR ComplexPortal; CPX-6841; N-acetylglucosamine-1-phosphotransferase complex. DR IntAct; Q3T906; 29. DR MINT; Q3T906; -. DR STRING; 9606.ENSP00000299314; -. DR BindingDB; Q3T906; -. DR CarbonylDB; Q3T906; -. DR GlyConnect; 1532; 7 N-Linked glycans (5 sites). DR GlyCosmos; Q3T906; 15 sites, 7 glycans. DR GlyGen; Q3T906; 32 sites, 6 N-linked glycans (3 sites), 3 O-linked glycans (13 sites). DR iPTMnet; Q3T906; -. DR PhosphoSitePlus; Q3T906; -. DR SwissPalm; Q3T906; -. DR BioMuta; GNPTAB; -. DR DMDM; 90185244; -. DR CPTAC; CPTAC-2218; -. DR EPD; Q3T906; -. DR jPOST; Q3T906; -. DR MassIVE; Q3T906; -. DR MaxQB; Q3T906; -. DR PaxDb; 9606-ENSP00000299314; -. DR PeptideAtlas; Q3T906; -. DR ProteomicsDB; 61878; -. [Q3T906-1] DR ProteomicsDB; 61879; -. [Q3T906-2] DR Pumba; Q3T906; -. DR Antibodypedia; 44958; 94 antibodies from 16 providers. DR DNASU; 79158; -. DR Ensembl; ENST00000299314.12; ENSP00000299314.7; ENSG00000111670.16. [Q3T906-1] DR Ensembl; ENST00000549940.5; ENSP00000449150.1; ENSG00000111670.16. [Q3T906-2] DR GeneID; 79158; -. DR KEGG; hsa:79158; -. DR MANE-Select; ENST00000299314.12; ENSP00000299314.7; NM_024312.5; NP_077288.2. DR UCSC; uc001tit.4; human. [Q3T906-1] DR AGR; HGNC:29670; -. DR CTD; 79158; -. DR DisGeNET; 79158; -. DR GeneCards; GNPTAB; -. DR GeneReviews; GNPTAB; -. DR HGNC; HGNC:29670; GNPTAB. DR HPA; ENSG00000111670; Low tissue specificity. DR MalaCards; GNPTAB; -. DR MIM; 252500; phenotype. DR MIM; 252600; phenotype. DR MIM; 607840; gene. DR neXtProt; NX_Q3T906; -. DR OpenTargets; ENSG00000111670; -. DR Orphanet; 576; Mucolipidosis type II. DR Orphanet; 423461; Mucolipidosis type III alpha/beta. DR PharmGKB; PA128394710; -. DR VEuPathDB; HostDB:ENSG00000111670; -. DR eggNOG; ENOG502QQMR; Eukaryota. DR GeneTree; ENSGT00390000006747; -. DR HOGENOM; CLU_002469_0_0_1; -. DR InParanoid; Q3T906; -. DR OMA; MIDRVVM; -. DR OrthoDB; 52303at2759; -. DR PhylomeDB; Q3T906; -. DR TreeFam; TF324175; -. DR BRENDA; 2.7.8.17; 2681. DR PathwayCommons; Q3T906; -. DR SignaLink; Q3T906; -. DR BioGRID-ORCS; 79158; 29 hits in 1191 CRISPR screens. DR ChiTaRS; GNPTAB; human. DR GenomeRNAi; 79158; -. DR Pharos; Q3T906; Tbio. DR PRO; PR:Q3T906; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q3T906; Protein. DR Bgee; ENSG00000111670; Expressed in tibia and 199 other cell types or tissues. DR ExpressionAtlas; Q3T906; baseline and differential. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0003976; F:UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity; IDA:UniProtKB. DR GO; GO:0046835; P:carbohydrate phosphorylation; IDA:UniProtKB. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB. DR GO; GO:0016256; P:N-glycan processing to lysosome; IMP:UniProtKB. DR GO; GO:0033299; P:secretion of lysosomal enzymes; IEA:Ensembl. DR CDD; cd21599; RRM1_GNPTAB; 1. DR CDD; cd21600; RRM2_GNPTAB; 1. DR Gene3D; 3.30.300.320; -; 1. DR InterPro; IPR010506; DMAP1-bd. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR041536; GNPTAB_reg. DR InterPro; IPR035993; Notch-like_dom_sf. DR InterPro; IPR000800; Notch_dom. DR InterPro; IPR047141; Stealth. DR InterPro; IPR031358; Stealth_CR1. DR InterPro; IPR021520; Stealth_CR2. DR InterPro; IPR031357; Stealth_CR3. DR InterPro; IPR031356; Stealth_CR4. DR PANTHER; PTHR24045; -; 1. DR PANTHER; PTHR24045:SF0; N-ACETYLGLUCOSAMINE-1-PHOSPHOTRANSFERASE SUBUNITS ALPHA_BETA; 1. DR Pfam; PF06464; DMAP_binding; 1. DR Pfam; PF18440; GlcNAc-1_reg; 1. DR Pfam; PF00066; Notch; 2. DR Pfam; PF17101; Stealth_CR1; 1. DR Pfam; PF11380; Stealth_CR2; 1. DR Pfam; PF17102; Stealth_CR3; 1. DR Pfam; PF17103; Stealth_CR4; 1. DR SMART; SM01137; DMAP_binding; 1. DR SMART; SM00004; NL; 2. DR SUPFAM; SSF90193; Notch domain; 1. DR PROSITE; PS51912; DMAP1_BIND; 1. DR PROSITE; PS00018; EF_HAND_1; 1. DR PROSITE; PS50222; EF_HAND_2; 1. DR PROSITE; PS50258; LNR; 2. DR Genevisible; Q3T906; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Disease variant; KW Disulfide bond; Glycoprotein; Golgi apparatus; Membrane; Metal-binding; KW Mucolipidosis; Reference proteome; Repeat; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..928 FT /note="N-acetylglucosamine-1-phosphotransferase subunit FT alpha" FT /id="PRO_0000225008" FT CHAIN 929..1256 FT /note="N-acetylglucosamine-1-phosphotransferase subunit FT beta" FT /id="PRO_0000225009" FT TRANSMEM 22..42 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 1215..1235 FT /note="Helical" FT /evidence="ECO:0000255" FT REPEAT 438..473 FT /note="LNR 1" FT REPEAT 505..545 FT /note="LNR 2" FT DOMAIN 699..798 FT /note="DMAP1-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01260" FT DOMAIN 1005..1040 FT /note="EF-hand" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 449 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 464 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 467 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 516 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 531 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 534 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT BINDING 1018 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 1020 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 1022 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 1029 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT SITE 928..929 FT /note="Cleavage; by MBTPS1" FT CARBOHYD 83 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 148 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 179 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 250 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 614 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 699 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 729 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 829 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1009 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1129 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 438..461 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT DISULFID 452..468 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT DISULFID 505..528 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT DISULFID 519..535 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00525" FT VAR_SEQ 471..490 FT /note="NSGGSRYIAGGGGTGSIGVG -> KDVLNCNSFIFMEYFLLNHY (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017338" FT VAR_SEQ 491..1256 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_017339" FT VARIANT 4 FT /note="K -> Q (in MLIIIA; also found in patients with FT intermediate phenotype between MLII and MLIIIA; no effect FT on protein abundance; decreased retention in the Golgi; FT mistargeted to lysosomes and plasma membrane; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs34159654)" FT /evidence="ECO:0000269|PubMed:16465621, FT ECO:0000269|PubMed:19617216, ECO:0000269|PubMed:19938078, FT ECO:0000269|PubMed:24045841, ECO:0000269|PubMed:24550498, FT ECO:0000269|PubMed:25505245" FT /id="VAR_027509" FT VARIANT 15 FT /note="S -> Y (in MLIIIA; uncertain significance; no effect FT on protein abundance; decreased protein cleavage into alpha FT and beta subunits; decreased retention in the Golgi; FT mistargeted to lysosomes and plasma membrane; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864947)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:24550498, ECO:0000269|PubMed:25505245" FT /id="VAR_073124" FT VARIANT 76 FT /note="D -> G (in MLII; loss of Golgi localization; defects FT in protein cleavage into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:28918368" FT /id="VAR_079713" FT VARIANT 81 FT /note="W -> L (in MLII and MLIIIA; no effect on protein FT abundance; decreased localization to the Golgi; defects in FT protein cleavage into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864953)" FT /evidence="ECO:0000269|PubMed:23566849, FT ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:25505245, FT ECO:0000269|PubMed:28918368" FT /id="VAR_070831" FT VARIANT 182 FT /note="V -> D (in MLII; uncertain significance; decreased FT localization to the Golgi; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864958)" FT /evidence="ECO:0000269|PubMed:19938078, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073125" FT VARIANT 190 FT /note="D -> V (in MLIIIA; also found in patients with FT intermediate phenotype between MLII and MLIIIA; uncertain FT significance; no effect on protein abundance; no effect on FT localization to the Golgi; no effect on protein cleavage FT into alpha and beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs34946266)" FT /evidence="ECO:0000269|PubMed:19617216" FT /id="VAR_053545" FT VARIANT 205 FT /note="Q -> P (in MLII; uncertain significance; FT dbSNP:rs281864959)" FT /evidence="ECO:0000269|PubMed:19938078" FT /id="VAR_073126" FT VARIANT 278..1256 FT /note="Missing (in MLIIIA)" FT /evidence="ECO:0000269|PubMed:28918368" FT /id="VAR_079714" FT VARIANT 334 FT /note="R -> L (in MLII; no effect on protein abundance; FT loss of localization to the Golgi; loss of protein cleavage FT into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864970)" FT /evidence="ECO:0000269|PubMed:19197337, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073127" FT VARIANT 334 FT /note="R -> Q (in MLIIIA; no effect on protein abundance; FT loss of localization to the Golgi; loss of protein cleavage FT into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864970)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073128" FT VARIANT 348 FT /note="I -> L (in MLII; uncertain significance; no effect FT on protein abundance; no effect on localization to the FT Golgi; no effect on protein cleavage into alpha and beta FT subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs7958709)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:25505245" FT /id="VAR_027510" FT VARIANT 374 FT /note="F -> L (in MLII and MLIIIA; no effect on protein FT abundance; no effect on localization to the Golgi; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs137852900)" FT /evidence="ECO:0000269|PubMed:19197337, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062807" FT VARIANT 385 FT /note="S -> L (in MLII; no loss of Golgi localization; no FT defects in protein cleavage into alpha and beta subunits; FT loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:28918368" FT /id="VAR_079715" FT VARIANT 399 FT /note="S -> F (in MLIIIA; no effect on protein abundance; FT loss of localization to the Golgi; defects in protein FT cleavage into alpha and beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865026)" FT /evidence="ECO:0000269|PubMed:16630736, FT ECO:0000269|PubMed:19617216, ECO:0000269|PubMed:23566849, FT ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:25505245, FT ECO:0000269|PubMed:25788519" FT /id="VAR_062808" FT VARIANT 403 FT /note="I -> T (in MLIIIA; loss of localization to the FT Golgi; loss of protein cleavage into alpha and beta FT subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281864973)" FT /evidence="ECO:0000269|PubMed:19634183, FT ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:25505245, FT ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368" FT /id="VAR_062809" FT VARIANT 407 FT /note="D -> A (in MLIIIA; no effect on protein abundance; FT no effect on localization to the Golgi; no effect on FT protein cleavage into alpha and beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs137852895)" FT /evidence="ECO:0000269|PubMed:16094673, FT ECO:0000269|PubMed:25505245" FT /id="VAR_025416" FT VARIANT 442 FT /note="C -> Y (in MLIIIA; no effect on localization to the FT Golgi; no effect on protein cleavage into alpha and beta FT subunits; loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity toward some FT substrates; dbSNP:rs281864975)" FT /evidence="ECO:0000269|PubMed:19634183, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062810" FT VARIANT 455 FT /note="A -> S (rare variant; found in individuals suffering FT from stuttering; uncertain significance; FT dbSNP:rs137853822)" FT /evidence="ECO:0000269|PubMed:20147709" FT /id="VAR_073219" FT VARIANT 461 FT /note="C -> G (in MLIIIA; no effect on protein abundance; FT no effect on localization to the Golgi; no effect on FT protein cleavage into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity toward some FT substrates; dbSNP:rs281864977)" FT /evidence="ECO:0000269|PubMed:19634183, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062811" FT VARIANT 468 FT /note="C -> S (in MLIIIA; patients with intermediate FT phenotype between MLII and MLIIIA; no effect on protein FT abundance; no effect on localization to the Golgi; no FT effect on protein cleavage into alpha and beta subunits; FT loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity toward some FT substrates; dbSNP:rs281864979)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073129" FT VARIANT 505 FT /note="C -> Y (in MLIIIA; uncertain significance; decreased FT localization to the Golgi; decreased protein cleavage into FT alpha and beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; reduces FT protein abundance; dbSNP:rs281864980)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:23566849, ECO:0000269|PubMed:25505245, FT ECO:0000269|PubMed:25788519, ECO:0000269|PubMed:28918368" FT /id="VAR_070832" FT VARIANT 523 FT /note="C -> R (found in a patient with mucolipidosis type FT II or III; uncertain significance; decreased localization FT to the Golgi; decreased protein cleavage into alpha and FT beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:24798265, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073130" FT VARIANT 575 FT /note="G -> R (in MLIIIA; significantly reduces protein FT cleavage into alpha and beta subunits; reduces protein FT abundance; significantly decreased localization to the FT Golgi; significantly reduces FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase)" FT /evidence="ECO:0000269|PubMed:25788519" FT /id="VAR_074206" FT VARIANT 587 FT /note="R -> P (in MLIIIA; decreased localization to the FT Golgi; decreased UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs143788461)" FT /evidence="ECO:0000269|PubMed:17034777, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073131" FT VARIANT 592 FT /note="A -> T (found in a patient with mucolipidosis type FT II or III; uncertain significance; decreased localization FT to the Golgi; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs149390820)" FT /evidence="ECO:0000269|PubMed:24767253, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073132" FT VARIANT 625 FT /note="F -> L (rare variant; found in individuals suffering FT from stuttering; uncertain significance; FT dbSNP:rs137853823)" FT /evidence="ECO:0000269|PubMed:20147709" FT /id="VAR_073220" FT VARIANT 644 FT /note="T -> M (in MLIIIA; reduces protein cleavage into FT alpha and beta subunits; reduces protein abundance; no FT effect on subcellular location in Golgi apparatus; mildly FT affects UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase; dbSNP:rs386765812)" FT /evidence="ECO:0000269|PubMed:25788519" FT /id="VAR_074207" FT VARIANT 662 FT /note="A -> G (in dbSNP:rs142172397)" FT /evidence="ECO:0000269|PubMed:16094673" FT /id="VAR_025417" FT VARIANT 732 FT /note="K -> N (in MLII; no effect on localization to the FT Golgi; loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity toward some FT substrates; dbSNP:rs281864989)" FT /evidence="ECO:0000269|PubMed:19938078, FT ECO:0000269|PubMed:23733939, ECO:0000269|PubMed:25505245" FT /id="VAR_070833" FT VARIANT 785 FT /note="L -> W (found in a patient with mucolipidosis type FT II or III; uncertain significance; no effect on FT localization to the Golgi; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity toward some FT substrates; dbSNP:rs144060383)" FT /evidence="ECO:0000269|PubMed:24767253, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073133" FT VARIANT 926 FT /note="Q -> P (in MLIIIA; no effect on localization to the FT Golgi; loss of protein cleavage into alpha and beta FT subunits; loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865002)" FT /evidence="ECO:0000269|PubMed:19634183, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062812" FT VARIANT 928 FT /note="K -> R (in MLII; uncertain significance; FT dbSNP:rs281865003)" FT /evidence="ECO:0000269|PubMed:19938078" FT /id="VAR_073134" FT VARIANT 937..972 FT /note="Missing (in MLII; abnormal protein cleavage into FT alpha and beta subunits; no effect on protein abundance; FT significantly decreased localization to the Golgi; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase)" FT /evidence="ECO:0000269|PubMed:25788519" FT /id="VAR_074208" FT VARIANT 955 FT /note="A -> V (in MLII; uncertain significance; no effect FT on protein abundance; no effect on localization to the FT Golgi; decreased UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs138390866)" FT /evidence="ECO:0000269|PubMed:19938078, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073135" FT VARIANT 956 FT /note="H -> R (in MLIIIA; uncertain significance; FT dbSNP:rs281865005)" FT /evidence="ECO:0000269|PubMed:19617216" FT /id="VAR_073136" FT VARIANT 956 FT /note="H -> Y (in MLIIIA; no effect on protein abundance; FT no effect on localization to the Golgi; dbSNP:rs281865004)" FT /evidence="ECO:0000269|PubMed:19197337, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062813" FT VARIANT 986 FT /note="R -> C (in MLII; decreased protein abundance; no FT effect on localization to the Golgi; no effect on protein FT cleavage into alpha and beta subunits; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs769587233)" FT /evidence="ECO:0000269|PubMed:22495880, FT ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:24798265, FT ECO:0000269|PubMed:25505245" FT /id="VAR_070834" FT VARIANT 1001 FT /note="L -> P (in MLII; no effect on protein abundance; FT decreased localization to the Golgi; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865006)" FT /evidence="ECO:0000269|PubMed:19634183, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062814" FT VARIANT 1018 FT /note="D -> G (in MLIIIA; uncertain significance; patients FT with intermediate phenotype between MLII and MLIIIA; no FT effect on protein abundance; decreased localization to the FT Golgi; loss of UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865007)" FT /evidence="ECO:0000269|PubMed:19617216, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073137" FT VARIANT 1054 FT /note="L -> V (in MLII; uncertain significance; no effect FT on localization to the Golgi; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865010)" FT /evidence="ECO:0000269|PubMed:19938078, FT ECO:0000269|PubMed:25505245" FT /id="VAR_073138" FT VARIANT 1111..1256 FT /note="Missing (in MLII)" FT /evidence="ECO:0000269|PubMed:28918368" FT /id="VAR_079716" FT VARIANT 1153 FT /note="N -> S (in MLIIIA; no effect on protein abundance; FT no effect on localization to the Golgi; loss of FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity; FT dbSNP:rs281865019)" FT /evidence="ECO:0000269|PubMed:19197337, FT ECO:0000269|PubMed:25505245" FT /id="VAR_062815" FT VARIANT 1200 FT /note="E -> K (may be a risk factor for stuttering; FT dbSNP:rs137853825)" FT /evidence="ECO:0000269|PubMed:20147709, FT ECO:0000269|PubMed:27535533" FT /id="VAR_073221" FT VARIANT 1223 FT /note="Missing (in MLIIIA; no effect on protein cleavage FT into alpha and beta subunits; no effect on protein FT abundance; no effect on subcellular location in cis-Golgi FT apparatus; slightly affects FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:25788519" FT /id="VAR_074209" FT VARIANT 1236 FT /note="K -> M (in MLII; decreased protein abundance; no FT effect on localization to the Golgi; does not suppress FT protein cleavage into alpha and beta subunits; decreased FT UDP-N-acetylglucosamine-lysosomal-enzyme FT N-acetylglucosaminephosphotransferase activity)" FT /evidence="ECO:0000269|PubMed:16835905, FT ECO:0000269|PubMed:24375680, ECO:0000269|PubMed:25505245" FT /id="VAR_027511" FT MUTAGEN 346 FT /note="I->A: Partially cleaved by MBTPS1." FT /evidence="ECO:0000269|PubMed:25788519" FT MUTAGEN 357 FT /note="W->A: Abolishes proteolytic cleavage by MBTPS1." FT /evidence="ECO:0000269|PubMed:25788519" FT MUTAGEN 925 FT /note="R->A: Abolishes proteolytic cleavage by MBTPS1." FT /evidence="ECO:0000269|PubMed:21719679" FT MUTAGEN 927 FT /note="L->A: Abolishes proteolytic cleavage by MBTPS1." FT /evidence="ECO:0000269|PubMed:21719679" FT MUTAGEN 928 FT /note="K->A: Abolishes proteolytic cleavage by MBTPS1." FT /evidence="ECO:0000269|PubMed:21719679" FT CONFLICT 392 FT /note="I -> V (in Ref. 2; AAV98624)" FT /evidence="ECO:0000305" FT CONFLICT 901 FT /note="Q -> L (in Ref. 2; AAV98624)" FT /evidence="ECO:0000305" FT HELIX 50..54 FT /evidence="ECO:0007829|PDB:7S05" FT TURN 55..57 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 75..80 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 86..110 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 138..141 FT /evidence="ECO:0007829|PDB:2N6D" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:2N6D" FT TURN 155..157 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 159..161 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 165..172 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 175..184 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 188..196 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 207..210 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 225..231 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 240..244 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 252..256 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 262..265 FT /evidence="ECO:0007829|PDB:2N6D" FT STRAND 267..272 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 274..280 FT /evidence="ECO:0007829|PDB:2N6D" FT HELIX 328..339 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 346..349 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:7S06" FT STRAND 365..368 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 370..373 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 377..379 FT /evidence="ECO:0007829|PDB:7S06" FT HELIX 385..390 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 391..394 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 400..405 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 407..411 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 417..419 FT /evidence="ECO:0007829|PDB:7S05" FT TURN 423..425 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 426..434 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 904..912 FT /evidence="ECO:0007829|PDB:7S06" FT STRAND 915..919 FT /evidence="ECO:0007829|PDB:7S06" FT HELIX 920..922 FT /evidence="ECO:0007829|PDB:7S06" FT HELIX 932..946 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 952..954 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 959..962 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 963..972 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 974..982 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 994..1002 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1010..1017 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1022..1025 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1027..1037 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1044..1060 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1088..1093 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1095..1104 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1108..1111 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1113..1116 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1118..1125 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1130..1142 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1146..1151 FT /evidence="ECO:0007829|PDB:7S05" FT STRAND 1156..1158 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1162..1175 FT /evidence="ECO:0007829|PDB:7S05" FT HELIX 1196..1203 FT /evidence="ECO:0007829|PDB:7S05" SQ SEQUENCE 1256 AA; 143622 MW; 8B861154C516943E CRC64; MLFKLLQRQT YTCLSHRYGL YVCFLGVVVT IVSAFQFGEV VLEWSRDQYH VLFDSYRDNI AGKSFQNRLC LPMPIDVVYT WVNGTDLELL KELQQVREQM EEEQKAMREI LGKNTTEPTK KSEKQLECLL THCIKVPMLV LDPALPANIT LKDLPSLYPS FHSASDIFNV AKPKNPSTNV SVVVFDSTKD VEDAHSGLLK GNSRQTVWRG YLTTDKEVPG LVLMQDLAFL SGFPPTFKET NQLKTKLPEN LSSKVKLLQL YSEASVALLK LNNPKDFQEL NKQTKKNMTI DGKELTISPA YLLWDLSAIS QSKQDEDISA SRFEDNEELR YSLRSIERHA PWVRNIFIVT NGQIPSWLNL DNPRVTIVTH QDVFRNLSHL PTFSSPAIES HIHRIEGLSQ KFIYLNDDVM FGKDVWPDDF YSHSKGQKVY LTWPVPNCAE GCPGSWIKDG YCDKACNNSA CDWDGGDCSG NSGGSRYIAG GGGTGSIGVG QPWQFGGGIN SVSYCNQGCA NSWLADKFCD QACNVLSCGF DAGDCGQDHF HELYKVILLP NQTHYIIPKG ECLPYFSFAE VAKRGVEGAY SDNPIIRHAS IANKWKTIHL IMHSGMNATT IHFNLTFQNT NDEEFKMQIT VEVDTREGPK LNSTAQKGYE NLVSPITLLP EAEILFEDIP KEKRFPKFKR HDVNSTRRAQ EEVKIPLVNI SLLPKDAQLS LNTLDLQLEH GDITLKGYNL SKSALLRSFL MNSQHAKIKN QAIITDETND SLVAPQEKQV HKSILPNSLG VSERLQRLTF PAVSVKVNGH DQGQNPPLDL ETTARFRVET HTQKTIGGNV TKEKPPSLIV PLESQMTKEK KITGKEKENS RMEENAENHI GVTEVLLGRK LQHYTDSYLG FLPWEKKKYF QDLLDEEESL KTQLAYFTDS KNTGRQLKDT FADSLRYVNK ILNSKFGFTS RKVPAHMPHM IDRIVMQELQ DMFPEEFDKT SFHKVRHSED MQFAFSYFYY LMSAVQPLNI SQVFDEVDTD QSGVLSDREI RTLATRIHEL PLSLQDLTGL EHMLINCSKM LPADITQLNN IPPTQESYYD PNLPPVTKSL VTNCKPVTDK IHKAYKDKNK YRFEIMGEEE IAFKMIRTNV SHVVGQLDDI RKNPRKFVCL NDNIDHNHKD AQTVKAVLRD FYESMFPIPS QFELPREYRN RFLHMHELQE WRAYRDKLKF WTHCVLATLI MFTIFSFFAE QLIALKRKIF PRRRIHKEAS PNRIRV //