GNPTA_HUMAN
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 03-AUG-2022, entry version 151.
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 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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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. {ECO:0000269|PubMed:19955174}.
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=5; 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 ---------------------------------------------------------------------------
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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 SMR; Q3T906; -.
DR BioGRID; 122576; 46.
DR ComplexPortal; CPX-6841; N-acetylglucosamine-1-phosphotransferase complex.
DR IntAct; Q3T906; 27.
DR MINT; Q3T906; -.
DR STRING; 9606.ENSP00000299314; -.
DR BindingDB; Q3T906; -.
DR CarbonylDB; Q3T906; -.
DR GlyConnect; 1532; 7 N-Linked glycans (5 sites).
DR GlyGen; Q3T906; 22 sites, 6 N-linked glycans (3 sites), 2 O-linked glycans (3 sites).
DR iPTMnet; Q3T906; -.
DR PhosphoSitePlus; 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; Q3T906; -.
DR PeptideAtlas; Q3T906; -.
DR PRIDE; Q3T906; -.
DR ProteomicsDB; 61878; -. [Q3T906-1]
DR ProteomicsDB; 61879; -. [Q3T906-2]
DR Antibodypedia; 44958; 79 antibodies from 15 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 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; NQTHYVL; -.
DR OrthoDB; 851009at2759; -.
DR PhylomeDB; Q3T906; -.
DR TreeFam; TF324175; -.
DR BRENDA; 2.7.8.17; 2681.
DR PathwayCommons; Q3T906; -.
DR SignaLink; Q3T906; -.
DR BioGRID-ORCS; 79158; 24 hits in 1095 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 197 other tissues.
DR ExpressionAtlas; Q3T906; baseline and differential.
DR Genevisible; Q3T906; HS.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ComplexPortal.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0070622; C:UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase complex; IPI:ComplexPortal.
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:ComplexPortal.
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 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; IPR031358; Stealth_CR1.
DR InterPro; IPR021520; Stealth_CR2.
DR InterPro; IPR031357; Stealth_CR3.
DR InterPro; IPR031356; Stealth_CR4.
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; SSF90193; 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.
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 N-
FT 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; unknown pathological
FT significance; no effect on protein abundance; decreased
FT protein cleavage into alpha and beta subunits; decreased
FT retention in the Golgi; mistargeted to lysosomes and plasma
FT membrane; decreased UDP-N-acetylglucosamine-lysosomal-
FT enzyme 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 N-
FT 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 UDP-
FT N-acetylglucosamine-lysosomal-enzyme N-
FT 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; unknown pathological significance;
FT decreased localization to the Golgi; decreased UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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; unknown
FT pathological significance; 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 N-
FT acetylglucosaminephosphotransferase activity;
FT dbSNP:rs34946266)"
FT /evidence="ECO:0000269|PubMed:19617216"
FT /id="VAR_053545"
FT VARIANT 205
FT /note="Q -> P (in MLII; unknown pathological 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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; unknown pathological significance;
FT no effect on protein abundance; no effect on localization
FT to the Golgi; no effect on protein cleavage into alpha and
FT beta subunits; decreased UDP-N-acetylglucosamine-lysosomal-
FT enzyme 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 N-
FT 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 N-
FT 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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 UDP-N-acetylglucosamine-lysosomal-
FT enzyme 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 N-
FT 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; unknown pathological 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 UDP-
FT N-acetylglucosamine-lysosomal-enzyme N-
FT 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 N-
FT 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; unknown pathological
FT significance; decreased localization to the Golgi;
FT decreased protein cleavage into alpha and beta subunits;
FT decreased UDP-N-acetylglucosamine-lysosomal-enzyme N-
FT 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; unknown pathological significance; decreased
FT localization to the Golgi; decreased protein cleavage into
FT alpha and beta subunits; decreased UDP-N-acetylglucosamine-
FT lysosomal-enzyme N-acetylglucosaminephosphotransferase
FT 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 UDP-N-acetylglucosamine-
FT lysosomal-enzyme 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; unknown pathological significance; decreased
FT localization to the Golgi; decreased UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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; unknown pathological 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 N-
FT 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 N-
FT 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; unknown pathological significance; no effect on
FT localization to the Golgi; loss of UDP-N-acetylglucosamine-
FT lysosomal-enzyme N-acetylglucosaminephosphotransferase
FT activity toward some 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; unknown pathological 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 N-
FT acetylglucosaminephosphotransferase)"
FT /evidence="ECO:0000269|PubMed:25788519"
FT /id="VAR_074208"
FT VARIANT 955
FT /note="A -> V (in MLII; unknown pathological significance;
FT no effect on protein abundance; no effect on localization
FT to the Golgi; decreased UDP-N-acetylglucosamine-lysosomal-
FT enzyme 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; unknown pathological
FT significance; 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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; patients with intermediate
FT phenotype between MLII and MLIIIA; unknown pathological
FT significance; no effect on protein abundance; decreased
FT localization to the Golgi; loss of UDP-N-acetylglucosamine-
FT lysosomal-enzyme N-acetylglucosaminephosphotransferase
FT activity; 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; unknown pathological significance;
FT no effect on localization to the Golgi; decreased UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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 UDP-N-
FT acetylglucosamine-lysosomal-enzyme N-
FT 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 UDP-N-acetylglucosamine-
FT lysosomal-enzyme N-acetylglucosaminephosphotransferase
FT 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 N-
FT 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 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"
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
