HGNAT_HUMAN
ID HGNAT_HUMAN Reviewed; 663 AA.
AC Q68CP4; B4E2V0;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Heparan-alpha-glucosaminide N-acetyltransferase;
DE EC=2.3.1.78;
DE AltName: Full=Transmembrane protein 76;
GN Name=HGSNAT; Synonyms=TMEM76;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Trachea;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 265-663 (ISOFORMS 1/2).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP INVOLVEMENT IN MPS3C, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=16960811; DOI=10.1086/508068;
RA Fan X., Zhang H., Zhang S., Bagshaw R.D., Tropak M.B., Callahan J.W.,
RA Mahuran D.J.;
RT "Identification of the gene encoding the enzyme deficient in
RT mucopolysaccharidosis IIIC (Sanfilippo disease type C).";
RL Am. J. Hum. Genet. 79:738-744(2006).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142.
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 [8]
RP FUNCTION, GLYCOSYLATION, CHARACTERIZATION OF VARIANT MPS3C THR-643, AND
RP CHARACTERIZATION OF VARIANTS PHE-104; PRO-165; GLN-265; ARG-290; LYS-301;
RP LEU-311; HIS-372; CYS-431; SER-452; LYS-499; LEU-509; LYS-510; GLU-517;
RP PHE-546; GLN-551; CYS-567; LEU-569; VAL-590 AND LEU-599.
RX PubMed=19823584; DOI=10.1371/journal.pone.0007434;
RA Feldhammer M., Durand S., Pshezhetsky A.V.;
RT "Protein misfolding as an underlying molecular defect in
RT mucopolysaccharidosis III type C.";
RL PLoS ONE 4:E7434-E7434(2009).
RN [9]
RP FUNCTION, ACTIVE SITE, ALTERNATIVE INITIATION (ISOFORMS 1 AND 2), SUBUNIT,
RP CHARACTERIZATION OF VARIANT PHE-104, MUTAGENESIS OF CYS-107; CYS-151;
RP CYS-179; LEU-236; ILE-237; HIS-297; CYS-333; CYS-402; CYS-462; HIS-479 AND
RP HIS-633, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20650889; DOI=10.1074/jbc.m110.141150;
RA Durand S., Feldhammer M., Bonneil E., Thibault P., Pshezhetsky A.V.;
RT "Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-
RT glucosaminide N-acetyltransferase provides insights into the mechanism
RT underlying its complete deficiency in mucopolysaccharidosis IIIC.";
RL J. Biol. Chem. 285:31233-31242(2010).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243 AND SER-245, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP INVOLVEMENT IN RP73, VARIANTS RP73 TRP-152; ALA-161 AND THR-643, AND
RP CHARACTERIZATION OF VARIANT RP73 THR-643.
RX PubMed=25859010; DOI=10.1093/hmg/ddv118;
RA Haer-Wigman L., Newman H., Leibu R., Bax N.M., Baris H.N., Rizel L.,
RA Banin E., Massarweh A., Roosing S., Lefeber D.J., Zonneveld-Vrieling M.N.,
RA Isakov O., Shomron N., Sharon D., Den Hollander A.I., Hoyng C.B.,
RA Cremers F.P., Ben-Yosef T.;
RT "Non-syndromic retinitis pigmentosa due to mutations in the
RT mucopolysaccharidosis type IIIC gene, heparan-alpha-glucosaminide N-
RT acetyltransferase (HGSNAT).";
RL Hum. Mol. Genet. 24:3742-3751(2015).
RN [13]
RP INVOLVEMENT IN MPS3C.
RX PubMed=28101780; DOI=10.1007/s12519-017-0005-x;
RA Ouesleti S., Coutinho M.F., Ribeiro I., Miled A., Mosbahi D.S., Alves S.;
RT "Update of the spectrum of mucopolysaccharidoses type III in Tunisia:
RT identification of three novel mutations and in silico structural analysis
RT of the missense mutations.";
RL World J. Pediatr. 13:374-380(2017).
RN [14]
RP VARIANTS MPS3C PHE-104; LEU-311; CYS-372; HIS-372; CYS-431; SER-452;
RP LYS-499; LYS-510; LEU-569; VAL-590; LEU-599 AND THR-643, VARIANTS GLN-265
RP AND GLN-551, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17033958; DOI=10.1086/508294;
RA Hrebicek M., Mrazova L., Seyrantepe V., Durand S., Roslin N.M., Noskova L.,
RA Hartmannova H., Ivanek R., Cizkova A., Poupetova H., Sikora J.,
RA Urinovska J., Stranecky V., Zeman J., Lepage P., Roquis D., Verner A.,
RA Ausseil J., Beesley C.E., Maire I., Poorthuis B.J.H.M., van de Kamp J.,
RA van Diggelen O.P., Wevers R.A., Hudson T.J., Fujiwara T.M., Majewski J.,
RA Morgan K., Kmoch S., Pshezhetsky A.V.;
RT "Mutations in TMEM76 cause mucopolysaccharidosis IIIC (Sanfilippo C
RT syndrome).";
RL Am. J. Hum. Genet. 79:807-819(2006).
RN [15]
RP VARIANTS MPS3C PRO-165 AND PHE-546, AND VARIANT GLN-265.
RX PubMed=17397050; DOI=10.1002/humu.9488;
RA Fedele A.O., Filocamo M., Di Rocco M., Sersale G., Luebke T., di Natale P.,
RA Cosma M.P., Ballabio A.;
RT "Mutational analysis of the HGSNAT gene in Italian patients with
RT mucopolysaccharidosis IIIC (Sanfilippo C syndrome). Mutation in brief #959.
RT Online.";
RL Hum. Mutat. 28:523-523(2007).
RN [16]
RP VARIANTS MPS3C PRO-165; ARG-280; LYS-301; CYS-372; LYS-499; PHE-546 AND
RP CYS-567, AND VARIANT GLN-265.
RX PubMed=18024218; DOI=10.1016/j.ymgme.2007.09.011;
RA Ruijter G.J.G., Valstar M.J., van de Kamp J.M., van der Helm R.M.,
RA Durand S., van Diggelen O.P., Wevers R.A., Poorthuis B.J.,
RA Pshezhetsky A.V., Wijburg F.A.;
RT "Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in
RT The Netherlands.";
RL Mol. Genet. Metab. 93:104-111(2008).
RN [17]
RP VARIANTS MPS3C PRO-165; LEU-311; CYS-372; CYS-431; LYS-499; GLU-514;
RP GLU-517; PHE-546; LEU-569 AND THR-643, VARIANTS GLN-265; LEU-509 AND
RP GLN-551, CHARACTERIZATION OF VARIANTS MPS3C CYS-431 AND THR-643, AND
RP CHARACTERIZATION OF VARIANTS GLN-265; LEU-509 AND GLN-551.
RX PubMed=19479962; DOI=10.1002/humu.20986;
RA Feldhammer M., Durand S., Mrazova L., Boucher R.-M., Laframboise R.,
RA Steinfeld R., Wraith J.E., Michelakakis H., van Diggelen O.P., Hrebicek M.,
RA Kmoch S., Pshezhetsky A.V.;
RT "Sanfilippo syndrome type C: mutation spectrum in the heparan sulfate
RT acetyl-CoA: alpha-glucosaminide N-acetyltransferase (HGSNAT) gene.";
RL Hum. Mutat. 30:918-925(2009).
RN [18]
RP CHARACTERIZATION OF VARIANTS MPS3C PHE-104; PRO-165; ARG-290; LEU-311;
RP CYS-372; CYS-431; SER-452; LYS-499; LYS-510; GLU-514; GLU-517; PHE-546;
RP CYS-567; LEU-569; VAL-590; LEU-599 AND THR-643, AND CHARACTERIZATION OF
RP VARIANTS GLN-265; LEU-509 AND GLN-551.
RX PubMed=20583299; DOI=10.1002/humu.21286;
RA Fedele A.O., Hopwood J.J.;
RT "Functional analysis of the HGSNAT gene in patients with
RT mucopolysaccharidosis IIIC (Sanfilippo C Syndrome).";
RL Hum. Mutat. 31:E1574-E1586(2010).
RN [19]
RP VARIANTS MPS3C VAL-82; PRO-141; VAL-452 AND PRO-473, VARIANT GLN-265,
RP CHARACTERIZATION OF VARIANTS MPS3C VAL-82; PRO-141; CYS-372; VAL-452;
RP PRO-473 AND PHE-546, AND CHARACTERIZATION OF VARIANT GLN-265.
RX PubMed=20825431; DOI=10.1111/j.1399-0004.2010.01525.x;
RA Canals I., Elalaoui S.C., Pineda M., Delgadillo V., Szlago M., Jaouad I.C.,
RA Sefiani A., Chabas A., Coll M.J., Grinberg D., Vilageliu L.;
RT "Molecular analysis of Sanfilippo syndrome type C in Spain: seven novel
RT HGSNAT mutations and characterization of the mutant alleles.";
RL Clin. Genet. 80:367-374(2011).
CC -!- FUNCTION: Lysosomal acetyltransferase that acetylates the non-reducing
CC terminal alpha-glucosamine residue of intralysosomal heparin or heparan
CC sulfate, converting it into a substrate for luminal alpha-N-acetyl
CC glucosaminidase. {ECO:0000269|PubMed:16960811,
CC ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:19823584,
CC ECO:0000269|PubMed:20650889}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + alpha-D-glucosaminyl-[heparan sulfate](n) = CoA +
CC H(+) + N-acetyl-alpha-D-glucosaminyl-[heparan sulfate](n);
CC Xref=Rhea:RHEA:15125, Rhea:RHEA-COMP:9830, Rhea:RHEA-COMP:11585,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:58388, ChEBI:CHEBI:70974; EC=2.3.1.78;
CC Evidence={ECO:0000269|PubMed:16960811};
CC -!- SUBUNIT: Homooligomer. Homooligomerization is necessary for enzyme
CC activity. {ECO:0000269|PubMed:20650889}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:16960811,
CC ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:17897319}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:16960811,
CC ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:17897319}.
CC Note=Colocalizes with the lysosomal marker LAMP2. The signal peptide is
CC not cleaved upon translocation into the endoplasmic reticulum; the
CC precursor is probably targeted to the lysosomes via the adapter protein
CC complex-mediated pathway that involves tyrosine- and/or dileucine-based
CC conserved amino acid motifs in the last C-terminus 16-amino acid
CC domain.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Comment=Isoform 1 and isoform 2 are correctly targeted to the
CC lysosomal compartment and are functional enzymes.;
CC Name=1;
CC IsoId=Q68CP4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68CP4-2; Sequence=VSP_040504;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest level in leukocytes,
CC heart, liver, skeletal muscle, lung, placenta and liver.
CC {ECO:0000269|PubMed:16960811, ECO:0000269|PubMed:17033958}.
CC -!- PTM: Undergoes intralysosomal proteolytic cleavage; occurs within the
CC end of the first and/or the beginning of the second luminal domain and
CC is essential for the activation of the enzyme.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:19823584}.
CC -!- DISEASE: Mucopolysaccharidosis 3C (MPS3C) [MIM:252930]: A form of
CC mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage
CC disease due to impaired degradation of heparan sulfate. MPS3 is
CC characterized by severe central nervous system degeneration, but only
CC mild somatic disease. Onset of clinical features usually occurs between
CC 2 and 6 years; severe neurologic degeneration occurs in most patients
CC between 6 and 10 years of age, and death occurs typically during the
CC second or third decade of life. {ECO:0000269|PubMed:16960811,
CC ECO:0000269|PubMed:17033958, ECO:0000269|PubMed:17397050,
CC ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962,
CC ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299,
CC ECO:0000269|PubMed:20825431, ECO:0000269|PubMed:28101780}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Retinitis pigmentosa 73 (RP73) [MIM:616544]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:25859010}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: A signal sequence is predicted but has been shown not to
CC be cleaved in the reticulum endoplasmic.
CC -!- MISCELLANEOUS: [Isoform 1]: Intralysosomal proteolytic cleavage is
CC faster and enzymatic activity higher than isoform 2.
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DR EMBL; AK304441; BAG65262.1; -; mRNA.
DR EMBL; AC113191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR749838; CAH18694.1; -; mRNA.
DR CCDS; CCDS47852.1; -. [Q68CP4-2]
DR RefSeq; NP_689632.2; NM_152419.2. [Q68CP4-2]
DR AlphaFoldDB; Q68CP4; -.
DR BioGRID; 126499; 9.
DR IntAct; Q68CP4; 3.
DR MINT; Q68CP4; -.
DR STRING; 9606.ENSP00000368965; -.
DR TCDB; 9.B.169.4.1; the integral membrane protein (8 -10 tmss) yeib or duf418 (yeib) family.
DR GlyConnect; 1307; 5 N-Linked glycans (2 sites).
DR GlyGen; Q68CP4; 5 sites, 5 N-linked glycans (2 sites).
DR iPTMnet; Q68CP4; -.
DR PhosphoSitePlus; Q68CP4; -.
DR SwissPalm; Q68CP4; -.
DR BioMuta; HGSNAT; -.
DR DMDM; 124007195; -.
DR EPD; Q68CP4; -.
DR jPOST; Q68CP4; -.
DR MassIVE; Q68CP4; -.
DR MaxQB; Q68CP4; -.
DR PaxDb; Q68CP4; -.
DR PeptideAtlas; Q68CP4; -.
DR PRIDE; Q68CP4; -.
DR ProteomicsDB; 66009; -. [Q68CP4-1]
DR ProteomicsDB; 66010; -. [Q68CP4-2]
DR Antibodypedia; 24209; 47 antibodies from 16 providers.
DR DNASU; 138050; -.
DR Ensembl; ENST00000379644.9; ENSP00000368965.4; ENSG00000165102.15. [Q68CP4-2]
DR GeneID; 138050; -.
DR KEGG; hsa:138050; -.
DR MANE-Select; ENST00000379644.9; ENSP00000368965.4; NM_152419.3; NP_689632.2. [Q68CP4-2]
DR UCSC; uc003xpx.5; human. [Q68CP4-1]
DR CTD; 138050; -.
DR DisGeNET; 138050; -.
DR GeneCards; HGSNAT; -.
DR GeneReviews; HGSNAT; -.
DR HGNC; HGNC:26527; HGSNAT.
DR HPA; ENSG00000165102; Low tissue specificity.
DR MalaCards; HGSNAT; -.
DR MIM; 252930; phenotype.
DR MIM; 610453; gene.
DR MIM; 616544; phenotype.
DR neXtProt; NX_Q68CP4; -.
DR OpenTargets; ENSG00000165102; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR Orphanet; 79271; Sanfilippo syndrome type C.
DR PharmGKB; PA162390851; -.
DR VEuPathDB; HostDB:ENSG00000165102; -.
DR eggNOG; KOG4683; Eukaryota.
DR GeneTree; ENSGT00390000001491; -.
DR HOGENOM; CLU_029171_3_2_1; -.
DR InParanoid; Q68CP4; -.
DR OMA; DNQSHRE; -.
DR OrthoDB; 1028480at2759; -.
DR PhylomeDB; Q68CP4; -.
DR TreeFam; TF324790; -.
DR BRENDA; 2.3.1.78; 2681.
DR PathwayCommons; Q68CP4; -.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-2206291; MPS IIIC - Sanfilippo syndrome C.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; Q68CP4; -.
DR SignaLink; Q68CP4; -.
DR BioGRID-ORCS; 138050; 12 hits in 1080 CRISPR screens.
DR ChiTaRS; HGSNAT; human.
DR GeneWiki; HGSNAT; -.
DR GenomeRNAi; 138050; -.
DR Pharos; Q68CP4; Tbio.
DR PRO; PR:Q68CP4; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q68CP4; protein.
DR Bgee; ENSG00000165102; Expressed in mucosa of stomach and 198 other tissues.
DR ExpressionAtlas; Q68CP4; baseline and differential.
DR Genevisible; Q68CP4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0016746; F:acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0015019; F:heparan-alpha-glucosaminide N-acetyltransferase activity; TAS:Reactome.
DR GO; GO:0007041; P:lysosomal transport; IDA:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB.
DR InterPro; IPR040208; HGSNAT.
DR InterPro; IPR012429; HGSNAT_cat.
DR PANTHER; PTHR31061:SF19; PTHR31061:SF19; 1.
DR Pfam; PF07786; HGSNAT_cat; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Alternative initiation; Disease variant; Disulfide bond;
KW Glycoprotein; Lysosome; Membrane; Mucopolysaccharidosis; Phosphoprotein;
KW Reference proteome; Retinitis pigmentosa; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..663
FT /note="Heparan-alpha-glucosaminide N-acetyltransferase"
FT /id="PRO_0000273153"
FT TOPO_DOM 1..190
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..302
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 367..374
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 396..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 421..441
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 442..500
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 501..521
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 522..529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..550
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 551..564
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 565..585
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 586..592
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..634
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 635..655
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 656..663
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 624..635
FT /note="Lysosomal targeting region"
FT ACT_SITE 297
FT /evidence="ECO:0000269|PubMed:20650889"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 151..462
FT /evidence="ECO:0000305"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_040504"
FT VARIANT 82
FT /note="A -> V (in MPS3C; shows practically no enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:20825431"
FT /id="VAR_075812"
FT VARIANT 104
FT /note="C -> F (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum; loss of intralysosomal
FT proteolytic cleavage)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299,
FT ECO:0000269|PubMed:20650889"
FT /id="VAR_063983"
FT VARIANT 141
FT /note="L -> P (in MPS3C; shows practically no enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:20825431"
FT /id="VAR_075813"
FT VARIANT 152
FT /note="R -> W (in RP73)"
FT /evidence="ECO:0000269|PubMed:25859010"
FT /id="VAR_075814"
FT VARIANT 161
FT /note="G -> A (in RP73)"
FT /evidence="ECO:0000269|PubMed:25859010"
FT /id="VAR_075815"
FT VARIANT 165
FT /note="L -> P (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17397050,
FT ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_063984"
FT VARIANT 265
FT /note="P -> Q (likely benign variant; does not influence
FT stability; does not influence activity; does not influence
FT cellular localization of the enzyme)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:17397050, ECO:0000269|PubMed:18024218,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299, ECO:0000269|PubMed:20825431"
FT /id="VAR_063985"
FT VARIANT 280
FT /note="I -> R (in MPS3C)"
FT /evidence="ECO:0000269|PubMed:18024218"
FT /id="VAR_063986"
FT VARIANT 290
FT /note="G -> R (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:18024218,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_063987"
FT VARIANT 301
FT /note="N -> K (in MPS3C; retained in the endoplasmic
FT reticulum; loss of enzymatic activity)"
FT /evidence="ECO:0000269|PubMed:18024218,
FT ECO:0000269|PubMed:19823584"
FT /id="VAR_063988"
FT VARIANT 311
FT /note="P -> L (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_030083"
FT VARIANT 372
FT /note="R -> C (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_030084"
FT VARIANT 372
FT /note="R -> H (in MPS3C; retained in the endoplasmic
FT reticulum; loss of enzymatic activity)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584"
FT /id="VAR_063989"
FT VARIANT 431
FT /note="W -> C (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_063990"
FT VARIANT 452
FT /note="G -> S (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_030085"
FT VARIANT 452
FT /note="G -> V (in MPS3C; shows practically no enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:20825431"
FT /id="VAR_075816"
FT VARIANT 473
FT /note="L -> P (in MPS3C; shows practically no enzyme
FT activity)"
FT /evidence="ECO:0000269|PubMed:20825431"
FT /id="VAR_075817"
FT VARIANT 499
FT /note="E -> K (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_030086"
FT VARIANT 509
FT /note="V -> L (likely benign variant; no loss of enzymatic
FT activity)"
FT /evidence="ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_063991"
FT VARIANT 510
FT /note="M -> K (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_030087"
FT VARIANT 514
FT /note="G -> E (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_063992"
FT VARIANT 517
FT /note="A -> E (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_063993"
FT VARIANT 546
FT /note="S -> F (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:17397050,
FT ECO:0000269|PubMed:18024218, ECO:0000269|PubMed:19479962,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299,
FT ECO:0000269|PubMed:20825431"
FT /id="VAR_063994"
FT VARIANT 551
FT /note="K -> Q (no loss of enzymatic activity;
FT dbSNP:rs73569592)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_063995"
FT VARIANT 567
FT /note="S -> C (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity; retained in
FT the endoplasmic reticulum)"
FT /evidence="ECO:0000269|PubMed:18024218,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_063996"
FT VARIANT 569
FT /note="S -> L (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299"
FT /id="VAR_030088"
FT VARIANT 590
FT /note="D -> V (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_030089"
FT VARIANT 599
FT /note="P -> L (in MPS3C; results in a negligible amount of
FT protein synthesis; very low enzyme activity)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19823584, ECO:0000269|PubMed:20583299"
FT /id="VAR_030090"
FT VARIANT 643
FT /note="A -> T (in RP73 and MPS3C; unknown pathological
FT significance; may act as a modifier of disease severity in
FT patients with retinitis pigmentosa; has a negligible effect
FT on the enzyme expression; moderately reduced enzyme
FT activity; dbSNP:rs112029032)"
FT /evidence="ECO:0000269|PubMed:17033958,
FT ECO:0000269|PubMed:19479962, ECO:0000269|PubMed:19823584,
FT ECO:0000269|PubMed:20583299, ECO:0000269|PubMed:25859010"
FT /id="VAR_063997"
FT MUTAGEN 107
FT /note="C->S: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity. Reduced oligomer formation."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 151
FT /note="C->S: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity. Reduced oligomer formation."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 179
FT /note="C->S: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 236
FT /note="L->A: Displayed both lysosomal and plasma membrane
FT localization, reduced intralysosomal proteolytic cleavage
FT and enzymatic activity; when associated with A-209."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 237
FT /note="I->A: Displayed both lysosomal and plasma membrane
FT localization, reduced intralysosomal proteolytic cleavage
FT and enzymatic activity; when associated with A-208."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 297
FT /note="H->A: Loss of enzymatic activity, but correctly
FT targeted and processed."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 333
FT /note="C->S: No loss of intralysosomal proteolytic cleavage
FT and enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 402
FT /note="C->S: No loss of intralysosomal proteolytic cleavage
FT and enzymatic activity."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 462
FT /note="C->S: Complete loss of intralysosomal proteolytic
FT cleavage and enzymatic activity. Reduced oligomer
FT formation."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 479
FT /note="H->A: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity, retained in the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 633
FT /note="H->A: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity, retained in the endoplasmic
FT reticulum."
FT /evidence="ECO:0000269|PubMed:20650889"
FT MUTAGEN 652..663
FT /note="Missing: Loss of intralysosomal proteolytic cleavage
FT and enzymatic activity. Localized in the plasma membrane."
SQ SEQUENCE 663 AA; 73293 MW; B05648474A3587B5 CRC64;
MTGARASAAE QRRAGRSGQA RAAERAAGMS GAGRALAALL LAASVLSAAL LAPGGSSGRD
AQAAPPRDLD KKRHAELKMD QALLLIHNEL LWTNLTVYWK SECCYHCLFQ VLVNVPQSPK
AGKPSAAAAS VSTQHGSILQ LNDTLEEKEV CRLEYRFGEF GNYSLLVKNI HNGVSEIACD
LAVNEDPVDS NLPVSIAFLI GLAVIIVISF LRLLLSLDDF NNWISKAISS RETDRLINSE
LGSPSRTDPL DGDVQPATWR LSALPPRLRS VDTFRGIALI LMVFVNYGGG KYWYFKHASW
NGLTVADLVF PWFVFIMGSS IFLSMTSILQ RGCSKFRLLG KIAWRSFLLI CIGIIIVNPN
YCLGPLSWDK VRIPGVLQRL GVTYFVVAVL ELLFAKPVPE HCASERSCLS LRDITSSWPQ
WLLILVLEGL WLGLTFLLPV PGCPTGYLGP GGIGDFGKYP NCTGGAAGYI DRLLLGDDHL
YQHPSSAVLY HTEVAYDPEG ILGTINSIVM AFLGVQAGKI LLYYKARTKD ILIRFTAWCC
ILGLISVALT KVSENEGFIP VNKNLWSLSY VTTLSSFAFF ILLVLYPVVD VKGLWTGTPF
FYPGMNSILV YVGHEVFENY FPFQWKLKDN QSHKEHLTQN IVATALWVLI AYILYRKKIF
WKI
