HGNAT_MOUSE
ID HGNAT_MOUSE Reviewed; 656 AA.
AC Q3UDW8; E9QNP9; Q3TWK5; Q8CBU7; Q8CIE1;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Heparan-alpha-glucosaminide N-acetyltransferase;
DE EC=2.3.1.78;
DE AltName: Full=Transmembrane protein 76;
GN Name=Hgsnat; Synonyms=D8Ertd354e, Tmem76;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] (ISOFORM 1/2).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 21-656 (ISOFORM 1/2).
RC STRAIN=FVB/N; 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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-249, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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).
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 -!- 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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:16960811};
CC Multi-pass membrane protein {ECO:0000269|PubMed:16960811}.
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 domain
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UDW8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UDW8-2; Sequence=VSP_040505;
CC -!- TISSUE SPECIFICITY: Expressed in the retina.
CC {ECO:0000269|PubMed:25859010}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing eye as early as 14
CC dpc, with equal high expression levels after birth (postnatal day 1
CC (P1) and postnatal day 30 (P30)). {ECO:0000269|PubMed:25859010}.
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. {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: A signal sequence is predicted but has been shown not to
CC be cleaved in the reticulum endoplasmic. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH24084.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC29006.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE31601.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE35261.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAE35603.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK035264; BAC29006.1; ALT_INIT; mRNA.
DR EMBL; AK149883; BAE29143.1; -; mRNA.
DR EMBL; AK152926; BAE31601.1; ALT_INIT; mRNA.
DR EMBL; AK159649; BAE35261.1; ALT_INIT; mRNA.
DR EMBL; AK160068; BAE35603.1; ALT_INIT; mRNA.
DR EMBL; AC093366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024084; AAH24084.1; ALT_INIT; mRNA.
DR CCDS; CCDS40309.1; -. [Q3UDW8-2]
DR RefSeq; NP_084160.1; NM_029884.1. [Q3UDW8-1]
DR AlphaFoldDB; Q3UDW8; -.
DR STRING; 10090.ENSMUSP00000040356; -.
DR GlyConnect; 2368; 2 N-Linked glycans (1 site).
DR GlyGen; Q3UDW8; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q3UDW8; -.
DR PhosphoSitePlus; Q3UDW8; -.
DR SwissPalm; Q3UDW8; -.
DR EPD; Q3UDW8; -.
DR jPOST; Q3UDW8; -.
DR MaxQB; Q3UDW8; -.
DR PaxDb; Q3UDW8; -.
DR PeptideAtlas; Q3UDW8; -.
DR PRIDE; Q3UDW8; -.
DR ProteomicsDB; 269743; -. [Q3UDW8-1]
DR ProteomicsDB; 269744; -. [Q3UDW8-2]
DR Antibodypedia; 24209; 47 antibodies from 16 providers.
DR DNASU; 52120; -.
DR Ensembl; ENSMUST00000037609; ENSMUSP00000040356; ENSMUSG00000037260. [Q3UDW8-1]
DR GeneID; 52120; -.
DR KEGG; mmu:52120; -.
DR UCSC; uc009lhg.1; mouse. [Q3UDW8-1]
DR CTD; 138050; -.
DR MGI; MGI:1196297; Hgsnat.
DR VEuPathDB; HostDB:ENSMUSG00000037260; -.
DR eggNOG; KOG4683; Eukaryota.
DR GeneTree; ENSGT00390000001491; -.
DR HOGENOM; CLU_029171_3_2_1; -.
DR InParanoid; Q3UDW8; -.
DR OMA; DNQSHRE; -.
DR PhylomeDB; Q3UDW8; -.
DR TreeFam; TF324790; -.
DR BRENDA; 2.3.1.78; 3474.
DR Reactome; R-MMU-2024096; HS-GAG degradation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 52120; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Hgsnat; mouse.
DR PRO; PR:Q3UDW8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q3UDW8; protein.
DR Bgee; ENSMUSG00000037260; Expressed in stroma of bone marrow and 257 other tissues.
DR ExpressionAtlas; Q3UDW8; baseline and differential.
DR Genevisible; Q3UDW8; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0016746; F:acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0015019; F:heparan-alpha-glucosaminide N-acetyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; ISS: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; Disulfide bond; Glycoprotein;
KW Lysosome; Membrane; Phosphoprotein; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..656
FT /note="Heparan-alpha-glucosaminide N-acetyltransferase"
FT /id="PRO_0000273154"
FT TOPO_DOM 1..185
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 207..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..289
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 290..295
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..359
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 360..367
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 389..413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..493
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 494..514
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 515..522
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 523..543
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 544..557
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..585
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 586..606
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 607..627
FT /note="Lumenal, vesicle"
FT /evidence="ECO:0000255"
FT TRANSMEM 628..648
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 649..656
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 234..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 641..656
FT /note="Lysosomal targeting region"
FT /evidence="ECO:0000250"
FT COMPBIAS 7..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 290
FT /evidence="ECO:0000250"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68CP4"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68CP4"
FT MOD_RES 249
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 146..455
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_040505"
FT CONFLICT 23
FT /note="R -> H (in Ref. 3; AAH24084)"
FT /evidence="ECO:0000305"
FT CONFLICT 24
FT /note="N -> S (in Ref. 3; AAH24084)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="T -> A (in Ref. 3; AAH24084)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="A -> G (in Ref. 1; BAE35261)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="L -> F (in Ref. 1; BAE29143)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 656 AA; 72504 MW; 8FAE5EBECED5CCE3 CRC64;
MTGGSSSRRR RAEERSSAAG TERNSRREAV GGMGAGPALA ALLLAGSVLS ATLLAPGRRA
EPDLDEKRNV ELKMDQALLL IHNELLGTSL TVYWKSDDCY QCTFQPLANV SHGGKPAKPS
VAPVSVSTQH GSILQVNSTS EERAACRLEY KFGEFGNYSL LVQHASSGAN KIACDIIVNE
NPVDSNLPVS IAFLVGLALI VAVSLLRLLL SLDDVNNWIS KTIASRETDR LINSELGSPS
RADPLSADYQ PETRRSSANR LRCVDTFRGL ALVLMVFVNY GGGKYWYFKH SSWNGLTVAD
LVFPWFVFIM GTSIFLSMTS ILQRGCSKLK LLGKIVWRSF LLICIGVIIV NPNYCLGPLS
WDKVRIPGVL QRLGVTYFVV AVLEFFFWKP VPDSCTLESS CFSLRDITSS WPQWLTILTL
ESIWLALTFF LPVPGCPTGY LGPGGIGDLG KYPHCTGGAA GYIDRLLLGD NHLYQHPSST
VLYHTEVAYD PEGVLGTINS IVMAFLGVQA GKILVYYKDQ TKAILTRFAA WCCILGLISI
VLTKVSANEG FIPINKNLWS ISYVTTLSCF AFFILLILYP VVDVKGLWTG TPFFYPGMNS
ILVYVGHEVL ENYFPFQWKL ADEQSHKEHL IQNIVATALW VLIAYVLYKK KLFWKI
