NDST4_MOUSE
ID NDST4_MOUSE Reviewed; 872 AA.
AC Q9EQW8; D3Z1R7;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 4;
DE EC=2.8.2.8;
DE AltName: Full=Glucosaminyl N-deacetylase/N-sulfotransferase 4;
DE Short=NDST-4;
DE AltName: Full=N-heparan sulfate sulfotransferase 4;
DE Short=N-HSST 4;
DE Includes:
DE RecName: Full=Heparan sulfate N-deacetylase 4;
DE EC=3.-.-.-;
DE Includes:
DE RecName: Full=Heparan sulfate N-sulfotransferase 4;
DE EC=2.8.2.-;
GN Name=Ndst4; Synonyms=Hsst4;
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 [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11087757; DOI=10.1074/jbc.m009606200;
RA Aikawa J., Grobe K., Tsujimoto M., Esko J.D.;
RT "Multiple isozymes of heparan sulfate/heparin GlcNAc N-deacetylase/GlcN N-
RT sulfotransferase. Structure and activity of the fourth member, NDST4.";
RL J. Biol. Chem. 276:5876-5882(2001).
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).
CC -!- FUNCTION: Essential bifunctional enzyme that catalyzes both the N-
CC deacetylation and the N-sulfation of glucosamine (GlcNAc) of the
CC glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA
CC disaccharide repeating sugar backbone to make N-sulfated heparosan, a
CC prerequisite substrate for later modifications in heparin biosynthesis.
CC Has low deacetylase activity but high sulfotransferase activity.
CC {ECO:0000269|PubMed:11087757}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan
CC sulfate](n) = adenosine 3',5'-bisphosphate + 2 H(+) + N-sulfo-alpha-
CC D-glucosaminyl-[heparan sulfate](n); Xref=Rhea:RHEA:21980, Rhea:RHEA-
CC COMP:9830, Rhea:RHEA-COMP:14602, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:58388,
CC ChEBI:CHEBI:140572; EC=2.8.2.8;
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at low level in brain and throughout
CC embryogenesis. Not expressed in other tissues.
CC {ECO:0000269|PubMed:11087757}.
CC -!- MISCELLANEOUS: The presence of 4 different heparan sulfate N-
CC deacetylase/N-sulfotransferase enzymes in mammals, as well as
CC differences in their enzyme activity suggest that some initiate heparan
CC sulfate modification/sulfation reactions, whereas other later on fill
CC in or extend already modified heparan sulfate sequences.
CC -!- SIMILARITY: Belongs to the sulfotransferase 1 family. NDST subfamily.
CC {ECO:0000305}.
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DR EMBL; AB036838; BAB18517.1; -; mRNA.
DR EMBL; AC111141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140797; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC164153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS17820.1; -.
DR RefSeq; NP_072087.2; NM_022565.2.
DR RefSeq; XP_017175172.1; XM_017319683.1.
DR AlphaFoldDB; Q9EQW8; -.
DR SMR; Q9EQW8; -.
DR BioGRID; 211087; 1.
DR STRING; 10090.ENSMUSP00000133341; -.
DR GlyGen; Q9EQW8; 5 sites.
DR PhosphoSitePlus; Q9EQW8; -.
DR MaxQB; Q9EQW8; -.
DR PaxDb; Q9EQW8; -.
DR PRIDE; Q9EQW8; -.
DR ProteomicsDB; 286163; -.
DR Antibodypedia; 2469; 106 antibodies from 16 providers.
DR DNASU; 64580; -.
DR Ensembl; ENSMUST00000173932; ENSMUSP00000133341; ENSMUSG00000027971.
DR GeneID; 64580; -.
DR KEGG; mmu:64580; -.
DR UCSC; uc008rfv.2; mouse.
DR CTD; 64579; -.
DR MGI; MGI:1932545; Ndst4.
DR VEuPathDB; HostDB:ENSMUSG00000027971; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000157168; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; Q9EQW8; -.
DR OMA; FQYQMVI; -.
DR OrthoDB; 388292at2759; -.
DR PhylomeDB; Q9EQW8; -.
DR TreeFam; TF313193; -.
DR BRENDA; 2.8.2.8; 3474.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 64580; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Ndst4; mouse.
DR PRO; PR:Q9EQW8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9EQW8; protein.
DR Bgee; ENSMUSG00000027971; Expressed in seminiferous tubule of testis and 46 other tissues.
DR ExpressionAtlas; Q9EQW8; baseline and differential.
DR Genevisible; Q9EQW8; MM.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0015016; F:[heparan sulfate]-glucosamine N-sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0019213; F:deacetylase activity; IDA:MGI.
DR GO; GO:0008146; F:sulfotransferase activity; IDA:MGI.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IBA:GO_Central.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR021930; Heparan_SO4_deacetylase.
DR InterPro; IPR037359; NST/OST.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000863; Sulfotransferase_dom.
DR PANTHER; PTHR10605; PTHR10605; 1.
DR Pfam; PF12062; HSNSD; 1.
DR Pfam; PF00685; Sulfotransfer_1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Hydrolase; Membrane;
KW Multifunctional enzyme; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..872
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 4"
FT /id="PRO_0000225662"
FT TOPO_DOM 1..13
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 14..34
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..872
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 36..588
FT /note="Heparan sulfate N-deacetylase 4"
FT REGION 589..872
FT /note="Heparan sulfate N-sulfotransferase 4"
FT ACT_SITE 604
FT /note="For sulfotransferase activity"
FT /evidence="ECO:0000250"
FT BINDING 604..608
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 702
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT BINDING 823..827
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250"
FT CARBOHYD 226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 391
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 793
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 808..818
FT /evidence="ECO:0000250"
FT CONFLICT 681
FT /note="A -> T (in Ref. 1; BAB18517)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 872 AA; 100655 MW; C56980F256C757E4 CRC64;
MNLILKFRRS FRTLIVLLAT FCLVSILISA YFLYSGYKQE MTLIETTAEA ECADIKDLPY
RSIELRTIKP IDTSKTDPTV LLFVESQYSQ LGQDIIAILE SSRFQYQMVI APGKGDIPPL
TDSGKGKYTL IIYENILKYV SMDSWNRELL EKYCIEYSVS IIGFHKANEN SLPTTQLKGF
PLNLFNNVAL KDCSVNPQSP LLHITKGPKV EKGPLPGEDW TIFQYNHSTY QPVLLTELQS
EKSLSFLSSQ TLYATIIQDL GLHDGIQRVL FGNNLNFWLH KLIFIDAISF LSGKRLTLSL
DRYILVDIDD IFVGKEGTRM NVKDVKALLE TQNLLRTQVA NFTFNLGFSG KFYHTGTEEE
DEGDDLLLRS VDEFWWFPHM WSHMQPHLFH NESSLVEQMI LNKEFALEHG IPINLGYAVA
PHHSGVYPVH IQLYAAWKKV WGIQVTSTEE YPHLKPARYR KGFIHNSIMV LPRQTCGLFT
HTIFYKEYPG GPQELDKSIK GGELFLTILL NPISIFMTHL SNYGNDRLGL YTFVNLANFV
HSWTNLKLQT LPPVQLAHKY FELFPEQKDP LWQNPCDDKR HKDIWSREKT CDHLPKFLVI
GPQKTGTTAL YLFLLMHPSI ISNLPSPKTF EEVQFFNGNN YHKGIEWYMD FFPTPSNITS
DFLFEKSANY FHSEEAPKRA ASLVPKAKII TILIDPSDRA YSWYQHQRSH EDPAALRFNF
YEVITTGHWA PPDLKTLQRR CLVPGWYAVH IERWLAYFST SQLLIIDGQQ LRSDPATVMD
EVQKFLGVTP HYNYSEALTF DPQKGFWCQL LEGGKTKCLG KSKGRKYPPM DSESRTFLSS
YYRDHNVELS KLLHRLGQPL PSWLRQELQK VR
