NDST4_HUMAN
ID NDST4_HUMAN Reviewed; 872 AA.
AC Q9H3R1; Q2KHM8;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
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 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).
RC TISSUE=Fetal 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].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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).
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 (By
CC similarity). {ECO:0000250}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H3R1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H3R1-2; Sequence=VSP_056256, VSP_056257, VSP_056258;
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB036429; BAB18535.1; -; mRNA.
DR EMBL; AC093656; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097519; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113075; AAI13076.1; -; mRNA.
DR CCDS; CCDS3706.1; -. [Q9H3R1-1]
DR RefSeq; NP_072091.1; NM_022569.2. [Q9H3R1-1]
DR AlphaFoldDB; Q9H3R1; -.
DR SMR; Q9H3R1; -.
DR BioGRID; 122205; 7.
DR IntAct; Q9H3R1; 1.
DR STRING; 9606.ENSP00000264363; -.
DR GlyGen; Q9H3R1; 5 sites.
DR iPTMnet; Q9H3R1; -.
DR PhosphoSitePlus; Q9H3R1; -.
DR BioMuta; NDST4; -.
DR DMDM; 74718249; -.
DR jPOST; Q9H3R1; -.
DR MassIVE; Q9H3R1; -.
DR MaxQB; Q9H3R1; -.
DR PaxDb; Q9H3R1; -.
DR PeptideAtlas; Q9H3R1; -.
DR PRIDE; Q9H3R1; -.
DR ProteomicsDB; 80743; -. [Q9H3R1-1]
DR Antibodypedia; 2469; 106 antibodies from 16 providers.
DR DNASU; 64579; -.
DR Ensembl; ENST00000264363.7; ENSP00000264363.2; ENSG00000138653.10. [Q9H3R1-1]
DR Ensembl; ENST00000504854.1; ENSP00000423218.1; ENSG00000138653.10. [Q9H3R1-2]
DR Ensembl; ENST00000613194.4; ENSP00000483949.1; ENSG00000138653.10. [Q9H3R1-2]
DR GeneID; 64579; -.
DR KEGG; hsa:64579; -.
DR MANE-Select; ENST00000264363.7; ENSP00000264363.2; NM_022569.3; NP_072091.1.
DR UCSC; uc003ibu.4; human. [Q9H3R1-1]
DR CTD; 64579; -.
DR DisGeNET; 64579; -.
DR GeneCards; NDST4; -.
DR HGNC; HGNC:20779; NDST4.
DR HPA; ENSG00000138653; Tissue enriched (brain).
DR MIM; 615039; gene.
DR neXtProt; NX_Q9H3R1; -.
DR OpenTargets; ENSG00000138653; -.
DR PharmGKB; PA134875549; -.
DR VEuPathDB; HostDB:ENSG00000138653; -.
DR eggNOG; KOG3703; Eukaryota.
DR GeneTree; ENSGT00940000157168; -.
DR HOGENOM; CLU_011357_2_0_1; -.
DR InParanoid; Q9H3R1; -.
DR OMA; FQYQMVI; -.
DR PhylomeDB; Q9H3R1; -.
DR TreeFam; TF313193; -.
DR BioCyc; MetaCyc:HS06527-MON; -.
DR BRENDA; 2.8.2.8; 2681.
DR PathwayCommons; Q9H3R1; -.
DR Reactome; R-HSA-2022928; HS-GAG biosynthesis.
DR SignaLink; Q9H3R1; -.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 64579; 6 hits in 1057 CRISPR screens.
DR ChiTaRS; NDST4; human.
DR GenomeRNAi; 64579; -.
DR Pharos; Q9H3R1; Tbio.
DR PRO; PR:Q9H3R1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9H3R1; protein.
DR Bgee; ENSG00000138653; Expressed in palpebral conjunctiva and 50 other tissues.
DR Genevisible; Q9H3R1; HS.
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; IBA:GO_Central.
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 Alternative splicing; Disulfide bond; Glycoprotein; Golgi apparatus;
KW Hydrolase; Membrane; Multifunctional enzyme; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..872
FT /note="Bifunctional heparan sulfate N-deacetylase/N-
FT sulfotransferase 4"
FT /id="PRO_0000225661"
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 VAR_SEQ 1..379
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056256"
FT VAR_SEQ 706..748
FT /note="HQRSHEDPAALRFNFYEVISTGHWAPSDLKTLQRRCLVPGWYA -> VGVQW
FT RDLGSLQPSPPRFMPFSCLSLLSSWDYSTNDHMKIQLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056257"
FT VAR_SEQ 749..872
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056258"
FT VARIANT 12
FT /note="R -> Q (in dbSNP:rs35181627)"
FT /id="VAR_061890"
SQ SEQUENCE 872 AA; 100716 MW; 9C4E2DD1F98EA859 CRC64;
MNLIVKLRRS FRTLIVLLAT FCLVSIVISA YFLYSGYKQE MTLIETTAEA ECTDIKILPY
RSMELKTVKP IDTSKTDPTV LLFVESQYSQ LGQDIIAILE SSRFQYHMVI APGKGDIPPL
TDNGKGKYTL VIYENILKYV SMDSWNRELL EKYCVEYSVS IIGFHKANEN SLPSTQLKGF
PLNLFNNLAL KDCFVNPQSP LLHITKAPKV EKGPLPGEDW TIFQYNHSTY QPVLLTELQT
EKSLSSLSSK TLFATVIQDL GLHDGIQRVL FGNNLNFWLH KLIFIDAISF LSGKRLTLSL
DRYILVDIDD IFVGKEGTRM NVKDVKALLE TQNLLRTQVA NFTFNLGFSG KFYHTGTEEE
DEGDDLLLRS VDEFWWFPHM WSHMQPHLFH NESSLVEQMI LNKEFALEHG IPINMGYAVA
PHHSGVYPVH IQLYAAWKKV WGIQVTSTEE YPHLKPARYR KGFIHNSIMV LPRQTCGLFT
HTIFYKEYPG GPQELDKSIR GGELFLTILL NPISIFMTHL SNYGNDRLGL YTFVNLVNFV
QSWTNLKLQT LPPVQLAHQY FELFPEQKDP LWQNPCDDKR HKDIWSREKT CDHLPKFLVI
GPQKTGTTAL YLFLLMHPSI ISNLPSPKTF EEVQFFNGNN YHKGIDWYMD FFPTPSNTTS
DFLFEKSANY FHSEEAPRRA ASLVPKAKII TILIDPSDRA YSWYQHQRSH EDPAALRFNF
YEVISTGHWA PSDLKTLQRR CLVPGWYAVH IERWLTYFAT SQLLIIDGQQ LRSDPATVMD
EVQKFLGVTP RYNYSEALTF DPQKGFWCQL LEGGKTKCLG KSKGRKYPPM DPESRTFLSN
YYRDHNVELS KLLHRLGQPL PSWLRQELQK VR
