H6ST2_DANRE
ID H6ST2_DANRE Reviewed; 468 AA.
AC Q800H9; A0MGZ6; Q6P0B4; Q7ZVQ5;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Heparan-sulfate 6-O-sulfotransferase 2;
DE Short=HS 6-OST-2;
DE Short=HS6ST-2;
DE EC=2.8.2.-;
GN Name=hs6st2; Synonyms=hs6st;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=12782624; DOI=10.1074/jbc.m213124200;
RA Bink R.J., Habuhi H., Lele Z., Dolk E., Joore J., Rauch G.-J., Geisler R.,
RA Wilson S.W., de Hertog J., Kimata K., Zivkovic D.;
RT "Heparan sulfate 6-o-sulfotransferase is essential for muscle development
RT in zebrafish.";
RL J. Biol. Chem. 278:31118-31127(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=16009360; DOI=10.1016/j.ydbio.2005.05.032;
RA Chen E., Stringer S.E., Rusch M.A., Selleck S.B., Ekker S.C.;
RT "A unique role for 6-O sulfation modification in zebrafish vascular
RT development.";
RL Dev. Biol. 284:364-376(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=17075883; DOI=10.1002/dvdy.20990;
RA Cadwallader A.B., Yost H.J.;
RT "Combinatorial expression patterns of heparan sulfate sulfotransferases in
RT zebrafish: II. The 6-O-sulfotransferase family.";
RL Dev. Dyn. 235:3432-3437(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB; TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: 6-O-sulfation enzyme which catalyzes the transfer of sulfate
CC from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the
CC N-sulfoglucosamine residue (GlcNS) of heparan sulfate. Required for
CC muscle development and angiogenesis. {ECO:0000269|PubMed:12782624,
CC ECO:0000269|PubMed:16009360}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan
CC sulfate](n) = 6-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n) +
CC adenosine 3',5'-bisphosphate + H(+); Xref=Rhea:RHEA:56604, Rhea:RHEA-
CC COMP:9830, Rhea:RHEA-COMP:14621, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:58388,
CC ChEBI:CHEBI:140604;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously during gastrulation. During
CC early somitogenesis, strong expression in head and presumptive brain.
CC During mid-somitogenesis, strong expression in eye, hindbrain and
CC somitic boundaries and weak expression in tail bud. During late
CC somitogenesis, strong expression in eye, hindbrain, branchial arch
CC primordia, spinal cord and ventral medial somites. At 24 hours post-
CC fertilization (hpf), strong expression throughout the head, with
CC expression receeding from the trunk spinal cord, ventral medial somites
CC and somitic boundaries; expressed in cells surrounding vascular
CC structures of the dorsal aorta and caudal vein in the tail. At 36 hpf,
CC expressed in lens, optic stalk, hindbrain and pectoral fin. At 48 hpf,
CC expressed in eye, brain, otic vesicle and branchial arches.
CC {ECO:0000269|PubMed:12782624, ECO:0000269|PubMed:16009360,
CC ECO:0000269|PubMed:17075883}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically
CC throughout the cleavage, gastrulation and somitogenesis stages.
CC {ECO:0000269|PubMed:16009360, ECO:0000269|PubMed:17075883}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in defects in the
CC branching morphogenesis of the caudal vein and defects in somite
CC specification with impaired muscle differentiation.
CC {ECO:0000269|PubMed:12782624, ECO:0000269|PubMed:16009360}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 6 family. {ECO:0000305}.
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DR EMBL; AJ505990; CAD44529.1; -; mRNA.
DR EMBL; AY575769; AAT80868.1; -; mRNA.
DR EMBL; DQ812995; ABH11457.1; -; mRNA.
DR EMBL; BC045453; AAH45453.1; -; mRNA.
DR EMBL; BC065683; AAH65683.1; -; mRNA.
DR RefSeq; NP_919402.1; NM_194421.1.
DR AlphaFoldDB; Q800H9; -.
DR SMR; Q800H9; -.
DR STRING; 7955.ENSDARP00000022497; -.
DR PaxDb; Q800H9; -.
DR Ensembl; ENSDART00000002250; ENSDARP00000022497; ENSDARG00000012025.
DR GeneID; 378450; -.
DR KEGG; dre:378450; -.
DR CTD; 90161; -.
DR ZFIN; ZDB-GENE-030909-14; hs6st2.
DR eggNOG; KOG3955; Eukaryota.
DR GeneTree; ENSGT00950000183071; -.
DR HOGENOM; CLU_027877_1_0_1; -.
DR InParanoid; Q800H9; -.
DR OMA; WWDLDEN; -.
DR OrthoDB; 1167623at2759; -.
DR PhylomeDB; Q800H9; -.
DR TreeFam; TF312835; -.
DR Reactome; R-DRE-2022928; HS-GAG biosynthesis.
DR PRO; PR:Q800H9; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000012025; Expressed in gastrula and 39 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017095; F:heparan sulfate 6-O-sulfotransferase activity; IMP:ZFIN.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0048048; P:embryonic eye morphogenesis; IMP:ZFIN.
DR GO; GO:0015015; P:heparan sulfate proteoglycan biosynthetic process, enzymatic modification; IBA:GO_Central.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR010635; Heparan_SO4-6-sulfoTrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005331; Sulfotransferase.
DR PANTHER; PTHR12812; PTHR12812; 1.
DR Pfam; PF03567; Sulfotransfer_2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 2: Evidence at transcript level;
KW Angiogenesis; Developmental protein; Differentiation; Glycoprotein;
KW Membrane; Myogenesis; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..468
FT /note="Heparan-sulfate 6-O-sulfotransferase 2"
FT /id="PRO_0000190808"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..468
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 409..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..441
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 103..111
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 133..134
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 150
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 160
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 197
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 205
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 209
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 329..331
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 335..336
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 106
FT /note="K -> R (in Ref. 4; AAH45453)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="D -> G (in Ref. 4; AAH45453)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="R -> Q (in Ref. 1; CAD44529, 2; AAT80868 and 3;
FT ABH11457)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="L -> S (in Ref. 1; CAD44529, 2; AAT80868 and 3;
FT ABH11457)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 54605 MW; 7E6771A7C818FF0C CRC64;
MDGKSNYSRL LIALLMILFF GGIVLQYICS TSDWQLLHLA SLSSRLGSRA PGDRLNGAGA
GDPYSSEDGA LVRFVPRFNF TTKDLSRAVD FHIKGDDVIV FLHIQKTGGT TFGRHLVRNI
QLERPCECHA GQKKCTCYRP GKRDTWLFSR FSTGWSCGLH ADWTELTNCV PSFMSNRESQ
ERRMTPSRNY YYITILRDPV WRYLSEWRHV QRGATWKASK HMCDGRLPTL TELPSCYPGD
DWSGCSLEEF MVCPYNLANN RQTRMLADLS LVGCYNLTVM SENQRWAMLL ESAKRNLRNM
AFFGLTEYQR KTQYLFEHTF RLSFIAPFTQ LNGTRAASVE VEPETQRRIR ELNQWDVELY
EYARDLFLQR FQFARQQERR EARQRRIQER RKLRAKVKSW LGVTGKAVFK PTKEPPMTEQ
SPAFAEEKQA DAERTLESET EGQVEENWLE EDDGEIMLDY LENVEQWR
