H6ST1_CRIGR
ID H6ST1_CRIGR Reviewed; 401 AA.
AC Q91ZB4; O70158;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 3.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Heparan-sulfate 6-O-sulfotransferase 1 {ECO:0000250|UniProtKB:O60243};
DE Short=HS6ST-1;
DE EC=2.8.2.- {ECO:0000269|PubMed:7876170};
GN Name=HS6ST1 {ECO:0000250|UniProtKB:O60243}; Synonyms=6OST1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=11551899; DOI=10.1074/jbc.m101441200;
RA Zhang L., Beeler D.L., Lawrence R., Lech M., Liu J., Davis J.C.,
RA Shriver Z., Sasisekharan R., Rosenberg R.D.;
RT "6-O-sulfotransferase-1 represents a critical enzyme in the anticoagulant
RT heparan sulfate biosynthetic pathway.";
RL J. Biol. Chem. 276:42311-42321(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-263, AND PROTEIN SEQUENCE OF 28-40; 58-65;
RP 95-99; 124-128; 158-163 AND 230-236.
RC TISSUE=Ovary;
RX PubMed=9535912; DOI=10.1074/jbc.273.15.9208;
RA Habuchi H., Kobayashi M., Kimata K.;
RT "Molecular characterization and expression of heparan-sulfate 6-
RT sulfotransferase.";
RL J. Biol. Chem. 273:9208-9213(1998).
RN [3]
RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP GLYCOSYLATION, AND CATALYTIC ACTIVITY.
RC TISSUE=Ovary;
RX PubMed=7876170; DOI=10.1074/jbc.270.8.4172;
RA Habuchi H., Habuchi O., Kimata K.;
RT "Purification and characterization of heparan sulfate 6-sulfotransferase
RT from the culture medium of Chinese hamster ovary cells.";
RL J. Biol. Chem. 270:4172-4179(1995).
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. Also transfers
CC sulfate to CDSNS-heparin and performs the crucial step modification in
CC the biosynthesis of anticoagulant heparan sulfate (HSact). Critical for
CC normal neuronal development where it may play a role in neuron
CC branching. May also play a role in limb development. May prefer
CC iduronic acid. {ECO:0000269|PubMed:11551899,
CC ECO:0000269|PubMed:7876170}.
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; Evidence={ECO:0000269|PubMed:7876170};
CC -!- ACTIVITY REGULATION: Inhibited by dithiothreitol and stimulated by
CC protamine. {ECO:0000269|PubMed:7876170}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.44 uM for PAPS {ECO:0000269|PubMed:7876170};
CC pH dependence:
CC Optimum pH is 6.3. {ECO:0000269|PubMed:7876170};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:7876170}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 6 family. {ECO:0000305}.
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DR EMBL; AY043180; AAL05593.1; -; mRNA.
DR EMBL; AB006180; BAA25761.1; -; mRNA.
DR AlphaFoldDB; Q91ZB4; -.
DR SMR; Q91ZB4; -.
DR STRING; 10029.XP_007627101.1; -.
DR eggNOG; KOG3955; Eukaryota.
DR SABIO-RK; Q91ZB4; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008146; F:sulfotransferase activity; IEA:InterPro.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Direct protein sequencing; Glycoprotein; Membrane; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..401
FT /note="Heparan-sulfate 6-O-sulfotransferase 1"
FT /id="PRO_0000190800"
FT TOPO_DOM 1..4
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 5..27
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..401
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 367..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 140
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 83..91
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 113..114
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 135
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 175
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 183
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 194
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 307..309
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 313..314
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 310
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 172..174
FT /note="TLL -> ILV (in Ref. 2; BAA25761)"
FT /evidence="ECO:0000305"
FT CONFLICT 261..263
FT /note="SKR -> RAA (in Ref. 2; BAA25761)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 401 AA; 47080 MW; 31FDB48A6FC4FB25 CRC64;
MVERASKFVL VVAGSACFML ILYQYAGPGL SLGAPGGRAP PDDLDLFPTP DPHYEKKYYF
PVRELERSLR FDMKGDDVIV FLHIQKTGGT TFGRHLVQNV RLEVPCDCRP GQKKCTCYRP
NRRETWLFSR FSTGWSCGLH ADWTELTNCV PGVLDRRDPA GLRSPRKFYY ITLLRDPVSR
YLSEWRHVQR GATWKTSLHM CDGRTPTPEE LPPCYEGTDW SGCTLQEFMD CPYNLANNRQ
VRMLADLSLV GCYNLSFIPE SKRAQLLLES AKKNLRGMAF FGLTEFQRKT QYLFERTFNL
KFIRPFMQYN STRAGGVEVD EDTIRHIEEL NDLDMQLYDY AKDLFQQRYQ YKRQLERREQ
RLRNREERLL HRSKEALPRE DTEEPGRVPT EDYMSHIIEK W
