H6ST1_MOUSE
ID H6ST1_MOUSE Reviewed; 411 AA.
AC Q9QYK5; Q3TK52; Q3TKK0; Q3TND4; Q3TZT5;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 4.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Heparan-sulfate 6-O-sulfotransferase 1 {ECO:0000305};
DE Short=HS6ST-1;
DE Short=mHS6ST-1;
DE EC=2.8.2.- {ECO:0000269|PubMed:10644753};
GN Name=Hs6st1 {ECO:0000312|MGI:MGI:1354958};
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, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND DOMAIN.
RC TISSUE=Brain;
RX PubMed=10644753; DOI=10.1074/jbc.275.4.2859;
RA Habuchi H., Tanaka M., Habuchi O., Yoshida K., Suzuki H., Ban K.,
RA Kimata K.;
RT "The occurrence of three isoforms of heparan sulfate 6-O-sulfotransferase
RT having different specificities for hexuronic acid adjacent to the targeted
RT N-sulfoglucosamine.";
RL J. Biol. Chem. 275:2859-2868(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Blastocyst, and Spleen;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 DISRUPTION PHENOTYPE.
RX PubMed=17405882; DOI=10.1074/jbc.m607434200;
RA Habuchi H., Nagai N., Sugaya N., Atsumi F., Stevens R.L., Kimata K.;
RT "Mice deficient in heparan sulfate 6-O-sulfotransferase-1 exhibit defective
RT heparan sulfate biosynthesis, abnormal placentation, and late embryonic
RT lethality.";
RL J. Biol. Chem. 282:15578-15588(2007).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=18196599; DOI=10.1002/dvg.20355;
RA Izvolsky K.I., Lu J., Martin G., Albrecht K.H., Cardoso W.V.;
RT "Systemic inactivation of Hs6st1 in mice is associated with late postnatal
RT mortality without major defects in organogenesis.";
RL Genesis 46:8-18(2008).
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. 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:10644753}.
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:10644753};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for CDSNS-heparin {ECO:0000269|PubMed:10644753};
CC KM=100 uM for NS-heparosan {ECO:0000269|PubMed:10644753};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal brain and liver.
CC {ECO:0000269|PubMed:10644753}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: According to PubMed:17405882 most mice die
CC between embryonic day 15.5 and the perinatal stage. Those that survive
CC are considerably smaller than their wild-type littermates and exhibit
CC development abnormalities including a reduction in the number of fetal
CC microvessels in the labyrinthine zone of the placenta. However,
CC according to PubMed:18196599, pups are viable and grossly normal at
CC birth. During early adulthood, however, mice fail to thrive and exhibit
CC growth retardation, bodyweight loss, enlargement of airspaces in the
CC lung and, in some cases, lethality. {ECO:0000269|PubMed:17405882,
CC ECO:0000269|PubMed:18196599}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 6 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH52316.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA89248.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB024566; BAA89248.1; ALT_INIT; mRNA.
DR EMBL; AK157556; BAE34122.1; -; mRNA.
DR EMBL; AK165385; BAE38155.1; -; mRNA.
DR EMBL; AK166962; BAE39145.1; -; mRNA.
DR EMBL; AK167151; BAE39293.1; -; mRNA.
DR EMBL; BC052316; AAH52316.1; ALT_INIT; mRNA.
DR CCDS; CCDS48237.1; -.
DR RefSeq; NP_056633.2; NM_015818.2.
DR AlphaFoldDB; Q9QYK5; -.
DR SMR; Q9QYK5; -.
DR STRING; 10090.ENSMUSP00000085499; -.
DR GlyConnect; 2371; 2 N-Linked glycans (1 site).
DR GlyGen; Q9QYK5; 2 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9QYK5; -.
DR PhosphoSitePlus; Q9QYK5; -.
DR MaxQB; Q9QYK5; -.
DR PaxDb; Q9QYK5; -.
DR PeptideAtlas; Q9QYK5; -.
DR PRIDE; Q9QYK5; -.
DR ProteomicsDB; 269762; -.
DR Antibodypedia; 33479; 115 antibodies from 17 providers.
DR DNASU; 50785; -.
DR Ensembl; ENSMUST00000088174; ENSMUSP00000085499; ENSMUSG00000045216.
DR GeneID; 50785; -.
DR KEGG; mmu:50785; -.
DR UCSC; uc007apn.2; mouse.
DR CTD; 9394; -.
DR MGI; MGI:1354958; Hs6st1.
DR VEuPathDB; HostDB:ENSMUSG00000045216; -.
DR eggNOG; KOG3955; Eukaryota.
DR GeneTree; ENSGT00950000183071; -.
DR HOGENOM; CLU_027877_1_0_1; -.
DR InParanoid; Q9QYK5; -.
DR OMA; ELPACYK; -.
DR OrthoDB; 1167623at2759; -.
DR PhylomeDB; Q9QYK5; -.
DR TreeFam; TF312835; -.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR SABIO-RK; Q9QYK5; -.
DR BioGRID-ORCS; 50785; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Hs6st1; mouse.
DR PRO; PR:Q9QYK5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9QYK5; protein.
DR Bgee; ENSMUSG00000045216; Expressed in cortical plate and 314 other tissues.
DR Genevisible; Q9QYK5; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0017095; F:heparan sulfate 6-O-sulfotransferase activity; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:MGI.
DR GO; GO:0015015; P:heparan sulfate proteoglycan biosynthetic process, enzymatic modification; IDA:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
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 Coiled coil; Glycoprotein; Membrane; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..411
FT /note="Heparan-sulfate 6-O-sulfotransferase 1"
FT /id="PRO_0000190802"
FT TOPO_DOM 1..19
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..37
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..411
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 380..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 352..386
FT /evidence="ECO:0000255"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 93..101
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 123..124
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 145
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 150
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 185
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 193
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 197
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 204
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 317..319
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT BINDING 323..324
FT /ligand="3'-phosphoadenylyl sulfate"
FT /ligand_id="ChEBI:CHEBI:58339"
FT /evidence="ECO:0000250|UniProtKB:A0MGZ7"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 125
FT /note="C -> S (in Ref. 2; BAE38155)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 411 AA; 48302 MW; 8A618806A8A1D6AE CRC64;
MRRRRAGGRT MVERASKFVL VVAGSACFML ILYQYAGPGL SLGAPGGRVP 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 DPEEPGRVPT EDYMSHIIEK W
