HS2ST_MOUSE
ID HS2ST_MOUSE Reviewed; 356 AA.
AC Q8R3H7; O88464; Q3TNP7; Q9JLK2;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Heparan sulfate 2-O-sulfotransferase 1;
DE Short=2-O-sulfotransferase;
DE Short=2-OST;
DE Short=2OST;
DE EC=2.8.2.-;
GN Name=Hs2st1; Synonyms=Hs2st;
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, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=9637690; DOI=10.1101/gad.12.12.1894;
RA Bullock S.L., Fletcher J.M., Beddington R.S.P., Wilson V.A.;
RT "Renal agenesis in mice homozygous for a gene trap mutation in the gene
RT encoding heparan sulfate 2-sulfotransferase.";
RL Genes Dev. 12:1894-1906(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ENZYME ACTIVITY.
RC TISSUE=Mast cell;
RX PubMed=10677367; DOI=10.1042/bj3460463;
RA Rong J., Habuchi H., Kimata K., Lindahl U., Kusche-Gullberg M.;
RT "Expression of heparan sulphate L-iduronyl 2-O-sulphotransferase in human
RT kidney 293 cells results in increased D-glucuronyl 2-O-sulphation.";
RL Biochem. J. 346:463-468(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Ovary, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary tumor;
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 [5]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=11331020; DOI=10.1021/bi002926p;
RA Rong J., Habuchi H., Kimata K., Lindahl U., Kusche-Gullberg M.;
RT "Substrate specificity of the heparan sulfate hexuronic acid 2-O-
RT sulfotransferase.";
RL Biochemistry 40:5548-5555(2001).
RN [6]
RP FUNCTION.
RX PubMed=11457822; DOI=10.1074/jbc.m100379200;
RA Merry C.L.R., Bullock S.L., Swan D.C., Backen A.C., Lyon M.,
RA Beddington R.S.P., Wilson V.A., Gallagher J.T.;
RT "The molecular phenotype of heparan sulfate in the Hs2st-/- mutant mouse.";
RL J. Biol. Chem. 276:35429-35434(2001).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GLCE.
RX PubMed=11687650; DOI=10.1073/pnas.241175798;
RA Pinhal M.A.S., Smith B., Olson S., Aikawa J., Kimata K., Esko J.D.;
RT "Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase
RT and 2-O-sulfotransferase interact in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12984-12989(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the transfer of sulfate to the C2-position of
CC selected hexuronic acid residues within the maturing heparan sulfate
CC (HS). 2-O-sulfation within HS, particularly of iduronate residues, is
CC essential for HS to participate in a variety of high-affinity ligand-
CC binding interactions and signaling processes. Required for metanephric
CC development of kidney formation, suggesting that 2-O-sulfation within
CC HS is essential for signaling between ureteric bud and metanephric
CC mesenchyme. Mediates 2-O-sulfation of both L-iduronyl and D-glucuronyl
CC residues. {ECO:0000269|PubMed:11331020, ECO:0000269|PubMed:11457822,
CC ECO:0000269|PubMed:9637690}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.7 uM for iduronic acid-containing substrate disaccharide units
CC {ECO:0000269|PubMed:11331020};
CC KM=19.3 uM for glucuronic acid-containing substrate disaccharide
CC units {ECO:0000269|PubMed:11331020};
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with the C5-epimerase
CC GLCE. {ECO:0000250, ECO:0000269|PubMed:11687650}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:11687650}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:11687650}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in lung
CC and brain. Weakly expressed in spleen. {ECO:0000269|PubMed:11331020,
CC ECO:0000269|PubMed:9637690}.
CC -!- DEVELOPMENTAL STAGE: At 7.5 dpc, it is expressed in all three germ
CC layers, although it appears to be more expressed in the embryonic
CC ectoderm and the node. Widespread expression persists at 8.5 dpc,
CC although it is clearly expressed at higher level in rhombomeres 2 and 4
CC and branchial arches 1 and 2 (which are populated by neural crest from
CC these rhombomeres). At 10.5 dpc, the dorsal and ventral aspects of the
CC neural tube, brain and midbrain-hindbrain junction show the most
CC intense expression. A day later in development, elevated expression is
CC found in the floor plate and the sclerotome. At 12.5 dpc, both the
CC floor plate and the roofplate exhibit strong expression as the
CC mesenchyme of the limb and of the developing whisker follicles. At 13.5
CC dpc, it is predominantly expressed in embryonic mesenchyme, especially
CC at sites of epithelial-mesenchymal interactions such as the developing
CC teeth and whisker follicles. Strong expression is also apparent in the
CC perichondria of the cartilaginous skeleton, an important site for the
CC regulation of skeletal differentiation.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice die in the neonatal period, exhibiting
CC bilateral renal agenesis and defects of the eye and the skeleton.
CC Uronate 2-O-sulfates are not detected in such mice, however, the domain
CC structure of the HS is conserved, due to a compensatory increase in
CC N- and 6-O-sulfation maintain the overall charge density.
CC {ECO:0000269|PubMed:9637690}.
CC -!- SIMILARITY: Belongs to the sulfotransferase 3 family. {ECO:0000305}.
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DR EMBL; AF060178; AAC40135.1; -; mRNA.
DR EMBL; AF169243; AAF59900.1; -; mRNA.
DR EMBL; AK088698; BAC40511.1; -; mRNA.
DR EMBL; AK165112; BAE38041.1; -; mRNA.
DR EMBL; BC025443; AAH25443.1; -; mRNA.
DR EMBL; BC059008; AAH59008.1; -; mRNA.
DR CCDS; CCDS17883.1; -.
DR RefSeq; NP_035958.3; NM_011828.3.
DR AlphaFoldDB; Q8R3H7; -.
DR SMR; Q8R3H7; -.
DR STRING; 10090.ENSMUSP00000043066; -.
DR GlyConnect; 2370; 3 N-Linked glycans (2 sites).
DR GlyGen; Q8R3H7; 2 sites, 3 N-linked glycans (2 sites).
DR PhosphoSitePlus; Q8R3H7; -.
DR EPD; Q8R3H7; -.
DR MaxQB; Q8R3H7; -.
DR PaxDb; Q8R3H7; -.
DR PeptideAtlas; Q8R3H7; -.
DR PRIDE; Q8R3H7; -.
DR ProteomicsDB; 273318; -.
DR DNASU; 23908; -.
DR Ensembl; ENSMUST00000043325; ENSMUSP00000043066; ENSMUSG00000040151.
DR GeneID; 23908; -.
DR KEGG; mmu:23908; -.
DR UCSC; uc012cyx.1; mouse.
DR CTD; 9653; -.
DR MGI; MGI:1346049; Hs2st1.
DR VEuPathDB; HostDB:ENSMUSG00000040151; -.
DR eggNOG; KOG3922; Eukaryota.
DR GeneTree; ENSGT00530000063408; -.
DR HOGENOM; CLU_045310_1_0_1; -.
DR InParanoid; Q8R3H7; -.
DR OMA; KWHEMKP; -.
DR OrthoDB; 877221at2759; -.
DR PhylomeDB; Q8R3H7; -.
DR TreeFam; TF315238; -.
DR Reactome; R-MMU-2022928; HS-GAG biosynthesis.
DR SABIO-RK; Q8R3H7; -.
DR BioGRID-ORCS; 23908; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Hs2st1; mouse.
DR PRO; PR:Q8R3H7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8R3H7; protein.
DR Bgee; ENSMUSG00000040151; Expressed in right lung and 247 other tissues.
DR ExpressionAtlas; Q8R3H7; baseline and differential.
DR Genevisible; Q8R3H7; MM.
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:0004394; F:heparan sulfate 2-O-sulfotransferase activity; IMP:MGI.
DR GO; GO:0008146; F:sulfotransferase activity; IBA:GO_Central.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0015015; P:heparan sulfate proteoglycan biosynthetic process, enzymatic modification; IBA:GO_Central.
DR GO; GO:0015014; P:heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process; IMP:MGI.
DR GO; GO:0030202; P:heparin metabolic process; IMP:MGI.
DR GO; GO:0060676; P:ureteric bud formation; IMP:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR007734; Heparan_SO4_2-O-STrfase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005331; Sulfotransferase.
DR PANTHER; PTHR12129; PTHR12129; 1.
DR Pfam; PF03567; Sulfotransfer_2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Golgi apparatus; Membrane;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..356
FT /note="Heparan sulfate 2-O-sulfotransferase 1"
FT /id="PRO_0000207675"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..356
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 140
FT /evidence="ECO:0000250"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 201..209
FT /evidence="ECO:0000250"
FT DISULFID 222..228
FT /evidence="ECO:0000250"
FT CONFLICT 271
FT /note="F -> V (in Ref. 1; AAC40135)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="R -> H (in Ref. 4; AAH25443)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 356 AA; 41813 MW; E83D315141E57475 CRC64;
MGLLRIMMPP KLQLLAVVAF AVAMLFLENQ IQKLEESRAK LERAIARHEV REIEQRHTMD
GPRQDATLDE EEDIIIIYNR VPKTASTSFT NIAYDLCAKN RYHVLHINTT KNNPVMSLQD
QVRFVKNITT WNEMKPGFYH GHISYLDFAK FGVKKKPIYI NVIRDPIERL VSYYYFLRFG
DDYRPGLRRR KQGDKKTFDE CVAEGGSDCA PEKLWLQIPF FCGHSSECWN VGSRWAMDQA
KSNLINEYFL VGVTEELEDF IMLLEAALPR FFRGATDLYR TGKKSHLRKT TEKKLPTKQT
IAKLQQSDIW KMENEFYEFA LEQFQFIRAH AVREKDGDLY ILAQNFFYEK IYPKSN
