CHSS1_MOUSE
ID CHSS1_MOUSE Reviewed; 800 AA.
AC Q6ZQ11;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Chondroitin sulfate synthase 1;
DE EC=2.4.1.175 {ECO:0000250|UniProtKB:Q86X52};
DE EC=2.4.1.226 {ECO:0000250|UniProtKB:Q86X52};
DE AltName: Full=Chondroitin glucuronyltransferase 1;
DE AltName: Full=Chondroitin synthase 1;
DE Short=ChSy-1;
DE AltName: Full=Glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase 1;
DE AltName: Full=N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase 1;
DE AltName: Full=N-acetylgalactosaminyltransferase 1;
GN Name=Chsy1; Synonyms=Kiaa0990;
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 [LARGE SCALE MRNA].
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
CC -!- FUNCTION: Has both beta-1,3-glucuronic acid and beta-1,4-N-
CC acetylgalactosamine transferase activity. Transfers glucuronic acid
CC (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-
CC GalNAc to the non-reducing end of the elongating chondroitin polymer.
CC Involved in the negative control of osteogenesis likely through the
CC modulation of NOTCH signaling. {ECO:0000250|UniProtKB:Q86X52}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-
CC (1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-
CC [protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-(beta-D-GalNAc-
CC (1->4)-beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-
CC beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] +
CC H(+) + UDP; Xref=Rhea:RHEA:20800, Rhea:RHEA-COMP:14058, Rhea:RHEA-
CC COMP:14059, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:67138,
CC ChEBI:CHEBI:138442, ChEBI:CHEBI:138443; EC=2.4.1.175;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20801;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GlcA-(1->3)-[beta-D-GalNAc-(1->4)-beta-D-GlcA-
CC (1->3)](n)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-
CC beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-
CC D-galactosamine = 3-O-([beta-D-GalNAc-(1->4)-beta-D-GlcA-
CC (1->3)](n+1)-beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-
CC (1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:55000, Rhea:RHEA-COMP:14060, Rhea:RHEA-COMP:14301,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:67138,
CC ChEBI:CHEBI:138444, ChEBI:CHEBI:138445; EC=2.4.1.175;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55001;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-
CC (1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-alpha-D-
CC glucuronate = 3-O-(beta-D-GlcA-(1->3)-beta-D-GalNAc-(1->4)-beta-D-
CC GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-
CC [protein] + H(+) + UDP; Xref=Rhea:RHEA:23428, Rhea:RHEA-COMP:12575,
CC Rhea:RHEA-COMP:14058, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:132105, ChEBI:CHEBI:138442;
CC EC=2.4.1.226; Evidence={ECO:0000250|UniProtKB:Q86X52};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23429;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-([beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)](n)-beta-D-
CC GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + UDP-alpha-D-glucuronate = 3-O-(beta-
CC D-GlcA-(1->3)-[beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)](n)-beta-D-
CC GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-
CC beta-D-Xyl)-L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:54996,
CC Rhea:RHEA-COMP:14060, Rhea:RHEA-COMP:14061, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:138444,
CC ChEBI:CHEBI:138445; EC=2.4.1.226;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54997;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC Name=Cd(2+); Xref=ChEBI:CHEBI:48775;
CC Evidence={ECO:0000250|UniProtKB:Q86X52};
CC Note=Divalent metal cations. Highest activities are measured with
CC Co(2+), Mn(2+) and Cd(2+). {ECO:0000250|UniProtKB:Q86X52};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q86X52}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q86X52}. Secreted
CC {ECO:0000250|UniProtKB:Q86X52}.
CC -!- SIMILARITY: Belongs to the chondroitin N-
CC acetylgalactosaminyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98065.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AK129255; BAC98065.1; ALT_INIT; mRNA.
DR CCDS; CCDS39978.1; -.
DR RefSeq; NP_001074632.1; NM_001081163.1.
DR AlphaFoldDB; Q6ZQ11; -.
DR SMR; Q6ZQ11; -.
DR BioGRID; 234731; 2.
DR STRING; 10090.ENSMUSP00000047487; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR CAZy; GT7; Glycosyltransferase Family 7.
DR GlyGen; Q6ZQ11; 2 sites.
DR iPTMnet; Q6ZQ11; -.
DR PhosphoSitePlus; Q6ZQ11; -.
DR EPD; Q6ZQ11; -.
DR MaxQB; Q6ZQ11; -.
DR PaxDb; Q6ZQ11; -.
DR PeptideAtlas; Q6ZQ11; -.
DR PRIDE; Q6ZQ11; -.
DR ProteomicsDB; 281672; -.
DR Antibodypedia; 43966; 152 antibodies from 23 providers.
DR Ensembl; ENSMUST00000036372; ENSMUSP00000047487; ENSMUSG00000032640.
DR GeneID; 269941; -.
DR KEGG; mmu:269941; -.
DR UCSC; uc009hhb.1; mouse.
DR CTD; 22856; -.
DR MGI; MGI:2681120; Chsy1.
DR VEuPathDB; HostDB:ENSMUSG00000032640; -.
DR eggNOG; KOG3588; Eukaryota.
DR GeneTree; ENSGT01050000244857; -.
DR HOGENOM; CLU_016244_2_0_1; -.
DR InParanoid; Q6ZQ11; -.
DR OMA; FEKNDPN; -.
DR OrthoDB; 442283at2759; -.
DR PhylomeDB; Q6ZQ11; -.
DR TreeFam; TF318303; -.
DR BRENDA; 2.4.1.175; 3474.
DR BRENDA; 2.4.1.226; 3474.
DR Reactome; R-MMU-2022870; Chondroitin sulfate biosynthesis.
DR BioGRID-ORCS; 269941; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Chsy1; mouse.
DR PRO; PR:Q6ZQ11; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q6ZQ11; protein.
DR Bgee; ENSMUSG00000032640; Expressed in humerus cartilage element and 227 other tissues.
DR Genevisible; Q6ZQ11; MM.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008376; F:acetylgalactosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0047238; F:glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity; ISO:MGI.
DR GO; GO:0016757; F:glycosyltransferase activity; IMP:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050510; F:N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity; ISO:MGI.
DR GO; GO:0060349; P:bone morphogenesis; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IGI:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:MGI.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:0009954; P:proximal/distal pattern formation; IMP:MGI.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0051923; P:sulfation; IMP:MGI.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR008428; Chond_GalNAc.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF05679; CHGN; 1.
DR SUPFAM; SSF53448; SSF53448; 2.
PE 2: Evidence at transcript level;
KW Glycoprotein; Golgi apparatus; Membrane; Metal-binding; Reference proteome;
KW Secreted; Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..800
FT /note="Chondroitin sulfate synthase 1"
FT /id="PRO_0000189559"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..800
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 36..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 632
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 746
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 800 AA; 91383 MW; F3DFBC6E7C78C21D CRC64;
MAARGRRAWL SMLLGLVLGF VLASRLVLPR ASELKRVGPR RRPSPEGCRP GQEASQPGGA
RGDARGAQLW PQGSAAEGVP RDRNFLFVGV MTAQKYLQTR AVAAYRTWSK TIPGKVEFFS
SEGSDTSIPI PVVPLRGVDD SYPPQKKSFM MLKYMHDHYL DKYEWFMRAD DDVYIKGDRL
ESFLRSLNSS EPLFLGQTGL GTTEEMGKLA LEPGENFCMG GPGVILSREV LRRMAPHIGK
CLREMYTTHE DVEVGRCVRR FAGVQCVWSY EMQQLFYENY EQNKKGYIRD LHSSKIHRAI
TLHPNKNPPY QYRLHSYMLS RKIAELRHRT IQLHREIVLM SKYSSTEIQK EDLQLGIPPS
FMRFQARQRE EILEWEFLTG KYLYSATDGQ PPRRGMDSAQ REALDDIVMQ VMEMINANAK
TRGRIIDFKE IQYGYRRVNP MYGAEYILDL LLLYKKHKGK KMTVPVRRHA YLQQTFSKMQ
FVEHEELDAQ ELADRINQDS GSLSFLSNSL KKLVAFQLPG SKTEHKEPKE KKINILIPLS
GRFDMFVRFM GNFEKTCLIP NLNVKLVILL FNSDSNPDKA KQVELMRDYR VKYPKADMQV
LPVSGGFSRA LALEVGSSQF NNESLLFFCD VDLVFTAEFL QRCRANTVLG QQIYFPIIFS
QYDPKIVYSG KVPSDNHFAF TQKTGFWRNY GFGITCIYKG DLVRVGGFDV SIQGWGLEDV
DLFNKVVQAG LKTFRSQEVG VVHIHHPVVC DPNLDPKQYK MCLGSKASTF GSTQQLAEMW
LEKNDPSYSK GGSHGSARTA
