CHSS3_HUMAN
ID CHSS3_HUMAN Reviewed; 882 AA.
AC Q70JA7; B2RP97; Q76L22; Q86Y52;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Chondroitin sulfate synthase 3;
DE EC=2.4.1.175;
DE EC=2.4.1.226;
DE AltName: Full=Carbohydrate synthase 2;
DE AltName: Full=Chondroitin glucuronyltransferase 3;
DE AltName: Full=Chondroitin synthase 2;
DE Short=ChSy-2;
DE AltName: Full=Glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase II;
DE AltName: Full=N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase 3;
DE AltName: Full=N-acetylgalactosaminyltransferase 3;
GN Name=CHSY3; Synonyms=CHSY2, CSS3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, COFACTOR, AND
RP TISSUE SPECIFICITY.
RX PubMed=12907687; DOI=10.1074/jbc.m304421200;
RA Yada T., Sato T., Kaseyama H., Gotoh M., Iwasaki H., Kikuchi N.,
RA Kwon Y.-D., Togayachi A., Kudo T., Watanabe H., Narimatsu H., Kimata K.;
RT "Chondroitin sulfate synthase-3. Molecular cloning and characterization.";
RL J. Biol. Chem. 278:39711-39725(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas, and Placenta;
RA Kamakari S., Chatzidakis I., Anagnou N.;
RT "A novel gene for chondroitin synthase in 5q23.3.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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).
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 Specific activity is much reduced compared to CHSY1.
CC {ECO:0000269|PubMed:12907687}.
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 -!- 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 -!- 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;
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 -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:12907687};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:12907687};
CC Name=Cd(2+); Xref=ChEBI:CHEBI:48775;
CC Evidence={ECO:0000269|PubMed:12907687};
CC Note=Divalent metal cations. Highest activities are measured with
CC Co(2+), Mn(2+) and Cd(2+). {ECO:0000269|PubMed:12907687};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane
CC {ECO:0000305|PubMed:12907687}; Single-pass type II membrane protein
CC {ECO:0000305|PubMed:12907687}.
CC -!- TISSUE SPECIFICITY: Detected at low levels in brain, cerebral cortex,
CC uterus and small intestine. {ECO:0000269|PubMed:12907687}.
CC -!- SIMILARITY: Belongs to the chondroitin N-
CC acetylgalactosaminyltransferase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD43233.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Chondroitin sulfate synthase 3;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_446";
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; AB086062; BAC98832.1; -; mRNA.
DR EMBL; AJ504664; CAD43233.1; ALT_INIT; mRNA.
DR EMBL; AJ578034; CAE17326.1; -; mRNA.
DR EMBL; BC137325; AAI37326.1; -; mRNA.
DR CCDS; CCDS34223.1; -.
DR RefSeq; NP_787052.3; NM_175856.4.
DR AlphaFoldDB; Q70JA7; -.
DR SMR; Q70JA7; -.
DR BioGRID; 130623; 36.
DR IntAct; Q70JA7; 15.
DR MINT; Q70JA7; -.
DR STRING; 9606.ENSP00000302629; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR CAZy; GT7; Glycosyltransferase Family 7.
DR GlyGen; Q70JA7; 6 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q70JA7; -.
DR PhosphoSitePlus; Q70JA7; -.
DR BioMuta; CHSY3; -.
DR DMDM; 145559453; -.
DR EPD; Q70JA7; -.
DR jPOST; Q70JA7; -.
DR MassIVE; Q70JA7; -.
DR MaxQB; Q70JA7; -.
DR PaxDb; Q70JA7; -.
DR PeptideAtlas; Q70JA7; -.
DR PRIDE; Q70JA7; -.
DR ProteomicsDB; 68561; -.
DR Antibodypedia; 25854; 107 antibodies from 25 providers.
DR DNASU; 337876; -.
DR Ensembl; ENST00000305031.5; ENSP00000302629.4; ENSG00000198108.4.
DR GeneID; 337876; -.
DR KEGG; hsa:337876; -.
DR MANE-Select; ENST00000305031.5; ENSP00000302629.4; NM_175856.5; NP_787052.3.
DR UCSC; uc003kvd.4; human.
DR CTD; 337876; -.
DR DisGeNET; 337876; -.
DR GeneCards; CHSY3; -.
DR HGNC; HGNC:24293; CHSY3.
DR HPA; ENSG00000198108; Low tissue specificity.
DR MIM; 609963; gene.
DR neXtProt; NX_Q70JA7; -.
DR OpenTargets; ENSG00000198108; -.
DR PharmGKB; PA162382259; -.
DR VEuPathDB; HostDB:ENSG00000198108; -.
DR eggNOG; KOG3588; Eukaryota.
DR GeneTree; ENSGT01050000244857; -.
DR HOGENOM; CLU_016244_2_0_1; -.
DR InParanoid; Q70JA7; -.
DR OMA; QGPQLPE; -.
DR OrthoDB; 442283at2759; -.
DR PhylomeDB; Q70JA7; -.
DR TreeFam; TF318303; -.
DR BioCyc; MetaCyc:HS11959-MON; -.
DR BRENDA; 2.4.1.175; 2681.
DR PathwayCommons; Q70JA7; -.
DR Reactome; R-HSA-2022870; Chondroitin sulfate biosynthesis.
DR SABIO-RK; Q70JA7; -.
DR SignaLink; Q70JA7; -.
DR BioGRID-ORCS; 337876; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; CHSY3; human.
DR GenomeRNAi; 337876; -.
DR Pharos; Q70JA7; Tdark.
DR PRO; PR:Q70JA7; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q70JA7; protein.
DR Bgee; ENSG00000198108; Expressed in calcaneal tendon and 141 other tissues.
DR Genevisible; Q70JA7; HS.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
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; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050510; F:N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity; TAS:Reactome.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IBA:GO_Central.
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 Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..882
FT /note="Chondroitin sulfate synthase 3"
FT /id="PRO_0000189562"
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..882
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 46..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 720
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT BINDING 834
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 710
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 878
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 615
FT /note="G -> E (in dbSNP:rs10068403)"
FT /id="VAR_027540"
FT VARIANT 764
FT /note="D -> G (in dbSNP:rs2015018)"
FT /id="VAR_021174"
FT CONFLICT 173
FT /note="L -> P (in Ref. 2; CAE17326)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="W -> R (in Ref. 2; CAE17326)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="R -> H (in Ref. 2; CAE17326)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="G -> E (in Ref. 2; CAE17326)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="Y -> H (in Ref. 1; BAC98832)"
FT /evidence="ECO:0000305"
FT CONFLICT 354..355
FT /note="GT -> RA (in Ref. 1; BAC98832)"
FT /evidence="ECO:0000305"
FT CONFLICT 361..362
FT /note="YE -> FQ (in Ref. 1; BAC98832)"
FT /evidence="ECO:0000305"
FT CONFLICT 856
FT /note="S -> N (in Ref. 2; CAD43233/CAE17326)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 882 AA; 100284 MW; 2FE26485B2CEA515 CRC64;
MAVRSRRPWM SVALGLVLGF TAASWLIAPR VAELSERKRR GSSLCSYYGR SAAGPRAGAQ
QPLPQPQSRP RQEQSPPPAR QDLQGPPLPE AAPGITSFRS SPWQQPPPLQ QRRRGREPEG
ATGLPGAPAA EGEPEEEDGG AAGQRRDGRP GSSHNGSGDG GAAAPSARPR DFLYVGVMTA
QKYLGSRALA AQRTWARFIP GRVEFFSSQQ PPNAGQPPPP LPVIALPGVD DSYPPQKKSF
MMIKYMHDHY LDKYEWFMRA DDDVYIKGDK LEEFLRSLNS SKPLYLGQTG LGNIEELGKL
GLEPGENFCM GGPGMIFSRE VLRRMVPHIG ECLREMYTTH EDVEVGRCVR RFGGTQCVWS
YEMQQLFHEN YEHNRKGYIQ DLHNSKIHAA ITLHPNKRPA YQYRLHNYML SRKISELRYR
TIQLHRESAL MSKLSNTEVS KEDQQLGVIP SFNHFQPRER NEVIEWEFLT GKLLYSAAEN
QPPRQSLSSI LRTALDDTVL QVMEMINENA KSRGRLIDFK EIQYGYRRVN PMHGVEYILD
LLLLYKRHKG RKLTVPVRRH AYLQQLFSKP FFRETEELDV NSLVESINSE TQSFSFISNS
LKILSSFQGA KEMGGHNEKK VHILVPLIGR YDIFLRFMEN FENMCLIPKQ NVKLVIILFS
RDSGQDSSKH IELIKGYQNK YPKAEMTLIP MKGEFSRGLG LEMASAQFDN DTLLLFCDVD
LIFREDFLQR CRDNTIQGQQ VYYPIIFSQY DPKVTNGGNP PTDDYFIFSK KTGFWRDYGY
GITCIYKSDL LGAGGFDTSI QGWGLEDVDL YNKVILSGLR PFRSQEVGVV HIFHPVHCDP
NLDPKQYKMC LGSKASTFAS TMQLAELWLE KHLGVRYNRT LS
