XYLT2_HUMAN
ID XYLT2_HUMAN Reviewed; 865 AA.
AC Q9H1B5; Q6UY41; Q86V00;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Xylosyltransferase 2;
DE EC=2.4.2.26 {ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:18023272, ECO:0000269|PubMed:25748573, ECO:0000269|PubMed:26027496};
DE AltName: Full=Peptide O-xylosyltransferase 1;
DE AltName: Full=Xylosyltransferase II {ECO:0000303|PubMed:17189265};
DE Short=XT-II {ECO:0000303|PubMed:11099377};
DE Short=XylT-II;
GN Name=XYLT2; Synonyms=XT2; ORFNames=UNQ3058/PRO9878;
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] (ISOFORM 1), VARIANT THR-305, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Chondrosarcoma;
RX PubMed=11099377; DOI=10.1006/jmbi.2000.4261;
RA Goetting C., Kuhn J., Zahn R., Brinkmann T., Kleesiek K.;
RT "Molecular cloning and expression of human UDP-D-xylose:proteoglycan core
RT protein beta-D-xylosyltransferase and its first isoform XT-II.";
RL J. Mol. Biol. 304:517-528(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-305.
RC TISSUE=Pancreas;
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 INVOLVEMENT IN PXE, VARIANT PXE ARG-801, AND VARIANTS ASN-56; LEU-115;
RP THR-305 AND LEU-418.
RX PubMed=16571645; DOI=10.1136/jmg.2006.040972;
RA Schon S., Schulz V., Prante C., Hendig D., Szliska C., Kuhn J.,
RA Kleesiek K., Gotting C.;
RT "Polymorphisms in the xylosyltransferase genes cause higher serum XT-I
RT activity in patients with pseudoxanthoma elasticum (PXE) and are involved
RT in a severe disease course.";
RL J. Med. Genet. 43:745-749(2006).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=17189265; DOI=10.1074/jbc.m611665200;
RA Poenighaus C., Ambrosius M., Casanova J.C., Prante C., Kuhn J., Esko J.D.,
RA Kleesiek K., Goetting C.;
RT "Human xylosyltransferase II is involved in the biosynthesis of the uniform
RT tetrasaccharide linkage region in chondroitin sulfate and heparan sulfate
RT proteoglycans.";
RL J. Biol. Chem. 282:5201-5206(2007).
RN [6]
RP CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=18023272; DOI=10.1016/j.bbrc.2007.10.206;
RA Casanova J.C., Kuhn J., Kleesiek K., Goetting C.;
RT "Heterologous expression and biochemical characterization of soluble human
RT xylosyltransferase II.";
RL Biochem. Biophys. Res. Commun. 365:678-684(2008).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INVOLVEMENT IN SOS.
RX PubMed=26027496; DOI=10.1016/j.ajhg.2015.04.017;
RA Munns C.F., Fahiminiya S., Poudel N., Munteanu M.C., Majewski J.,
RA Sillence D.O., Metcalf J.P., Biggin A., Glorieux F., Fassier F., Rauch F.,
RA Hinsdale M.E.;
RT "Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular
RT syndrome with bone fragility, cataracts, and hearing defects.";
RL Am. J. Hum. Genet. 96:971-978(2015).
RN [8]
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=25748573; DOI=10.1016/j.bbrc.2015.02.129;
RA Kuhn J., Goetting C., Beahm B.J., Bertozzi C.R., Faust I., Kuzaj P.,
RA Knabbe C., Hendig D.;
RT "Xylosyltransferase II is the predominant isoenzyme which is responsible
RT for the steady-state level of xylosyltransferase activity in human serum.";
RL Biochem. Biophys. Res. Commun. 459:469-474(2015).
CC -!- FUNCTION: Catalyzes the first step in the biosynthesis of chondroitin
CC sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as
CC DCN. Transfers D-xylose from UDP-D-xylose to specific serine residues
CC of the core protein. {ECO:0000269|PubMed:17189265,
CC ECO:0000269|PubMed:26027496}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-seryl-[protein] + UDP-alpha-D-xylose = 3-O-(beta-D-xylosyl)-
CC L-seryl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:50192, Rhea:RHEA-
CC COMP:9863, Rhea:RHEA-COMP:12567, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:57632, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132085; EC=2.4.2.26;
CC Evidence={ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:18023272,
CC ECO:0000269|PubMed:25748573, ECO:0000269|PubMed:26027496};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:18023272};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:18023272};
CC Note=Active with either Mg(2+) or Mn(2+), but activity is highest when
CC both are present. {ECO:0000269|PubMed:18023272};
CC -!- PATHWAY: Glycan metabolism; chondroitin sulfate biosynthesis.
CC {ECO:0000269|PubMed:17189265}.
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:26027496}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q86Y38}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}. Secreted
CC {ECO:0000269|PubMed:17189265, ECO:0000269|PubMed:25748573}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H1B5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H1B5-2; Sequence=VSP_013758, VSP_013759;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed at higher level in
CC kidney and pancreas. {ECO:0000269|PubMed:11099377}.
CC -!- PTM: Contains disulfide bonds. {ECO:0000250|UniProtKB:Q86Y38}.
CC -!- DISEASE: Spondyloocular syndrome (SOS) [MIM:605822]: A syndrome
CC characterized by cataract, loss of vision due to retinal detachment,
CC facial dysmorphism, facial hypotonia, normal height with
CC disproportional short trunk, osteoporosis, immobile spine with thoracic
CC kyphosis and reduced lumbal lordosis. {ECO:0000269|PubMed:26027496}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Pseudoxanthoma elasticum (PXE) [MIM:264800]: A multisystem
CC disorder characterized by accumulation of mineralized and fragmented
CC elastic fibers in the skin, vascular walls, and Burch membrane in the
CC eye. Clinically, patients exhibit characteristic lesions of the
CC posterior segment of the eye including peau d'orange, angioid streaks,
CC and choroidal neovascularizations, of the skin including soft, ivory
CC colored papules in a reticular pattern that predominantly affect the
CC neck and large flexor surfaces, and of the cardiovascular system with
CC peripheral and coronary arterial occlusive disease as well as
CC gastrointestinal bleedings. {ECO:0000269|PubMed:16571645}. Note=The
CC gene represented in this entry acts as a disease modifier. PXE patients
CC carrying causative ABCC6 mutations, manifest a more severe disease
CC course characterized by earlier onset, frequent skin lesions and higher
CC organ involvement, in the presence of XYLT2 variants.
CC {ECO:0000269|PubMed:16571645}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 14 family. XylT
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ277442; CAC16788.1; -; mRNA.
DR EMBL; AY358090; AAQ88457.1; -; mRNA.
DR EMBL; BC052262; AAH52262.2; -; mRNA.
DR CCDS; CCDS11563.1; -. [Q9H1B5-1]
DR RefSeq; NP_071450.2; NM_022167.3. [Q9H1B5-1]
DR AlphaFoldDB; Q9H1B5; -.
DR SMR; Q9H1B5; -.
DR BioGRID; 122081; 66.
DR IntAct; Q9H1B5; 14.
DR STRING; 9606.ENSP00000017003; -.
DR CAZy; GT14; Glycosyltransferase Family 14.
DR GlyGen; Q9H1B5; 7 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9H1B5; -.
DR PhosphoSitePlus; Q9H1B5; -.
DR BioMuta; XYLT2; -.
DR DMDM; 126302616; -.
DR EPD; Q9H1B5; -.
DR jPOST; Q9H1B5; -.
DR MassIVE; Q9H1B5; -.
DR MaxQB; Q9H1B5; -.
DR PaxDb; Q9H1B5; -.
DR PeptideAtlas; Q9H1B5; -.
DR PRIDE; Q9H1B5; -.
DR ProteomicsDB; 80393; -. [Q9H1B5-1]
DR ProteomicsDB; 80394; -. [Q9H1B5-2]
DR Antibodypedia; 2239; 99 antibodies from 15 providers.
DR DNASU; 64132; -.
DR Ensembl; ENST00000017003.7; ENSP00000017003.2; ENSG00000015532.10. [Q9H1B5-1]
DR GeneID; 64132; -.
DR KEGG; hsa:64132; -.
DR MANE-Select; ENST00000017003.7; ENSP00000017003.2; NM_022167.4; NP_071450.2.
DR UCSC; uc002iqo.5; human. [Q9H1B5-1]
DR CTD; 64132; -.
DR DisGeNET; 64132; -.
DR GeneCards; XYLT2; -.
DR HGNC; HGNC:15517; XYLT2.
DR HPA; ENSG00000015532; Tissue enriched (stomach).
DR MalaCards; XYLT2; -.
DR MIM; 264800; phenotype.
DR MIM; 605822; phenotype.
DR MIM; 608125; gene.
DR neXtProt; NX_Q9H1B5; -.
DR OpenTargets; ENSG00000015532; -.
DR Orphanet; 85194; Spondylo-ocular syndrome.
DR PharmGKB; PA37974; -.
DR VEuPathDB; HostDB:ENSG00000015532; -.
DR eggNOG; KOG0799; Eukaryota.
DR GeneTree; ENSGT00940000158326; -.
DR HOGENOM; CLU_012840_0_0_1; -.
DR InParanoid; Q9H1B5; -.
DR OMA; AVYHERH; -.
DR PhylomeDB; Q9H1B5; -.
DR TreeFam; TF315534; -.
DR BioCyc; MetaCyc:HS00371-MON; -.
DR BRENDA; 2.4.2.26; 2681.
DR PathwayCommons; Q9H1B5; -.
DR Reactome; R-HSA-1971475; A tetrasaccharide linker sequence is required for GAG synthesis.
DR SignaLink; Q9H1B5; -.
DR UniPathway; UPA00755; -.
DR UniPathway; UPA00756; -.
DR BioGRID-ORCS; 64132; 154 hits in 1078 CRISPR screens.
DR GeneWiki; XYLT2; -.
DR GenomeRNAi; 64132; -.
DR Pharos; Q9H1B5; Tbio.
DR PRO; PR:Q9H1B5; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9H1B5; protein.
DR Bgee; ENSG00000015532; Expressed in body of stomach and 152 other tissues.
DR ExpressionAtlas; Q9H1B5; baseline and differential.
DR Genevisible; Q9H1B5; HS.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0030158; F:protein xylosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0030206; P:chondroitin sulfate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0050650; P:chondroitin sulfate proteoglycan biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; NAS:UniProtKB.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; TAS:Reactome.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IMP:UniProtKB.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:Ensembl.
DR InterPro; IPR003406; Glyco_trans_14.
DR InterPro; IPR043538; XYLT.
DR InterPro; IPR024448; XylT_C.
DR PANTHER; PTHR46025; PTHR46025; 1.
DR Pfam; PF02485; Branch; 1.
DR Pfam; PF12529; Xylo_C; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Disulfide bond; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Magnesium; Manganese; Membrane;
KW Metal-binding; Reference proteome; Secreted; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..865
FT /note="Xylosyltransferase 2"
FT /id="PRO_0000191406"
FT TOPO_DOM 1..15
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..865
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 41..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 846..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..72
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 239
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT BINDING 267
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT BINDING 296..298
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT BINDING 400..401
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT BINDING 481
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT BINDING 504..505
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 683
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 162..190
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT DISULFID 206..448
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT DISULFID 467..480
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT DISULFID 469..478
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT DISULFID 581..833
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT DISULFID 826..839
FT /evidence="ECO:0000250|UniProtKB:Q86Y38"
FT VAR_SEQ 583..638
FT /note="FEPRGLPSSVHLYFYDDHFQGYLVTQAVQPSAQGPAETLEMWLMPQGSLKLL
FT GRSD -> LALIGTPKSVFSGTLGGYWGRWTSLWPCSAGPGAPTSQPQWSGSTQPMWWP
FT HLMTS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013758"
FT VAR_SEQ 639..865
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013759"
FT VARIANT 56
FT /note="D -> N (in dbSNP:rs113835371)"
FT /evidence="ECO:0000269|PubMed:16571645"
FT /id="VAR_071276"
FT VARIANT 60
FT /note="G -> R (in dbSNP:rs739990)"
FT /id="VAR_049328"
FT VARIANT 115
FT /note="P -> L (in dbSNP:rs748114111)"
FT /evidence="ECO:0000269|PubMed:16571645"
FT /id="VAR_071277"
FT VARIANT 305
FT /note="R -> T (in dbSNP:rs12451299)"
FT /evidence="ECO:0000269|PubMed:11099377,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16571645"
FT /id="VAR_022453"
FT VARIANT 418
FT /note="P -> L (in dbSNP:rs72832454)"
FT /evidence="ECO:0000269|PubMed:16571645"
FT /id="VAR_071278"
FT VARIANT 801
FT /note="T -> R (in PXE; acts as a modifier of disease
FT severity; more frequent in patients with a severe disease
FT course; dbSNP:rs6504649)"
FT /evidence="ECO:0000269|PubMed:16571645"
FT /id="VAR_022454"
SQ SEQUENCE 865 AA; 96767 MW; EF477B7C3C1B964B CRC64;
MVASARVQKL VRRYKLAIAT ALAILLLQGL VVWSFSGLEE DEAGEKGRQR KPRPLDPGEG
SKDTDSSAGR RGSTGRRHGR WRGRAESPGV PVAKVVRAVT SRQRASRRVP PAPPPEAPGR
QNLSGAAAGE ALVGAAGFPP HGDTGSVEGA PQPTDNGFTP KCEIVGKDAL SALARASTKQ
CQQEIANVVC LHQAGSLMPK AVPRHCQLTG KMSPGIQWDE SQAQQPMDGP PVRIAYMLVV
HGRAIRQLKR LLKAVYHEQH FFYIHVDKRS DYLHREVVEL AQGYDNVRVT PWRMVTIWGG
ASLLRMYLRS MRDLLEVPGW AWDFFINLSA TDYPTRTNEE LVAFLSKNRD KNFLKSHGRD
NSRFIKKQGL DRLFHECDSH MWRLGERQIP AGIVVDGGSD WFVLTRSFVE YVVYTDDPLV
AQLRQFYTYT LLPAESFFHT VLENSLACET LVDNNLRVTN WNRKLGCKCQ YKHIVDWCGC
SPNDFKPQDF LRLQQVSRPT FFARKFESTV NQEVLEILDF HLYGSYPPGT PALKAYWENT
YDAADGPSGL SDVMLTAYTA FARLSLHHAA TAAPPMGTPL CRFEPRGLPS SVHLYFYDDH
FQGYLVTQAV QPSAQGPAET LEMWLMPQGS LKLLGRSDQA SRLQSLEVGT DWDPKERLFR
NFGGLLGPLD EPVAVQRWAR GPNLTATVVW IDPTYVVATS YDITVDTETE VTQYKPPLSR
PLRPGPWTVR LLQFWEPLGE TRFLVLPLTF NRKLPLRKDD ASWLHAGPPH NEYMEQSFQG
LSSILNLPQP ELAEEAAQRH TQLTGPALEA WTDRELSSFW SVAGLCAIGP SPCPSLEPCR
LTSWSSLSPD PKSELGPVKA DGRLR
