XXLT1_HUMAN
ID XXLT1_HUMAN Reviewed; 393 AA.
AC Q8NBI6; D3DNW5; Q8NAL3; Q8WV03; Q96ME0;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Xyloside xylosyltransferase 1 {ECO:0000303|PubMed:22117070};
DE EC=2.4.2.62 {ECO:0000269|PubMed:22117070, ECO:0000269|PubMed:8982869};
DE AltName: Full=UDP-xylose:alpha-xyloside alpha-1,3-xylosyltransferase;
GN Name=XXYLT1; Synonyms=C3orf21; ORFNames=PSEC0251;
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), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=22117070; DOI=10.1074/jbc.m111.302406;
RA Sethi M.K., Buettner F.F., Ashikov A., Krylov V.B., Takeuchi H.,
RA Nifantiev N.E., Haltiwanger R.S., Gerardy-Schahn R., Bakker H.;
RT "Molecular cloning of a xylosyltransferase that transfers the second xylose
RT to O-glucosylated epidermal growth factor repeats of Notch.";
RL J. Biol. Chem. 287:2739-2748(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Neuron;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8982869; DOI=10.1093/oxfordjournals.jbchem.a021492;
RA Minamida S., Aoki K., Natsuka S., Omichi K., Fukase K., Kusumoto S.,
RA Hase S.;
RT "Detection of UDP-D-xylose: alpha-D-xyloside alpha 1-->3xylosyltransferase
RT activity in human hepatoma cell line HepG2.";
RL J. Biochem. 120:1002-1006(1996).
CC -!- FUNCTION: Alpha-1,3-xylosyltransferase, which elongates the O-linked
CC xylose-glucose disaccharide attached to EGF-like repeats in the
CC extracellular domain of target proteins by catalyzing the addition of
CC the second xylose (PubMed:22117070, PubMed:8982869). Known targets
CC include Notch proteins and coagulation factors, such as F9
CC (PubMed:22117070, PubMed:8982869). {ECO:0000269|PubMed:22117070,
CC ECO:0000269|PubMed:8982869}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-L-seryl-[EGF-like
CC domain protein] + UDP-alpha-D-xylose = 3-O-[alpha-D-xylosyl-(1->3)-
CC alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-L-seryl-[EGF-like domain
CC protein] + H(+) + UDP; Xref=Rhea:RHEA:22820, Rhea:RHEA-COMP:14611,
CC Rhea:RHEA-COMP:14619, ChEBI:CHEBI:15378, ChEBI:CHEBI:57632,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:140575, ChEBI:CHEBI:140599;
CC EC=2.4.2.62; Evidence={ECO:0000269|PubMed:22117070,
CC ECO:0000269|PubMed:8982869};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8982869};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:8982869};
CC Note=Has the highest in vitro activity with 20 mM Mn(2+), a
CC concentration entirely out of the physiological range. Can also utilize
CC Mg(2+), suggesting this may be the physiological cofactor.
CC {ECO:0000269|PubMed:8982869};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.28 mM for UDP-alpha-D-xylose {ECO:0000269|PubMed:8982869};
CC pH dependence:
CC Optimum pH is 7.2. {ECO:0000269|PubMed:8982869};
CC -!- SUBUNIT: Homodimer (PubMed:22117070). Dimer formation may be essential
CC for the retention in endoplasmic reticulum (Probable).
CC {ECO:0000269|PubMed:22117070, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22117070}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:22117070}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8NBI6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NBI6-2; Sequence=VSP_018315, VSP_018317;
CC Name=3;
CC IsoId=Q8NBI6-3; Sequence=VSP_018315, VSP_018316, VSP_018318;
CC -!- SIMILARITY: Belongs to the glycosyltransferase 8 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-14 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH19036.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK057046; BAB71355.1; -; mRNA.
DR EMBL; AK092474; BAC03899.1; -; mRNA.
DR EMBL; AK075551; BAC11694.1; -; mRNA.
DR EMBL; CH471052; EAW78028.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78029.1; -; Genomic_DNA.
DR EMBL; BC019036; AAH19036.1; ALT_INIT; mRNA.
DR EMBL; BC039067; AAH39067.2; -; mRNA.
DR CCDS; CCDS43188.1; -. [Q8NBI6-1]
DR RefSeq; NP_689744.3; NM_152531.4. [Q8NBI6-1]
DR RefSeq; XP_016861239.1; XM_017005750.1. [Q8NBI6-2]
DR AlphaFoldDB; Q8NBI6; -.
DR SMR; Q8NBI6; -.
DR BioGRID; 127415; 59.
DR IntAct; Q8NBI6; 8.
DR STRING; 9606.ENSP00000309640; -.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR GlyGen; Q8NBI6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8NBI6; -.
DR PhosphoSitePlus; Q8NBI6; -.
DR BioMuta; XXYLT1; -.
DR DMDM; 74751171; -.
DR EPD; Q8NBI6; -.
DR jPOST; Q8NBI6; -.
DR MassIVE; Q8NBI6; -.
DR MaxQB; Q8NBI6; -.
DR PaxDb; Q8NBI6; -.
DR PeptideAtlas; Q8NBI6; -.
DR PRIDE; Q8NBI6; -.
DR ProteomicsDB; 72773; -. [Q8NBI6-1]
DR ProteomicsDB; 72774; -. [Q8NBI6-2]
DR ProteomicsDB; 72775; -. [Q8NBI6-3]
DR Antibodypedia; 53804; 52 antibodies from 12 providers.
DR DNASU; 152002; -.
DR Ensembl; ENST00000310380.11; ENSP00000309640.6; ENSG00000173950.16. [Q8NBI6-1]
DR Ensembl; ENST00000356740.5; ENSP00000349179.5; ENSG00000173950.16. [Q8NBI6-3]
DR Ensembl; ENST00000437101.5; ENSP00000409865.1; ENSG00000173950.16. [Q8NBI6-2]
DR GeneID; 152002; -.
DR KEGG; hsa:152002; -.
DR MANE-Select; ENST00000310380.11; ENSP00000309640.6; NM_152531.5; NP_689744.3.
DR UCSC; uc003fuk.4; human. [Q8NBI6-1]
DR CTD; 152002; -.
DR DisGeNET; 152002; -.
DR GeneCards; XXYLT1; -.
DR HGNC; HGNC:26639; XXYLT1.
DR HPA; ENSG00000173950; Low tissue specificity.
DR MIM; 614552; gene.
DR neXtProt; NX_Q8NBI6; -.
DR OpenTargets; ENSG00000173950; -.
DR PharmGKB; PA134925222; -.
DR VEuPathDB; HostDB:ENSG00000173950; -.
DR eggNOG; KOG3765; Eukaryota.
DR GeneTree; ENSGT00940000158154; -.
DR HOGENOM; CLU_048175_0_0_1; -.
DR InParanoid; Q8NBI6; -.
DR OMA; TIYDVKV; -.
DR OrthoDB; 830935at2759; -.
DR PhylomeDB; Q8NBI6; -.
DR TreeFam; TF323210; -.
DR BRENDA; 2.4.2.62; 2681.
DR PathwayCommons; Q8NBI6; -.
DR SignaLink; Q8NBI6; -.
DR SIGNOR; Q8NBI6; -.
DR BioGRID-ORCS; 152002; 20 hits in 1077 CRISPR screens.
DR ChiTaRS; XXYLT1; human.
DR GenomeRNAi; 152002; -.
DR Pharos; Q8NBI6; Tbio.
DR PRO; PR:Q8NBI6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8NBI6; protein.
DR Bgee; ENSG00000173950; Expressed in oocyte and 116 other tissues.
DR ExpressionAtlas; Q8NBI6; baseline and differential.
DR Genevisible; Q8NBI6; HS.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0035252; F:UDP-xylosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0140560; F:xylosyl alpha-1,3-xylosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016266; P:O-glycan processing; IDA:UniProtKB.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR002495; Glyco_trans_8.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR042465; XXLT1.
DR PANTHER; PTHR46612; PTHR46612; 1.
DR Pfam; PF01501; Glyco_transf_8; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Endoplasmic reticulum;
KW Glycosyltransferase; Magnesium; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..393
FT /note="Xyloside xylosyltransferase 1"
FT /id="PRO_0000234427"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:22117070"
FT TRANSMEM 24..44
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 45..393
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:22117070"
FT REGION 263..266
FT /note="Interaction with target proteins"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 104..106
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 226
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 227
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 228
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 290
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 328
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 331
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_note="substrate"
FT /ligand_part="3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-
FT L-seryl residue"
FT /ligand_part_id="ChEBI:CHEBI:140575"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 331
FT /ligand="UDP-alpha-D-xylose"
FT /ligand_id="ChEBI:CHEBI:57632"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 360
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_note="substrate"
FT /ligand_part="3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-
FT L-seryl residue"
FT /ligand_part_id="ChEBI:CHEBI:140575"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 383
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT BINDING 385
FT /ligand="a glycoprotein"
FT /ligand_id="ChEBI:CHEBI:17089"
FT /ligand_note="substrate"
FT /ligand_part="3-O-[alpha-D-xylosyl-(1->3)-beta-D-glucosyl]-
FT L-seryl residue"
FT /ligand_part_id="ChEBI:CHEBI:140575"
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT DISULFID 350..375
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT DISULFID 357..386
FT /evidence="ECO:0000250|UniProtKB:Q3U4G3"
FT VAR_SEQ 1..203
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018315"
FT VAR_SEQ 204..217
FT /note="IFFLSVAMHQIMPK -> MWPPRCKDPGRQSA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018317"
FT VAR_SEQ 204..206
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018316"
FT VAR_SEQ 207..262
FT /note="LSVAMHQIMPKEILQIIQLDLDLKFKTNIRELFEEFDSFLPGAIIGIAREMQ
FT PVYR -> MNGMSVLMKETLKSSVTPSPYEETGERQPSVNWAVSPHQTQNQWARWSWTS
FT QPLEL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_018318"
SQ SEQUENCE 393 AA; 43807 MW; 3C788AFDF933A23D CRC64;
MGLLRGGLPC ARAMARLGAV RSHYCALLLA AALAVCAFYY LGSGRETFSS ATKRLKEARA
GAPAAPSPPA LELARGSVAP APGAKAKSLE GGGAGPVDYH LLMMFTKAEH NAALQAKARV
ALRSLLRLAK FEAHEVLNLH FVSEEASREV AKGLLRELLP PAAGFKCKVI FHDVAVLTDK
LFPIVEAMQK HFSAGLGTYY SDSIFFLSVA MHQIMPKEIL QIIQLDLDLK FKTNIRELFE
EFDSFLPGAI IGIAREMQPV YRHTFWQFRH ENPQTRVGGP PPEGLPGFNS GVMLLNLEAM
RQSPLYSRLL EPAQVQQLAD KYHFRGHLGD QDFFTMIGME HPKLFHVLDC TWNRQLCTWW
RDHGYSDVFE AYFRCEGHVK IYHGNCNTPI PED
