ID   PLGT3_HUMAN             Reviewed;         507 AA.
AC   Q7Z4H8; Q6UWW2; Q6ZUM9; Q8N7L8; Q8NE24;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   25-JUL-2006, sequence version 2.
DT   27-MAR-2024, entry version 147.
DE   RecName: Full=Protein O-glucosyltransferase 3 {ECO:0000305|PubMed:30127001};
DE            EC=2.4.1.- {ECO:0000269|PubMed:30127001};
DE   AltName: Full=KDEL motif-containing protein 2 {ECO:0000312|HGNC:HGNC:28496};
DE   AltName: Full=Protein O-xylosyltransferase POGLUT3 {ECO:0000305|PubMed:30127001};
DE            EC=2.4.2.- {ECO:0000269|PubMed:30127001};
DE   Flags: Precursor;
GN   Name=POGLUT3 {ECO:0000303|PubMed:30127001,
GN   ECO:0000312|HGNC:HGNC:28496};
GN   Synonyms=KDELC2 {ECO:0000312|HGNC:HGNC:28496};
GN   ORFNames=UNQ1904/PRO4350;
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).
RC   TISSUE=Testis;
RA   Ding P., Han W., Xia D., Wu C., Liu Y., Wu C., Ma D.;
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
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 3), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 324-507 (ISOFORMS 1/2).
RC   TISSUE=Placenta, and Uterus;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-319.
RC   TISSUE=Testis;
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   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-61 AND ASN-306.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBSTRATE SPECIFICITY.
RX   PubMed=30127001; DOI=10.1073/pnas.1804005115;
RA   Takeuchi H., Schneider M., Williamson D.B., Ito A., Takeuchi M.,
RA   Handford P.A., Haltiwanger R.S.;
RT   "Two novel protein O-glucosyltransferases that modify sites distinct from
RT   POGLUT1 and affect Notch trafficking and signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 115:E8395-E8402(2018).
RN   [9]
RP   FUNCTION.
RX   PubMed=34411563; DOI=10.1016/j.jbc.2021.101055;
RA   Williamson D.B., Sohn C.J., Ito A., Haltiwanger R.S.;
RT   "POGLUT2 and POGLUT3 O-glucosylate multiple EGF repeats in fibrillin-1, -2,
RT   and LTBP1 and promote secretion of fibrillin-1.";
RL   J. Biol. Chem. 297:101055-101055(2021).
CC   -!- FUNCTION: Protein glucosyltransferase that catalyzes the transfer of
CC       glucose from UDP-glucose to a serine residue within the consensus
CC       sequence peptide C-X-N-T-X-G-S-F-X-C (PubMed:30127001). Can also
CC       catalyze the transfer of xylose from UDP-xylose but less efficiently
CC       (PubMed:30127001). Specifically targets extracellular EGF repeats of
CC       proteins such as NOTCH1, NOTCH3, FBN1, FBN2 and LTBP1 (PubMed:30127001,
CC       PubMed:34411563). May regulate the transport of NOTCH1 and NOTCH3 to
CC       the plasma membrane and thereby the Notch signaling pathway
CC       (PubMed:30127001). {ECO:0000269|PubMed:30127001,
CC       ECO:0000269|PubMed:34411563}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[EGF-like domain protein] + UDP-alpha-D-glucose = 3-O-
CC         (beta-D-glucosyl)-L-seryl-[EGF-like domain protein] + H(+) + UDP;
CC         Xref=Rhea:RHEA:58116, Rhea:RHEA-COMP:14610, Rhea:RHEA-COMP:16010,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:58885, ChEBI:CHEBI:140576;
CC         Evidence={ECO:0000269|PubMed:30127001};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[EGF-like domain protein] + UDP-alpha-D-xylose = 3-O-
CC         (beta-D-xylosyl)-L-seryl-[EGF-like domain protein] + H(+) + UDP;
CC         Xref=Rhea:RHEA:62016, Rhea:RHEA-COMP:16010, Rhea:RHEA-COMP:16011,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:57632,
CC         ChEBI:CHEBI:58223, ChEBI:CHEBI:132085;
CC         Evidence={ECO:0000269|PubMed:30127001};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000269|PubMed:30127001}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC       ProRule:PRU10138}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q7Z4H8-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7Z4H8-2; Sequence=VSP_019944, VSP_019945;
CC       Name=3;
CC         IsoId=Q7Z4H8-3; Sequence=VSP_019944, VSP_019945, VSP_019946,
CC                                  VSP_019947;
CC   -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC       premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC       decay. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the KDELC family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAC05260.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF533708; AAQ09021.1; -; mRNA.
DR   EMBL; AY358616; AAQ88979.1; -; mRNA.
DR   EMBL; AK098206; BAC05260.1; ALT_INIT; mRNA.
DR   EMBL; AK125519; BAC86191.1; -; mRNA.
DR   EMBL; BC036526; AAH36526.3; -; mRNA.
DR   CCDS; CCDS41711.1; -. [Q7Z4H8-1]
DR   RefSeq; NP_714916.3; NM_153705.4. [Q7Z4H8-1]
DR   AlphaFoldDB; Q7Z4H8; -.
DR   SMR; Q7Z4H8; -.
DR   BioGRID; 126822; 118.
DR   IntAct; Q7Z4H8; 9.
DR   MINT; Q7Z4H8; -.
DR   STRING; 9606.ENSP00000315386; -.
DR   GlyConnect; 1431; 8 N-Linked glycans (2 sites).
DR   GlyCosmos; Q7Z4H8; 2 sites, 7 glycans.
DR   GlyGen; Q7Z4H8; 9 sites, 9 N-linked glycans (2 sites), 2 O-linked glycans (5 sites).
DR   iPTMnet; Q7Z4H8; -.
DR   PhosphoSitePlus; Q7Z4H8; -.
DR   SwissPalm; Q7Z4H8; -.
DR   BioMuta; KDELC2; -.
DR   DMDM; 110810398; -.
DR   EPD; Q7Z4H8; -.
DR   jPOST; Q7Z4H8; -.
DR   MassIVE; Q7Z4H8; -.
DR   MaxQB; Q7Z4H8; -.
DR   PaxDb; 9606-ENSP00000315386; -.
DR   PeptideAtlas; Q7Z4H8; -.
DR   ProteomicsDB; 69187; -. [Q7Z4H8-1]
DR   ProteomicsDB; 69188; -. [Q7Z4H8-2]
DR   ProteomicsDB; 69189; -. [Q7Z4H8-3]
DR   Pumba; Q7Z4H8; -.
DR   Antibodypedia; 50833; 69 antibodies from 16 providers.
DR   DNASU; 143888; -.
DR   Ensembl; ENST00000323468.10; ENSP00000315386.5; ENSG00000178202.14. [Q7Z4H8-1]
DR   Ensembl; ENST00000434945.6; ENSP00000413429.2; ENSG00000178202.14. [Q7Z4H8-2]
DR   Ensembl; ENST00000530529.5; ENSP00000431796.1; ENSG00000178202.14. [Q7Z4H8-3]
DR   GeneID; 143888; -.
DR   KEGG; hsa:143888; -.
DR   MANE-Select; ENST00000323468.10; ENSP00000315386.5; NM_153705.5; NP_714916.3.
DR   UCSC; uc001pki.3; human. [Q7Z4H8-1]
DR   AGR; HGNC:28496; -.
DR   CTD; 143888; -.
DR   DisGeNET; 143888; -.
DR   GeneCards; POGLUT3; -.
DR   HGNC; HGNC:28496; POGLUT3.
DR   HPA; ENSG00000178202; Low tissue specificity.
DR   MIM; 618503; gene.
DR   neXtProt; NX_Q7Z4H8; -.
DR   OpenTargets; ENSG00000178202; -.
DR   PharmGKB; PA134904072; -.
DR   VEuPathDB; HostDB:ENSG00000178202; -.
DR   eggNOG; KOG2458; Eukaryota.
DR   GeneTree; ENSGT00940000159028; -.
DR   HOGENOM; CLU_041919_0_0_1; -.
DR   InParanoid; Q7Z4H8; -.
DR   OMA; GITAWFF; -.
DR   OrthoDB; 1826823at2759; -.
DR   PhylomeDB; Q7Z4H8; -.
DR   TreeFam; TF323280; -.
DR   PathwayCommons; Q7Z4H8; -.
DR   SignaLink; Q7Z4H8; -.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 143888; 6 hits in 1161 CRISPR screens.
DR   ChiTaRS; KDELC2; human.
DR   GenomeRNAi; 143888; -.
DR   Pharos; Q7Z4H8; Tdark.
DR   PRO; PR:Q7Z4H8; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q7Z4H8; Protein.
DR   Bgee; ENSG00000178202; Expressed in calcaneal tendon and 177 other cell types or tissues.
DR   ExpressionAtlas; Q7Z4H8; baseline and differential.
DR   GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0140561; F:EGF-domain serine glucosyltransferase activity; IEA:RHEA.
DR   GO; GO:0140562; F:EGF-domain serine xylosyltransferase activity; IEA:RHEA.
DR   GO; GO:0046527; F:glucosyltransferase activity; IBA:GO_Central.
DR   GO; GO:0035251; F:UDP-glucosyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0035252; F:UDP-xylosyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0018242; P:protein O-linked glycosylation via serine; IDA:UniProtKB.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR006598; CAP10.
DR   InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR   InterPro; IPR001298; Filamin/ABP280_rpt.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR014756; Ig_E-set.
DR   PANTHER; PTHR12203; KDEL LYS-ASP-GLU-LEU CONTAINING - RELATED; 1.
DR   PANTHER; PTHR12203:SF18; PROTEIN O-GLUCOSYLTRANSFERASE 3; 1.
DR   Pfam; PF00630; Filamin; 1.
DR   Pfam; PF05686; Glyco_transf_90; 1.
DR   SMART; SM00672; CAP10; 1.
DR   SMART; SM00557; IG_FLMN; 1.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   PROSITE; PS00014; ER_TARGET; 1.
DR   PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR   Genevisible; Q7Z4H8; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW   Glycosyltransferase; Reference proteome; Signal; Transferase.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..507
FT                   /note="Protein O-glucosyltransferase 3"
FT                   /id="PRO_0000247196"
FT   REPEAT          24..134
FT                   /note="Filamin"
FT   MOTIF           504..507
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   CARBOHYD        61
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        306
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   VAR_SEQ         1..56
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:12975309,
FT                   ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019944"
FT   VAR_SEQ         57..67
FT                   /note="SEGQNLTRSPA -> MVELFIFLFLL (in isoform 2 and isoform
FT                   3)"
FT                   /evidence="ECO:0000303|PubMed:12975309,
FT                   ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019945"
FT   VAR_SEQ         432..465
FT                   /note="ENDEEAKKIAKEGQLMARDLLQPHRLYCYYYQVL -> SFTLSPRLECSGTI
FT                   STHCNLCLPGSRNFVPQPPE (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019946"
FT   VAR_SEQ         466..507
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_019947"
FT   VARIANT         319
FT                   /note="R -> L (in dbSNP:rs17853654)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_027086"
FT   CONFLICT        101
FT                   /note="L -> S (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        115
FT                   /note="K -> T (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        132
FT                   /note="L -> S (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        158
FT                   /note="T -> N (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        161
FT                   /note="P -> T (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        185
FT                   /note="R -> S (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        188
FT                   /note="D -> Y (in Ref. 1; AAQ09021)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   507 AA;  58572 MW;  5D268DBE5D7EDB99 CRC64;
     MRRLPRALLL QLRLALLVAA GAPEVLVSAP RSLVWGPGLQ AAVVLPVRYF YLQAVNSEGQ
     NLTRSPAGET PFKVVVKSLS PKELVRIHVP KPLDRNDGTF LMRYRMYETV DEGLKIEVLY
     GDEHVAQSPY ILKGPVYHEY CECPEDPQAW QKTLSCPTKE PQIAKDFASF PSINLQQMLK
     EVPKRFGDER GAIVHYTILN NHVYRRSLGK YTDFKMFSDE ILLSLTRKVL LPDLEFYVNL
     GDWPLEHRKV NGTPSPIPII SWCGSLDSRD VVLPTYDITH SMLEAMRGVT NDLLSIQGNT
     GPSWINKTER AFFRGRDSRE ERLQLVQLSK ENPQLLDAGI TGYFFFQEKE KELGKAKLMG
     FFDFFKYKYQ VNVDGTVAAY RYPYLMLGDS LVLKQDSPYY EHFYMALEPW KHYVPIKRNL
     SDLLEKVKWA KENDEEAKKI AKEGQLMARD LLQPHRLYCY YYQVLQKYAE RQSSKPEVRD
     GMELVPQPED STAICQCHRK KPSREEL
//