<?xml version='1.0' encoding='UTF-8'?>
<ProteomeXchangeDataset id="PXD058951" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <CvList>
    <Cv id="MS" fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-Cv/master/psi-ms.obo"/>
    <Cv id="MOD" fullName="PSI-MOD" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-mod-CV/master/PSI-MOD.obo"/>
    <Cv id="UNIMOD" fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo"/>
  </CvList>
  <DatasetSummary announceDate="2025-03-20" hostingRepository="PanoramaPublic" title="Marfan syndrome variation of the POGLUT2 and POGLUT3 consensus sequence can produce aberrant fibrillin-1 O-glucosylation">
    <Description>Fibrillin-1 (FBN1) is an essential component of the extracellular matrix, forming microfibril bundles that are important for proper development of elastic tissues found in the aorta and lung, as well as non-elastic tissue found in the eyes and skeleton. Many missense mutations in the FBN1 gene are associated with Marfan syndrome (MFS), a common developmental disorder.  FBN1 contains 47 Epidermal Growth Factor-Like (EGF) repeats, which are protein domains characterized by six cysteines and three disulfide bonds. Over half of these EGF repeats are modified with an O-glucose monosaccharide added by Protein O-glucosyltransferase 2 and/or 3 (POGLUT2/3). Previous studies showed that O-glucose modifies the serine within the putative consensus sequence between cysteines 3 and 4: C3-x-N-T-x-G-S-F/Y-x-C4. These residues are common among modified EGFs, but it is unknown if they are required for O-glucosylation. To address this, we used a glycoproteomic approach by analyzing O-glucosylation levels of individual EGF repeats from overexpressed N-terminal FBN1 variants in HEK293T cells. Surprisingly, only the serine (S) was required for O-glucosylation, leading to the revised consensus sequence, C3-x-x-x-x-x-S-x-x-C4. Using this open consensus in database searches, the possible number of POGLUT2/3 substrates in humans has doubled. While some variants displayed reduced O-glucose monosaccharide modification, other variants, including MFS variants, displayed elongation of the O-glucose monosaccharide by additional glycosyltransferases. MFS variants reduction or elongation of O-glucose warrants further investigation on their influence on FBN1 function, which could play a role in the molecular mechanism of the disease.</Description>
    <ReviewLevel>
      <cvParam cvRef="MS" accession="MS:1002854" name="Peer-reviewed dataset"/>
    </ReviewLevel>
    <RepositorySupport>
      <cvParam cvRef="MS" accession="MS:1002856" name="Supported dataset by repository"/>
    </RepositorySupport>
  </DatasetSummary>
  <DatasetIdentifierList>
    <DatasetIdentifier>
      <cvParam cvRef="MS" accession="MS:1001919" name="ProteomeXchange accession number" value="PXD058951"/>
      <cvParam cvRef="MS" accession="MS:1001921" name="ProteomeXchange accession number version number" value="1"/>
    </DatasetIdentifier>
    <DatasetIdentifier>
      <cvParam cvRef="MS" accession="MS:1002872" name="Panorama Public dataset identifier" value="https://panoramaweb.org/fh79bx.url"/>
    </DatasetIdentifier>
  </DatasetIdentifierList>
  <DatasetOriginList>
    <DatasetOrigin>
      <cvParam cvRef="MS" accession="MS:1002868" name="Original data"/>
    </DatasetOrigin>
  </DatasetOriginList>
  <SpeciesList>
    <Species>
      <cvParam cvRef="MS" accession="MS:1001469" name="taxonomy: scientific name" value="Homo sapiens"/>
      <cvParam cvRef="MS" accession="MS:1001467" name="taxonomy: NCBI TaxID" value="9606"/>
    </Species>
  </SpeciesList>
  <InstrumentList>
    <Instrument id="instrument_1">
      <cvParam cvRef="MS" accession="MS:1002634" name="Q Exactive Plus"/>
    </Instrument>
  </InstrumentList>
  <ModificationList>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:34" name="Methyl"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:1444" name="Hex(2)NeuAc(1)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:1428" name="Hex(1)Pent(2)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:35" name="Oxidation"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:1426" name="Hex(1)Pent(1)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:27" name="Glu->pyro-Glu"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:149" name="Hex(1)HexNAc(1)NeuAc(1)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:1425" name="Pentose"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:1930" name="Pent(2)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:36" name="Dimethyl"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:512" name="Hex(2)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:4" name="Carbamidomethyl"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:295" name="dHex"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:41" name="Hex"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:28" name="Gln->pyro-Glu"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:43" name="HexNAc"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:793" name="Hex(1)HexNAc(1)"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:26" name="Pyro-carbamidomethyl"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:7" name="Deamidated"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:37" name="Trimethyl"/>
    <cvParam cvRef="UNIMOD" accession="UNIMOD:425" name="Dioxidation"/>
  </ModificationList>
  <ContactList>
    <Contact id="lab_head">
      <cvParam cvRef="MS" accession="MS:1002332" name="lab head"/>
      <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Robert Haltiwanger"/>
      <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="rhalti@uga.edu"/>
      <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="Univesity of Georgia"/>
    </Contact>
    <Contact id="dataset_submitter">
      <cvParam cvRef="MS" accession="MS:1002037" name="dataset submitter"/>
      <cvParam cvRef="MS" accession="MS:1000586" name="contact name" value="Nicholas Kegley"/>
      <cvParam cvRef="MS" accession="MS:1000589" name="contact email" value="nkegley@uga.edu"/>
      <cvParam cvRef="MS" accession="MS:1000590" name="contact affiliation" value="University of Georgia"/>
    </Contact>
  </ContactList>
  <PublicationList>
    <Publication id="pubmed_id_pending">
      <cvParam cvRef="MS" accession="MS:1002866" name="Reference" value="Kegley, N. R., Ito, A., Williamson, D. B., McArdle, C. C., and Haltiwanger, R. S. Marfan syndrome variation of the POGLUT2 and POGLUT3 consensus sequence can produce aberrant fibrillin-1 O-glucosylation. Journal of Biological Chemistry"/>
    </Publication>
  </PublicationList>
  <KeywordList>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="extracellular matrix"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="fibrillin"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="glycoprotein"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="glycosyltransferase"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="mass spectrometry"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="Marfan syndrome"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="O-glucose"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="POGLUT2"/>
    <cvParam cvRef="MS" accession="MS:1001925" name="submitter keyword" value="POGLUT3"/>
  </KeywordList>
  <FullDatasetLinkList>
    <FullDatasetLink>
      <cvParam cvRef="MS" accession="MS:1002873" name="Panorama Public dataset URI" value="https://panoramaweb.org/fh79bx.url"/>
    </FullDatasetLink>
  </FullDatasetLinkList>
</ProteomeXchangeDataset>