COMMENT Method: conceptual translation. FEATURES Location/Qualifiers source 1..249 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="X" Protein 1..249 /product="tetraspanin 7, isoform CRA_a" Region 14..241 /region_name="Tetraspannin" /note="Tetraspanin family; pfam00335" /db_xref="CDD:249779" Region 110..213 /region_name="TM4SF2_6_like_LEL" /note="Tetraspanin, extracellular domain or large extracellular loop (LEL), TM4SF2_6_like subfamily. Tetraspanins are trans-membrane proteins with 4 trans-membrane segments. Both the N- and C-termini lie on the intracellular side of the membrane. This alignment...; cd03161" /db_xref="CDD:239414" Site order(111,116,120,122..123,126,140,143..144,147..148) /site_type="other" /note="dimer interface [polypeptide binding]" /db_xref="CDD:239414" CDS 1..249 /gene="TSPAN7" /locus_tag="hCG_18324" /coded_by="join(CH471141.2:1274072..1274152, CH471141.2:1378638..1378826,CH471141.2:1383893..1383967, CH471141.2:1386738..1386833,CH471141.2:1388222..1388377, CH471141.2:1393722..1393805,CH471141.2:1400117..1400185)" /note="gene_id=hCG18324.3 transcript_id=hCT1969285.1 protein_id=hCP1782967.1 isoform=CRA_a" /db_xref="GeneID:7102" ORIGIN 1 masrrmetkp vitclktlli iysfvfwitg villavgvwg kltlgtyisl iaenstnapy 61 vligtgttiv vfglfgcfat crgspwmlkl yamflslvfl aelvagisgf vfrheikdtf 121 lrtytdamqt yngndersra vdhvqrslsc cgvqnytnws tspyflehgi ppsccmnetd 181 cnpqdlhnlt vaatkvnqkg cydlvtsfme tnmgiiagva fgiafsqlig mllacclsrf 241 itanqyemv // Essentiellit aminohapot muodostavat proteiinin alkupäässä muutamia pitkiä
jaksoja jopa 7 ja 6 essentielliä aminohappoa peräkkäin
Diabetes. 2016 Mar 7. pii: db151058. [Epub ahead of print]
Identification of Tetraspanin-7 as a Target of Autoantibodies in Type 1 Diabetes.
McLaughlin KA1, Richardson CC2, Ravishankar A1, Brigatti C3, Liberati D4, Lampasona V4, Piemonti L3, Morgan D5, Feltbower RG5, Christie MR6.
Abstract
The
presence of autoantibodies to multiple islet autoantigens confers high
risk for development of Type 1 diabetes. Four major autoantigens are
established (insulin, glutamate decarboxylase, IA-2, and zinc
transporter-8), but the molecular identity of a fifth, a 38kDa membrane
glycoprotein (Glima), is unknown. Glima antibodies have been detectable
only by immunoprecipitation from extracts of radiolabeled islet or
neuronal cells. We sought to identify Glima to enable efficient assay of
these autoantibodies. Mouse brain and lung were shown to express Glima.
Membrane glycoproteins from extracts of these organs were enriched by
detergent phase separation, lectin affinity chromatography and SDS-PAGE.
Proteins were also immunoaffinity purified from brain extracts using
autoantibodies from diabetic patients' sera before SDS-PAGE. Eluates
from gel regions equivalent to 38kDa were analyzed by LC-MS/MS for
protein identification. Three proteins were detected in samples from the
brain and lung extracts, and in the immunoaffinity purified sample, but
not the negative control. Only tetraspanin-7, a multipass transmembrane
glycoprotein with neuroendocrine expression, had physical
characteristics expected of Glima. Tetraspanin-7 was confirmed as an
autoantigen by demonstrating binding to autoantibodies in Type 1
diabetes. We identify tetraspanin-7 as a target of autoimmunity in
diabetes, allowing its exploitation for diabetes prediction and
immunotherapy.
© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
