SP140L, an Evolutionarily Recent Member of the SP100 Family, Is an Autoantigen in Primary Biliary Cirrhosis.
The SP100 family members comprise a set of closely related genes on chromosome 2q37.1. The widely expressed SP100 and the leukocyte-specific proteins SP110 and SP140 have been associated with transcriptional regulation and various human diseases. Here, we have characterized the SP100 family member SP140L. The genome sequence analysis showed the formation of SP140L gene through rearrangements of the two neighboring genes, SP100 and SP140, during the evolution of higher primates. The SP140L expression is interferon-inducible with high transcript levels in B cells and other peripheral blood mononuclear cells. Subcellularly, SP140L colocalizes with SP100 and SP140 in nuclear structures that are devoid of SP110, PML, or p300 proteins. Similarly to SP100 and SP140 protein, we detected serum autoantibodies to SP140L in patients with primary biliary cirrhosis using luciferase immunoprecipitation system and immunoblotting assays. In conclusion, our results show that SP140L is phylogenetically recent member of SP100 proteins and acts as an autoantigen in primary biliary cirrhosis patients.
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Mario
M
Saare
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Uku
U
Hämarik
Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
Rainis
R
Venta
Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Marina
M
Panarina
Biomolecular NMR Laboratory, Dulbecco Telethon Institute c/o S. Raffaele Scientific Institute, 20132 Milan, Italy.
Chiara
C
Zucchelli
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Maire
M
Pihlap
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Anu
A
Remm
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Kai
K
Kisand
Icosagen AS, 61713 Tartumaa, Estonia.
Urve
U
Toots
Icosagen AS, 61713 Tartumaa, Estonia.
Kaidi
K
Möll
Department of Internal Medicine, Tartu University Hospital, 51014 Tartu, Estonia.
Riina
R
Salupere
Biomolecular NMR Laboratory, Dulbecco Telethon Institute c/o S. Raffaele Scientific Institute, 20132 Milan, Italy.
Giovanna
G
Musco
Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Raivo
R
Uibo
Molecular Pathology Group, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia.
Pärt
P
Peterson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D020440:Gene Duplication; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D017930:Genes, Reporter; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D005810:Multigene Family; D010802:Phylogeny; D011323:Primates; D021381:Protein Transport; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation
D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D018076:DNA, Complementary; C102470:SP140 protein, human; D014157:Transcription Factors; D007372:Interferons