Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse, fish, fly, and worm.
OBJECTIVE
To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species.


METHODS
By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse, zebrafish, fly, and worm.


RESULTS
The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis (AIH) patients.


CONCLUSIONS
The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evolution, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.
Wang
Chun-Xia
CX
Department of Medicine, University Medical Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. jherkel@uke.uni-mainz.de.
Teufel
Andreas
A
Cheruti
Uta
U
Grötzinger
Joachim
J
Galle
Peter R
PR
Lohse
Ansgar W
AW
Herkel
Johannes
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D017124:Conserved Sequence; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish
D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; C490635:SLA protein, human; D016392:Proto-Oncogene Proteins pp60(c-src)