Characterization of the human homolog of the IL-4 induced gene-1 (Fig1).
Mouse interleukin-four induced gene-1 (mFig1) maps to a region of susceptibility for systemic lupus erythematosus (SLE) that includes the Sle3 locus. To begin examining this relationship in humans, we have isolated and characterized the human homolog of mFig1. Human Fig1 (hFig1) has the same eight exon genomic structure as mFig1. The predicted 63-kDa protein, like mFig1, contains a signal peptide, a large internal sequence that is most similar (43% identical over 484 amino acids) to L-amino acid oxidase (LAAO), and a carboxy terminal domain with no similarity to known genes. When compared to the LAAO crystal structure, hFig1 conserves key residues thought to be involved in catalysis and binding of the flavin adenine dinucleotide cofactor. Surprisingly, the carboxy terminal domains of hFig1 and mFig1 have little similarity (<11% identity), different lengths and amino acid composition. Like mFig1, hFig1 RNA is induced by interleukin-4 (IL-4) in B lymphocytes, and is primarily found in immune tissues. Finally, hFig1 maps to the predicted mFig1 syntenic region on human chromosome 19q13.3-19q13.4, a hot spot for susceptibility to several autoimmune diseases, including SLE.
Chavan
Sangeeta S
SS
Department of Medicine, New York University School of Medicine, New York, NY, USA
Tian
Wenzhi
W
Hsueh
Kevin
K
Jawaheer
Damini
D
Gregersen
Peter K
PK
Chu
Charles C
CC
D000594:Amino Acid Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000201:enzymology*; D001483:Base Sequence; D002384:Catalysis; D002888:Chromosomes, Human, Pair 19; D018076:DNA, Complementary / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005420:Flavoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D015847:Interleukin-4; D050830:L-Amino Acid Oxidase; D008969:Molecular Sequence Data; D012313:RNA / Q000032:analysis / Q000096:biosynthesis; D016415:Sequence Alignment; D013379:Substrate Specificity
D018076:DNA, Complementary; D005420:Flavoproteins; D015847:Interleukin-4; D012313:RNA; D000594:Amino Acid Oxidoreductases; C105158:IL4I1 protein, human; C484538:Il4i1 protein, mouse; D050830:L-Amino Acid Oxidase