The HGO gene

The human HGO gene maps to chromosome 3 (3q21-23) (Fernandez-Cañón et al. (1996)) (View map). It spans 54,363 bp and codes for a 1,715 n-long transcript which is split in 14 exons ranging from 35 to 360 bp (Granadino et al. (1997). The HGO gene encodes a protein of 445 amino acids (click here to see a diagram of the HGO gene). The HGO introns, 605 to 17,687 bp in length, contain representatives of the major classes of repetitive elements, including ALUs, LINEs, SINEs, LTRs and several simple sequence repeats (SSRs) (Click here to see a diagram of the SSRs within the HGO gene). Three of the SSRs, a (CA)n repeat in intron 4 (HGO-3, D3S4556), a (CT)n repeat in intron 4 (HGO-1, D3S4496) and a (CA)n repeat in intron 13 (HGO-2, D3S4497), were found to be polymorphic (Granadino et al. (1997);Beltrán-Valero de Bernabé et al. (1998)). In addition to these polymorphic sites the HGO gene contains several single nucleotide polymorphisms (SNPs) (Click FIGURE-pol or TABLE-pol to see a detailed description of HGO polymorphisms). Over forty HGO mutations have been characterized in AKU patients (Click FIGURE-mut or TABLE-mut to see a detailed description of HGO mutations). Most of these AKU mutations (60%) are missense mutations that have been expressed in E. coli to show that they are loss-of-function mutations (Fernandez-Cañón et al. (1996); Rodríguez et al., 2000)(Click here to see the functional data).

Northern blot analysis has revealed strong expression of the human HGO gene in liver, kidney, prostate, small intestine and colon (Fernandez-Cañón et al. (1996)). Computer searches for potential cis-acting regulatory elements and functional analysis using a CAT reporter gene construct revealed that sequences from -1074 to +89 (relative to the HGO transcription start site) are sufficient to promote transcription of the reporter gene in human liver cells and that this fragment contains potential binding sites for liver-enriched transcription factors that might be involved in the regulation of HGO expression in liver(Granadino et al. (1997)).

HGO complete genomic sequence:

NCBI GenBank entry AF000573

Complete sequence (cDNA) of the HGO transcript:

NCBI GenBank entry NM000187

Crystal structure of the HGO protein:
The crystal structure of human homogentisate dioxygenase has been determined in Dr. David Timm's laboratory, at the Indiana State University School of Medicine (Titus et al., 2000), which has allowed the prediction of the structural consequences of the amino acid substitutions resulting from AKU mutations (Rodríguez et al., 2000). PDB accession codes: 1EY2 and 1EYB.

Protein database entry NP_000178
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Click here to see the HGO hexamer