Gene structure and transcript analysis of the human and mouse EGF-TM7 molecule, FIRE

Abstract

The epidermal growth factor-transmembrane seven (EGF-TM7) family are proteins that express EGF-like domains at their extracellular N-terminus coupled to a classical seven transmembrane (TM7) cassette. Recently, we identified, in mice, a novel member of this family termed FIRE (EMR-4). Here, we present the structure of the mouse and human FIRE genes. The structures of the two genes are strikingly similar, with the positions of the introns, relative to the deduced protein sequences, highly conserved. Moreover, the gene structures are typical of other members of the EGF-TM7 family. Other researchers have identified a point deletion in exon eight of the human FIRE gene, which introduces a frame shift into the cDNA leading to a premature stop codon. Thus, human FIRE is predicted to be expressed only as a soluble protein; even though sequence potentially encoding the TM7 cassette is found in a separate open reading frame of the same mRNA transcript. We explored the possibility that a cell surface expressed form of human FIRE did exist, either as an allelic variant, or as an alternatively spliced transcript. Although, we did identify two alternatively spliced human FIRE transcripts, neither are predicted to express the TM7 cassette. Thus if human FIRE exists, it is likely to be expressed as a soluble secreted molecule.

• EGF-TM7 family
• FIRE
• EMR4

Abbreviations
DC	=	dendritic cells
PMNC	=	peripheral mononuclear cells;
EGF-TM7	=	epidermal growth factor - transmembrane 7
HFIRE-RF1	=	human FIRE - reading frame 1
PCR	=	polymerase chain reaction
MoDC	=	monocyte derived Dendritic cell
GMCSF	=	Granulocyte Macrophage Colony Stimulating Factor; IL-4, Interleukin 4

Abbreviations
DC	=	dendritic cells
PMNC	=	peripheral mononuclear cells;
EGF-TM7	=	epidermal growth factor - transmembrane 7
HFIRE-RF1	=	human FIRE - reading frame 1
PCR	=	polymerase chain reaction
MoDC	=	monocyte derived Dendritic cell
GMCSF	=	Granulocyte Macrophage Colony Stimulating Factor; IL-4, Interleukin 4

Acknowledgements

We thank Bruce Loveland and Anne Zhao for providing some DC samples, Annemiek van Spriel for her expertise in isolation and stimulation of PMNC and Greg Moseley for his critical reading of this manuscript. This work was supported by the Australian National Health and Medical Research Council, and the Co-operative Research Centre for Vaccine Technology.