Comparative analysis of the human gimap gene cluster encoding a novel GTPase family

Abstract

There is a growing family of novel GTPases conserved among higher plants and vertebrates, abbreviated as AIG1, IAP, IMAP, and IAN, respectively. Here, we comparatively analyze the human gene family encoding GTPases of the immunity-associated protein family recently re-termed GIMAP. Chromosome 7q36.1 contains, within 300 kb, a gimap gene cluster with seven functional genes and one pseudogene (h gimap3). The six genes h gimap1, h gimap2, h gimap4, h gimap5, h gimap6, and h gimap7 encode 33–46 kDa proteins with one GTP-binding domain, whereas h gimap8 encodes a very unusual 75-kDa protein with three GTP-binding domains. All h gimap genes except h gimap2 have orthologs in the mouse. Major expression sites of hgimap mRNAs are the spleen and lymph nodes, but also other organs such as muscle, heart, placenta, and digestive tract display detectable hgimap mRNA levels. The proteins hGIMAP4 and hGIMAP7 can be localized at ER and Golgi apparatus, but not in mitochondria, lysosomes and nuclei. All h gimap genes were expressed at very low levels—if at all—in diverse cancer cell lines. Our data support the view that the GIMAP proteins are involved in the control of cell survival not only in cells of the immune system as commonly anticipated.