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The GIMAP Gene Family

Introduction
	The GTPase of Immunity Associated Protein (GIMAP) family is a functionally uncharacterized group of genes expressed in vertebrate immune cells. This family shares a predicted Avirulence Induced Gene, (AIG1) domain in the N-terminus which contains putative GTP binding domains and conserved hydrophobic boxes. However, not all Gimap C-termini are the same. Tightly clustered together, GIMAP families have been found on rat chromosome 4, mouse chromosome 6 and human chromosome 7. Similar genes have also been found in other animals and plants. GIMAP 4 has been shown to be involved with T-cell death in mice (Schnell, et al.), and a frameshift mutation in GIMAP 5 in Bio Breeding (BBDR.lyp)1 rats has been shown to cause lymphopenia (MacMurray, et al.). This suggests that the GIMAP genes are involved in immune system development, selection, and maturation, but their contribution to Type 1 diabetes is unclear. This suggests that the Gimap genes are involved in the immune system, but their contribution to Type 1 diabetes is unclear. 1BBDR.lyp is from the BioBreeding Diabetes Resistant rat (with the lymphopenia locus introgressed on it) rat line, which is kept in heterozygous state so that breeding results in lyp/lyp, lyp/+ or +/+.
Mammalian Synteny
	Graphical representation of the GIMAP family in Human, Mouse, Rat, and Dog. The GIMAP family consists of tightly linked, conserved genes. Each number represents a different GIMAP member with GIMAP 8 being the most distal gene. Numbers with a “ps” next to it represent pseudogenes. Dog GIMAP 1s is a predicted gene similar to GIMAP 1.
Current Reseach in Rat Gimap Expression
	BioBreeding (BB) rats are involved with many aspects of research with Type 1 Diabetes and the GIMAP family. Current research by the Diabetes and Endocrinology Research Center on GIMAP family expression levels can be found here. Gimap in Rat
Secondary Structure
	The GIMAP family is characterized by an AIG1 domain which contains putative GTPase function. Although random coils and alpha helices are predicted throughout the proteins, all human, mouse and rat GIMAP genes predict an alpha helix in the carboxy terminus of the AIG1 domain. Click below for more information on each gene. View secondary structures by gimap gene.   Gimap 4 Gimap 4 Gimap 4 has been found in human, mouse, and rat genomes, and is located in the Gimap cluster. In human and rat, Gimap4 mRNA is made up of three exons with the coding sequence in exons 2 and 3. In mouse, two isoforms are found. The mRNA for mGimap 4 Isoform A is made up of three exons with the coding sequence in exons 2 and 3. mGimap 4 Isoform B is made up of five exons and coding sequence is on exons 4 and 5. Isoform A codes for a 328 AA protein and Isoform B codes for a 39 AA protein. Human and Rat Gimap 4 code for 329 and 311 AA proteins respectively.   Gimap 5 Gimap 5 GIMAP 5 is found in humans, rats, and mice. GIMAP5 transcripts are made up of 3 exons with the open reading frame spanning exons 2 and 3 in humans, rats, and mice. GIMAP 5 is an average length protein for the GIMAP family encoding 307, 308, and 309 amino acids in Humans, Rats, and Mice respectively. A frameshift mutation in GIMAP 5 in BB rats has been shown to be responsible for a lymphopenic phenotype (1) and is also required for mitochondrial integrity and T cell survival (2). GIMAP 5 also plays roles in T cell selection, differentiation, maturation (3) and activation state (4).   Gimap 6 Gimap 6 GIMAP 6 is found in humans, mice, and rats. GIMAP 6 transcripts are made up of 3 exons in humans, mice, and rats. In humans, the open reading frame span exons 2 and 3, and in mice and rats, the open reading frame spans all exons. GIMAP 6 is average length for a GIMAP family protein. Humans code for a 292 amino acid protein and mice and rats code for 305 amino acids.   Gimap 7 Gimap 7 GIMAP 7 is found in humans, mice, and rats. GIMAP 7 transcripts in human, mice, and rats contain 2 exons with the open reading frame only contained in the second exon. Protein lengths are typical of the GIMAP family with 300, 293, and 291 amino acids for humans, mice, and rats respectively.   Gimap 8 Gimap 8 GIMAP 8 has been found in humans, rats, and mice and is part of the GIMAP family. GIMAP 8 transcripts in humans contain five exons with its open reading frame spanning exons 2 through 5. In mice and rats, GIMAP 8 transcripts also contain five exons and the open reading frame spans all the exons. GIMAP8 is the longest protein of the family, coding for 665, 688, and 689 amino acids in Human, Mouse, and Rat respectively. Mouse GIMAP 8 has been shown to have anti-apoptotic effects in anisomycin-induced cell death and suppressed expression when infected with Malaria (Krucken, et al.).   Gimap 9 Gimap 9 GIMAP 9 is found in mice and rats. No pseudo genes are found in humans. GIMAP 9 transcripts are made up of 2 exons in mice and rats with the open reading frame only in the second exon. GIMAP 9 is typical length for a GIMAP gene containing 291 amino acids in mice, and 294 in rats.
Secondary Structure Prediction Methods
	GIMAP amino acid sequences were run through PSORTII (Nakai, et al.) to predict coiled coils. AA sequence was also checked against the NCBI Conserved Domain Database using rpsBLAST to find conserved domains (Marchler-Bauer, et al.). Random coils and alpha helices were predicted using GOR4 (Combet, et al.). Transmembrane helices were predicted using TMHMM version 2.0 (Moller et al.). Exon borders were found using GESTALT (Glusman, et al.) and direct comparison of GIMAP mRNA to Genomic DNA from University of California Santa Cruz. Graphical representations of predicted protein characteristics were made using VectorNTI.
	Methods
	To predict coiled coils, Gimap 4 amino acid sequences were run through PSORTII (Nakai, et al.). AA sequence was also checked against the NCBI Conserved Domain Database using rpsBLAST to find conserved domains (Marchler-Bauer, et al.). Random Coils were predicted using GOR4 (Combet, et al.). Exon borders were found using GESTALT (Glusman, et al.) and direct comparison of Gimap 4 mRNA to Genomic DNA from University of California Santa Cruz. Graphical representations of predicted protein characteristics were made using VectorNTI.
Folders
Related Papers:
	Gimap4 accelerates T-cell death. Schnell S, Démollière C, van den Berk P, Jacobs H Blood. 2006 PubMed ID: 16569770   Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene. MacMurray AJ, Moralejo DH, Kwitek AE, Rutledge EA, Van Yserloo B, Gohlke P, Speros SJ, Snyder B, Schaefer J, Bieg S, Jiang J, Ettinger RA, Fuller J, Daniels TL, Pettersson A, Orlebeke K, Birren B, Jacob HJ, Lander ES, Lernmark A Genome Res. 2002 PubMed ID: 12097339

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