Human ortholog to mouse gene imap38 encoding an ER-localizable G-protein belongs to a gene family clustered on chromosome 7q32–36

Stamm, Olaf; Krücken, Jürgen; Schmitt-Wrede, Hans-Peter; Benten, W. Peter M.; Wunderlich, Frank

doi:10.1016/s0378-1119(01)00837-x

Cited by 35 publications

(54 citation statements)

References 32 publications

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“…This expression pattern is similar to the expression pattern of mIan1, mIan4, rIan4 and himap1. 4,6,11,12 The pattern of expression of Ian family members thus far characterized (AIG, imap38, mIan1, mIan4, hIan1, hIan5, himap1 ¼ hIan2) is consistent with a function in immune cells and seems to be confined to the same tissues suggesting that different Ian family members may act in concert to mediate their functions. There are now three members of the Ian family that have been linked to leukemia (mIan4, hIan1), and the current report extends these findings to B-cell lymphoid malignancies.…”

mentioning

confidence: 73%

“…In humans, three Ian members have been characterized so far: the HIMAP1 (human immunity-associated protein 1/hIan2) 34 kDa protein is localized at the endoplasmic reticulum (ER). 12 It contains a GTP-binding domain and is highly similar to the other known Ian family members. The himap1 gene is predominantly expressed in the spleen and to a lesser extent in lymph nodes.…”

Section: Introductionmentioning

confidence: 96%

“…14 Taken together, the investigation of the function of Ian family members suggests that Ian proteins are a distinct group of GTP-binding proteins that play a role in immune responses (plant: hypersensitivity; mammals: thymocyte development (autoimmunity)) and are involved in the control of lymphocyte apoptosis (lymphopenia). 4,6,7,[9][10][11][12][13][14] Here we describe the characterization of hIan5, the human ortholog to rIan4/Iddm1/lyp. HIan5 consists of 307 amino acids with a predicted molecular weight of 35 kDa.…”

Section: Introductionmentioning

confidence: 99%

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hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

et al. 2004

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The family of immune associated nucleotide binding proteins (Ian) is a distinct family of GTP-binding proteins conserved in plants, mice, rats and humans that are associated with immune functions, suggesting involvement in conserved defense mechanisms. Recently, the rat Ian4 (rIan4) was cloned and it appears to be identical to the gene Iddm1/lyp responsible for severe lymphopenia and the development of insulin-dependent diabetes in the BB-DP rat. Here we describe the characterization of a new human member of the Ian family: hIan5. hIan5 is highly homologous to rIan4, has a predicted molecular weight of 35 kDa and contains distinct G motifs of GTP-binding proteins (G-1 to G-4) in the N-terminus. Human Ian5 is anchored to the mitochondria by the hydrophobic COOH-terminal domain. Human Ian5 is highly expressed in lymph node and spleen. Different blood fractions show high hIan5 expression in CD4-and CD8-positive T cells and monocytes, but not in B lymphocytes. In contrast, in B-CLL (chronic lymphocytic leukemia) and mantle cell lymphoma samples, hIan5 mRNA was upregulated. The current data underline the role of hIan5 in T-lymphocyte development and function, and for the first time suggest that upregulation of Ian proteins is associated with B-cell malignancy, possibly by inhibiting apoptosis.

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mentioning

confidence: 73%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

et al. 2004

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“…This approximate 9-fold decrease in splenic T-cell abundance may be attributed to (1) an approximately 20-fold reduction in the frequency of CD8 ϩ T cells (Table 1; Figure 2B), (2) an approximately 2-fold reduction in the frequency of CD4 ϩ T cells (Table 1; Figure 2B), and (3) an approximately 2-fold reduction in total splenic cellularity (wildtype, n ϭ 5, 92.6 Ϯ 9.9; gimap5 Ϫ/Ϫ , n ϭ 7, 42.4 Ϯ 7.1 ϫ 10 6 cells, Ϯ SEM; P Ͻ .005; Table 1; Figure 2B). A significant paucity Figure 2B).…”

Section: Gimap5 ؊/؊ Mice Exhibit Peripheral T-cell Lymphopeniamentioning

confidence: 98%

“…Gimap5 (GTPase of the immune-associated protein 5; alternate names: imap3, 1 iROD, 2 IAN4L1, 3,4 IAN4, [5][6][7] ) is a member of a family of Gimap genes that are conserved in mammals, birds, fish, and in higher plants, and are clustered in a single chromosomal locus in each species. Mouse gimap5 mRNA is predominantly expressed in the thymus, spleen, lymph nodes, and lung 8 and is present in splenic T and B cells and in all maturation stages of thymic T cells.…”

Section: Introductionmentioning

confidence: 99%

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Schulteis

Chu

Dai

et al. 2008

Blood

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Partial activation precedes apoptotic death in T cells harboring an IAN gene mutation

et al. 2004

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The Biobreeding diabetes-prone rat suffers from a profound peripheral lymphopenia and yet succumbs to a T cell-dependent autoimmune disease. Lymphopenia segregates with a mutated chromosomal locus, termed lyp, recently identified as a frameshift mutation in IAN4. Others have correlated loss of IAN4 function with decreased mitochondrial integrity resulting in T cell apoptosis. Here we report that IAN4 -/-T cells enter a state similar to that of partial activation wherein they down-regulate CD62L and undergo incomplete blasting yet do not progress through mitosis. When given a strong stimulus, this partial activation phenotype can be overcome. This phenotype can be recapitulated in wild-type T cells through suboptimal stimulation. The phenotype is not simply a reaction to the lymphopenic environment, as spontaneous CD62L down-regulation occurs in mature single-positive medullary thymocytes that develop within a non-lymphopenic environment, and normal T cells do not undergo similar blasting when parked in a lymphopenic environment. Finally, we show that IAN4-/-T cells are more readily triggered via TCR stimulation. Thus, in addition to their role in apoptosis, IAN family members may also play a role in regulating the T cell activation state through modulation of TCR signaling strength.

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Human ortholog to mouse gene imap38 encoding an ER-localizable G-protein belongs to a gene family clustered on chromosome 7q32–36

Cited by 35 publications

References 32 publications

hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

hIan5: the human ortholog to the rat Ian4/Iddm1/lyp is a new member of the Ian family that is overexpressed in B-cell lymphoid malignancies

Impaired survival of peripheral T cells, disrupted NK/NKT cell development, and liver failure in mice lacking Gimap5

Partial activation precedes apoptotic death in T cells harboring an IAN gene mutation

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