GIMAP5
Function
Plays a role in T lymphocyte development and the optimal generation of CD4/CD8 double-positive thymocytes (By similarity). Inhibitor of GSK3A, possibly by sequestering GSK3A in cytoplasmic vesicles and impairing its translocation to the nucleus. Consequently, impairs GSK3A-dependent transcriptional program and regulation of the DNA damage response occurring during T cells proliferation (PubMed:29382851). Required for the survival of peripheral T cells, natural killer (NK) and NK T-cell development and the maintenance of normal liver function (By similarity). May promote the survival of mature T lymphocytes upon cytokine withdrawal (By similarity). May regulate Ca(2+) homeostasis by modulating lysosomal Ca(2+) stores, preventing its accumulation in the absence of T cell activation (By similarity). May play a role in mitochondrial DNA segregation in hematopoietic tissues (By similarity). Is a regulator of liver endothelial cell homeostasis (By similarity).
Involvement in disease
Portal hypertension, non-cirrhotic, 2
NCPH2
An autosomal recessive disorder characterized by portal hypertension associated with hepatosplenomegaly, in absence of cirrhosis. Portal hypertension is defined by a portal venous system pressure that is at least 5 mm Hg higher than the pressure in the inferior vena cava. High pressure in the portal venous system leads to shunting of blood through vessels that are poorly suited to carrying large blood volumes, resulting in collateral circulation and splenomegaly. NCPH2 patients have jaundice, hyperbilirubinemia, pancytopenia, including neutropenia, lymphopenia, and thrombocytopenia, hepatosplenomegaly, and esophageal varices. Some patients may have recurrent infections or features suggestive of an immunodeficiency.
None
The disease may be caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.
Tissue Specificity
Widely expressed with high levels in lymph node and spleen (PubMed:14724691). High expression found in T lymphocytes, including CD4 and CD8-positive T-cells, and monocytes (PubMed:14724691, PubMed:29382851). Very low expression levels in B-lymphocytes (PubMed:14724691).
Cellular localization
- Lysosome membrane
- Single-pass type IV membrane protein
- Endosome
- Multivesicular body membrane
- Single-pass type IV membrane protein
- Endosome membrane
- Single-pass type IV membrane protein
- The mitochondrial localization originally reported was observed with C-terminally tagged protein and was not confirmed in later publications.
Alternative names
IAN4L1, IAN5, IMAP3, GIMAP5, GTPase IMAP family member 5, Immune-associated nucleotide-binding protein 5, Immunity-associated nucleotide 4-like 1 protein, Immunity-associated nucleotide 5 protein, Immunity-associated protein 3, IAN-5, hIAN5