Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppresor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2008]
Function:
Probable role in regulating transcription of specific genes. May regulate through NFKB1 the expression of the CCL2/MCP-1 chemokine. May play a role in tumor necrosis factor alpha (TNF-alpha) gene expression.
Subcellular Location:
Lysosome membrane. Associated with membranes of lysosomes.
Tissue Specificity:
Ubiquitously and abundantly expressed. Expressed predominantly in the placenta, peripheral blood leukocytes, lymph nodes and spleen.
DISEASE:
Defects in LITAF are the cause of Charcot-Marie-Tooth disease type 1C (CMT1C) [MIM:60220]. CMT1C is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
Note=Defects in LITAF may be involved in extramammary Paget disease (EMPD) carcinogenesis. EMPD is a cancerous disease representing about 8% of all malignant skin cancers; it usually appears in the anogenital area and can be fatal by metastasizing to internal organs when left untreated for a long time. The clinical features are usually those of eczematous eruptions with weeping and crust formation.
SWISS:
Q99732
Gene ID:
9516
Database links:
Entrez Gene: 374125 Chicken
Entrez Gene: 520564 Cow
Entrez Gene: 9516 Human
Entrez Gene: 56722 Mouse
Entrez Gene: 65161 Rat
Omim: 603795 Human
SwissProt: Q99732 Human
SwissProt: Q9JLJ0 Mouse
SwissProt: P0C0T0 Rat
Unigene: 459940 Human
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