LITAF
Domain
The PPxY motif mediates interaction with WWOX and NEDD4.
The LITAF domain is stabilized by a bound zinc ion (PubMed:27582497, PubMed:27927196). The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes (PubMed:23166352, PubMed:27582497, PubMed:27927196). It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate (PubMed:27927196).
Function
Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation (PubMed:23166352). Plays a role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps down-regulate downstream signaling cascades (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, HGS and STAM to cytoplasmic membranes (PubMed:23166352). Probably plays a role in regulating protein degradation via its interaction with NEDD4 (PubMed:15776429). May also contribute to the regulation of gene expression in the nucleus (PubMed:10200294, PubMed:15793005). Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:10200294, PubMed:15793005).
Involvement in disease
Charcot-Marie-Tooth disease, demyelinating, 1C
CMT1C
A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies 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.
None
The disease is caused by variants affecting the gene represented in this entry.
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.
Post-translational modifications
Phosphorylated on tyrosine residues in response to EGF.
Sequence Similarities
Belongs to the CDIP1/LITAF family.
Tissue Specificity
Ubiquitously and abundantly expressed. Expressed predominantly in the placenta, peripheral blood leukocytes, lymph nodes and spleen.
Cellular localization
- Cytoplasm
- Nucleus
- Lysosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Early endosome membrane
- Late endosome membrane
- Endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Golgi apparatus membrane
- Associated with membranes of lysosomes, early and late endosomes (PubMed:11274176, PubMed:27582497, PubMed:27927196). Can translocate from the cytoplasm into the nucleus (PubMed:15793005). Detected at Schmidt-Lanterman incisures and in nodal regions of myelinating Schwann cells (By similarity).
Alternative names
PIG7, SIMPLE, LITAF, Lipopolysaccharide-induced tumor necrosis factor-alpha factor, LPS-induced TNF-alpha factor, Small integral membrane protein of lysosome/late endosome, p53-induced gene 7 protein