Symbol STARD3 HUGO 17579 RefSeq NM_006804 | Entrez 10948 OMIM 607048 UniProt Q14849 | |
StAR-related lipid transfer domain protein 3 (STARD3) also known as metastatic lymph node 64 protein (MLN64) is a late endosomal integral membrane protein involved in cholesterol transport.
Contents
Function
MLN64 is hypothesized to regulate cholesterol transport between the late endosome where it is tethered and cytoplasmic membranes. Some data further suggest that endogenous MLN64 can cause cholesterol transport to the mitochondria.
The closest homolog to MLN64 is the steroidogenic acute regulatory protein (StAR/StarD1), which initiates the production of steroids by moving cholesterol inside the mitochondrion. Thus, MLN64 is also proposed to move cholesterol inside the mitochondria under certain conditions to initiate StAR-independent steroidogenesis, such as in the human placenta which lacks StAR yet produces steroids. This functional role is supported by evidence that MLN64 expression can stimulate steroid production in a model cell system.
A recent study indicates that this protein also specifically binds lutein in the retina.
Structure
Its C-terminus contains a StAR-related transfer domain (START) that is homologous to the StAR. X-ray crystallography of the C-terminus indicates that this domain forms a pocket that can bind cholesterol. This places MLN64 within the StarD1/D3 subfamily of START domain-containing proteins.
The N-terminus consists of a MENTAL (MLN64 N-terminal) domain similar to the protein MLN64 N-terminal homologue (MENTHO) with unclear function. This domain is buried in the late endosomal membrane and may associate with the same domain in MENTHO.
Tissue distribution
MLN64 is expressed in all tissues in the body at various levels. In the brain, MLN64 is detectable in many but not all cells. Many malignant tumors highly express MLN64 as a result of its gene being part of a Her2/erbB2-containing gene locus that is duplicated.
Pathology
Loss of MLN64 has little effect in mice. At the cellular level, changes in MLN64 can disrupt trafficking of endosomes and cause accumulation of cholesterol in late endosomes.