STARD3
| StAR-related lipid transfer (START) domain containing 3 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | STARD3 | ||||||
| NCBI gene | 10948 | ||||||
| HGNC | 17579 | ||||||
| OMIM | 607048 | ||||||
| RefSeq | NM_006804 | ||||||
| UniProt | Q14849 | ||||||
| Other data | |||||||
| Locus | Chr. 17 q11-q12 | ||||||
| |||||||
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.[1]
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.[2]
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.[3] This functional role is supported by evidence that MLN64 expression can stimulate steroid production in a model cell system.[3]
A recent study indicates that this protein also specifically binds lutein in the retina.[4]
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.[5] 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.[6] 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.[7] At the cellular level, changes in MLN64 can disrupt trafficking of endosomes and cause accumulation of cholesterol in late endosomes.
References
- ^ Alpy F, Tomasetto C (June 2006). "MLN64 and MENTHO, two mediators of endosomal cholesterol transport". Biochem. Soc. Trans. 34 (Pt 3): 343–5. doi:10.1042/BST0340343. PMID 16709157.
- ^ Charman M, Kennedy BE, Osborne N, Karten B (October 2009). "MLN64 mediates egress of cholesterol from endosomes to mitochondria in the absence of functional Niemann-Pick Type C1 protein". J. Lipid Res. 51 (5): 1023–34. doi:10.1194/jlr.M002345. PMID 19965586.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Watari H, Arakane F, Moog-Lutz C, Kallen CB, Tomasetto C, Gerton GL, Rio MC, Baker ME, Strauss JF (August 1997). "MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis". Proc. Natl. Acad. Sci. U.S.A. 94 (16): 8462–7. doi:10.1073/pnas.94.16.8462. PMC 22957. PMID 9237999.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Li B, Vachali P, Frederick JM, Bernstein PS (April 2011). "Identification of StARD3 as a lutein-binding protein in the macula of the primate retina". Biochemistry. 50 (13): 2541–9. doi:10.1021/bi101906y. PMC 3070171. PMID 21322544.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Tsujishita Y, Hurley JH (May 2000). "Structure and lipid transport mechanism of a StAR-related domain". Nat. Struct. Biol. 7 (5): 408–14. doi:10.1038/75192. PMID 10802740.
- ^ King SR, Smith AG, Alpy F, Tomasetto C, Ginsberg SD, Lamb DJ (2006). "Characterization of the putative cholesterol transport protein metastatic lymph node 64 in the brain". Neuroscience. 139 (3): 1031–8. doi:10.1016/j.neuroscience.2006.01.063. PMID 16549269.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Kishida T, Kostetskii I, Zhang Z, Martinez F, Liu P, Walkley SU, Dwyer NK, Blanchette-Mackie EJ, Radice GL, Strauss JF (April 2004). "Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism". J. Biol. Chem. 279 (18): 19276–85. doi:10.1074/jbc.M400717200. PMID 14963026.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
External links
- MLN64+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)