MLN64

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MLN64
Identifiers
Symbol STARD3
Entrez 10948
HUGO 17579
OMIM 607048
RefSeq NM_006804
UniProt Q14849
Other data
Locus Chr. 17 q11-q12

Metastatic lymph node 64 protein (MLN64 or STARD3) is a late endosomal integral membrane protein involved in cholesterol transport.[1]

Contents

[edit] Function

MLN64 is hypothesized to regulate cholesterol transport between the late endosome and cytoplasmic membranes. It has also been proposed to mediate StAR-independent steroidogenesis, such as in the human placenta.[2]

[edit] Structure

Its C-terminus contains a StAR-related transfer domain (START) that is homologous to the steroidogenic acute regulatory protein (StAR). X-ray crystallography indicates that this domain forms a pocket that can bind cholesterol.[3] Its N-terminus consists of a MENTAL (MLN64 N-terminal) domain similar to the protein MLN64 N-terminal homologue (MENTHO) with unclear function.

[edit] Production

MLN64 is expressed in all tissues in the body at various levels. In the brain, MLN64 is detectable in many but not all cells.[4] Many malignant tumors highly express MLN64 as a result of its gene being part of a Her2/erbB2-containing gene locus that is duplicated.

[edit] Pathology

Loss of MLN64 has little effect in mice.[5] At the cellular level, changes in MLN64 can disrupt trafficking of endosomes and cause accumulation of cholesterol in late endosomes.

[edit] References

  1. ^ Alpy F, Tomasetto C. MLN64 and MENTHO, two mediators of endosomal cholesterol transport. Biochem Soc Trans. 2006 Jun;34(Pt 3):343-5. PMID: 16709157
  2. ^ Watari H, Arakane F, Moog-Lutz C, Kallen CB, Tomasetto C, Gerton GL, Rio MC, Baker ME, Strauss III JF. MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis. Proc Natl Acad Sci USA 94(16):8462-7, 1997. PMID: 9237999
  3. ^ Tsujishita, Y., and Hurley, J.H. (2000). Structure and lipid transport mechanism of a StAR-related domain. Nature Struct. Biol. 7, 408-414.
  4. ^ King SR, Smith AG, Alpy F, Tomasetto C, Ginsberg SD, Lamb DJ. Characterization of the putative cholesterol transport protein metastatic lymph node 64 in the brain. Neuroscience 139(3):1031-8, 2006. PMID: 16549269
  5. ^ Kishida T, Kostetskii I, Zhang Z, Martinez F, Liu P, Walkley SU, Dwyer NK, Blanchette-Mackie EJ, Radice GL, Strauss III JF. Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism. J Biol Chem 2004;279(18):19276-85. PMID: 14963026

[edit] External links