MLN64
Encyclopedia
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.
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
.
(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.
, 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.
Endosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
involved in cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
transport.
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
Steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR , is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones...
(StAR/StarD1), which initiates the production of steroids by moving cholesterol inside the mitochondrion
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
. 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
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
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
Lutein
Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. Lutein is synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables such as spinach and kale...
in the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
.
Structure
Its C-terminus contains a StAR-related transfer domainStAR-related transfer domain
START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR , a mitochondrial protein that is synthesized in steroid-producing cells. StAR and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in...
(START) that is homologous
Homology (chemistry)
In chemistry, homology refers to the appearance of homologues. A homologue is a compound belonging to a series of compounds differing from each other by a repeating unit, such as a methylene group, a peptide residue, etcetera....
to the StAR. X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
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
MENTAL domain
The MENTAL or MLN64 NH2-terminal domain is a membrane-spanning domain that is conserved in two late endosomal proteins in vertebrates, MLN64 and MENTHO. The domain is 170 amino acids long....
(MLN64 N-terminal) domain similar to the protein MLN64 N-terminal homologue (MENTHO
STARD3NL
MENTHO or STARD3 N-terminal like protein is an integral membrane protein of unknown function. As the alternate name implies, MENTHO, short for "MLN64 N-terminal homologue", contains a region in its N-terminus similar to that found in STARD3, also known as MLN64, but lacks the StAR-related transfer...
) 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 brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, 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
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
that is duplicated.