STARD5

StAR-related lipid transfer protein 5 is a is_associated_with::protein that in humans is encoded by the STARD5 is_associated_with::gene. The protein is a 213 is_associated_with::amino acids long, consisting almost entirely of a StAR-related transfer (START) domain. It is also part of the StarD4 subfamily of START domain proteins, sharing 34% sequence identity with is_associated_with::STARD4.

Function
The protein is most prevalent in the kidney and the liver where it is found in is_associated_with::Kupffer cells. STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the is_associated_with::endoplasmic reticulum with which the protein associates and/or the is_associated_with::plasma membrane. Increased levels of StarD5 increase free cholesterol in the cell.

Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., is_associated_with::SREBP1) and by is_associated_with::liver X receptors (e.g., LXRA). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD5.

Model organisms
is_associated_with::Model organisms have been used in the study of STARD5 function. A conditional is_associated_with::knockout mouse line, called Stard5tm1a(KOMP)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty four tests were carried out on is_associated_with::homozygous is_associated_with::mutant mice and one significant abnormality was observed: abnormal vertebral is_associated_with::transverse processes.