STARD5

StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene.[5][6] The protein is a 213 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 STARD4.

STARD5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2R55
Identifiers
Aliases	STARD5, StAR related lipid transfer domain containing 5
External IDs	OMIM: 607050 MGI: 2156765 HomoloGene: 11346 GeneCards: STARD5
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q25.1 Start 81,309,053 bp[1] End 81,324,183 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 D3|7 47.43 cM Start 83,631,959 bp[2] End 83,653,127 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • bile acid binding • lipid binding • cholesterol binding • GO:0017127 cholesterol transfer activity Cellular component • cytosol • mitochondrion Biological process • lipid transport • cholesterol import • bile acid and bile salt transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	80765	170460
Ensembl	ENSG00000172345	ENSMUSG00000046027
UniProt	Q9NSY2	Q9EPQ7
RefSeq (mRNA)	NM_030574 NM_181900	NM_023377
RefSeq (protein)	NP_871629	NP_075866
Location (UCSC)	Chr 15: 81.31 – 81.32 Mb	Chr 7: 83.63 – 83.65 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein is most prevalent in the kidney and the liver where it is found in Kupffer cells.[5][7] STARD5 binds both cholesterol and 25-hydroxycholesterol and appears to function to redistribute cholesterol to the endoplasmic reticulum with which the protein associates and/or the plasma membrane.[5][8][9] Increased levels of StarD5 increase free cholesterol in the cell.[8]

Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1) and by 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.[5][6]

Model organisms

Stard5 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Abnormal[10]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[11]
Citrobacter infection	Normal[12]
All tests and analysis from[13][14]

Model organisms have been used in the study of STARD5 function. A conditional knockout mouse line, called Stard5^{tm1a(KOMP)Wtsi}[15][16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty four tests were carried out on homozygous mutant mice and one significant abnormality was observed: abnormal vertebral transverse processes.[13]

References

1. GRCh38: Ensembl release 89: ENSG00000172345 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046027 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Soccio RE, Adams RM, Romanowski MJ, Sehayek E, Burley SK, Breslow JL (May 2002). "The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6". Proceedings of the National Academy of Sciences of the United States of America. 99 (10): 6943–8. doi:10.1073/pnas.052143799. PMC 124508. PMID 12011452.
6. "Entrez Gene: STARD5 START domain containing 5".
7. Rodriguez-Agudo D, Ren S, Hylemon PB, Montañez R, Redford K, Natarajan R, Medina MA, Gil G, Pandak WM (June 2006). "Localization of StarD5 cholesterol binding protein". Journal of Lipid Research. 47 (6): 1168–75. doi:10.1194/jlr.M500447-JLR200. PMID 16534142.
8. Rodriguez-Agudo D, Ren S, Hylemon PB, Redford K, Natarajan R, Del Castillo A, Gil G, Pandak WM (August 2005). "Human StarD5, a cytosolic StAR-related lipid binding protein". Journal of Lipid Research. 46 (8): 1615–23. doi:10.1194/jlr.M400501-JLR200. PMID 15897605.
9. Chen YC, Meier RK, Zheng S, Khundmiri SJ, Tseng MT, Lederer ED, Epstein PN, Clark BJ (August 2009). "Steroidogenic acute regulatory-related lipid transfer domain protein 5 localization and regulation in renal tubules". American Journal of Physiology. Renal Physiology. 297 (2): F380-8. doi:10.1152/ajprenal.90433.2008. PMC 2724253. PMID 19474188.
10. "Radiography data for Stard5". Wellcome Trust Sanger Institute.
11. "Salmonella infection data for Stard5". Wellcome Trust Sanger Institute.
12. "Citrobacter infection data for Stard5". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
18. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
19. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Strauss JF, Kishida T, Christenson LK, Fujimoto T, Hiroi H (April 2003). "START domain proteins and the intracellular trafficking of cholesterol in steroidogenic cells". Molecular and Cellular Endocrinology. 202 (1–2): 59–65. doi:10.1016/S0303-7207(03)00063-7. PMID 12770731.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Wines ME, Lee L, Katari MS, Zhang L, DeRossi C, Shi Y, Perkins S, Feldman M, McCombie WR, Holdener BC (February 2001). "Identification of mesoderm development (mesd) candidate genes by comparative mapping and genome sequence analysis". Genomics. 72 (1): 88–98. doi:10.1006/geno.2000.6466. PMID 11247670.
• Soccio RE, Adams RM, Maxwell KN, Breslow JL (May 2005). "Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress". The Journal of Biological Chemistry. 280 (19): 19410–8. doi:10.1074/jbc.M501778200. PMID 15760897.
• Rodriguez-Agudo D, Ren S, Hylemon PB, Redford K, Natarajan R, Del Castillo A, Gil G, Pandak WM (August 2005). "Human StarD5, a cytosolic StAR-related lipid binding protein". Journal of Lipid Research. 46 (8): 1615–23. doi:10.1194/jlr.M400501-JLR200. PMID 15897605.
• Rodriguez-Agudo D, Ren S, Hylemon PB, Montañez R, Redford K, Natarajan R, Medina MA, Gil G, Pandak WM (June 2006). "Localization of StarD5 cholesterol binding protein". Journal of Lipid Research. 47 (6): 1168–75. doi:10.1194/jlr.M500447-JLR200. PMID 16534142.