STARD8 explained

StAR-related lipid transfer domain protein 8 (STARD8) also known as deleted in liver cancer 3 protein (DLC-3) is a protein that in humans is encoded by the STARD8 gene^{[1] [2]} and is a member of the DLC family.

Structure and function

The protein is 1103 amino acids long, which like other DLC proteins consists of a sterile alpha motif (SAM), RhoGAP and a StAR-related lipid-transfer (START) domains.

The protein is a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases. STARD8 is characterized as activating Rho GTPases. Its expression inhibits the growth of human breast and prostate cancer cells in culture.

Tissue distribution and pathology

The protein is expressed in tissues throughout the body, but is absent or reduced in many kinds of tumor cells.^[3]

While there are no known disorders caused by STARD8, partial loss of the STARD8 gene occurs in cases of craniofrontonasal syndrome where the EFNB1 gene (which causes the syndrome) is completely deleted.^{[4] [5]}

Further reading

• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD . Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip . American Journal of Human Genetics . 85 . 5 . 628–42 . Nov 2009 . 19913121 . 2775832 . 10.1016/j.ajhg.2009.10.014 .
• Qian X, Li G, Asmussen HK, Asnaghi L, Vass WC, Braverman R, Yamada KM, Popescu NC, Papageorge AG, Lowy DR . Oncogenic inhibition by a deleted in liver cancer gene requires cooperation between tensin binding and Rho-specific GTPase-activating protein activities . Proceedings of the National Academy of Sciences of the United States of America . 104 . 21 . 9012–7 . May 2007 . 17517630 . 1868654 . 10.1073/pnas.0703033104 . 2007PNAS..104.9012Q . free .
• Twigg SR, Matsumoto K, Kidd AM, Goriely A, Taylor IB, Fisher RB, Hoogeboom AJ, Mathijssen IM, Lourenco MT, Morton JE, Sweeney E, Wilson LC, Brunner HG, Mulliken JB, Wall SA, Wilkie AO . The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males . American Journal of Human Genetics . 78 . 6 . 999–1010 . Jun 2006 . 16685650 . 1474108 . 10.1086/504440 .
• Kawai K, Kiyota M, Seike J, Deki Y, Yagisawa H . START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology . Biochemical and Biophysical Research Communications . 364 . 4 . 783–9 . Dec 2007 . 17976533 . 10.1016/j.bbrc.2007.10.052 .
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S . Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study . Diabetes Care . 33 . 10 . 2250–3 . Oct 2010 . 20628086 . 2945168 . 10.2337/dc10-0452 .

Notes and References

1. Web site: Entrez Gene: StAR-related lipid transfer (START) domain containing 8.
2. Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N . Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1 . DNA Research . 3 . 1 . 17–24 . Feb 1996 . 8724849 . 10.1093/dnares/3.1.17 . free .
3. Durkin ME, Ullmannova V, Guan M, Popescu NC . Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth . Oncogene . 26 . 31 . 4580–9 . Jul 2007 . 17297465 . 10.1038/sj.onc.1210244 . 5867743 .
4. Twigg SR, Matsumoto K, Kidd AM, Goriely A, Taylor IB, Fisher RB, Hoogeboom AJ, Mathijssen IM, Lourenco MT, Morton JE, Sweeney E, Wilson LC, Brunner HG, Mulliken JB, Wall SA, Wilkie AO . The origin of EFNB1 mutations in craniofrontonasal syndrome: frequent somatic mosaicism and explanation of the paucity of carrier males . American Journal of Human Genetics . 78 . 6 . 999–1010 . Jun 2006 . 16685650 . 1474108 . 10.1086/504440 .
5. Wieland I, Weidner C, Ciccone R, Lapi E, McDonald-McGinn D, Kress W, Jakubiczka S, Collmann H, Zuffardi O, Zackai E, Wieacker P . Contiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome . Clinical Genetics . 72 . 6 . 506–16 . Dec 2007 . 17941886 . 10.1111/j.1399-0004.2007.00905.x . 33823266 .