STARD8

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[5][6] and is a member of the DLC family.

STARD8
Identifiers
Aliases	STARD8, ARHGAP38, DLC3, STARTGAP3, StAR related lipid transfer domain containing 8
External IDs	OMIM: 300689 MGI: 2448556 HomoloGene: 22837 GeneCards: STARD8
Gene location (Human) Chr. X chromosome (human)[1] Band Xq13.1 Start 68,647,666 bp[1] End 68,725,842 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X C3 Start 99,003,248 bp[2] End 99,074,728 bp[2]
Gene ontology Molecular function • lipid binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • cytosol • cell junction • focal adhesion Biological process • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • regulation of small GTPase mediated signal transduction • signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9754	236920
Ensembl	ENSG00000130052	ENSMUSG00000031216
UniProt	Q92502	Q8K031
RefSeq (mRNA)	NM_001142503 NM_001142504 NM_014725	NM_199018
RefSeq (protein)	NP_001135975 NP_001135976 NP_055540	NP_950183
Location (UCSC)	Chr X: 68.65 – 68.73 Mb	Chr X: 99 – 99.07 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[7]

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.[7]

Tissue distribution and pathology

The protein is expressed in tissues throughout the body, but is absent or reduced in many kinds of tumor cells.[7]

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.[8][9]

Model organisms

Model organisms have been used in the study of STARD8 function. A conditional knockout mouse line called Stard8^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[10] Male and female animals underwent a standardized phenotypic screen[11] to determine the effects of deletion.[12][13][14][15] Additional screens performed: - In-depth immunological phenotyping[16]

Stard8 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[11][16]
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000130052 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031216 - 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. "Entrez Gene: StAR-related lipid transfer (START) domain containing 8".
6. Nagase T, Seki N, Ishikawa K, Tanaka A, Nomura N (Feb 1996). "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. doi:10.1093/dnares/3.1.17. PMID 8724849.
7. Durkin ME, Ullmannova V, Guan M, Popescu NC (Jul 2007). "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. doi:10.1038/sj.onc.1210244. PMID 17297465.
8. 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 (Jun 2006). "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. doi:10.1086/504440. PMC 1474108. PMID 16685650.
9. Wieland I, Weidner C, Ciccone R, Lapi E, McDonald-McGinn D, Kress W, Jakubiczka S, Collmann H, Zuffardi O, Zackai E, Wieacker P (Dec 2007). "Contiguous gene deletions involving EFNB1, OPHN1, PJA1 and EDA in patients with craniofrontonasal syndrome". Clinical Genetics. 72 (6): 506–16. doi:10.1111/j.1399-0004.2007.00905.x. PMID 17941886.
10. 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.
11. "International Mouse Phenotyping Consortium".
12. 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 (Jun 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.
13. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
14. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
15. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
16. "Infection and Immunity Immunophenotyping (3i) Consortium".

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 (Nov 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
• Qian X, Li G, Asmussen HK, Asnaghi L, Vass WC, Braverman R, Yamada KM, Popescu NC, Papageorge AG, Lowy DR (May 2007). "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. doi:10.1073/pnas.0703033104. PMC 1868654. PMID 17517630.
• 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 (Jun 2006). "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. doi:10.1086/504440. PMC 1474108. PMID 16685650.
• Kawai K, Kiyota M, Seike J, Deki Y, Yagisawa H (Dec 2007). "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. doi:10.1016/j.bbrc.2007.10.052. PMID 17976533.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, Keavney B, Yusuf S, Gerstein HC, Engert JC, Anand S (Oct 2010). "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. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.