STARD13

StAR-related lipid transfer domain protein 13 (STARD13) also known as deleted in liver cancer 2 protein (DLC-2) is a protein that in humans is encoded by the STARD13 gene and a member of the DLC family of proteins.[5][6]

STARD13
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2H80, 2JW2, 2PSO
Identifiers
Aliases	STARD13, ARHGAP37, DLC2, GT650, LINC00464, StAR related lipid transfer domain containing 13
External IDs	OMIM: 609866 MGI: 2385331 HomoloGene: 64844 GeneCards: STARD13
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q13.1-q13.2 Start 33,103,137 bp[1] End 33,350,630 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 G3 Start 151,037,510 bp[2] End 151,233,836 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • lipid binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity Cellular component • cytoplasm • cytosol • lipid droplet • mitochondrial membranes • mitochondrion • membrane Biological process • negative regulation of cell migration involved in sprouting angiogenesis • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • endothelial tube lumen extension • regulation of small GTPase mediated signal transduction • endothelial cell migration • signal transduction Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	90627	243362
Ensembl	ENSG00000133121	ENSMUSG00000016128
UniProt	Q9Y3M8	Q923Q2
RefSeq (mRNA)	NM_001243466 NM_001243474 NM_001243476 NM_052851 NM_178006 NM_178007 NM_178008	NM_001163493 NM_146258 NM_001359985
RefSeq (protein)	NP_001230395 NP_001230403 NP_001230405 NP_443083 NP_821074 NP_821075	NP_001156965 NP_666370 NP_001346914
Location (UCSC)	Chr 13: 33.1 – 33.35 Mb	Chr 5: 151.04 – 151.23 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function and structure

STARD13 serves as a Rho GTPase-activating protein (GAP), a type of protein that regulates members of the Rho family of GTPases.[7] It selectively activates RhoA and CDC42 and suppresses cell growth by inhibiting actin stress fiber assembly.[7]

The protein consists of an N-terminal sterile alpha motif (SAM) domain,[8] a serine-rich domain, a RhoGAP domain and at the C-terminus, a StAR-related lipid-transfer domain (START).

Tissue distribution and pathology

The protein was identified in part through its differential expression in cancers. A low level of STARD13 was observed in less differentiated hepatocellular carcinoma tissue with higher RhoA expression. A small patient study finds that the absence of STARD13 in hepatocellular carcinomas correlates with higher levels of RhoA and a poorer prognosis than patients with carcinomas that were STARD13-positive.[9]

Model organisms

Stard13 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	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Abnormal[10]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal[11]
Citrobacter infection	Abnormal[12]
All tests and analysis from[13][14]

Model organisms have been used in the study of STARD13 function. A conditional knockout mouse line, called Stard13^{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 — at the Wellcome Trust Sanger Institute.[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 mutant mice and two significant abnormalities were observed. Female homozygous mutants had an increased susceptibility to Citrobacter infection and displayed a decreased hematocrit and hemoglobin content.[13]

Another study of mice lacking STARD13, found it may promote blood vessel formation (angiogenesis), especially by tumor cells.[21] The promotion of angiogenesis with the loss of STARD13 occurs through the actions of RhoA.[21]

References

1. GRCh38: Ensembl release 89: ENSG00000133121 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000016128 - 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. Couch FJ, Rommens JM, Neuhausen SL, Bélanger C, Dumont M, Abel K, Bell R, Berry S, Bogden R, Cannon-Albright L, Farid L, Frye C, Hattier T, Janecki T, Jiang P, Kehrer R, Leblanc JF, McArthur-Morrison J, Meney D, Miki Y, Peng Y, Samson C, Schroeder M, Snyder SC, Simard J (August 1996). "Generation of an integrated transcription map of the BRCA2 region on chromosome 13q12-q13". Genomics. 36 (1): 86–99. doi:10.1006/geno.1996.0428. PMID 8812419.
6. "Entrez Gene: STARD13 START domain containing 13".
7. Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO (March 2003). "Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma". The Journal of Biological Chemistry. 278 (12): 10824–30. doi:10.1074/jbc.M208310200. PMID 12531887.
8. Li, Hongyan; Fung, King-Leung; Jin, Dong-Yan; Chung, Stephen S. M.; Ching, Yick-Pang; Ng, Irene Oi-lin; Sze, Kong-Hung; Ko, Ben C. B.; Sun, Hongzhe (2007-06-01). "Solution structures, dynamics, and lipid-binding of the sterile alpha-motif domain of the deleted in liver cancer 2". Proteins. 67 (4): 1154–1166. doi:10.1002/prot.21361. ISSN 1097-0134. PMID 17380510.
9. Xiaorong L, Wei W, Liyuan Q, Kaiyan Y (2008). "Underexpression of deleted in liver cancer 2 (DLC2) is associated with overexpression of RhoA and poor prognosis in hepatocellular carcinoma". BMC Cancer. 8: 205. doi:10.1186/1471-2407-8-205. PMC 2496915. PMID 18651974.
10. "Haematology data for Stard13". Wellcome Trust Sanger Institute.
11. "Salmonella infection data for Stard13". Wellcome Trust Sanger Institute.
12. "Citrobacter infection data for Stard13". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). 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.
21. Lin Y, Chen NT, Shih YP, Liao YC, Xue L, Lo SH (May 2010). "DLC2 modulates angiogenic responses in vascular endothelial cells by regulating cell attachment and migration". Oncogene. 29 (20): 3010–6. doi:10.1038/onc.2010.54. PMC 2874629. PMID 20208559.

Further reading

• Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IO (March 2003). "Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma". The Journal of Biological Chemistry. 278 (12): 10824–30. doi:10.1074/jbc.M208310200. PMID 12531887.
• Day CL, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian LY, Huang DC, Hinds MG (February 2004). "Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands". The Biochemical Journal. 377 (Pt 3): 597–605. doi:10.1042/BJ20031251. PMC 1223895. PMID 14561217.
• Nagaraja GM, Kandpal RP (January 2004). "Chromosome 13q12 encoded Rho GTPase activating protein suppresses growth of breast carcinoma cells, and yeast two-hybrid screen shows its interaction with several proteins". Biochemical and Biophysical Research Communications. 313 (3): 654–65. doi:10.1016/j.bbrc.2003.12.001. PMID 14697242.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Leung TH, Ching YP, Yam JW, Wong CM, Yau TO, Jin DY, Ng IO (October 2005). "Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity". Proceedings of the National Academy of Sciences of the United States of America. 102 (42): 15207–12. doi:10.1073/pnas.0504501102. PMC 1250229. PMID 16217026.