STARD13

StAR-related lipid transfer (START) domain containing 13

PDB rendering based on 2h80.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols STARD13 ; ARHGAP37; DLC2; GT650; LINC00464
External IDs OMIM: 609866 MGI: 2385331 HomoloGene: 64844 GeneCards: STARD13 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 90627 243362
Ensembl ENSG00000133121 ENSMUSG00000016128
UniProt Q9Y3M8 Q923Q2
RefSeq (mRNA) NM_001243466 NM_001163493
RefSeq (protein) NP_001230395 NP_001156965
Location (UCSC) Chr 13:
33.1 – 33.35 Mb		 Chr 5:
151.04 – 151.23 Mb
PubMed search

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.[1][2]

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.[3] It selectively activates RhoA and CDC42 and suppresses cell growth by inhibiting actin stress fiber assembly.[3]

The protein consists of an N-terminal sterile alpha motif (SAM) domain, 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.[4]

Model organisms

Model organisms have been used in the study of STARD13 function. A conditional knockout mouse line, called Stard13tm1a(KOMP)Wtsi[10][11] 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.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] 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.[8]

Another study of mice lacking STARD13, found it may promote blood vessel formation (angiogenesis), especially by tumor cells.[16] The promotion of angiogenesis with the loss of STARD13 occurs through the actions of RhoA.[16]

References

  1. ↑ Couch FJ, Rommens JM, Neuhausen SL, Belanger 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; et al. (Feb 1997). "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.
  2. ↑ "Entrez Gene: STARD13 START domain containing 13".
  3. 1 2 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.". J. Biol. Chem. 278 (12): 10824–30. doi:10.1074/jbc.M208310200. PMID 12531887.
  4. ↑ 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.
  5. ↑ "Haematology data for Stard13". Wellcome Trust Sanger Institute.
  6. ↑ "Salmonella infection data for Stard13". Wellcome Trust Sanger Institute.
  7. ↑ "Citrobacter infection data for Stard13". Wellcome Trust Sanger Institute.
  8. 1 2 3 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.
  9. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ↑ "International Knockout Mouse Consortium".
  11. ↑ "Mouse Genome Informatics".
  12. ↑ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  13. ↑ Dolgin E (June 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 (January 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  15. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  16. 1 2 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

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