RhoBTB

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Rho-related BTB domain containing 1
Identifiers
SymbolRHOBTB1
Entrez9886
HUGO18738
OMIM607351
RefSeqNM_014836
UniProtO94844
Other data
LocusChr. 10 q22.1
Rho-related BTB domain containing 2
Identifiers
SymbolRHOBTB2
Entrez23221
HUGO18756
OMIM607352
RefSeqNM_001160036
UniProtQ9BYZ6
Other data
LocusChr. 8 p21.2
Rho-related BTB domain containing 3
Identifiers
SymbolRHOBTB3
Entrez22836
HUGO18757
OMIM607353
RefSeqNM_014899
UniProtO94955
Other data
LocusChr. 5 q15

The RhoBTB family is a subgroup of the Rho family of small GTPases. They are a highly divergent class and are all characterized by an N-terminal Rho-related domain followed by at least one C-terminal BTB domain.

Discovery

The RhoBTB family of molecules was unknowingly discovered in 1993 by analyzing the Dictyostelium genome looking for members of the Ras superfamily of GTPases. The authors began by doing Southern blots looking for cDNAs that cross-hybridize with a very conservative probe from hRas.[1] They identified 19 new genes that belonged to the Ras superfamily and sequenced approximately 600 nucleotides from the start of the transcript.[1] If they were looking for a normal Ras-like GTPase, this would have been sufficient. One of their clones, they called RacA, was more divergent than most of the others and the transcript didn’t terminate in a stop codon like the rest.[1] The authors, however, didn’t comment on this and RhoBTB went undiscovered for another eight years.

A very careful analysis by Francisco Rivero and coworkers ensued to find all of the Rho GTPases in Dictyostelium. During their endeavor, they found that the open reading frame of RacA was actually 400 amino acids longer than what Bush had published 8 years earlier.[2] Instead of a 168 amino acid protein, RacA encoded a 598 residue protein with a Rho GTPase domain at the N-terminus and two BTB domains toward the C-terminus. BTB (Broad-Complex, Tramtrack and Bric-a-Brac) domains are known to involve hetero and homo associations with other BTB domain-containing proteins.[3][4] Because this novel RhoBTB protein was in Dictostelium, the authors were curious if any homologous proteins exist in humans. They found three and called them RhoBTB1, RhoBTB2, and RhoBTB3.[2]

Localization and expression

RhoBTB1 and RhoBTB2 are much more homologous than RhoBTB3.[2] Further analysis revealed that the intron-exon structure of RhoBTB1 and 2 are also quite similar and have only one common intron with RhoBTB3.[5]

RhoBTB1 and 2 were not detected during mouse development, but RhoBTB3 was detected strongly between embryonic days 11.5 through 17.5.[5] Additionally, RhoBTB1 and 2 are localized to vesicular structures,[6] while RhoBTB3 is localized to the trans-Golgi network.[7]

References

  1. 1.0 1.1 1.2 Bush J, Franek K, Cardelli J (December 1993). "Cloning and characterization of seven novel Dictyostelium discoideum rac-related genes belonging to the rho family of GTPases". Gene. 136 (1–2): 61–8. doi:10.1016/0378-1119(93)90448-C. PMID 8294042.
  2. 2.0 2.1 2.2 Rivero F, Dislich H, Glöckner G, Noegel AA (March 2001). "The Dictyostelium discoideum family of Rho-related proteins". Nucleic Acids Res. 29 (5): 1068–79. doi:10.1093/nar/29.5.1068. PMC 29714. PMID 11222756.
  3. Zollman S, Godt D, Privé GG, Couderc JL, Laski FA (October 1994). "The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila". Proc. Natl. Acad. Sci. U.S.A. 91 (22): 10717–21. doi:10.1073/pnas.91.22.10717. PMC 45093. PMID 7938017.
  4. Ahmad KF, Engel CK, Privé GG (October 1998). "Crystal structure of the BTB domain from PLZF". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12123–8. doi:10.1073/pnas.95.21.12123. PMC 22795. PMID 9770450.
  5. 5.0 5.1 Ramos S, Khademi F, Somesh BP, Rivero F (October 2002). "Genomic organization and expression profile of the small GTPases of the RhoBTB family in human and mouse". Gene. 298 (2): 147–57. doi:10.1016/S0378-1119(02)00980-0. PMID 12426103.
  6. Aspenström P, Fransson A, Saras J (January 2004). "Rho GTPases have diverse effects on the organization of the actin filament system". Biochem. J. 377 (Pt 2): 327–37. doi:10.1042/BJ20031041. PMC 1223866. PMID 14521508.
  7. Espinosa EJ, Calero M, Sridevi K, Pfeffer SR (May 2009). "RhoBTB3: A Rho GTPase-family ATPase required for endosome to Golgi transport". Cell. 137 (5): 938–48. doi:10.1016/j.cell.2009.03.043. PMC 2801561. PMID 19490898.

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