The RhoBTB family is a subgroup of the

Rho family The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found ...

of small

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...

s. They are a highly divergent class and are all characterized by an

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

Rho-related domain followed by at least one

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

BTB domain.

Discovery

The RhoBTB family of

molecules A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

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 blot A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detecti ...

s looking for

cDNAs In genetics, complementary DNA (cDNA) is DNA synthesized from a single-stranded RNA (e.g., messenger RNA (mRNA) or microRNA (miRNA)) template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to express a spe ...

that cross-hybridize with a very conservative probe from hRas. They identified 19 new

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

that belonged to the

Ras Ras or RAS may refer to: Arts and media * RAS Records Real Authentic Sound, a reggae record label * Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service * Rás 1, an Icelandic radio station * Rás 2, an Icelandic radio stati ...

superfamily and sequenced approximately 600 nucleotides from the start of the transcript. 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. 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. 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. 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 Rho-related BTB domain-containing protein 1 is a protein that in humans is encoded by the ''RHOBTB1'' gene. The protein encoded by this gene belongs to the Rho family of the Ras superfamily The Ras superfamily, derived from "Rat sarcoma virus" ...

RhoBTB2 Rho-related BTB domain-containing protein 2 is a protein that in humans is encoded by the ''RHOBTB2'' gene. RHOBTB2 is a member of the evolutionarily-conserved RhoBTB subfamily of Rho GTPases. For background information on RhoBTBs, see RHOBTB1 (M ...

, and RhoBTB3.

Localization and expression

RhoBTB1 and RhoBTB2 are much more homologous than RhoBTB3. Further analysis revealed that the intron-exon structure of RhoBTB1 and 2 are also quite similar and have only one common intron with RhoBTB3. RhoBTB1 and 2 were not detected during mouse development, but RhoBTB3 was detected strongly between embryonic days 11.5 through 17.5. Additionally, RhoBTB1 and 2 are localized to vesicular structures, while RhoBTB3 is localized to the trans-Golgi network.

References

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