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Literature summary for 3.6.5.2 extracted from

  • Mori, R.; Toda, T.
    The dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GAP for GTPase Alp41/Arl2 (2013), Mol. Biol. Cell, 24; 1713-24, S1-8.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
Tbc1/cofactor C acts as a GTPase-activating protein, GAP, in regulating GTPase Alp41/Arl2. Tbc1 and Alp41 directly interact. Tbc1 is the orthologue of cofactor C and is able to form a supercomplex with Alp1D and Alp21E. Temperature-sensitive mutants of tbc1 show loss of microtubules. If Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state Schizosaccharomyces pombe

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of His6-tagged Alp41 in Escherichia coli, coexpression with activator Tbc1. HAT-tagged Tbc1 coimmunoprecipitates with GFP-tagged Alp41 Schizosaccharomyces pombe

Protein Variants

Protein Variants Comment Organism
additional information overproduction of GTP or GDP form of Alp41 is toxic to the cell Schizosaccharomyces pombe

Localization

Localization Comment Organism GeneOntology No. Textmining

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Schizosaccharomyces pombe

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
GTP + H2O Schizosaccharomyces pombe
-
GDP + phosphate
-
?
GTP + H2O Schizosaccharomyces pombe 972
-
GDP + phosphate
-
?
additional information Schizosaccharomyces pombe Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP ?
-
?
additional information Schizosaccharomyces pombe 972 Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP ?
-
?

Organism

Organism UniProt Comment Textmining
Schizosaccharomyces pombe Q09767 gene alp41
-
Schizosaccharomyces pombe 972 Q09767 gene alp41
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
GTP + H2O
-
Schizosaccharomyces pombe GDP + phosphate
-
?
GTP + H2O
-
Schizosaccharomyces pombe 972 GDP + phosphate
-
?
additional information Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP Schizosaccharomyces pombe ?
-
?
additional information Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP Schizosaccharomyces pombe 972 ?
-
?

Synonyms

Synonyms Comment Organism
Alp41
-
Schizosaccharomyces pombe
Alp41/Arl2
-
Schizosaccharomyces pombe
GTPase Alp41/Arl2
-
Schizosaccharomyces pombe
small GTPase
-
Schizosaccharomyces pombe

General Information

General Information Comment Organism
evolution Alp41/Arl2 is a highly conserved small GTPase Schizosaccharomyces pombe
malfunction if Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state. Overproduction of GTP or GDP form of Alp41 is toxic to the cell Schizosaccharomyces pombe
metabolism the tubulin cofactor pathway consists of a specific set of chap­erones that aid the folding of alpha- and beta-tubulin monomers into a functional heterodimer, with the introduction of cofactor C, GTP hydrolysis occurs, triggering the release of the newly folded alpha/beta-tubulin heterodimer for addition to the plus end of the microtubule, modeling of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP Schizosaccharomyces pombe
physiological function dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GTPase activating protein for GTPase Alp41/Arl2, Tbc1 and Alp41 directly interact, mutational analysis, overview. Tbc1 is the cofactor C involved in correct folding of alphabeta-tubulin heterodimers, critical for microtubule dynamics. The expression of GDP- or GTP-bound Alp41 shows a micro­tubule loss phenotype, continuous cycling between these forms seems important for its functions. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP, GDP-bound Alp41 sequesters overproduced Alp1D from microtubules and rescues abnormal microtubule structures Schizosaccharomyces pombe