Target type: cellularcomponent
A highly conserved protein complex comprised of two ATP-dependent DNA helicases (Rvb1p and Rvb2p in yeast, Pontin52 and Reptin52 in humans), Pih1p in yeast or PIH1D1 in humans, and Tah1 in yeast or RPAP3 in humans. The complex associates with Hsp90 and is thought to have a role in assembly of large protein or protein/nucleic acid complexes. In this role it is involved in multiple processes such as box C/D snoRNP biogenesis, phosphatidylinositol-3 kinase-related protein kinase (PIKK) signaling, RNA polymerase II assembly, and others. [GOC:mcc, PMID:15766533, PMID:21925213]
The R2TP complex is a highly conserved multi-protein complex that plays a vital role in the assembly and maturation of diverse cellular components, including ribosomes, tRNA synthetases, and chaperones. It consists of four core subunits: R2TP, RPAP3, TAH1, and PIH1D1. This complex functions as a molecular chaperone, assisting in the folding and proper assembly of its target proteins.
**R2TP**, the namesake subunit, is a 97 kDa protein containing a highly conserved AAA+ ATPase domain, responsible for ATP binding and hydrolysis. This domain is crucial for R2TP's ability to unfold and refold its target proteins, ensuring their proper conformation.
**RPAP3**, also known as p37, is a 37 kDa protein. It acts as a scaffold, providing a platform for the assembly of the R2TP complex. RPAP3 interacts with both R2TP and TAH1, stabilizing the complex and facilitating its interaction with target proteins.
**TAH1**, also known as Tel1p-associated homolog 1, is a 55 kDa protein. It possesses a unique domain, the TAH1 domain, which is involved in recognizing and binding specific peptide motifs present in its target proteins. This binding interaction is crucial for the initial recruitment of target proteins to the R2TP complex.
**PIH1D1**, also known as PIH1 domain-containing protein 1, is a 48 kDa protein. It contains a PIH1 domain, which is responsible for interacting with the C-terminal tail of TAH1. This interaction further stabilizes the R2TP complex and promotes its activity.
The R2TP complex operates in a tightly regulated manner, employing a series of intricate mechanisms to ensure the proper assembly and maturation of its target proteins. This includes the ATP-dependent unfolding and refolding of misfolded or partially assembled proteins, and the precise coordination of interactions with other chaperones and cellular factors.
**The cellular component of the R2TP complex is highly dynamic and intricate. It exists within the nucleus and cytoplasm, suggesting its involvement in a variety of cellular processes.** Its specific localization varies depending on the target protein and the cellular context. Overall, the R2TP complex plays a fundamental role in maintaining cellular homeostasis by ensuring the proper assembly and function of critical cellular components.'
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Protein | Definition | Taxonomy |
---|---|---|
RuvB-like 1 | A RuvB-like 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y265] | Homo sapiens (human) |
RuvB-like 2 | A RuvB-like 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y230] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
sorafenib | (trifluoromethyl)benzenes; aromatic ether; monochlorobenzenes; phenylureas; pyridinecarboxamide | angiogenesis inhibitor; anticoronaviral agent; antineoplastic agent; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; ferroptosis inducer; tyrosine kinase inhibitor | |
rottlerin | rottlerin : A chromenol that is 2,2-dimethyl-2H-chromene substituted by hydroxy groups at positions 5 and 7, a 3-acetyl-2,4,6-trihydroxy-5-methylbenzyl group at position 6 and a (1E)-3-oxo-1-phenylprop-1-en-3-yl group at position 8. A potassium channel opener, it is isolated from Mallotus philippensis. rottlerin: an angiogenesis inhibitor; an inhibitor of protein kinase Cdelta (PKCdelta) and calmodulin kinase III; RN refers to (E)-isomer; do not confuse this chalcone with an anthraquinone that is also called rottlerin (RN 481-72-1); | aromatic ketone; benzenetriol; chromenol; enone; methyl ketone | anti-allergic agent; antihypertensive agent; antineoplastic agent; apoptosis inducer; K-ATP channel agonist; metabolite |
akt-i-1,2 compound | Akt-I-1,2 compound: an aminopeptidase P inhibitor; structure in first source |