The THUMP domain (named after THioUridine synthases, RNA Methylases and Pseudouridine synthases) is a module of approximately 110 amino acid residues involved in RNA metabolism. It is found in enzymes responsible for various RNA modifications, including methylation, pseudouridylation, thiouridylation, deamination, and acetylation. The THUMP domain can occur independently or in association with … expand

The THUMP domain (named after THioUridine synthases, RNA Methylases and Pseudouridine synthases) is a module of approximately 110 amino acid residues involved in RNA metabolism. It is found in enzymes responsible for various RNA modifications, including methylation, pseudouridylation, thiouridylation, deamination, and acetylation. The THUMP domain can occur independently or in association with different catalytic domains, such as methylase, pseudo U-synthase, or PP-loop domains [ PUBMED:36833309 ].

The THUMP domain can occur in stand-alone form or in association with a variety of catalytic domains, like methylase, pseudo U-synthase or rhodanese. THUMP is an ancient domain that apparently evolved prior to the divergence of the primary divisions of life. It was initially predicted to have RNA-binding capacity but it was shown later that it associates with the adjacent FLD domain (IPR000241) to display the RNA-binding ability, leading to the delivery of a variety of RNA modification enzymes to their targets. The domain adopts an α/β fold, with two helices packed against a β-sheet [ PUBMED:11295541 PUBMED:16343540 PUBMED:16687654 PUBMED:17010378 ].

Recent structural and biochemical studies have established that the THUMP domain plays a crucial role in capturing the 3'-end of RNA substrates, particularly the CCA-terminus of tRNAs. This function is essential for the proper positioning of the RNA substrate for modification by the associated catalytic domains [ PUBMED:36833309 ].

THUMP-containing proteins have been identified in all domains of life, including bacteria, archaea, and eukaryotes, indicating their ancient evolutionary origin. Recent studies have also revealed that some THUMP-related proteins are involved in modifications of other RNA types beyond tRNA, such as rRNA [ PUBMED:36833309 ].

Some proteins known to contain a THUMP domain are listed below:

• Bacterial and archaeal thiI-like 4-thiouridine synthases (also known as tRNA sulfurtransferases).
• Bacterial, archaeal and eukaryotic RNA methyltransferases including tRNA methyltransferases.
• tRNA pseudouridine synthase Pus10.
• tRNA acetyltransferases.
• THUMP domain-containing protein.