THIF-type NAD/FAD binding fold
IPR000594
Definition
This domain is a NAD/FAD-binding fold found in ubiquitin activating E1 family and members of the bacterial ThiF/MoeB/HesA family. It is repeated in Ubiquitin-activating enzyme E1 [[cite:PMID:11713534], [cite:PMID:15660128], [cite:PMID:18662542]]. ThiF/MoeB/HesA are involved in molybdopterin and thiamine biosynthesis. The common reaction mechanism catalysed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD and ThiS, respectively, on the alpha-phosphate of an ATP molecule bound at the active site of the activating enzymes, leading to the formation of a high-energy acyladenylate intermediate and subsequently to the formation of a thiocarboxylate at the C termini of MoaD and ThiS. MoeB, as the MPT synthase (MoaE/MoaD complex) sulfurase, is involved in the biosynthesis of the molybdenum cofactor, a derivative of the tricyclic pterin, molybdopterin (MPT) PMID:11713534. ThiF catalyses the adenylation of ThiS, as part of the biosynthesis pathway of thiamin pyrophosphate (vitamin B1) PMID:9632726. The post-translational attachment of ubiquitin ([interpro:IPR000626]) to proteins (ubiquitinylation) alters the function, location or trafficking of a protein, or targets it to the 26S proteasome for degradation [[cite:PMID:15556404], [cite:PMID:15454246], [cite:PMID:15196553]]. Ubiquitinylation is an ATP-dependent process that involves the action of at least three enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2, [interpro:IPR000608]), and a ubiquitin ligase (E3, [interpro:IPR000569], [interpro:IPR003613]), which work sequentially in a cascade PMID:14998368. The E1 enzyme is responsible for activating ubiquitin, the first step in ubiquitinylation. The E1 enzyme hydrolyses ATP and adenylates the C-terminal glycine residue of ubiquitin, and then links this residue to the active site cysteine of E1, yielding a ubiquitin-thioester and free AMP. To be fully active, E1 must non-covalently bind to and adenylate a second ubiquitin molecule. The E1 enzyme can then transfer the thioester-linked ubiquitin molecule to a cysteine residue on the ubiquitin-conjugating enzyme, E2, in an ATP-dependent reaction.
10 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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