Protein: Diphthamide biosynthesis protein 3 (CSL-type zinc finger-containing protein 2) (Diphtheria toxin and Pseudomonas exotoxin A sensitivity-required protein 1) (Q6VUC1)
Organism: Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Function: Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase. Acts as an electron donor to reduce the Fe-S cluster in DPH1-DPH2 keeping the [4Fe-4S] clusters in the active and reduced state. Restores iron to DPH1-DPH2 iron-sulfur clusters which have degraded from [4Fe-4S] to [3Fe-4S] by donating an iron atom to reform [4Fe-4S] clusters, in a manner dependent on the presence of elongation factor 2 and SAM. Associates with the elongator complex and is required for tRNA Wobble base modifications mediated by the elongator complex. The elongator complex is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q96FX2}. Nucleus {ECO:0000250|UniProtKB:Q96FX2}.
Sequence: MAVFHDEVEIEDFQYDEDSETYFYPCPCGDNFSITKEDLENGEDVATCPSCSLIIKVIYDKDQFMCGETVPAPSTNKELVKC
InterPro domains: - IPR007872: DPH-type metal-binding domain (domain) [4-60]
- IPR036671: DPH-type metal-binding domain superfamily (homologous_superfamily) [1-79]
- IPR044248: Diphthamide biosynthesis protein 3/4-like (family) [3-67]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0065009 (regulation of molecular function), GO:0051051 (negative regulation of transport), GO:0048523 (negative regulation of cellular process), GO:0032879 (regulation of localization), GO:0050794 (regulation of cellular process), GO:1903530 (regulation of secretion by cell), GO:0044093 (positive regulation of molecular function), GO:0051049 (regulation of transport), GO:0051098 (regulation of binding), GO:1903828 (negative regulation of protein localization), GO:0060341 (regulation of cellular localization), GO:0051048 (negative regulation of secretion), GO:0051224 (negative regulation of protein transport), GO:1903531 (negative regulation of secretion by cell), GO:0051099 (positive regulation of binding), GO:0050709 (negative regulation of protein secretion), GO:0051046 (regulation of secretion), GO:0051223 (regulation of protein transport), GO:0032880 (regulation of protein localization), GO:0050708 (regulation of protein secretion), GO:1904950 (negative regulation of establishment of protein localization), GO:0070201 (regulation of establishment of protein localization)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)