DPH3_CAEEL
ID DPH3_CAEEL Reviewed; 80 AA.
AC Q21102;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Diphthamide biosynthesis protein 3 {ECO:0000305};
GN Name=dph-3 {ECO:0000305}; ORFNames=K01H12.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
CC -!- FUNCTION: Required for the first step of diphthamide biosynthesis, a
CC post-translational modification of histidine which occurs in elongation
CC factor 2. Dph-1 and dph-2 transfer a 3-amino-3-carboxypropyl (ACP)
CC group from S-adenosyl-L-methionine (SAM) to a histidine residue, the
CC reaction is assisted by a reduction system comprising dph-3 and a NADH-
CC dependent reductase. Acts as an electron donor to reduce the Fe-S
CC cluster in dph1-dph2 keeping the [4Fe-4S] clusters in the active and
CC reduced state. Restores iron to dph-1-dph-2 iron-sulfur clusters which
CC have degraded from [4Fe-4S] to [3Fe-4S] by donating an iron atom to
CC reform [4Fe-4S] clusters, in a manner dependent on the presence of
CC elongation factor 2 and SAM. Associates with the elongator complex and
CC is required for tRNA Wobble base modifications mediated by the
CC elongator complex. The elongator complex is required for multiple tRNA
CC modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s
CC 2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-
CC carbamoylmethyl uridine). {ECO:0000250|UniProtKB:Q3E840}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[3Fe-4S](1+)-[protein] + Fe(2+)-[Dph3] = [3Fe-4S](0)-[protein]
CC + Fe(3+)-[Dph3]; Xref=Rhea:RHEA:71235, Rhea:RHEA-COMP:17996,
CC Rhea:RHEA-COMP:17997, Rhea:RHEA-COMP:18002, Rhea:RHEA-COMP:18003,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:33751,
CC ChEBI:CHEBI:47402, ChEBI:CHEBI:83228;
CC Evidence={ECO:0000250|UniProtKB:Q3E840};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 [3Fe-4S](0)-[protein] + 2 Fe(2+)-[Dph3] + NADH = 2 [4Fe-
CC 4S](1+)-[protein] + 2 [Dph3] + H(+) + NAD(+); Xref=Rhea:RHEA:71239,
CC Rhea:RHEA-COMP:17997, Rhea:RHEA-COMP:17998, Rhea:RHEA-COMP:18001,
CC Rhea:RHEA-COMP:18002, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:33723, ChEBI:CHEBI:47402, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:83228;
CC Evidence={ECO:0000250|UniProtKB:Q3E840};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q3E840};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000305}.
CC -!- SUBUNIT: Component of the 2-(3-amino-3-carboxypropyl)histidine synthase
CC complex composed of dph-1, dph-2, dph-3 and a NADH-dependent reductase.
CC {ECO:0000250|UniProtKB:Q3E840}.
CC -!- DOMAIN: The DPH-type metal-binding (MB) domain can also bind zinc.
CC However, iron is the physiological binding partner as zinc binding
CC impairs the protein electron donor function.
CC {ECO:0000250|UniProtKB:Q3E840}.
CC -!- SIMILARITY: Belongs to the DPH3 family. {ECO:0000305}.
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DR EMBL; Z68218; CAA92471.1; -; Genomic_DNA.
DR PIR; T23206; T23206.
DR RefSeq; NP_001255419.1; NM_001268490.1.
DR AlphaFoldDB; Q21102; -.
DR SMR; Q21102; -.
DR STRING; 6239.K01H12.1a; -.
DR EPD; Q21102; -.
DR PaxDb; Q21102; -.
DR EnsemblMetazoa; K01H12.1a.1; K01H12.1a.1; WBGene00010484.
DR GeneID; 186854; -.
DR KEGG; cel:CELE_K01H12.1; -.
DR UCSC; K01H12.1; c. elegans.
DR CTD; 186854; -.
DR WormBase; K01H12.1a; CE03453; WBGene00010484; dph-3.
DR eggNOG; KOG2923; Eukaryota.
DR GeneTree; ENSGT00940000171548; -.
DR HOGENOM; CLU_155991_3_0_1; -.
DR InParanoid; Q21102; -.
DR OMA; IYDPDMF; -.
DR OrthoDB; 1634836at2759; -.
DR PhylomeDB; Q21102; -.
DR Reactome; R-CEL-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR PRO; PR:Q21102; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00010484; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR ExpressionAtlas; Q21102; baseline and differential.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:WormBase.
DR GO; GO:0008198; F:ferrous iron binding; ISS:UniProtKB.
DR GO; GO:0034986; F:iron chaperone activity; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; ISS:UniProtKB.
DR GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; ISS:UniProtKB.
DR GO; GO:0002098; P:tRNA wobble uridine modification; IBA:GO_Central.
DR Gene3D; 3.10.660.10; -; 1.
DR InterPro; IPR044248; DPH3/4-like.
DR InterPro; IPR007872; DPH_MB_dom.
DR InterPro; IPR036671; DPH_MB_sf.
DR PANTHER; PTHR21454; PTHR21454; 1.
DR Pfam; PF05207; zf-CSL; 1.
DR SUPFAM; SSF144217; SSF144217; 1.
DR PROSITE; PS51074; DPH_MB; 1.
PE 3: Inferred from homology;
KW Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..80
FT /note="Diphthamide biosynthesis protein 3"
FT /id="PRO_0000082624"
FT DOMAIN 4..60
FT /note="DPH-type MB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00456"
FT BINDING 26
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 28
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 48
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 51
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
SQ SEQUENCE 80 AA; 9303 MW; 0BD281DC9FC06979 CRC64;
MSVFHDEVEI EDFEFDEEKD VYHYPCPCGD RFEIPREMLE MGEDVAQCPS CSLLIRVIYD
PEDFVKLETI STSKPIAEPV
