DPH3_CRIGR
ID DPH3_CRIGR Reviewed; 82 AA.
AC Q6VUC1;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Diphthamide biosynthesis protein 3 {ECO:0000305};
DE AltName: Full=CSL-type zinc finger-containing protein 2;
DE AltName: Full=Diphtheria toxin and Pseudomonas exotoxin A sensitivity-required protein 1;
GN Name=DPH3; Synonyms=DESR1, ZCSL2;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=14527407; DOI=10.1016/j.molcel.2003.08.003;
RA Liu S., Leppla S.H.;
RT "Retroviral insertional mutagenesis identifies a small protein required for
RT synthesis of diphthamide, the target of bacterial ADP-ribosylating
RT toxins.";
RL Mol. Cell 12:603-613(2003).
CC -!- FUNCTION: Required for the first step of diphthamide biosynthesis, a
CC post-translational modification of histidine which occurs in elongation
CC factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group
CC from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction
CC is assisted by a reduction system comprising DPH3 and a NADH-dependent
CC reductase. Acts as an electron donor to reduce the Fe-S cluster in
CC DPH1-DPH2 keeping the [4Fe-4S] clusters in the active and reduced
CC state. Restores iron to DPH1-DPH2 iron-sulfur clusters which have
CC degraded from [4Fe-4S] to [3Fe-4S] by donating an iron atom to reform
CC [4Fe-4S] clusters, in a manner dependent on the presence of elongation
CC factor 2 and SAM. Associates with the elongator complex and is required
CC for tRNA Wobble base modifications mediated by the elongator complex.
CC The elongator complex is required for multiple tRNA modifications,
CC including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s 2U (5-
CC methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl
CC 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 DPH1, DPH2, DPH3 and a NADH-dependent reductase (By
CC similarity). Interacts with SERGEF (By similarity).
CC {ECO:0000250|UniProtKB:Q3E840, ECO:0000250|UniProtKB:Q96FX2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96FX2}. Nucleus
CC {ECO:0000250|UniProtKB:Q96FX2}.
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; AY326451; AAQ83755.1; -; Genomic_DNA.
DR RefSeq; NP_001231467.1; NM_001244538.1.
DR RefSeq; XP_003495350.1; XM_003495302.3.
DR AlphaFoldDB; Q6VUC1; -.
DR SMR; Q6VUC1; -.
DR STRING; 10029.NP_001231467.1; -.
DR Ensembl; ENSCGRT00001010981; ENSCGRP00001006985; ENSCGRG00001009461.
DR Ensembl; ENSCGRT00001014306; ENSCGRP00001010086; ENSCGRG00001012063.
DR GeneID; 100689295; -.
DR GeneID; 100768092; -.
DR KEGG; cge:100768092; -.
DR CTD; 285381; -.
DR eggNOG; KOG2923; Eukaryota.
DR GeneTree; ENSGT00390000007225; -.
DR OMA; IYDPDMF; -.
DR OrthoDB; 1634836at2759; -.
DR UniPathway; UPA00559; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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:0050709; P:negative regulation of protein secretion; ISS:UniProtKB.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IDA:UniProtKB.
DR GO; GO:0051099; P:positive regulation of binding; ISS:UniProtKB.
DR GO; GO:0002926; P:tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation; ISS:UniProtKB.
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 Cytoplasm; Iron; Metal-binding; Nucleus.
FT CHAIN 1..82
FT /note="Diphthamide biosynthesis protein 3"
FT /id="PRO_0000082619"
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:Q96FX2"
FT BINDING 28
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q96FX2"
FT BINDING 48
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q96FX2"
FT BINDING 51
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q96FX2"
SQ SEQUENCE 82 AA; 9302 MW; 3BD9F2EFF8CE7670 CRC64;
MAVFHDEVEI EDFQYDEDSE TYFYPCPCGD NFSITKEDLE NGEDVATCPS CSLIIKVIYD
KDQFMCGETV PAPSTNKELV KC
