DPH3_ENCCU
ID DPH3_ENCCU Reviewed; 93 AA.
AC Q8STR6;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Diphthamide biosynthesis protein 3;
GN Name=DPH3; OrderedLocusNames=ECU09_1005;
OS Encephalitozoon cuniculi (strain GB-M1) (Microsporidian parasite).
OC Eukaryota; Fungi; Fungi incertae sedis; Microsporidia; Unikaryonidae;
OC Encephalitozoon.
OX NCBI_TaxID=284813;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=GB-M1;
RX PubMed=11719806; DOI=10.1038/35106579;
RA Katinka M.D., Duprat S., Cornillot E., Metenier G., Thomarat F.,
RA Prensier G., Barbe V., Peyretaillade E., Brottier P., Wincker P.,
RA Delbac F., El Alaoui H., Peyret P., Saurin W., Gouy M., Weissenbach J.,
RA Vivares C.P.;
RT "Genome sequence and gene compaction of the eukaryote parasite
RT Encephalitozoon cuniculi.";
RL Nature 414:450-453(2001).
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 KTI11/DPH3 and a NADH-
CC dependent reductase, predominantly CBR1. Acts as an electron donor to
CC reduce the Fe-S cluster in DPH1-DPH2 keeping the [4Fe-4S] clusters in
CC the active and reduced state. Restores iron to DPH1-DPH2 iron-sulfur
CC clusters which have degraded from [4Fe-4S] to [3Fe-4S] by donating an
CC iron atom to reform [4Fe-4S] clusters, in a manner dependent on the
CC presence of elongation factor 2 and SAM. Associates with the elongator
CC complex and is required for tRNA Wobble base modifications mediated by
CC the elongator complex. The elongator complex is required for multiple
CC tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine),
CC mcm5s 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:0000250|UniProtKB:Q3E840}.
CC -!- SUBUNIT: Component of the 2-(3-amino-3-carboxypropyl)histidine synthase
CC complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase,
CC predominantly CBR1. {ECO:0000250|UniProtKB:Q3E840}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
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; AL590451; CAD27074.1; -; Genomic_DNA.
DR RefSeq; XP_955655.1; XM_950562.1.
DR AlphaFoldDB; Q8STR6; -.
DR SMR; Q8STR6; -.
DR STRING; 284813.Q8STR6; -.
DR GeneID; 860440; -.
DR KEGG; ecu:ECU09_1005; -.
DR VEuPathDB; MicrosporidiaDB:ECU09_1005; -.
DR HOGENOM; CLU_155991_2_0_1; -.
DR InParanoid; Q8STR6; -.
DR OMA; IYDPDMF; -.
DR OrthoDB; 1634836at2759; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000000819; Chromosome IX.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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 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; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..93
FT /note="Diphthamide biosynthesis protein 3"
FT /id="PRO_0000082632"
FT DOMAIN 29..85
FT /note="DPH-type MB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00456"
FT BINDING 51
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 53
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 73
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 76
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
SQ SEQUENCE 93 AA; 10949 MW; BA129862E50B0D94 CRC64;
MSFRPEYKEY FKQGATARIY NGAFEDAGFY DEVDIKEFEY SREEKTFYYP CPCGDRFEIS
LEDLRNGEVV ARCPSCSLIV CTVYEAEDLE KYL
