DPH3_NEUCR
ID DPH3_NEUCR Reviewed; 82 AA.
AC Q7SC15;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Diphthamide biosynthesis protein 3;
GN Name=dph-3; ORFNames=B10K17.050, NCU09465;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12655011; DOI=10.1093/nar/gkg293;
RA Mannhaupt G., Montrone C., Haase D., Mewes H.-W., Aign V., Hoheisel J.D.,
RA Fartmann B., Nyakatura G., Kempken F., Maier J., Schulte U.;
RT "What's in the genome of a filamentous fungus? Analysis of the Neurospora
RT genome sequence.";
RL Nucleic Acids Res. 31:1944-1954(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(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. 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, predominantly cbr-1. 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 dph-1-dph-2 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 dph-1, dph-2, dph-3 and a NADH-dependent reductase,
CC predominantly cbr-1. {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; BX842596; CAE75713.1; -; Genomic_DNA.
DR EMBL; CM002237; EAA33984.1; -; Genomic_DNA.
DR RefSeq; XP_963220.1; XM_958127.2.
DR AlphaFoldDB; Q7SC15; -.
DR SMR; Q7SC15; -.
DR STRING; 5141.EFNCRP00000009309; -.
DR EnsemblFungi; EAA33984; EAA33984; NCU09465.
DR GeneID; 3879368; -.
DR KEGG; ncr:NCU09465; -.
DR VEuPathDB; FungiDB:NCU09465; -.
DR HOGENOM; CLU_155991_4_1_1; -.
DR InParanoid; Q7SC15; -.
DR OMA; IYDPDMF; -.
DR UniPathway; UPA00559; -.
DR Proteomes; UP000001805; Chromosome 6, Linkage Group II.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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 Cytoplasm; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..82
FT /note="Diphthamide biosynthesis protein 3"
FT /id="PRO_0000082635"
FT DOMAIN 8..64
FT /note="DPH-type MB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00456"
FT BINDING 30
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 32
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 52
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
FT BINDING 55
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q3E840"
SQ SEQUENCE 82 AA; 8959 MW; A6040276AB1CC719 CRC64;
MSDEEYSIYD EVEIEDMTYD PALQTYSYPC PCGDKFEIAL ADLQDGQDIA VCPSCSLMVR
VIFEVDNLPK APDAAASIAV SA
