ID   DPH3_BOVIN              Reviewed;          82 AA.
AC   Q1LZC9;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 1.
DT   03-AUG-2022, entry version 89.
DE   RecName: Full=Diphthamide biosynthesis protein 3 {ECO:0000305};
DE   AltName: Full=CSL-type zinc finger-containing protein 2;
GN   Name=DPH3; Synonyms=ZCSL2;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Ascending colon;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
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; BC116080; AAI16081.1; -; mRNA.
DR   RefSeq; NP_001106770.1; NM_001113299.2.
DR   RefSeq; NP_001290470.1; NM_001303541.1.
DR   AlphaFoldDB; Q1LZC9; -.
DR   SMR; Q1LZC9; -.
DR   STRING; 9913.ENSBTAP00000005113; -.
DR   PaxDb; Q1LZC9; -.
DR   Ensembl; ENSBTAT00000005113; ENSBTAP00000005113; ENSBTAG00000003916.
DR   GeneID; 511579; -.
DR   KEGG; bta:511579; -.
DR   CTD; 285381; -.
DR   VEuPathDB; HostDB:ENSBTAG00000003916; -.
DR   VGNC; VGNC:53537; DPH3.
DR   eggNOG; KOG2923; Eukaryota.
DR   GeneTree; ENSGT00390000007225; -.
DR   HOGENOM; CLU_155991_3_0_1; -.
DR   InParanoid; Q1LZC9; -.
DR   OMA; IYDPDMF; -.
DR   OrthoDB; 1634836at2759; -.
DR   TreeFam; TF315102; -.
DR   UniPathway; UPA00559; -.
DR   Proteomes; UP000009136; Chromosome 1.
DR   Bgee; ENSBTAG00000003916; Expressed in semitendinosus and 102 other tissues.
DR   ExpressionAtlas; Q1LZC9; baseline and differential.
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; Reference proteome.
FT   CHAIN           1..82
FT                   /note="Diphthamide biosynthesis protein 3"
FT                   /id="PRO_0000260220"
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;  9288 MW;  3BD728A93FCE7670 CRC64;
     MAVFHDEVEI EDFQYDEDSE TYFYPCPCGD NFCITKEDLE NGEDVATCPS CSLIIKVIYD
     KDQFTCGETV PAPSTNKELV KC