DPH3_MOUSE
ID DPH3_MOUSE Reviewed; 82 AA.
AC Q8K0W9;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Diphthamide biosynthesis protein 3 {ECO:0000303|PubMed:16648478};
DE AltName: Full=CSL-type zinc finger-containing protein 2;
DE AltName: Full=DelGEF-interacting protein 1;
DE Short=DelGIP1;
GN Name=Dph3 {ECO:0000303|PubMed:16648478};
GN Synonyms=Desr1 {ECO:0000303|Ref.6}, Zcsl2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
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).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16648478; DOI=10.1128/mcb.26.10.3835-3841.2006;
RA Liu S., Wiggins J.F., Sreenath T., Kulkarni A.B., Ward J.M., Leppla S.H.;
RT "Dph3, a small protein required for diphthamide biosynthesis, is essential
RT in mouse development.";
RL Mol. Cell. Biol. 26:3835-3841(2006).
RN [5]
RP DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/6J;
RX PubMed=23185508; DOI=10.1371/journal.pone.0049988;
RA Wang L., Shi Y., Ju P., Liu R., Yeo S.P., Xia Y., Owlanj H., Feng Z.;
RT "Silencing of diphthamide synthesis 3 (Dph3) reduces metastasis of murine
RT melanoma.";
RL PLoS ONE 7:e49988-e49988(2012).
RN [6]
RP STRUCTURE BY NMR OF 1-70 IN COMPLEX WITH ZINC IONS.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the mouse Desr1.";
RL Submitted (AUG-2005) to the PDB data bank.
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 -!- TISSUE SPECIFICITY: Widely expressed with highest levels in heart,
CC liver, kidney and testis. {ECO:0000269|PubMed:14527407}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, expressed during all stages of
CC development. {ECO:0000269|PubMed:14527407}.
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 -!- DISRUPTION PHENOTYPE: Embryonic lethal about 11.5 days after
CC fertilization (PubMed:16648478). Decreases metastasis in a mouse model
CC of melanoma (PubMed:23185508). {ECO:0000269|PubMed:16648478,
CC ECO:0000269|PubMed:23185508}.
CC -!- SIMILARITY: Belongs to the DPH3 family. {ECO:0000305}.
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DR EMBL; AK048097; BAC33240.1; -; mRNA.
DR EMBL; AK011448; BAC25335.1; -; mRNA.
DR EMBL; BC029910; AAH29910.1; -; mRNA.
DR EMBL; BC039954; AAH39954.1; -; mRNA.
DR CCDS; CCDS36861.1; -.
DR RefSeq; NP_001040898.1; NM_001047433.2.
DR RefSeq; NP_001271275.1; NM_001284346.1.
DR RefSeq; NP_758458.1; NM_172254.4.
DR PDB; 1WGE; NMR; -; A=1-70.
DR PDBsum; 1WGE; -.
DR AlphaFoldDB; Q8K0W9; -.
DR SMR; Q8K0W9; -.
DR STRING; 10090.ENSMUSP00000068491; -.
DR iPTMnet; Q8K0W9; -.
DR PhosphoSitePlus; Q8K0W9; -.
DR EPD; Q8K0W9; -.
DR MaxQB; Q8K0W9; -.
DR PaxDb; Q8K0W9; -.
DR PRIDE; Q8K0W9; -.
DR ProteomicsDB; 279476; -.
DR Antibodypedia; 26896; 41 antibodies from 11 providers.
DR Ensembl; ENSMUST00000022461; ENSMUSP00000022461; ENSMUSG00000021905.
DR Ensembl; ENSMUST00000067955; ENSMUSP00000068491; ENSMUSG00000021905.
DR GeneID; 105638; -.
DR KEGG; mmu:105638; -.
DR UCSC; uc007syc.2; mouse.
DR CTD; 285381; -.
DR MGI; MGI:1922658; Dph3.
DR VEuPathDB; HostDB:ENSMUSG00000021905; -.
DR eggNOG; KOG2923; Eukaryota.
DR GeneTree; ENSGT00390000007225; -.
DR HOGENOM; CLU_155991_3_0_1; -.
DR InParanoid; Q8K0W9; -.
DR OMA; IYDPDMF; -.
DR OrthoDB; 1634836at2759; -.
DR PhylomeDB; Q8K0W9; -.
DR TreeFam; TF315102; -.
DR Reactome; R-MMU-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 105638; 16 hits in 62 CRISPR screens.
DR ChiTaRS; Dph3; mouse.
DR EvolutionaryTrace; Q8K0W9; -.
DR PRO; PR:Q8K0W9; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8K0W9; protein.
DR Bgee; ENSMUSG00000021905; Expressed in morula and 228 other tissues.
DR ExpressionAtlas; Q8K0W9; baseline and differential.
DR Genevisible; Q8K0W9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; IMP: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 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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Iron; Metal-binding; Nucleus; Reference proteome.
FT CHAIN 1..82
FT /note="Diphthamide biosynthesis protein 3"
FT /id="PRO_0000082621"
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"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1WGE"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:1WGE"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:1WGE"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:1WGE"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:1WGE"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:1WGE"
FT HELIX 36..40
FT /evidence="ECO:0007829|PDB:1WGE"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:1WGE"
FT TURN 49..51
FT /evidence="ECO:0007829|PDB:1WGE"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1WGE"
FT HELIX 61..65
FT /evidence="ECO:0007829|PDB:1WGE"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:1WGE"
SQ SEQUENCE 82 AA; 9286 MW; 3BC612EFE72E7670 CRC64;
MAVFHDEVEI EDFQYDEDSE TYFYPCPCGD NFAITKEDLE NGEDVATCPS CSLIIKVIYD
KDQFMCGETV PAPSTNKELV KC
