DPH1_MOUSE
ID DPH1_MOUSE Reviewed; 438 AA.
AC Q5NCQ5; Q80UX6; Q8R445;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 {ECO:0000305};
DE EC=2.5.1.108 {ECO:0000305|PubMed:15485916};
DE AltName: Full=Diphthamide biosynthesis protein 1;
DE AltName: Full=Diphtheria toxin resistance protein 1 {ECO:0000305};
DE AltName: Full=Ovarian cancer-associated gene 1 protein homolog;
DE AltName: Full=S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 1 {ECO:0000305};
GN Name=Dph1 {ECO:0000303|PubMed:15485916};
GN Synonyms=Dph2l1, Ovca1 {ECO:0000303|PubMed:11527402};
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 [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=11527402; DOI=10.1006/bbrc.2001.5488;
RA Chen C.-M., Behringer R.R.;
RT "Cloning, structure, and expression of the mouse Ovca1 gene.";
RL Biochem. Biophys. Res. Commun. 286:1019-1026(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-438.
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14744934; DOI=10.1101/gad.1162204;
RA Chen C.-M., Behringer R.R.;
RT "Ovca1 regulates cell proliferation, embryonic development, and
RT tumorigenesis.";
RL Genes Dev. 18:320-332(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH DPH2.
RX PubMed=15485916; DOI=10.1128/mcb.24.21.9487-9497.2004;
RA Liu S., Milne G.T., Kuremsky J.G., Fink G.R., Leppla S.H.;
RT "Identification of the proteins required for biosynthesis of diphthamide,
RT the target of bacterial ADP-ribosylating toxins on translation elongation
RT factor 2.";
RL Mol. Cell. Biol. 24:9487-9497(2004).
RN [6]
RP FUNCTION.
RX PubMed=15661533; DOI=10.1016/j.gde.2004.12.006;
RA Chen C.M., Behringer R.R.;
RT "OVCA1: tumor suppressor gene.";
RL Curr. Opin. Genet. Dev. 15:49-54(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP INTERACTION WITH DPH2.
RX PubMed=21203470; DOI=10.1371/journal.pone.0015753;
RA Roy V., Ghani K., Caruso M.;
RT "A dominant-negative approach that prevents diphthamide formation confers
RT resistance to Pseudomonas exotoxin A and diphtheria toxin.";
RL PLoS ONE 5:e15753-e15753(2010).
RN [9]
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=24895408; DOI=10.1093/hmg/ddu273;
RA Yu Y.R., You L.R., Yan Y.T., Chen C.M.;
RT "Role of OVCA1/DPH1 in craniofacial abnormalities of Miller-Dieker
RT syndrome.";
RL Hum. Mol. Genet. 23:5579-5596(2014).
CC -!- FUNCTION: Catalyzes the first step of diphthamide biosynthesis, a post-
CC translational modification of histidine which occurs in elongation
CC factor 2 (PubMed:15485916, PubMed:24895408). DPH1 and DPH2 transfer a
CC 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM)
CC to a histidine residue, the reaction is assisted by a reduction system
CC comprising DPH3 and a NADH-dependent reductase (By similarity). Acts as
CC a tumor suppressor (PubMed:14744934, PubMed:15661533, PubMed:24895408).
CC {ECO:0000250|UniProtKB:P40487, ECO:0000269|PubMed:14744934,
CC ECO:0000269|PubMed:15485916, ECO:0000269|PubMed:15661533,
CC ECO:0000269|PubMed:24895408}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidyl-[translation elongation factor 2] + S-adenosyl-L-
CC methionine = 2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation
CC elongation factor 2] + H(+) + S-methyl-5'-thioadenosine;
CC Xref=Rhea:RHEA:36783, Rhea:RHEA-COMP:9748, Rhea:RHEA-COMP:9749,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:29979,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:73995; EC=2.5.1.108;
CC Evidence={ECO:0000305|PubMed:15485916};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P40487};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000250|UniProtKB:P40487};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
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 DPH2 (PubMed:15485916, PubMed:21203470).
CC Interacts with RBM8A (By similarity). {ECO:0000250|UniProtKB:P40487,
CC ECO:0000250|UniProtKB:Q9BZG8, ECO:0000269|PubMed:15485916,
CC ECO:0000269|PubMed:21203470}.
CC -!- INTERACTION:
CC Q5NCQ5; Q9CR25: Dph2; NbExp=2; IntAct=EBI-1561119, EBI-1561134;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11527402}. Cytoplasm
CC {ECO:0000269|PubMed:11527402}. Note=Punctate, primarily perinuclear
CC localization.
CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney and liver. Moderately
CC expressed in brain, skin and testis. Weakly expressed in heart, lung,
CC small intestine, spleen, stomach and thymus.
CC {ECO:0000269|PubMed:11527402}.
CC -!- DEVELOPMENTAL STAGE: Expressed in heart, neural tube, forebrain,
CC mandible, tongue and body walls at 10.5 to 14.5 dpc (at protein level)
CC (PubMed:24895408). Expressed in lung, stomach, brain, heart, kidney and
CC gonads at 14.5 dpc (PubMed:11527402). {ECO:0000269|PubMed:11527402,
CC ECO:0000269|PubMed:24895408}.
CC -!- DISRUPTION PHENOTYPE: Global developmental delay (PubMed:14744934,
CC PubMed:24895408). Abnormal palatogenesis; palatine bone absent,
CC micrognathia, cleft palate and small skull (PubMed:14744934,
CC PubMed:24895408). Results in death during gestation or soon after birth
CC with a small body size (PubMed:14744934). May also result in preaxial
CC polydactyly of the right hindlimb and abnormal hepatic development
CC (PubMed:14744934). Knockout mice leads to an increased frequency of
CC tumor formation (PubMed:14744934, PubMed:24895408).
CC {ECO:0000269|PubMed:14744934, ECO:0000269|PubMed:24895408}.
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AY078170; AAM14629.1; -; mRNA.
DR EMBL; AL603905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044663; AAH44663.1; -; mRNA.
DR CCDS; CCDS25042.1; -.
DR PIR; JC7758; JC7758.
DR RefSeq; NP_652762.2; NM_144491.2.
DR AlphaFoldDB; Q5NCQ5; -.
DR SMR; Q5NCQ5; -.
DR IntAct; Q5NCQ5; 1.
DR STRING; 10090.ENSMUSP00000042162; -.
DR iPTMnet; Q5NCQ5; -.
DR PhosphoSitePlus; Q5NCQ5; -.
DR EPD; Q5NCQ5; -.
DR MaxQB; Q5NCQ5; -.
DR PaxDb; Q5NCQ5; -.
DR PeptideAtlas; Q5NCQ5; -.
DR PRIDE; Q5NCQ5; -.
DR ProteomicsDB; 277381; -.
DR Antibodypedia; 22821; 216 antibodies from 25 providers.
DR DNASU; 116905; -.
DR Ensembl; ENSMUST00000044949; ENSMUSP00000042162; ENSMUSG00000078789.
DR GeneID; 116905; -.
DR KEGG; mmu:116905; -.
DR UCSC; uc007kdg.1; mouse.
DR CTD; 1801; -.
DR MGI; MGI:2151233; Dph1.
DR VEuPathDB; HostDB:ENSMUSG00000078789; -.
DR eggNOG; KOG2648; Eukaryota.
DR GeneTree; ENSGT00940000153694; -.
DR HOGENOM; CLU_037146_1_2_1; -.
DR InParanoid; Q5NCQ5; -.
DR OMA; PGQVLGC; -.
DR OrthoDB; 750182at2759; -.
DR PhylomeDB; Q5NCQ5; -.
DR TreeFam; TF105746; -.
DR Reactome; R-MMU-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 116905; 14 hits in 72 CRISPR screens.
DR ChiTaRS; Dph1; mouse.
DR PRO; PR:Q5NCQ5; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5NCQ5; protein.
DR Bgee; ENSMUSG00000078789; Expressed in proximal tubule and 59 other tissues.
DR ExpressionAtlas; Q5NCQ5; baseline and differential.
DR Genevisible; Q5NCQ5; MM.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0090560; F:2-(3-amino-3-carboxypropyl)histidine synthase activity; IGI:FlyBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IMP:UniProtKB.
DR Gene3D; 3.40.50.11840; -; 1.
DR Gene3D; 3.40.50.11850; -; 1.
DR Gene3D; 3.40.50.11860; -; 1.
DR InterPro; IPR016435; DPH1/DPH2.
DR InterPro; IPR042263; DPH1/DPH2_1.
DR InterPro; IPR042264; DPH1/DPH2_2.
DR InterPro; IPR042265; DPH1/DPH2_3.
DR PANTHER; PTHR10762; PTHR10762; 1.
DR Pfam; PF01866; Diphthamide_syn; 1.
DR SFLD; SFLDS00032; Radical_SAM_3-amino-3-carboxyp; 1.
DR TIGRFAMs; TIGR00322; diphth2_R; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Iron; Iron-sulfur; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; Tumor suppressor.
FT CHAIN 1..438
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase
FT subunit 1"
FT /id="PRO_0000307883"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..438
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 110
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT BINDING 214
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT BINDING 342
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT MOD_RES 418
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 98
FT /note="E -> K (in Ref. 1; AAM14629)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="P -> L (in Ref. 1; AAM14629)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="S -> P (in Ref. 1; AAM14629)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 438 AA; 48004 MW; 07CA505B08F72AB7 CRC64;
MAALVVSETA EPGSRVGPGR GRISRGRLAN QIPPEVLNNP QLQAAVQVLP SNYNFEIPKT
IWRIQQAQAK KVALQMPEGL LLFACTIVDI LERFTEAEVM VMGDVTYGAC CVDDFTARAL
GVDFLVHYGH SCLVPMDTSV QDFRVLYVFV DIRIDTAHLL DSVRLTFTPG SSLALVSTIQ
FVSTLQAAAQ ELKADYHISV PQCKPLSPGE ILGCTSPRLS KEVEAVVYLG DGRFHLESVM
IANPNIPAYR YDPYGKVLSR EYYDHQRMQA TRQEAIAAAR SAKSWGLILG TLGRQGSPKI
LEHLESQLRN LGLPFVRLLL SEIFPSKLSL LPEVDVWVQV ACPRLSIDWG SAFPKPLLTP
YEAAVALKDI SWQQPYPMDF YSGSSLGPWT VNYGRDRAPR GLCQPASDKV QQGSRGGSPA
PACESCNCAD QKATSPAP
