DPH1_YEAST
ID DPH1_YEAST Reviewed; 425 AA.
AC P40487; D6VVI4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 {ECO:0000305};
DE EC=2.5.1.108 {ECO:0000269|PubMed:24422557, ECO:0000305|PubMed:15485916, ECO:0000305|PubMed:31463593};
DE AltName: Full=Diphthamide biosynthesis protein 1;
DE AltName: Full=Diphtheria toxin resistance protein 1 {ECO:0000305};
DE AltName: Full=S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 1 {ECO:0000305};
GN Name=DPH1; OrderedLocusNames=YIL103W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP INTERACTION WITH KTI11.
RX PubMed=12940988; DOI=10.1046/j.1365-2958.2003.03632.x;
RA Fichtner L., Jablonowski D., Schierhorn A., Kitamoto H.K., Stark M.J.R.,
RA Schaffrath R.;
RT "Elongator's toxin-target (TOT) function is nuclear localization sequence
RT dependent and suppressed by post-translational modification.";
RL Mol. Microbiol. 49:1297-1307(2003).
RN [4]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [5]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, 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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [8]
RP IDENTIFICATION IN THE 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE SYNTHASE
RP COMPLEX, INTERACTION WITH KTI11, AND DISRUPTION PHENOTYPE.
RX PubMed=18627462; DOI=10.1111/j.1365-2958.2008.06350.x;
RA Baer C., Zabel R., Liu S., Stark M.J., Schaffrath R.;
RT "A versatile partner of eukaryotic protein complexes that is involved in
RT multiple biological processes: Kti11/Dph3.";
RL Mol. Microbiol. 69:1221-1233(2008).
RN [9]
RP IDENTIFICATION IN THE 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE SYNTHASE
RP COMPLEX, AND INTERACTION WITH DPH2 AND KTI11.
RX PubMed=23645155; DOI=10.3390/toxins5050958;
RA Abdel-Fattah W., Scheidt V., Uthman S., Stark M.J., Schaffrath R.;
RT "Insights into diphthamide, key diphtheria toxin effector.";
RL Toxins 5:958-968(2013).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND IDENTIFICATION IN THE
RP 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE SYNTHASE COMPLEX.
RX PubMed=24422557; DOI=10.1021/ja4118957;
RA Dong M., Su X., Dzikovski B., Dando E.E., Zhu X., Du J., Freed J.H.,
RA Lin H.;
RT "Dph3 is an electron donor for Dph1-Dph2 in the first step of eukaryotic
RT diphthamide biosynthesis.";
RL J. Am. Chem. Soc. 136:1754-1757(2014).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE
RP SYNTHASE COMPLEX, INTERACTION WITH KTI11, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=27694803; DOI=10.1038/nchembio.2190;
RA Lin Z., Dong M., Zhang Y., Lee E.A., Lin H.;
RT "Cbr1 is a Dph3 reductase required for the tRNA wobble uridine
RT modification.";
RL Nat. Chem. Biol. 12:995-997(2016).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, IDENTIFICATION IN THE
RP 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE SYNTHASE COMPLEX, INTERACTION WITH
RP DPH2, AND MUTAGENESIS OF CYS-133; CYS-239 AND CYS-368.
RX PubMed=31463593; DOI=10.1007/s00775-019-01702-0;
RA Dong M., Dando E.E., Kotliar I., Su X., Dzikovski B., Freed J.H., Lin H.;
RT "The asymmetric function of Dph1-Dph2 heterodimer in diphthamide
RT biosynthesis.";
RL J. Biol. Inorg. Chem. 24:777-782(2019).
RN [13]
RP FUNCTION.
RX PubMed=34154323; DOI=10.1021/jacs.1c03956;
RA Zhang Y., Su D., Dzikovski B., Majer S.H., Coleman R., Chandrasekaran S.,
RA Fenwick M.K., Crane B.R., Lancaster K.M., Freed J.H., Lin H.;
RT "Dph3 Enables Aerobic Diphthamide Biosynthesis by Donating One Iron Atom to
RT Transform a [3Fe-4S] to a [4Fe-4S] Cluster in Dph1-Dph2.";
RL J. Am. Chem. Soc. 143:9314-9319(2021).
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:24422557, PubMed:27694803,
CC PubMed:31463593, PubMed:34154323). In association with DPH2, transfers
CC a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine
CC (SAM) to a histidine residue, the reaction is assisted by a reduction
CC system comprising KTI11/DPH3 and a NADH-dependent reductase,
CC predominantly CBR1 (PubMed:15485916, PubMed:31463593, PubMed:34154323,
CC PubMed:24422557, PubMed:27694803). {ECO:0000269|PubMed:15485916,
CC ECO:0000269|PubMed:24422557, ECO:0000269|PubMed:27694803,
CC ECO:0000269|PubMed:31463593, ECO:0000269|PubMed:34154323}.
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:0000269|PubMed:24422557, ECO:0000305|PubMed:15485916,
CC ECO:0000305|PubMed:31463593};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:31463593, ECO:0000305|PubMed:24422557};
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:0000269|PubMed:31463593};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000305|PubMed:15485916}.
CC -!- SUBUNIT: Component of the 2-(3-amino-3-carboxypropyl)histidine synthase
CC complex composed of DPH1, DPH2, KTI11/DPH3 and a NADH-dependent
CC reductase, predominantly CBR1 (PubMed:15485916, PubMed:18627462,
CC PubMed:23645155, PubMed:24422557, PubMed:27694803, PubMed:31463593).
CC Interacts with DPH2; the interaction is direct (PubMed:15485916,
CC PubMed:23645155, PubMed:31463593). Interacts with KTI11/DPH3
CC (PubMed:12940988, PubMed:18627462, PubMed:23645155, PubMed:27694803).
CC {ECO:0000269|PubMed:12940988, ECO:0000269|PubMed:15485916,
CC ECO:0000269|PubMed:18627462, ECO:0000269|PubMed:23645155,
CC ECO:0000269|PubMed:24422557, ECO:0000269|PubMed:27694803,
CC ECO:0000269|PubMed:31463593}.
CC -!- INTERACTION:
CC P40487; P32461: DPH2; NbExp=3; IntAct=EBI-25162, EBI-6090;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- DISRUPTION PHENOTYPE: Increases translational -1 frameshifting
CC (PubMed:18627462). Abolishes the formation of the 2-(3-amino-3-
CC carboxypropyl)histidine synthase complex (PubMed:18627462). Resistance
CC to sordarin and zymocin (PubMed:18627462).
CC {ECO:0000269|PubMed:18627462}.
CC -!- MISCELLANEOUS: Present with 2526 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z38125; CAA86277.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08450.1; -; Genomic_DNA.
DR PIR; S48469; S48469.
DR RefSeq; NP_012163.1; NM_001179451.1.
DR AlphaFoldDB; P40487; -.
DR SMR; P40487; -.
DR BioGRID; 34888; 79.
DR DIP; DIP-5653N; -.
DR IntAct; P40487; 14.
DR MINT; P40487; -.
DR STRING; 4932.YIL103W; -.
DR iPTMnet; P40487; -.
DR MaxQB; P40487; -.
DR PaxDb; P40487; -.
DR PRIDE; P40487; -.
DR EnsemblFungi; YIL103W_mRNA; YIL103W; YIL103W.
DR GeneID; 854703; -.
DR KEGG; sce:YIL103W; -.
DR SGD; S000001365; DPH1.
DR VEuPathDB; FungiDB:YIL103W; -.
DR eggNOG; KOG2648; Eukaryota.
DR GeneTree; ENSGT00940000153694; -.
DR HOGENOM; CLU_037146_1_1_1; -.
DR InParanoid; P40487; -.
DR OMA; PGQVLGC; -.
DR BioCyc; MetaCyc:MON-15578; -.
DR BioCyc; YEAST:MON-15578; -.
DR Reactome; R-SCE-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR PRO; PR:P40487; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40487; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0090560; F:2-(3-amino-3-carboxypropyl)histidine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IDA: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 InterPro; IPR035435; DPH1/DPH2_euk_archaea.
DR PANTHER; PTHR10762; PTHR10762; 1.
DR Pfam; PF01866; Diphthamide_syn; 1.
DR PIRSF; PIRSF004967; DPH1; 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; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..425
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase
FT subunit 1"
FT /id="PRO_0000083381"
FT REGION 1..60
FT /note="Required for function but dispensable for
FT interaction with DPH2 and DPH3"
FT /evidence="ECO:0000269|PubMed:23645155"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..425
FT /note="Required for function but dispensable for
FT interaction with DPH2 and DPH3"
FT /evidence="ECO:0000269|PubMed:23645155"
FT BINDING 133
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT BINDING 239
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT BINDING 368
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:O58832"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT MUTAGEN 133
FT /note="C->A,S: Resistance to diphtheria toxin."
FT /evidence="ECO:0000269|PubMed:31463593"
FT MUTAGEN 239
FT /note="C->A,S: Resistance to diphtheria toxin. Abolishes
FT [4Fe-4S] cluster binding and catalytic activity; when
FT associated with S-368."
FT /evidence="ECO:0000269|PubMed:31463593"
FT MUTAGEN 368
FT /note="C->A,S: Resistance to diphtheria toxin. Abolishes
FT [4Fe-4S] cluster binding and catalytic activity; when
FT associated with S-239."
FT /evidence="ECO:0000269|PubMed:31463593"
SQ SEQUENCE 425 AA; 48311 MW; 22E93852E03C6722 CRC64;
MSGSTESKKQ PRRRFIGRKS GNSNNDKLTT VAENGNEIIH KQKSRIALGR SVNHVPEDIL
NDKELNEAIK LLPSNYNFEI HKTVWNIRKY NAKRIALQMP EGLLIYSLII SDILEQFCGV
ETLVMGDVSY GACCIDDFTA RALDCDFIVH YAHSCLVPID VTKIKVLYVF VTINIQEDHI
IKTLQKNFPK GSRIATFGTI QFNPAVHSVR DKLLNDEEHM LYIIPPQIKP LSRGEVLGCT
SERLDKEQYD AMVFIGDGRF HLESAMIHNP EIPAFKYDPY NRKFTREGYD QKQLVEVRAE
AIEVARKGKV FGLILGALGR QGNLNTVKNL EKNLIAAGKT VVKIILSEVF PQKLAMFDQI
DVFVQVACPR LSIDWGYAFN KPLLTPYEAS VLLKKDVMFS EKYYPMDYYE AKGYGRGETP
KHAIE
