ID DPH1_EREGS Reviewed; 426 AA. AC Q75AZ9; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 08-NOV-2023, entry version 96. DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 {ECO:0000305}; DE EC=2.5.1.108 {ECO:0000250|UniProtKB:P40487}; 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=ADL229W; OS Eremothecium gossypii (strain ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL OS Y-1056) (Yeast) (Ashbya gossypii). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Eremothecium. OX NCBI_TaxID=284811; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056; RX PubMed=15001715; DOI=10.1126/science.1095781; RA Dietrich F.S., Voegeli S., Brachat S., Lerch A., Gates K., Steiner S., RA Mohr C., Poehlmann R., Luedi P., Choi S., Wing R.A., Flavier A., RA Gaffney T.D., Philippsen P.; RT "The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces RT cerevisiae genome."; RL Science 304:304-307(2004). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 10895 / CBS 109.51 / FGSC 9923 / NRRL Y-1056; RX PubMed=23749448; DOI=10.1534/g3.112.002881; RA Dietrich F.S., Voegeli S., Kuo S., Philippsen P.; RT "Genomes of Ashbya fungi isolated from insects reveal four mating-type RT loci, numerous translocations, lack of transposons, and distinct gene RT duplications."; RL G3 (Bethesda) 3:1225-1239(2013). CC -!- FUNCTION: Catalyzes the first step of diphthamide biosynthesis, a post- CC 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, predominantly CBR1. {ECO:0000250|UniProtKB:P40487}. 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:0000250|UniProtKB:P40487}; 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, CC predominantly CBR1. {ECO:0000250|UniProtKB:P40487}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P40487}. CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE016817; AAS51691.1; -; Genomic_DNA. DR RefSeq; NP_983867.1; NM_209220.1. DR AlphaFoldDB; Q75AZ9; -. DR SMR; Q75AZ9; -. DR STRING; 33169.AAS51691; -. DR EnsemblFungi; AAS51691; AAS51691; AGOS_ADL229W. DR GeneID; 4620002; -. DR KEGG; ago:AGOS_ADL229W; -. DR eggNOG; KOG2648; Eukaryota. DR HOGENOM; CLU_037146_1_1_1; -. DR InParanoid; Q75AZ9; -. DR OMA; PGQVLGC; -. DR OrthoDB; 5472575at2759; -. DR UniPathway; UPA00559; -. DR Proteomes; UP000000591; Chromosome IV. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0032991; C:protein-containing complex; ISS: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; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0017183; P:protein histidyl modification to diphthamide; ISS:UniProtKB. DR Gene3D; 3.40.50.11840; Diphthamide synthesis DPH1/DPH2 domain 1; 1. DR Gene3D; 3.40.50.11850; Diphthamide synthesis DPH1/DPH2 domain 2; 1. DR Gene3D; 3.40.50.11860; Diphthamide synthesis DPH1/DPH2 domain 3; 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 NCBIfam; TIGR00322; diphth2_R; 1. DR PANTHER; PTHR10762:SF1; 2-(3-AMINO-3-CARBOXYPROPYL)HISTIDINE SYNTHASE SUBUNIT 1; 1. DR PANTHER; PTHR10762; DIPHTHAMIDE BIOSYNTHESIS PROTEIN; 1. DR Pfam; PF01866; Diphthamide_syn; 1. DR PIRSF; PIRSF004967; DPH1; 1. DR SFLD; SFLDG01121; Diphthamide_biosynthesis; 1. DR SFLD; SFLDS00032; Radical_SAM_3-amino-3-carboxyp; 1. PE 3: Inferred from homology; KW Cytoplasm; Iron; Iron-sulfur; Metal-binding; Reference proteome; KW S-adenosyl-L-methionine; Transferase. FT CHAIN 1..426 FT /note="2-(3-amino-3-carboxypropyl)histidine synthase FT subunit 1" FT /id="PRO_0000083367" 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" SQ SEQUENCE 426 AA; 48184 MW; F080D8449B600DDD CRC64; MSTADEVTKK PRRRFVGVSR GENKVSTKQV SGDEAKELVR SAKSNTGARR AINQIPDEIL NDENLQEAIK LLPSNYNFEI HKTVWNIRKH NAKRVALQMP EGLLIYSLVI SDILEQFCNC ETVVMGDVSY GACCIDDFTA RALGCDFIVH YAHSCLVPVD VTSIKILYVF VTIGIDEDHL MKTLQKNFAK GTSLAVFGTI QFNPAIHSIR EKLLYSESHM LYITPPQIKP LSKGEVLGCT SQRLPKEQFA AMVYVGDGRF HLESAMIHNP DIPAFRYDPY SRKFTRETYD QHQLVEVRSS AIEKARNSQC FGLILGALGR QGNLATVANL EKKLRAAGKK VVRIILSEIF PQKLAMFDHI DAFVQVACPR LSIDWGYAFN KPLLTPYETN VMLGQDRMFN EKYYPMDYYE VNGYGRGKQP THDNVI //