DPH1_SCHPO
ID DPH1_SCHPO Reviewed; 436 AA.
AC O59713;
DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, 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: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; ORFNames=SPBC3B8.05;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=28775286; DOI=10.1038/s41598-017-07647-1;
RA Villahermosa D., Fleck O.;
RT "Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress
RT responses through tRNALysUUU modifications.";
RL Sci. Rep. 7:7225-7225(2017).
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 {ECO:0000250|UniProtKB:P40487}.
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 -!- DISRUPTION PHENOTYPE: Sensitive to methyl methanesulfonate (MMS, causes
CC DNA breaks) and hydroxyurea (HU, ribonucleotide reductase inhibitor).
CC {ECO:0000269|PubMed:28775286}.
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily.
CC {ECO:0000305}.
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DR EMBL; CU329671; CAA18294.1; -; Genomic_DNA.
DR PIR; T40335; T40335.
DR RefSeq; NP_596409.1; NM_001022328.2.
DR AlphaFoldDB; O59713; -.
DR SMR; O59713; -.
DR BioGRID; 276826; 14.
DR STRING; 4896.SPBC3B8.05.1; -.
DR MaxQB; O59713; -.
DR PaxDb; O59713; -.
DR EnsemblFungi; SPBC3B8.05.1; SPBC3B8.05.1:pep; SPBC3B8.05.
DR GeneID; 2540295; -.
DR KEGG; spo:SPBC3B8.05; -.
DR PomBase; SPBC3B8.05; dph1.
DR VEuPathDB; FungiDB:SPBC3B8.05; -.
DR eggNOG; KOG2648; Eukaryota.
DR HOGENOM; CLU_037146_1_1_1; -.
DR InParanoid; O59713; -.
DR OMA; PGQVLGC; -.
DR PhylomeDB; O59713; -.
DR Reactome; R-SPO-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR PRO; PR:O59713; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
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:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; ISS:UniProtKB.
DR GO; GO:2000765; P:regulation of cytoplasmic translation; IC:PomBase.
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 3: Inferred from homology;
KW Cytoplasm; Iron; Iron-sulfur; Metal-binding; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..436
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase
FT subunit 1"
FT /id="PRO_0000083378"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 417..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 130
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 436 AA; 48795 MW; 01A544115C69ACC4 CRC64;
MAEVKKSIPK RRFVGKKNRK ENNLDGSNRD VENAALVTIN SKRSAGRVAT QIPEDILNDK
AINEAIKLLP QNYNFEIHKT IWHIRLRKAK RVALQLPEGL LMFGCILSDI FEQFCQVETI
VMGDVTYGAC CIDDFTARAL DCDFLVHYGH SCLIPVDQTP IKVLYVFVDI KIDLQHVVSS
LKHNLPSNSR LALVGTIQFV GSLNSIKDAL QIQDEDGKGG FYVVIPQAKP LSPGEALGCT
SPYIEKGSVD ALIYIGDGRF HLESVMIANP DLPAYRYDPY SHKLSIESYA HEEMKSIRYS
AVEKARTAKK FGLIQGTLGR QGSPKVLENL KNTLRKNNKD FVCVLMSEIF PSRLGQFSDI
DAWIQVACPR LSIDWGYAFP APLLTPYEAS AAFNVVPWKE VYPMDFYATN SLGNWTPNNP
ENRPLPNRKK TGPVSS
