DPH1_CRIGR
ID DPH1_CRIGR Reviewed; 438 AA.
AC A0A8C2MDK8; Q5KR93;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 {ECO:0000305};
DE EC=2.5.1.108 {ECO:0000250|UniProtKB:Q5NCQ5};
DE AltName: Full=Diphthamide biosynthesis protein 1 {ECO:0000305};
DE AltName: Full=Diphtheria toxin resistance protein 1 {ECO:0000305};
DE AltName: Full=Ovarian cancer-associated gene 1 protein homolog {ECO:0000305};
DE AltName: Full=S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 1 {ECO:0000305};
GN Name=DPH1 {ECO:0000250|UniProtKB:Q9BZG8};
GN Synonyms=OVCA1 {ECO:0000303|PubMed:15637051};
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-20, FUNCTION, AND PATHWAY.
RX PubMed=15637051; DOI=10.1074/jbc.m413017200;
RA Nobukuni Y., Kohno K., Miyagawa K.;
RT "Gene trap mutagenesis-based forward genetic approach reveals that the
RT tumor suppressor OVCA1 is a component of the biosynthetic pathway of
RT diphthamide on elongation factor 2.";
RL J. Biol. Chem. 280:10572-10577(2005).
RN [2]
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).
CC -!- FUNCTION: Catalyzes the first step of diphthamide biosynthesis, a post-
CC translational modification of histidine which occurs in elongation
CC factor 2 (PubMed:15637051). DPH1 and DPH2 transfer a 3-amino-3-
CC carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a
CC histidine residue, the reaction is assisted by a reduction system
CC comprising DPH3 and a NADH-dependent reductase (By similarity).
CC {ECO:0000250|UniProtKB:P40487, ECO:0000269|PubMed:15637051}.
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:Q5NCQ5};
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:0000305|PubMed:15637051}.
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:21203470). Interacts with
CC RBM8A (By similarity). {ECO:0000250|UniProtKB:P40487,
CC ECO:0000250|UniProtKB:Q9BZG8, ECO:0000269|PubMed:21203470}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5NCQ5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q5NCQ5}. Note=Punctate, primarily perinuclear
CC localization. {ECO:0000250|UniProtKB:Q5NCQ5}.
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH1 subfamily.
CC {ECO:0000305}.
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DR EMBL; AB194396; BAD86738.1; -; mRNA.
DR Ensembl; ENSCGRT00001022016.1; ENSCGRP00001017772.1; ENSCGRG00001017722.1.
DR GeneTree; ENSGT00940000153694; -.
DR UniPathway; UPA00559; -.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0090560; F:2-(3-amino-3-carboxypropyl)histidine synthase activity; IEA:InterPro.
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; 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 S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..438
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase
FT subunit 1"
FT /id="PRO_0000455975"
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:0000250|UniProtKB:Q5NCQ5"
SQ SEQUENCE 438 AA; 47771 MW; 7265D9E6DCA03B47 CRC64;
MAALVVSETA EPGSRVGPGR GRISRGRLAN QIPPEILNNP QLQAAVQALP SNYNFEIPKT
IWRIQQAQAK KVALQMPEGL LLFACTIVDI LERFTKAEVM VMGDVTYGAC CVDDFTARAL
GVDFLVHYGH SCLVPMDTSV QDFRVLYVFV DIRIDTAHLL DSVRLTFAPG SSLALVSTIQ
FVSTLQAAAQ ELKAEYHVSV PQCKPLSPGE ILGCTSPRLP KEVEAVVYLG DGRFHLESVM
IANPNVPAYR YDPYSKVLSR EHYDHQRMQA TRQEAIAAAR SAKTWGLILG TLGRQGSPKI
LEHLESRLKG LGLPFVRLLL SEIFPSKLSL LPMVDVWVQV ACPRLSIDWG SAFPKPLLTP
YEAAVALKDI SWQQPYPMDF YAGNSLGPWT VNHGRDPGPR GLGQPASGKV QQGFRGQSPA
PACEGCSCAD LKAALPAS
