DPH2_MOUSE
ID DPH2_MOUSE Reviewed; 489 AA.
AC Q9CR25; Q8K0L8;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 {ECO:0000305};
DE AltName: Full=Diphthamide biosynthesis protein 2;
DE AltName: Full=Diphtheria toxin resistance protein 2 {ECO:0000305};
DE AltName: Full=MmDph2;
DE AltName: Full=S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase DPH2 {ECO:0000305};
GN Name=Dph2; Synonyms=Dph2l2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cecum, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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].
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 INTERACTION WITH DPH1.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Pancreas, 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 [7]
RP INTERACTION WITH DPH1.
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: Required for the first step of diphthamide biosynthesis, a
CC post-translational modification of histidine which occurs in elongation
CC factor 2 (PubMed:15485916). 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 Facilitates the reduction of the catalytic iron-sulfur cluster found in
CC the DPH1 subunit (By similarity). {ECO:0000250|UniProtKB:P32461,
CC ECO:0000269|PubMed:15485916}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P32461};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the
CC reduction of the catalytic iron-sulfur cluster in the DPH1 subunit.
CC {ECO:0000250|UniProtKB:P32461};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000305}.
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 DPH1 (PubMed:15485916, PubMed:21203470).
CC {ECO:0000250|UniProtKB:P32461, ECO:0000269|PubMed:15485916,
CC ECO:0000269|PubMed:21203470}.
CC -!- INTERACTION:
CC Q9CR25; Q5NCQ5: Dph1; NbExp=2; IntAct=EBI-1561134, EBI-1561119;
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. DPH2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AK011199; BAB27462.1; -; mRNA.
DR EMBL; AK018638; BAB31322.1; -; mRNA.
DR EMBL; AL627128; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC031124; AAH31124.1; -; mRNA.
DR CCDS; CCDS18541.1; -.
DR RefSeq; NP_080620.1; NM_026344.3.
DR AlphaFoldDB; Q9CR25; -.
DR SMR; Q9CR25; -.
DR IntAct; Q9CR25; 1.
DR STRING; 10090.ENSMUSP00000030265; -.
DR iPTMnet; Q9CR25; -.
DR PhosphoSitePlus; Q9CR25; -.
DR EPD; Q9CR25; -.
DR MaxQB; Q9CR25; -.
DR PaxDb; Q9CR25; -.
DR PeptideAtlas; Q9CR25; -.
DR PRIDE; Q9CR25; -.
DR ProteomicsDB; 279764; -.
DR Antibodypedia; 32411; 401 antibodies from 24 providers.
DR DNASU; 67728; -.
DR Ensembl; ENSMUST00000030265; ENSMUSP00000030265; ENSMUSG00000028540.
DR GeneID; 67728; -.
DR KEGG; mmu:67728; -.
DR UCSC; uc008ujd.1; mouse.
DR CTD; 1802; -.
DR MGI; MGI:1914978; Dph2.
DR VEuPathDB; HostDB:ENSMUSG00000028540; -.
DR eggNOG; KOG2648; Eukaryota.
DR GeneTree; ENSGT00940000153694; -.
DR HOGENOM; CLU_015210_0_0_1; -.
DR InParanoid; Q9CR25; -.
DR OMA; PFNNMYD; -.
DR OrthoDB; 750182at2759; -.
DR PhylomeDB; Q9CR25; -.
DR TreeFam; TF313832; -.
DR BRENDA; 2.5.1.108; 3474.
DR Reactome; R-MMU-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 67728; 19 hits in 73 CRISPR screens.
DR PRO; PR:Q9CR25; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9CR25; protein.
DR Bgee; ENSMUSG00000028540; Expressed in ear vesicle and 195 other tissues.
DR ExpressionAtlas; Q9CR25; baseline and differential.
DR Genevisible; Q9CR25; MM.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0090560; F:2-(3-amino-3-carboxypropyl)histidine synthase activity; ISO:MGI.
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 Gene3D; 3.40.50.11840; -; 1.
DR Gene3D; 3.40.50.11860; -; 1.
DR InterPro; IPR010014; DHP2.
DR InterPro; IPR016435; DPH1/DPH2.
DR InterPro; IPR042263; DPH1/DPH2_1.
DR InterPro; IPR042265; DPH1/DPH2_3.
DR PANTHER; PTHR10762; PTHR10762; 1.
DR PANTHER; PTHR10762:SF2; PTHR10762:SF2; 1.
DR Pfam; PF01866; Diphthamide_syn; 1.
DR SFLD; SFLDS00032; Radical_SAM_3-amino-3-carboxyp; 1.
DR TIGRFAMs; TIGR00322; diphth2_R; 1.
DR TIGRFAMs; TIGR00272; DPH2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Iron; Iron-sulfur; Metal-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..489
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase
FT subunit 2"
FT /id="PRO_0000307890"
FT BINDING 89
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P32461"
FT BINDING 110
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P32461"
FT BINDING 341
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P32461"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQC3"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQC3"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQC3"
FT MOD_RES 467
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQC3"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQC3"
FT CONFLICT 290
FT /note="T -> I (in Ref. 3; AAH31124)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 489 AA; 52365 MW; 2D94A8FEDE63DD39 CRC64;
MESTFSSPAE AALQREAGVP GQFTPPEDLD RVYELERVTK FVCDLGCQRV TLQFPDQLLG
DAGAVAARLE EVTGAKMFIL GDTAYGSCCV DVLGAEQAGA QALVHFGPAC LSPPASQLPI
TFVLGQRPVA LELCAKAFEA QNPDPTAPVV LLSEPACAHA LEPLAMLLLP KYQDLLISRP
ALPLPVGSPS SQPESLERFG RCFPLNPGRR LEEYGAFYVG ASQASSDSSL DPDLSRLLLG
WTPGRPFFSC CPDTGQTQDQ GAKAGRLRAR RLYLIERARD ARVVGLLAGT LGVARHREAL
AHLRKLTEAA GKRSYVLAVG KPTPAKLANF PEMDVFVLLA CPLGALAPQP SGGFFRPVLT
PCELEAACNP AWPPPGLAPH LTHYAELLPG SPFHVPLPPP ESELWDTPDV SLISGELRPP
PPWKSSDDTR CSALIPRPQL ELAESSPAAS FLSSRNWQGL EPRLGQTPVK EAVRGRRGIA
IAYEDEGSS
