ID DPH7_HUMAN Reviewed; 452 AA.
AC Q9BTV6; Q96AB7;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 27-MAR-2024, entry version 162.
DE RecName: Full=Diphthine methyltransferase;
DE EC=3.1.1.97;
DE AltName: Full=Diphthamide biosynthesis protein 7;
DE AltName: Full=WD repeat-containing protein 85;
GN Name=DPH7; Synonyms=C9orf112, WDR85;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Skin;
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.
RX PubMed=19965467; DOI=10.1126/science.1178955;
RA Carette J.E., Guimaraes C.P., Varadarajan M., Park A.S., Wuethrich I.,
RA Godarova A., Kotecki M., Cochran B.H., Spooner E., Ploegh H.L.,
RA Brummelkamp T.R.;
RT "Haploid genetic screens in human cells identify host factors used by
RT pathogens.";
RL Science 326:1231-1235(2009).
RN [5]
RP FUNCTION IN DIPHTHAMIDE BIOSYNTHESIS.
RX PubMed=23486472; DOI=10.1074/jbc.m113.461343;
RA Wei H., Bera T.K., Wayne A.S., Xiang L., Colantonio S., Chertov O.,
RA Pastan I.;
RT "A modified form of diphthamide causes immunotoxin resistance in a lymphoma
RT cell line with a deletion of the WDR85 gene.";
RL J. Biol. Chem. 288:12305-12312(2013).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-353, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP INTERACTION WITH INCA1.
RX PubMed=21750715; DOI=10.1371/journal.pone.0021505;
RA Zhang F., Baeumer N., Rode M., Ji P., Zhang T., Berdel W.E.,
RA Mueller-Tidow C.;
RT "The inhibitor of growth protein 5 (ING5) depends on INCA1 as a co-factor
RT for its antiproliferative effects.";
RL PLoS ONE 6:E21505-E21505(2011).
CC -!- FUNCTION: Catalyzes the demethylation of diphthine methyl ester to form
CC diphthine, an intermediate diphthamide biosynthesis, a post-
CC translational modification of histidine which occurs in translation
CC elongation factor 2 (EEF2) which can be ADP-ribosylated by diphtheria
CC toxin and by Pseudomonas exotoxin A (Eta).
CC {ECO:0000250|UniProtKB:P38332, ECO:0000269|PubMed:19965467,
CC ECO:0000269|PubMed:23486472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphthine methyl ester-[translation elongation factor 2] + H2O
CC = diphthine-[translation elongation factor 2] + H(+) + methanol;
CC Xref=Rhea:RHEA:42656, Rhea:RHEA-COMP:10172, Rhea:RHEA-COMP:10173,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17790,
CC ChEBI:CHEBI:79005, ChEBI:CHEBI:82696; EC=3.1.1.97;
CC Evidence={ECO:0000250|UniProtKB:P38332};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC -!- SUBUNIT: Interacts with INCA1. {ECO:0000269|PubMed:21750715}.
CC -!- INTERACTION:
CC Q9BTV6; Q0VD86: INCA1; NbExp=2; IntAct=EBI-11059920, EBI-6509505;
CC -!- SIMILARITY: Belongs to the DPH7 family. {ECO:0000305}.
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DR EMBL; AK075115; BAC11411.1; -; mRNA.
DR EMBL; AL365502; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003123; AAH03123.2; -; mRNA.
DR EMBL; BC017335; AAH17335.1; -; mRNA.
DR CCDS; CCDS7047.1; -.
DR RefSeq; NP_620133.1; NM_138778.4.
DR AlphaFoldDB; Q9BTV6; -.
DR SMR; Q9BTV6; -.
DR BioGRID; 124971; 22.
DR IntAct; Q9BTV6; 11.
DR STRING; 9606.ENSP00000277540; -.
DR GlyGen; Q9BTV6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BTV6; -.
DR PhosphoSitePlus; Q9BTV6; -.
DR BioMuta; DPH7; -.
DR DMDM; 68565266; -.
DR EPD; Q9BTV6; -.
DR jPOST; Q9BTV6; -.
DR MassIVE; Q9BTV6; -.
DR MaxQB; Q9BTV6; -.
DR PaxDb; 9606-ENSP00000277540; -.
DR PeptideAtlas; Q9BTV6; -.
DR ProteomicsDB; 79014; -.
DR Pumba; Q9BTV6; -.
DR Antibodypedia; 19075; 119 antibodies from 19 providers.
DR DNASU; 92715; -.
DR Ensembl; ENST00000277540.7; ENSP00000277540.2; ENSG00000148399.13.
DR GeneID; 92715; -.
DR KEGG; hsa:92715; -.
DR MANE-Select; ENST00000277540.7; ENSP00000277540.2; NM_138778.5; NP_620133.1.
DR UCSC; uc004cnk.1; human.
DR AGR; HGNC:25199; -.
DR CTD; 92715; -.
DR DisGeNET; 92715; -.
DR GeneCards; DPH7; -.
DR HGNC; HGNC:25199; DPH7.
DR HPA; ENSG00000148399; Low tissue specificity.
DR MIM; 613210; gene.
DR neXtProt; NX_Q9BTV6; -.
DR OpenTargets; ENSG00000148399; -.
DR PharmGKB; PA134942088; -.
DR VEuPathDB; HostDB:ENSG00000148399; -.
DR eggNOG; KOG0280; Eukaryota.
DR GeneTree; ENSGT00390000018644; -.
DR HOGENOM; CLU_036100_2_1_1; -.
DR InParanoid; Q9BTV6; -.
DR OMA; LDMKWLP; -.
DR OrthoDB; 102275at2759; -.
DR PhylomeDB; Q9BTV6; -.
DR TreeFam; TF324407; -.
DR BRENDA; 3.1.1.97; 2681.
DR PathwayCommons; Q9BTV6; -.
DR Reactome; R-HSA-5358493; Synthesis of diphthamide-EEF2.
DR SignaLink; Q9BTV6; -.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 92715; 32 hits in 1145 CRISPR screens.
DR ChiTaRS; DPH7; human.
DR GenomeRNAi; 92715; -.
DR Pharos; Q9BTV6; Tbio.
DR PRO; PR:Q9BTV6; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9BTV6; Protein.
DR Bgee; ENSG00000148399; Expressed in right uterine tube and 143 other cell types or tissues.
DR Genevisible; Q9BTV6; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0061685; F:diphthine methylesterase activity; IBA:GO_Central.
DR GO; GO:0017183; P:protein histidyl modification to diphthamide; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001680; WD40_rpt.
DR PANTHER; PTHR46042; DIPHTHINE METHYLTRANSFERASE; 1.
DR PANTHER; PTHR46042:SF1; DIPHTHINE METHYLTRANSFERASE; 1.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; WD40 repeat-like; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Phosphoprotein; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..452
FT /note="Diphthine methyltransferase"
FT /id="PRO_0000050906"
FT REPEAT 79..130
FT /note="WD 1"
FT REPEAT 131..185
FT /note="WD 2"
FT REPEAT 186..229
FT /note="WD 3"
FT REPEAT 230..273
FT /note="WD 4"
FT REPEAT 274..313
FT /note="WD 5"
FT REPEAT 314..403
FT /note="WD 6"
FT REPEAT 404..448
FT /note="WD 7"
FT REGION 371..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..390
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 158
FT /note="G -> R (in dbSNP:rs821314)"
FT /id="VAR_053437"
SQ SEQUENCE 452 AA; 50575 MW; B79D25EE38096733 CRC64;
MMGCFALQTV DTELTADSVE WCPLQGCRHL LACGTYQLRR PEDRPAGPQN KGGMEVKEPQ
VRLGRLFLYS FNDNNSIHPL VEVQRKDTSA ILDMKWCHIP VAGHALLGLA DASGSIQLLR
LVESEKSHVL EPLSSLALEE QCLALSLDWS TGKTGRAGDQ PLKIISSDST GQLHLLMVNE
TRPRLQKVAS WQAHQFEAWI AAFNYWHPEI VYSGGDDGLL RGWDTRVPGK FLFTSKRHTM
GVCSIQSSPH REHILATGSY DEHILLWDTR NMKQPLADTP VQGGVWRIKW HPFHHHLLLA
ACMHSGFKIL NCQKAMEERQ EATVLTSHTL PDSLVYGADW SWLLFRSLQR APSWSFPSNL
GTKTADLKGA SELPTPCHEC REDNDGEGHA RPQSGMKPLT EGMRKNGTWL QATAATTRDC
GVNPEEADSA FSLLATCSFY DHALHLWEWE GN
//
