DPH6_HUMAN
ID DPH6_HUMAN Reviewed; 267 AA.
AC Q7L8W6; B3KWG1; Q96HJ6;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Diphthine--ammonia ligase {ECO:0000305};
DE EC=6.3.1.14 {ECO:0000305|PubMed:23169644};
DE AltName: Full=ATP-binding domain-containing protein 4;
DE AltName: Full=Diphthamide synthase;
DE AltName: Full=Diphthamide synthetase;
DE AltName: Full=Protein DPH6 homolog;
GN Name=DPH6 {ECO:0000312|HGNC:HGNC:30543}; Synonyms=ATPBD4;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Thalamus, and Uterus;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow, 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23169644; DOI=10.1073/pnas.1214346109;
RA Su X., Lin Z., Chen W., Jiang H., Zhang S., Lin H.;
RT "Chemogenomic approach identified yeast YLR143W as diphthamide
RT synthetase.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19983-19987(2012).
CC -!- FUNCTION: Amidase that may catalyze the last step of diphthamide
CC biosynthesis using ammonium and ATP (PubMed:23169644). Diphthamide
CC biosynthesis consists in the conversion of an L-histidine residue in
CC the translation elongation factor (EEF2) to diphthamide (By
CC similarity). {ECO:0000250|UniProtKB:Q12429,
CC ECO:0000269|PubMed:23169644}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + diphthine-[translation elongation factor 2] + NH4(+) =
CC AMP + diphosphate + diphthamide-[translation elongation factor 2] +
CC H(+); Xref=Rhea:RHEA:19753, Rhea:RHEA-COMP:10172, Rhea:RHEA-
CC COMP:10174, ChEBI:CHEBI:15378, ChEBI:CHEBI:16692, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:82696,
CC ChEBI:CHEBI:456215; EC=6.3.1.14;
CC Evidence={ECO:0000305|PubMed:23169644};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7L8W6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7L8W6-2; Sequence=VSP_042933;
CC -!- MISCELLANEOUS: When transfected in S.cerevisiae, able to restore
CC diphthamide biosynthesis in a strain lacking DPH6.
CC {ECO:0000305|PubMed:23169644}.
CC -!- SIMILARITY: Belongs to the Diphthine--ammonia ligase family.
CC {ECO:0000305}.
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DR EMBL; AK094007; BAC04266.1; -; mRNA.
DR EMBL; AK125017; BAG54123.1; -; mRNA.
DR EMBL; AC015994; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008485; AAH08485.2; -; mRNA.
DR EMBL; BC066652; AAH66652.1; -; mRNA.
DR CCDS; CCDS10043.1; -. [Q7L8W6-1]
DR CCDS; CCDS45213.1; -. [Q7L8W6-2]
DR RefSeq; NP_001135444.1; NM_001141972.1. [Q7L8W6-2]
DR RefSeq; NP_542381.1; NM_080650.3. [Q7L8W6-1]
DR AlphaFoldDB; Q7L8W6; -.
DR SMR; Q7L8W6; -.
DR BioGRID; 124651; 23.
DR IntAct; Q7L8W6; 10.
DR STRING; 9606.ENSP00000256538; -.
DR GlyGen; Q7L8W6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7L8W6; -.
DR PhosphoSitePlus; Q7L8W6; -.
DR BioMuta; DPH6; -.
DR DMDM; 317373478; -.
DR EPD; Q7L8W6; -.
DR jPOST; Q7L8W6; -.
DR MassIVE; Q7L8W6; -.
DR MaxQB; Q7L8W6; -.
DR PaxDb; Q7L8W6; -.
DR PeptideAtlas; Q7L8W6; -.
DR PRIDE; Q7L8W6; -.
DR ProteomicsDB; 68840; -. [Q7L8W6-1]
DR ProteomicsDB; 68841; -. [Q7L8W6-2]
DR Antibodypedia; 51931; 59 antibodies from 16 providers.
DR DNASU; 89978; -.
DR Ensembl; ENST00000256538.9; ENSP00000256538.4; ENSG00000134146.12. [Q7L8W6-1]
DR Ensembl; ENST00000440392.3; ENSP00000406976.2; ENSG00000134146.12. [Q7L8W6-2]
DR GeneID; 89978; -.
DR KEGG; hsa:89978; -.
DR MANE-Select; ENST00000256538.9; ENSP00000256538.4; NM_080650.4; NP_542381.1.
DR UCSC; uc001zja.4; human. [Q7L8W6-1]
DR CTD; 89978; -.
DR DisGeNET; 89978; -.
DR GeneCards; DPH6; -.
DR HGNC; HGNC:30543; DPH6.
DR HPA; ENSG00000134146; Low tissue specificity.
DR MIM; 618391; gene.
DR neXtProt; NX_Q7L8W6; -.
DR OpenTargets; ENSG00000134146; -.
DR PharmGKB; PA142672572; -.
DR VEuPathDB; HostDB:ENSG00000134146; -.
DR eggNOG; KOG2316; Eukaryota.
DR GeneTree; ENSGT00420000029820; -.
DR HOGENOM; CLU_010289_0_1_1; -.
DR InParanoid; Q7L8W6; -.
DR OMA; NYALYWA; -.
DR OrthoDB; 1362375at2759; -.
DR PhylomeDB; Q7L8W6; -.
DR TreeFam; TF313566; -.
DR PathwayCommons; Q7L8W6; -.
DR Reactome; R-HSA-5358493; Synthesis of diphthamide-EEF2.
DR SignaLink; Q7L8W6; -.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 89978; 290 hits in 1047 CRISPR screens.
DR ChiTaRS; DPH6; human.
DR GenomeRNAi; 89978; -.
DR Pharos; Q7L8W6; Tbio.
DR PRO; PR:Q7L8W6; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q7L8W6; protein.
DR Bgee; ENSG00000134146; Expressed in calcaneal tendon and 139 other tissues.
DR ExpressionAtlas; Q7L8W6; baseline and differential.
DR Genevisible; Q7L8W6; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017178; F:diphthine-ammonia ligase activity; EXP:Reactome.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IBA:GO_Central.
DR CDD; cd01994; Alpha_ANH_like_IV; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR002761; Diphthami_syn_dom.
DR InterPro; IPR030662; DPH6/MJ0570.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR12196; PTHR12196; 1.
DR Pfam; PF01902; Diphthami_syn_2; 1.
DR PIRSF; PIRSF039123; Diphthamide_synthase; 1.
DR TIGRFAMs; TIGR00290; MJ0570_dom; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Ligase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..267
FT /note="Diphthine--ammonia ligase"
FT /id="PRO_0000282397"
FT MOD_RES 97
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9CQ28"
FT VAR_SEQ 105..267
FT /note="EKEEVEGISVGAILSDYQRIRVENVCKRLNLQPLAYLWQRNQEDLLREMISS
FT NIQAMIIKVAALGLDPDKHLGKTLDQMEPYLIELSKKYGVHVCGEGGEYETFTLDCPLF
FT KKKIIVDSSEVVIHSADAFAPVAYLRFLELHLEDKVSSVPDNYRTSNYIYNF -> GIT
FT RMTLLAEYDALNLQDFHMHLKVGSQAIVYRTPNELCTHSKFDKHTFPPFISEIAKCEV
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042933"
FT VARIANT 41
FT /note="G -> E (in dbSNP:rs34907758)"
FT /id="VAR_031403"
FT VARIANT 236
FT /note="P -> R (in dbSNP:rs10519996)"
FT /id="VAR_031404"
SQ SEQUENCE 267 AA; 30307 MW; 16BB1094F4D3513D CRC64;
MRVAALISGG KDSCYNMMQC IAAGHQIVAL ANLRPAENQV GSDELDSYMY QTVGHHAIDL
YAEAMALPLY RRTIRGRSLD TRQVYTKCEG DEVEDLYELL KLVKEKEEVE GISVGAILSD
YQRIRVENVC KRLNLQPLAY LWQRNQEDLL REMISSNIQA MIIKVAALGL DPDKHLGKTL
DQMEPYLIEL SKKYGVHVCG EGGEYETFTL DCPLFKKKII VDSSEVVIHS ADAFAPVAYL
RFLELHLEDK VSSVPDNYRT SNYIYNF
