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Protein

Diphthine--ammonia ligase

Gene

DPH6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Amidase that catalyzes the last step of diphthamide biosynthesis using ammonium and ATP. Diphthamide biosynthesis consists in the conversion of an L-histidine residue in the translation elongation factor (EEF2) to diphthamide (By similarity).By similarity1 Publication

Catalytic activityi

ATP + diphthine-[translation elongation factor 2] + NH3 = AMP + diphosphate + diphthamide-[translation elongation factor 2].

Pathwayi: peptidyl-diphthamide biosynthesis

This protein is involved in the pathway peptidyl-diphthamide biosynthesis, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway peptidyl-diphthamide biosynthesis and in Protein modification.

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • diphthine-ammonia ligase activity Source: UniProtKB

GO - Biological processi

  • cellular protein metabolic process Source: Reactome
  • peptidyl-diphthamide biosynthetic process from peptidyl-histidine Source: UniProtKB
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • post-translational protein modification Source: Reactome
  • regulation of protein stability Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-5358493. Synthesis of diphthamide-EEF2.
UniPathwayiUPA00559.

Names & Taxonomyi

Protein namesi
Recommended name:
Diphthine--ammonia ligase (EC:6.3.1.14)
Alternative name(s):
ATP-binding domain-containing protein 4
Diphthamide synthase
Diphthamide synthetase
Protein DPH6 homolog
Gene namesi
Name:DPH6
Synonyms:ATPBD4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:30543. DPH6.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142672572.

Polymorphism and mutation databases

BioMutaiDPH6.
DMDMi317373478.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 267267Diphthine--ammonia ligasePRO_0000282397Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei97 – 971PhosphotyrosineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ7L8W6.
MaxQBiQ7L8W6.
PaxDbiQ7L8W6.
PRIDEiQ7L8W6.

PTM databases

iPTMnetiQ7L8W6.
PhosphoSiteiQ7L8W6.

Expressioni

Gene expression databases

BgeeiQ7L8W6.
CleanExiHS_ATPBD4.
ExpressionAtlasiQ7L8W6. baseline and differential.
GenevisibleiQ7L8W6. HS.

Organism-specific databases

HPAiHPA042976.

Interactioni

Protein-protein interaction databases

BioGridi124651. 9 interactions.
STRINGi9606.ENSP00000256538.

Structurei

3D structure databases

ProteinModelPortaliQ7L8W6.
SMRiQ7L8W6. Positions 3-251.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Diphthine--ammonia ligase family.Curated

Phylogenomic databases

eggNOGiKOG2316. Eukaryota.
COG2102. LUCA.
GeneTreeiENSGT00420000029820.
HOGENOMiHOG000229449.
HOVERGENiHBG100452.
InParanoidiQ7L8W6.
KOiK06927.
OMAiYGLGKEW.
OrthoDBiEOG77127Q.
PhylomeDBiQ7L8W6.
TreeFamiTF313566.

Family and domain databases

Gene3Di3.40.50.620. 1 hit.
InterProiIPR002761. Diphthami_syn_dom.
IPR030662. DPH6/MJ0570.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERiPTHR12196. PTHR12196. 1 hit.
PfamiPF01902. Diphthami_syn_2. 1 hit.
[Graphical view]
PIRSFiPIRSF039123. Diphthamide_synthase. 1 hit.
TIGRFAMsiTIGR00290. MJ0570_dom. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7L8W6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRVAALISGG KDSCYNMMQC IAAGHQIVAL ANLRPAENQV GSDELDSYMY
60 70 80 90 100
QTVGHHAIDL YAEAMALPLY RRTIRGRSLD TRQVYTKCEG DEVEDLYELL
110 120 130 140 150
KLVKEKEEVE GISVGAILSD YQRIRVENVC KRLNLQPLAY LWQRNQEDLL
160 170 180 190 200
REMISSNIQA MIIKVAALGL DPDKHLGKTL DQMEPYLIEL SKKYGVHVCG
210 220 230 240 250
EGGEYETFTL DCPLFKKKII VDSSEVVIHS ADAFAPVAYL RFLELHLEDK
260
VSSVPDNYRT SNYIYNF
Length:267
Mass (Da):30,307
Last modified:January 11, 2011 - v3
Checksum:i16BB1094F4D3513D
GO
Isoform 2 (identifier: Q7L8W6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     105-267: EKEEVEGISV...YRTSNYIYNF → GITRMTLLAE...FISEIAKCEV

Note: No experimental confirmation available.
Show »
Length:165
Mass (Da):18,657
Checksum:i14398C0D0ABC39AE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411G → E.
Corresponds to variant rs34907758 [ dbSNP | Ensembl ].
VAR_031403
Natural varianti236 – 2361P → R.
Corresponds to variant rs10519996 [ dbSNP | Ensembl ].
VAR_031404

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei105 – 267163EKEEV…YIYNF → GITRMTLLAEYDALNLQDFH MHLKVGSQAIVYRTPNELCT HSKFDKHTFPPFISEIAKCE V in isoform 2. 1 PublicationVSP_042933Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK094007 mRNA. Translation: BAC04266.1.
AK125017 mRNA. Translation: BAG54123.1.
AC015994 Genomic DNA. No translation available.
AC019288 Genomic DNA. No translation available.
BC008485 mRNA. Translation: AAH08485.2.
BC066652 mRNA. Translation: AAH66652.1.
CCDSiCCDS10043.1. [Q7L8W6-1]
CCDS45213.1. [Q7L8W6-2]
RefSeqiNP_001135444.1. NM_001141972.1. [Q7L8W6-2]
NP_542381.1. NM_080650.3. [Q7L8W6-1]
UniGeneiHs.107196.

Genome annotation databases

EnsembliENST00000256538; ENSP00000256538; ENSG00000134146. [Q7L8W6-1]
ENST00000440392; ENSP00000406976; ENSG00000134146. [Q7L8W6-2]
GeneIDi89978.
KEGGihsa:89978.
UCSCiuc001zja.4. human. [Q7L8W6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK094007 mRNA. Translation: BAC04266.1.
AK125017 mRNA. Translation: BAG54123.1.
AC015994 Genomic DNA. No translation available.
AC019288 Genomic DNA. No translation available.
BC008485 mRNA. Translation: AAH08485.2.
BC066652 mRNA. Translation: AAH66652.1.
CCDSiCCDS10043.1. [Q7L8W6-1]
CCDS45213.1. [Q7L8W6-2]
RefSeqiNP_001135444.1. NM_001141972.1. [Q7L8W6-2]
NP_542381.1. NM_080650.3. [Q7L8W6-1]
UniGeneiHs.107196.

3D structure databases

ProteinModelPortaliQ7L8W6.
SMRiQ7L8W6. Positions 3-251.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124651. 9 interactions.
STRINGi9606.ENSP00000256538.

PTM databases

iPTMnetiQ7L8W6.
PhosphoSiteiQ7L8W6.

Polymorphism and mutation databases

BioMutaiDPH6.
DMDMi317373478.

Proteomic databases

EPDiQ7L8W6.
MaxQBiQ7L8W6.
PaxDbiQ7L8W6.
PRIDEiQ7L8W6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000256538; ENSP00000256538; ENSG00000134146. [Q7L8W6-1]
ENST00000440392; ENSP00000406976; ENSG00000134146. [Q7L8W6-2]
GeneIDi89978.
KEGGihsa:89978.
UCSCiuc001zja.4. human. [Q7L8W6-1]

Organism-specific databases

CTDi89978.
GeneCardsiDPH6.
HGNCiHGNC:30543. DPH6.
HPAiHPA042976.
neXtProtiNX_Q7L8W6.
PharmGKBiPA142672572.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2316. Eukaryota.
COG2102. LUCA.
GeneTreeiENSGT00420000029820.
HOGENOMiHOG000229449.
HOVERGENiHBG100452.
InParanoidiQ7L8W6.
KOiK06927.
OMAiYGLGKEW.
OrthoDBiEOG77127Q.
PhylomeDBiQ7L8W6.
TreeFamiTF313566.

Enzyme and pathway databases

UniPathwayiUPA00559.
ReactomeiR-HSA-5358493. Synthesis of diphthamide-EEF2.

Miscellaneous databases

GenomeRNAii89978.
NextBioi76470.
PROiQ7L8W6.

Gene expression databases

BgeeiQ7L8W6.
CleanExiHS_ATPBD4.
ExpressionAtlasiQ7L8W6. baseline and differential.
GenevisibleiQ7L8W6. HS.

Family and domain databases

Gene3Di3.40.50.620. 1 hit.
InterProiIPR002761. Diphthami_syn_dom.
IPR030662. DPH6/MJ0570.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERiPTHR12196. PTHR12196. 1 hit.
PfamiPF01902. Diphthami_syn_2. 1 hit.
[Graphical view]
PIRSFiPIRSF039123. Diphthamide_synthase. 1 hit.
TIGRFAMsiTIGR00290. MJ0570_dom. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Thalamus and Uterus.
  2. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Bone marrow and Skin.
  4. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. "Chemogenomic approach identified yeast YLR143W as diphthamide synthetase."
    Su X., Lin Z., Chen W., Jiang H., Zhang S., Lin H.
    Proc. Natl. Acad. Sci. U.S.A. 109:19983-19987(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiDPH6_HUMAN
AccessioniPrimary (citable) accession number: Q7L8W6
Secondary accession number(s): B3KWG1, Q96HJ6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: January 11, 2011
Last modified: March 16, 2016
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

When transfected in S.cerevisiae, able to restore diphthamide biosynthesis in a strain lacking DPH6.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.