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Protein

2-(3-amino-3-carboxypropyl)histidine synthase subunit 1

Gene

DPH1

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

Functioni

Required for the first step in the synthesis of diphthamide, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2). When overexpressed, suppresses colony formation ability and growth rate of ovarian cancer cells. Acts also as a tumor suppressor in lung and breast cancers (By similarity). Plays a role in embryonic growth, organogenesis and postnatal survival (By similarity).By similarity1 Publication

Caution

It is uncertain whether Met-1 or Met-6 is the initiator.Curated

Catalytic activityi

L-histidine-[translation elongation factor 2] + S-adenosyl-L-methionine = 2-((3S)-3-amino-3-carboxypropyl)-L-histidine-[translation elongation factor 2] + S-methyl-5'-thioadenosine.By similarity

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

GO - Biological processi

Keywordsi

Molecular functionTransferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-HSA-5358493 Synthesis of diphthamide-EEF2
UniPathwayiUPA00559

Names & Taxonomyi

Protein namesi
Recommended name:
2-(3-amino-3-carboxypropyl)histidine synthase subunit 1Curated (EC:2.5.1.108By similarity)
Alternative name(s):
Diphthamide biosynthesis protein 1
Diphtheria toxin resistance protein 1Curated
Ovarian cancer-associated gene 1 protein
S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 1Curated
Gene namesi
Name:DPH1
Synonyms:DPH2L, DPH2L1, OVCA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108963.17
HGNCiHGNC:3003 DPH1
MIMi603527 gene
neXtProtiNX_Q9BZG8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Developmental delay with short stature, dysmorphic features, and sparse hair (DEDSSH)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive syndrome characterized by intellectual disability, short stature, and craniofacial and ectodermal anomalies including scaphocephaly with or without craniosynostosis, prominent forehead, sparse eyebrows and hair, hypoplastic toenails and, in some cases, dental anomalies.
See also OMIM:616901
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0764126M → K in DEDSSH. 1 PublicationCorresponds to variant dbSNP:rs757167361EnsemblClinVar.1
Natural variantiVAR_076413234L → P in DEDSSH. 1 PublicationCorresponds to variant dbSNP:rs730882250EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dwarfism, Ectodermal dysplasia, Hypotrichosis, Mental retardation, Tumor suppressor

Organism-specific databases

DisGeNETi1801
MalaCardsiDPH1
MIMi616901 phenotype
OpenTargetsiENSG00000108963
PharmGKBiPA27461

Polymorphism and mutation databases

BioMutaiDPH1
DMDMi269849559

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003078821 – 4432-(3-amino-3-carboxypropyl)histidine synthase subunit 1Add BLAST443

Proteomic databases

EPDiQ9BZG8
MaxQBiQ9BZG8
PaxDbiQ9BZG8
PeptideAtlasiQ9BZG8
PRIDEiQ9BZG8

PTM databases

iPTMnetiQ9BZG8
PhosphoSitePlusiQ9BZG8

Expressioni

Tissue specificityi

Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, mammary gland, colon, small intestine, testis and ovary. Reduced expression in primary breast and ovarian tumors.2 Publications

Gene expression databases

BgeeiENSG00000108963
CleanExiHS_DPH1
ExpressionAtlasiQ9BZG8 baseline and differential
GenevisibleiQ9BZG8 HS

Organism-specific databases

HPAiHPA069750

Interactioni

Subunit structurei

Interacts with DPH2 (By similarity). Interacts with RBM8A.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TFCP2Q128003EBI-10303200,EBI-717422

Protein-protein interaction databases

BioGridi108135, 41 interactors
IntActiQ9BZG8, 2 interactors
STRINGi9606.ENSP00000263083

Structurei

3D structure databases

ProteinModelPortaliQ9BZG8
SMRiQ9BZG8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the DPH1/DPH2 family. DPH1 subfamily.Curated

Phylogenomic databases

eggNOGiKOG2648 Eukaryota
COG1736 LUCA
GeneTreeiENSGT00550000075112
HOGENOMiHOG000164743
HOVERGENiHBG107822
InParanoidiQ9BZG8
KOiK07561
OMAiPGQVLGC
OrthoDBiEOG091G08DQ
PhylomeDBiQ9BZG8
TreeFamiTF105746

Family and domain databases

InterProiView protein in InterPro
IPR016435 DPH1/DPH2
IPR035435 DPH1/DPH2_euk_archaea
PANTHERiPTHR10762 PTHR10762, 1 hit
PfamiView protein in Pfam
PF01866 Diphthamide_syn, 1 hit
PIRSFiPIRSF004967 DPH1, 1 hit
SFLDiSFLDS00032 Radical_SAM_3-amino-3-carboxyp, 1 hit
TIGRFAMsiTIGR00322 diphth2_R, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BZG8-1) [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
MRRQVMAALV VSGAAEQGGR DGPGRGRAPR GRVANQIPPE ILKNPQLQAA
60 70 80 90 100
IRVLPSNYNF EIPKTIWRIQ QAQAKKVALQ MPEGLLLFAC TIVDILERFT
110 120 130 140 150
EAEVMVMGDV TYGACCVDDF TARALGADFL VHYGHSCLIP MDTSAQDFRV
160 170 180 190 200
LYVFVDIRID TTHLLDSLRL TFPPATALAL VSTIQFVSTL QAAAQELKAE
210 220 230 240 250
YRVSVPQCKP LSPGEILGCT SPRLSKEVEA VVYLGDGRFH LESVMIANPN
260 270 280 290 300
VPAYRYDPYS KVLSREHYDH QRMQAARQEA IATARSAKSW GLILGTLGRQ
310 320 330 340 350
GSPKILEHLE SRLRALGLSF VRLLLSEIFP SKLSLLPEVD VWVQVACPRL
360 370 380 390 400
SIDWGTAFPK PLLTPYEAAV ALRDISWQQP YPMDFYAGSS LGPWTVNHGQ
410 420 430 440
DRRPHAPGRP ARGKVQEGSA RPPSAVACED CSCRDEKVAP LAP
Length:443
Mass (Da):48,805
Last modified:November 24, 2009 - v2
Checksum:i6AF0FD0D8EE35E2D
GO
Isoform 2 (identifier: Q9BZG8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-80: Missing.

Show »
Length:363
Mass (Da):40,040
Checksum:i4BBD3117060A0841
GO
Isoform 3 (identifier: Q9BZG8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-140: Missing.

Show »
Length:303
Mass (Da):33,516
Checksum:i9896AAF8EC70CE26
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8A → V in AAK13428 (PubMed:10519411).Curated1
Sequence conflicti162T → I in AAH96088 (PubMed:15489334).Curated1
Sequence conflicti358F → S in AAD10198 (PubMed:8603384).Curated1
Sequence conflicti358F → S in AAB36297 (PubMed:8603384).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0764126M → K in DEDSSH. 1 PublicationCorresponds to variant dbSNP:rs757167361EnsemblClinVar.1
Natural variantiVAR_0367027A → V in breast and ovarian cancer. 1 PublicationCorresponds to variant dbSNP:rs778705666Ensembl.1
Natural variantiVAR_03670334A → D in breast and ovarian cancer. 1 Publication1
Natural variantiVAR_05925551I → M. Corresponds to variant dbSNP:rs8070453Ensembl.1
Natural variantiVAR_055706226K → R1 PublicationCorresponds to variant dbSNP:rs1131600Ensembl.1
Natural variantiVAR_076413234L → P in DEDSSH. 1 PublicationCorresponds to variant dbSNP:rs730882250EnsemblClinVar.1
Natural variantiVAR_036704335L → V in breast and ovarian cancer; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs35394823Ensembl.1
Natural variantiVAR_036705389S → R in breast and ovarian cancer. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0288511 – 140Missing in isoform 3. 1 PublicationAdd BLAST140
Alternative sequenceiVSP_0288521 – 80Missing in isoform 2. 1 PublicationAdd BLAST80

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S81752 mRNA Translation: AAB36297.1
U34880 mRNA Translation: AAD10198.1
AF321876 mRNA Translation: AAK13428.1
AC099684 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90567.1
CH471108 Genomic DNA Translation: EAW90569.1
BC003099 mRNA Translation: AAH03099.2
BC096088 mRNA Translation: AAH96088.1
BT019878 mRNA Translation: AAV38681.1
CCDSiCCDS42228.1 [Q9BZG8-1]
RefSeqiNP_001333505.1, NM_001346576.1 [Q9BZG8-3]
NP_001374.3, NM_001383.4 [Q9BZG8-1]
UniGeneiHs.513856

Genome annotation databases

EnsembliENST00000263083; ENSP00000263083; ENSG00000108963 [Q9BZG8-1]
ENST00000570477; ENSP00000458726; ENSG00000108963 [Q9BZG8-2]
GeneIDi1801
KEGGihsa:1801
UCSCiuc002fts.4 human [Q9BZG8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDPH1_HUMAN
AccessioniPrimary (citable) accession number: Q9BZG8
Secondary accession number(s): D3DTI3
, Q16439, Q4VBA2, Q9BTW7, Q9UCY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: November 24, 2009
Last modified: May 23, 2018
This is version 115 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

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