Tchem DHPS Deoxyhypusine synthase

Protein Summary

Description

Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. This is the first step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function. This gene encodes a protein that is required for the formation of hypusine, a unique amino acid formed by the posttranslational modification of only one protein, eukaryotic translation initiation factor 5A. The encoded protein catalyzes the first step in hypusine formation by transferring the butylamine moiety of spermidine to a specific lysine residue of the eukaryotic translation initiation factor 5A precursor, forming an intermediate deoxyhypusine residue. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2011]

Uniprot Accession IDs

• P49366
• A8K688
• M0R1I5
• Q13184
• Q13276
• Q9UDG0
• DHS

Gene Name

• DHPS

Ensembl ID

• ENST00000210060
• ENSP00000210060
• ENSG00000095059
• ENST00000351660
• ENSP00000221303
• ENST00000594424
• ENSP00000471886

Symbol

• DS
• DS
• DHS
• MIG13

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.85
kinase perturbation	0.76
transcription factor perturbation	0.74
histone modification site profile	0.73
biological process	0.7

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.14   (req: < 5)

Gene RIFs: 9   (req: <= 3)

Antibodies: 281   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.14   (req: >= 5)

Gene RIFs: 9   (req: > 3)

Antibodies: 281   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 6

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 6

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

Show Full Sequence

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Active Ligands (6)

Explore Active Ligands

1 – 6 of 6

CHEMBL4555677

DHPSTchem Enzyme

pIC50 : 7.21

CHEMBL4543218

DHPSTchem Enzyme

pIC50 : 7.04

CHEMBL4462702

DHPSTchem Enzyme

pIC50 : 6.92

N-1-guanyl-1,7-diaminoheptane

DHPSTchem Enzyme

pIC50 : 6.85

CHEMBL4442298

DHPSTchem Enzyme

pIC50 : 6.37

4-tert-butyl-N-(1H-indol-4-yl)benzamide

DHPSTchem Enzyme

pIC50 : 6.08

Protein-Protein Interactions (91)

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1 – 10 of 91

• See Interactions on String-DB

BYSL

Tbio

Novelty:  0.01919968

p_int:  0.999999572

p_ni:  4.28e-7

Score:  0.231

Data Source:  BioPlex,STRINGDB

EIF5A2

Tbio

Novelty:  0.01527502

p_int:  0.999999571

p_ni:  4.29e-7

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

SUSD4

Tbio

Novelty:  0.22201938

p_int:  0.999994801

p_ni:  0.000005199

Data Source:  BioPlex

FAM19A3

Tdark

Novelty:  0.37183557

p_int:  0.999986834

p_ni:  0.000013166

Data Source:  BioPlex

SAFB2

Tbio

Novelty:  0.12354864

p_int:  0.99978159

p_ni:  0.00021841

Score:  0.17

Data Source:  BioPlex,STRINGDB

ARHGAP15

Tbio

Family:  Enzyme

Novelty:  0.09749237

p_int:  0.999600234

p_ni:  0.000399766

Score:  0.252

Data Source:  BioPlex,STRINGDB

TIRAP

Tbio

Novelty:  0.00600495

p_int:  0.999568534

p_ni:  0.000431466

Score:  0.198

Data Source:  BioPlex,STRINGDB

ZNF276

Tdark

Family:  TF

Novelty:  0.3082638

p_int:  0.999540755

p_ni:  0.000459245

Data Source:  BioPlex

ZNF414

Tdark

Novelty:  1.29024829

p_int:  0.993129431

p_ni:  0.006870569

Data Source:  BioPlex

RPL9

Tbio

Novelty:  0.00845583

p_int:  0.98779076

p_ni:  0.012209235

p_wrong:  6e-9

Score:  0.344

Data Source:  BioPlex,STRINGDB

Pathways (5)

Reactome (4)

UniProt (1)

Gamma carboxylation, hypusine formation and arylsulfatase activation (R-HSA-163841)

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Gamma carboxylation, hypusine formation and arylsulfatase activation	39 targets	R-HSA-163841
Reactome	Hypusine synthesis from eIF5A-lysine	4 targets	R-HSA-204626
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Post-translational protein modification	1450 targets	R-HSA-597592

Name	Explore in Pharos	Explore in Source
Gamma carboxylation, hypusine formation and arylsulfatase activation	39 targets	R-HSA-163841
Hypusine synthesis from eIF5A-lysine	4 targets	R-HSA-204626
Metabolism of proteins	2050 targets	R-HSA-392499
Post-translational protein modification	1450 targets	R-HSA-597592

Gene Ontology Terms (7)

Functions (2)

Components (1)

Processes (4)

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10

1 – 2 of 2

GO Term	Evidence	Assigned by
deoxyhypusine synthase activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct

GWAS Traits (3)

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5

1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cathepsin L1 measurement	EFO_0010619	1	1	1		42.3
body height	EFO_0004339	1	1	1		24.5
emphysema	EFO_0000464	1	1	1		8.3

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 3 of 3

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
cathepsin L1 measurement	EFO_0010619	1		42.3
body height	EFO_0004339	1		24.5
emphysema	EFO_0000464	1		8.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Complete proteome
Direct protein sequencing
Hypusine biosynthesis
NAD
Phosphoprotein
Polymorphism
Reference proteome
Transferase

GWAS Trait Find Similar Targets

No Header	No Header
body height
cathepsin L1 measurement
emphysema

MGI Phenotype Find Similar Targets

No Header	No Header
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
renal/urinary system phenotype

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	deoxyhypusine synthase	VGNC:2572	455746
Macaque	deoxyhypusine synthase		716213
Mouse	deoxyhypusine synthase	MGI:2683592	330817
Rat	deoxyhypusine synthase	RGD:1303326	288923
Dog	deoxyhypusine synthase	VGNC:39931	476702

Species	Name	OMA	EggNOG	Inparanoid
Chimp	deoxyhypusine synthase
Macaque	deoxyhypusine synthase
Mouse	deoxyhypusine synthase
Rat	deoxyhypusine synthase
Dog	deoxyhypusine synthase

Publication Statistics

PubMed Score 126.14

PubMed score by year

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PubTator Score 161.13

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