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Protein

Deoxyhypusine synthase

Gene

DHPS

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

Functioni

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.

Catalytic activityi

[eIF5A-precursor]-lysine + spermidine = [eIF5A-precursor]-deoxyhypusine + propane-1,3-diamine.

Cofactori

Pathwayi: eIF5A hypusination

This protein is involved in the pathway eIF5A hypusination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway eIF5A hypusination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei137NAD1 Publication1
Binding sitei238NAD1 Publication1
Binding sitei243SpermidineCurated1
Binding sitei283NAD; via amide nitrogen1 Publication1
Binding sitei288SpermidineCurated1
Active sitei329Nucleophile1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi105 – 109NAD1 Publication5
Nucleotide bindingi131 – 133NAD1 Publication3
Nucleotide bindingi308 – 309NAD1 Publication2
Nucleotide bindingi342 – 343NAD1 Publication2

GO - Molecular functioni

  • deoxyhypusine synthase activity Source: UniProtKB
  • identical protein binding Source: IntAct

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processHypusine biosynthesis
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS01810-MONOMER
BRENDAi2.5.1.46 2681
ReactomeiR-HSA-204626 Hypusine synthesis from eIF5A-lysine
SABIO-RKiP49366
UniPathwayi
UPA00354

Names & Taxonomyi

Protein namesi
Recommended name:
Deoxyhypusine synthase (EC:2.5.1.46)
Short name:
DHS
Gene namesi
Name:DHPS
Synonyms:DS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000095059.15
HGNCiHGNC:2869 DHPS
MIMi600944 gene
neXtProtiNX_P49366

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106N → A: Strongly reduced NAD and spermidine binding. Reduced activity. 1 Publication1
Mutagenesisi109S → A: Strongly reduced spermidine binding. Reduced activity. 1 Publication1
Mutagenesisi137E → A: Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. 1 Publication1
Mutagenesisi238D → A: Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. 1 Publication1
Mutagenesisi243D → A: Reduces spermidine binding by 98%. Strongly reduced formation of covalent intermediate. 1 Publication1
Mutagenesisi287K → A: Reduces covalent intermediate formation and deoxyhypusine synthesis by 99.5%. Retains low spermidine cleavage activity. 1 Publication1
Mutagenesisi288H → A: Reduces spermidine binding by 98%. Strongly reduced NAD binding. Strongly reduced formation of covalent intermediate. 1 Publication1
Mutagenesisi305Y → A: Strongly reduced NAD binding. No effect on enzyme activity. 1 Publication1
Mutagenesisi313D → A: Strongly reduced NAD binding. 1 Publication1
Mutagenesisi316D → A: Reduces spermidine binding by 98%. Loss of covalent intermediate formation and deoxyhypusine synthesis. 1 Publication1
Mutagenesisi317S → A: Strongly reduced NAD binding. No effect on enzyme activity. 1 Publication1
Mutagenesisi323E → A: Reduces spermidine binding by 98%. Strongly reduced formation of covalent intermediate. 1 Publication1
Mutagenesisi327W → A: Reduces spermidine binding by 98%. Loss of covalent intermediate formation and deoxyhypusine synthesis. 1 Publication1
Mutagenesisi329K → A or R: Loss of covalent intermediate formation and deoxyhypusine synthesis. 1 Publication1
Mutagenesisi342D → A: Strongly reduced NAD binding. Strongly reduced activity. 1 Publication1

Organism-specific databases

DisGeNETi1725
OpenTargetsiENSG00000095059
PharmGKBiPA27329

Chemistry databases

ChEMBLiCHEMBL4415
DrugBankiDB03639 1-Guanidinium-7-Aminoheptane

Polymorphism and mutation databases

BioMutaiDHPS
DMDMi1352267

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001344691 – 369Deoxyhypusine synthaseAdd BLAST369

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP49366
MaxQBiP49366
PaxDbiP49366
PeptideAtlasiP49366
PRIDEiP49366
ProteomicsDBi55996
55997 [P49366-2]

PTM databases

iPTMnetiP49366
PhosphoSitePlusiP49366

Expressioni

Gene expression databases

BgeeiENSG00000095059 Expressed in 226 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_DHPS
ExpressionAtlasiP49366 baseline and differential
GenevisibleiP49366 HS

Organism-specific databases

HPAiHPA014461
HPA029413

Interactioni

Subunit structurei

Homotetramer formed by a dimer of dimers.3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108070, 61 interactors
IntActiP49366, 21 interactors
MINTiP49366
STRINGi9606.ENSP00000210060

Structurei

Secondary structure

1369
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP49366
SMRiP49366
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49366

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni136 – 137Spermidine bindingCurated2
Regioni314 – 316Spermidine bindingCurated3
Regioni323 – 329Spermidine bindingCurated7

Sequence similaritiesi

Belongs to the deoxyhypusine synthase family.Curated

Phylogenomic databases

eggNOGiKOG2924 Eukaryota
COG1899 LUCA
GeneTreeiENSGT00390000008063
HOGENOMiHOG000228838
HOVERGENiHBG000852
InParanoidiP49366
KOiK00809
PhylomeDBiP49366
TreeFamiTF300625

Family and domain databases

Gene3Di3.40.910.10, 1 hit
InterProiView protein in InterPro
IPR002773 Deoxyhypusine_synthase
IPR036982 Deoxyhypusine_synthase_sf
IPR029035 DHS-like_NAD/FAD-binding_dom
PANTHERiPTHR11703 PTHR11703, 1 hit
PfamiView protein in Pfam
PF01916 DS, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
TIGRFAMsiTIGR00321 dhys, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: P49366-1) [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
MEGSLEREAP AGALAAVLKH SSTLPPESTQ VRGYDFNRGV NYRALLEAFG
60 70 80 90 100
TTGFQATNFG RAVQQVNAMI EKKLEPLSQD EDQHADLTQS RRPLTSCTIF
110 120 130 140 150
LGYTSNLISS GIRETIRYLV QHNMVDVLVT TAGGVEEDLI KCLAPTYLGE
160 170 180 190 200
FSLRGKELRE NGINRIGNLL VPNENYCKFE DWLMPILDQM VMEQNTEGVK
210 220 230 240 250
WTPSKMIARL GKEINNPESV YYWAQKNHIP VFSPALTDGS LGDMIFFHSY
260 270 280 290 300
KNPGLVLDIV EDLRLINTQA IFAKCTGMII LGGGVVKHHI ANANLMRNGA
310 320 330 340 350
DYAVYINTAQ EFDGSDSGAR PDEAVSWGKI RVDAQPVKVY ADASLVFPLL
360
VAETFAQKMD AFMHEKNED
Length:369
Mass (Da):40,971
Last modified:February 1, 1996 - v1
Checksum:i5314FED620AC9EE7
GO
Isoform Short (identifier: P49366-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     262-308: Missing.

Note: Inactive.
Show »
Length:322
Mass (Da):35,916
Checksum:i1F44CC2AB89F7A2E
GO
Isoform 3 (identifier: P49366-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-68: MEGSLEREAP...FGRAVQQVNA → MPIIPAFWEAEAGGSREEEFETSLAN

Note: No experimental confirmation available.
Show »
Length:327
Mass (Da):36,583
Checksum:i313374BBDB63A758
GO

Computationally mapped potential isoform sequencesi

There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5J8M5Q5J8M5_HUMAN
Deoxyhypusine synthase
DHPS
277Annotation score:
M0R0V2M0R0V2_HUMAN
Deoxyhypusine synthase
DHPS
159Annotation score:
A0A087WZK0A0A087WZK0_HUMAN
Deoxyhypusine synthase
DHPS
370Annotation score:
M0R264M0R264_HUMAN
Deoxyhypusine synthase
DHPS
182Annotation score:
M0R1T2M0R1T2_HUMAN
Deoxyhypusine synthase
DHPS
138Annotation score:
M0R253M0R253_HUMAN
Deoxyhypusine synthase
DHPS
132Annotation score:
M0QX43M0QX43_HUMAN
Deoxyhypusine synthase
DHPS
132Annotation score:
B4E3M2B4E3M2_HUMAN
Deoxyhypusine synthase
DHPS
139Annotation score:
M0R1T4M0R1T4_HUMAN
Deoxyhypusine synthase
DHPS
115Annotation score:
M0R0J4M0R0J4_HUMAN
Deoxyhypusine synthase
DHPS
68Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence AL520040 differs from that shown. Reason: Frameshift at positions 329, 344 and 355.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11A → R in AAB02175 (PubMed:8615810).Curated1
Sequence conflicti11A → R in AAB02179 (PubMed:8615810).Curated1
Sequence conflicti13 – 14AL → R in AAB02175 (PubMed:8615810).Curated2
Sequence conflicti13 – 14AL → R in AAB02179 (PubMed:8615810).Curated2
Sequence conflicti85A → G in AAB02175 (PubMed:8615810).Curated1
Sequence conflicti85A → G in AAB02179 (PubMed:8615810).Curated1
Sequence conflicti196T → I in AAB02175 (PubMed:8615810).Curated1
Sequence conflicti196T → I in AAB02179 (PubMed:8615810).Curated1
Sequence conflicti199V → A in AAB02175 (PubMed:8615810).Curated1
Sequence conflicti199V → A in AAB02179 (PubMed:8615810).Curated1
Sequence conflicti220V → A in AAB02175 (PubMed:8615810).Curated1
Sequence conflicti220V → A in AAB02179 (PubMed:8615810).Curated1
Sequence conflicti228H → K AA sequence (PubMed:7750572).Curated1
Sequence conflicti296 – 297MR → SG in AAB02179 (PubMed:8615810).Curated2
Sequence conflicti311E → EE in AAB02179 (PubMed:8615810).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043005174E → D. Corresponds to variant dbSNP:rs10425108Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0475641 – 68MEGSL…QQVNA → MPIIPAFWEAEAGGSREEEF ETSLAN in isoform 3. 1 PublicationAdd BLAST68
Alternative sequenceiVSP_001351262 – 308Missing in isoform Short. 1 PublicationAdd BLAST47

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L39068 mRNA Translation: AAA86282.1
U40579 mRNA Translation: AAA96151.1
U32178 mRNA Translation: AAB02179.1
U26266 mRNA Translation: AAB02175.1
AJ001701
, AJ001702, AJ001703, AJ001704 Genomic DNA Translation: CAA04940.1
U79262 mRNA Translation: AAB50208.1
AL520040 mRNA No translation available.
AK291553 mRNA Translation: BAF84242.1
AC010422 Genomic DNA No translation available.
CH471106 Genomic DNA Translation: EAW84288.1
BC000333 mRNA Translation: AAH00333.1
BC014016 mRNA Translation: AAH14016.1
CCDSiCCDS12276.1 [P49366-1]
CCDS12277.1 [P49366-2]
CCDS59354.1 [P49366-3]
PIRiS68692
RefSeqiNP_001193903.1, NM_001206974.1 [P49366-3]
NP_001921.1, NM_001930.3 [P49366-1]
NP_037538.1, NM_013406.2 [P49366-2]
XP_011526072.1, XM_011527770.1 [P49366-1]
UniGeneiHs.79064

Genome annotation databases

EnsembliENST00000210060; ENSP00000210060; ENSG00000095059 [P49366-1]
ENST00000351660; ENSP00000221303; ENSG00000095059 [P49366-2]
ENST00000594424; ENSP00000471886; ENSG00000095059 [P49366-3]
GeneIDi1725
KEGGihsa:1725
UCSCiuc002mug.3 human [P49366-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L39068 mRNA Translation: AAA86282.1
U40579 mRNA Translation: AAA96151.1
U32178 mRNA Translation: AAB02179.1
U26266 mRNA Translation: AAB02175.1
AJ001701
, AJ001702, AJ001703, AJ001704 Genomic DNA Translation: CAA04940.1
U79262 mRNA Translation: AAB50208.1
AL520040 mRNA No translation available.
AK291553 mRNA Translation: BAF84242.1
AC010422 Genomic DNA No translation available.
CH471106 Genomic DNA Translation: EAW84288.1
BC000333 mRNA Translation: AAH00333.1
BC014016 mRNA Translation: AAH14016.1
CCDSiCCDS12276.1 [P49366-1]
CCDS12277.1 [P49366-2]
CCDS59354.1 [P49366-3]
PIRiS68692
RefSeqiNP_001193903.1, NM_001206974.1 [P49366-3]
NP_001921.1, NM_001930.3 [P49366-1]
NP_037538.1, NM_013406.2 [P49366-2]
XP_011526072.1, XM_011527770.1 [P49366-1]
UniGeneiHs.79064

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DHSX-ray2.20A9-369[»]
1RLZX-ray2.15A1-369[»]
1ROZX-ray2.21A/B1-369[»]
1RQDX-ray3.00A/B1-369[»]
ProteinModelPortaliP49366
SMRiP49366
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108070, 61 interactors
IntActiP49366, 21 interactors
MINTiP49366
STRINGi9606.ENSP00000210060

Chemistry databases

ChEMBLiCHEMBL4415
DrugBankiDB03639 1-Guanidinium-7-Aminoheptane

PTM databases

iPTMnetiP49366
PhosphoSitePlusiP49366

Polymorphism and mutation databases

BioMutaiDHPS
DMDMi1352267

Proteomic databases

EPDiP49366
MaxQBiP49366
PaxDbiP49366
PeptideAtlasiP49366
PRIDEiP49366
ProteomicsDBi55996
55997 [P49366-2]

Protocols and materials databases

DNASUi1725
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000210060; ENSP00000210060; ENSG00000095059 [P49366-1]
ENST00000351660; ENSP00000221303; ENSG00000095059 [P49366-2]
ENST00000594424; ENSP00000471886; ENSG00000095059 [P49366-3]
GeneIDi1725
KEGGihsa:1725
UCSCiuc002mug.3 human [P49366-1]

Organism-specific databases

CTDi1725
DisGeNETi1725
EuPathDBiHostDB:ENSG00000095059.15
GeneCardsiDHPS
HGNCiHGNC:2869 DHPS
HPAiHPA014461
HPA029413
MIMi600944 gene
neXtProtiNX_P49366
OpenTargetsiENSG00000095059
PharmGKBiPA27329
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2924 Eukaryota
COG1899 LUCA
GeneTreeiENSGT00390000008063
HOGENOMiHOG000228838
HOVERGENiHBG000852
InParanoidiP49366
KOiK00809
PhylomeDBiP49366
TreeFamiTF300625

Enzyme and pathway databases

UniPathwayi
UPA00354

BioCyciMetaCyc:HS01810-MONOMER
BRENDAi2.5.1.46 2681
ReactomeiR-HSA-204626 Hypusine synthesis from eIF5A-lysine
SABIO-RKiP49366

Miscellaneous databases

ChiTaRSiDHPS human
EvolutionaryTraceiP49366
GeneWikiiDHPS
GenomeRNAii1725
PROiPR:P49366
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000095059 Expressed in 226 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_DHPS
ExpressionAtlasiP49366 baseline and differential
GenevisibleiP49366 HS

Family and domain databases

Gene3Di3.40.910.10, 1 hit
InterProiView protein in InterPro
IPR002773 Deoxyhypusine_synthase
IPR036982 Deoxyhypusine_synthase_sf
IPR029035 DHS-like_NAD/FAD-binding_dom
PANTHERiPTHR11703 PTHR11703, 1 hit
PfamiView protein in Pfam
PF01916 DS, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
TIGRFAMsiTIGR00321 dhys, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDHYS_HUMAN
AccessioniPrimary (citable) accession number: P49366
Secondary accession number(s): A8K688
, M0R1I5, Q13184, Q13276, Q9UDG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 7, 2018
This is version 181 of the entry and version 1 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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