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Protein

Deoxyhypusine synthase

Gene

DHPS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue.

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

GO - Biological processi

  • deoxyhypusine biosynthetic process from spermidine Source: ProtInc
  • glucose homeostasis Source: Ensembl
  • peptidyl-lysine modification to peptidyl-hypusine Source: GO_Central
  • positive regulation of cell proliferation Source: ProtInc
  • positive regulation of T cell proliferation Source: Ensembl
  • protein homotetramerization Source: Ensembl
  • translation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Hypusine biosynthesis

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciMetaCyc:HS01810-MONOMER.
ZFISH:HS01810-MONOMER.
BRENDAi2.5.1.46. 2681.
ReactomeiR-HSA-204626. Hypusine synthesis from eIF5A-lysine.
SABIO-RKP49366.
UniPathwayiUPA00354.

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

HGNCiHGNC:2869. DHPS.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

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.

PTM databases

iPTMnetiP49366.
PhosphoSitePlusiP49366.

Expressioni

Gene expression databases

BgeeiENSG00000095059.
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

WithEntry#Exp.IntActNotes
itself3EBI-741925,EBI-741925
EIF5AP632413EBI-741925,EBI-373150
EIF5A2Q9GZV46EBI-741925,EBI-748028
MAPK3P273613EBI-741925,EBI-73995
NIF3L1Q9GZT83EBI-741925,EBI-740897
NUDT18Q6ZVK83EBI-741925,EBI-740486
PTPRHQ9HD433EBI-741925,EBI-1267176
RAB27BO001945EBI-741925,EBI-10179046
RELQ048643EBI-741925,EBI-307352
RPL9P9P329696EBI-741925,EBI-358122
VASH1Q7L8A93EBI-741925,EBI-10256546
WDYHV1Q96HA83EBI-741925,EBI-741158
ZNF138P52744-23EBI-741925,EBI-10213071

Protein-protein interaction databases

BioGridi108070. 47 interactors.
IntActiP49366. 17 interactors.
MINTiMINT-1436761.
STRINGi9606.ENSP00000210060.

Structurei

Secondary structure

1369
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi11 – 17Combined sources7
Helixi36 – 38Combined sources3
Helixi42 – 47Combined sources6
Helixi48 – 51Combined sources4
Helixi54 – 73Combined sources20
Helixi79 – 85Combined sources7
Beta strandi96 – 103Combined sources8
Helixi106 – 109Combined sources4
Helixi112 – 121Combined sources10
Beta strandi126 – 130Combined sources5
Helixi132 – 140Combined sources9
Turni141 – 143Combined sources3
Helixi155 – 160Combined sources6
Beta strandi163 – 166Combined sources4
Beta strandi169 – 172Combined sources4
Helixi174 – 196Combined sources23
Helixi203 – 214Combined sources12
Helixi220 – 226Combined sources7
Turni234 – 237Combined sources4
Helixi240 – 251Combined sources12
Helixi260 – 271Combined sources12
Beta strandi274 – 282Combined sources9
Helixi284 – 295Combined sources12
Turni296 – 298Combined sources3
Beta strandi299 – 307Combined sources9
Helixi321 – 327Combined sources7
Beta strandi337 – 341Combined sources5
Helixi343 – 353Combined sources11
Helixi355 – 358Combined sources4
Helixi359 – 365Combined sources7

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...

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.
InterProiIPR002773. Deoxyhypusine_synthase.
IPR029035. DHS-like_NAD/FAD-binding_dom.
[Graphical view]
PANTHERiPTHR11703. PTHR11703. 1 hit.
PfamiPF01916. DS. 1 hit.
[Graphical view]
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

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

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 rs10425108dbSNPEnsembl.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

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. 47 interactors.
IntActiP49366. 17 interactors.
MINTiMINT-1436761.
STRINGi9606.ENSP00000210060.

Chemistry databases

ChEMBLiCHEMBL4415.

PTM databases

iPTMnetiP49366.
PhosphoSitePlusiP49366.

Polymorphism and mutation databases

BioMutaiDHPS.
DMDMi1352267.

Proteomic databases

EPDiP49366.
MaxQBiP49366.
PaxDbiP49366.
PeptideAtlasiP49366.
PRIDEiP49366.

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.
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

UniPathwayiUPA00354.
BioCyciMetaCyc:HS01810-MONOMER.
ZFISH:HS01810-MONOMER.
BRENDAi2.5.1.46. 2681.
ReactomeiR-HSA-204626. Hypusine synthesis from eIF5A-lysine.
SABIO-RKP49366.

Miscellaneous databases

ChiTaRSiDHPS. human.
EvolutionaryTraceiP49366.
GeneWikiiDHPS.
GenomeRNAii1725.
PROiP49366.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000095059.
CleanExiHS_DHPS.
ExpressionAtlasiP49366. baseline and differential.
GenevisibleiP49366. HS.

Family and domain databases

Gene3Di3.40.910.10. 1 hit.
InterProiIPR002773. Deoxyhypusine_synthase.
IPR029035. DHS-like_NAD/FAD-binding_dom.
[Graphical view]
PANTHERiPTHR11703. PTHR11703. 1 hit.
PfamiPF01916. DS. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 168 of the entry and version 1 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

Keywords - Technical termi

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

Documents

  1. Human chromosome 19
    Human chromosome 19: 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. 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.