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Protein

N(G),N(G)-dimethylarginine dimethylaminohydrolase 1

Gene

DDAH1

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

Functioni

Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.

Catalytic activityi

N(omega),N(omega)-dimethyl-L-arginine + H2O = dimethylamine + L-citrulline.2 Publications

Activity regulationi

Inhibited by zinc ions (By similarity). Enzyme purified in the absence of 1,10-phenanthroline contains on average 0.4 zinc atoms per subunit. Inhibited by 4-hydroxy-nonenal through the formation of a covalent adduct with His-173. Competitively inhibited by N5-iminopropyl-ornithine.By similarity2 Publications

Kineticsi

  1. KM=69 µM for asymmetric dimethylarginine (ADMA)2 Publications
  2. KM=54 µM for monomethyl-L-arginine (MMA)2 Publications
  3. KM=3.1 µM for S-methyl-L-thiocitrulline2 Publications
  1. Vmax=356 nmol/min/mg enzyme with ADMA2 Publications
  2. Vmax=154 nmol/min/mg enzyme with NMA2 Publications

pH dependencei

Optimum pH is 8.5.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei30Substrate; via carbonyl oxygen1
Binding sitei73Substrate1
Binding sitei98Substrate1
Binding sitei145Substrate1
Active sitei173Proton donor1 Publication1
Binding sitei268Substrate; via carbonyl oxygen1
Active sitei274Nucleophile1 Publication1
Metal bindingi274ZincBy similarity1

GO - Molecular functioni

  • amino acid binding Source: GO_Central
  • catalytic activity Source: ProtInc
  • dimethylargininase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.3.18 2681
ReactomeiR-HSA-203615 eNOS activation

Names & Taxonomyi

Protein namesi
Recommended name:
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (EC:3.5.3.18)
Short name:
DDAH-1
Short name:
Dimethylarginine dimethylaminohydrolase 1
Alternative name(s):
DDAHI
Dimethylargininase-1
Gene namesi
Name:DDAH1
Synonyms:DDAH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000153904.18
HGNCiHGNC:2715 DDAH1
MIMi604743 gene
neXtProtiNX_O94760

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
Mutagenesisi30L → A: Reduces enzyme activity and affinity for asymmetric dimethylarginine about 12-fold. 1 Publication1
Mutagenesisi78E → A: Reduces enzyme activity about 1000-fold, and affinity for asymmetric dimethylarginine about 100-fold. 1 Publication1
Mutagenesisi271L → G: Reduces enzyme activity about 10-fold, and affinity for asymmetric dimethylarginine about 7-fold. 1 Publication1

Organism-specific databases

DisGeNETi23576
OpenTargetsiENSG00000153904
PharmGKBiPA27185

Chemistry databases

ChEMBLiCHEMBL6036
DrugBankiDB00155 L-Citrulline
GuidetoPHARMACOLOGYi1247

Polymorphism and mutation databases

BioMutaiDDAH1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001711182 – 285N(G),N(G)-dimethylarginine dimethylaminohydrolase 1Add BLAST284

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei222S-nitrosocysteineBy similarity1
Modified residuei274S-nitrosocysteineBy similarity1

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

EPDiO94760
MaxQBiO94760
PaxDbiO94760
PeptideAtlasiO94760
PRIDEiO94760
ProteomicsDBi50422
50423 [O94760-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00220342

PTM databases

iPTMnetiO94760
PhosphoSitePlusiO94760
SwissPalmiO94760

Expressioni

Tissue specificityi

Detected in brain, liver, kidney and pancreas, and at low levels in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000153904 Expressed in 230 organ(s), highest expression level in endothelial cell
CleanExiHS_DDAH1
ExpressionAtlasiO94760 baseline and differential
GenevisibleiO94760 HS

Organism-specific databases

HPAiHPA006308

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi117114, 16 interactors
DIPiDIP-61582N
IntActiO94760, 8 interactors
STRINGi9606.ENSP00000284031

Chemistry databases

BindingDBiO94760

Structurei

Secondary structure

1285
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO94760
SMRiO94760
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94760

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni78 – 79Substrate binding2

Sequence similaritiesi

Belongs to the DDAH family.Curated

Phylogenomic databases

eggNOGiENOG410IFS6 Eukaryota
COG1834 LUCA
GeneTreeiENSGT00390000009331
HOGENOMiHOG000161035
HOVERGENiHBG055937
InParanoidiO94760
KOiK01482
OMAiCNGIALI
OrthoDBiEOG091G0M5S
PhylomeDBiO94760
TreeFamiTF314737

Family and domain databases

InterProiView protein in InterPro
IPR033199 DDAH/AD
IPR033197 DDAH1
PANTHERiPTHR12737 PTHR12737, 1 hit
PTHR12737:SF17 PTHR12737:SF17, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O94760-1) [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
MAGLGHPAAF GRATHAVVRA LPESLGQHAL RSAKGEEVDV ARAERQHQLY
60 70 80 90 100
VGVLGSKLGL QVVELPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK
110 120 130 140 150
EVDMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG
160 170 180 190 200
AEILADTFKD YAVSTVPVAD GLHLKSFCSM AGPNLIAIGS SESAQKALKI
210 220 230 240 250
MQQMSDHRYD KLTVPDDIAA NCIYLNIPNK GHVLLHRTPE EYPESAKVYE
260 270 280
KLKDHMLIPV SMSELEKVDG LLTCCSVLIN KKVDS
Length:285
Mass (Da):31,122
Last modified:January 23, 2007 - v3
Checksum:iCD8875DF267EF39B
GO
Isoform 2 (identifier: O94760-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-103: Missing.

Show »
Length:182
Mass (Da):20,189
Checksum:i0612A4D0E824A1EE
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DYP1B4DYP1_HUMAN
N(G),N(G)-dimethylarginine dimethyl...
DDAH1
185Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0438131 – 103Missing in isoform 2. 1 PublicationAdd BLAST103

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001915 mRNA Translation: BAA37117.1
BX648145 mRNA Translation: CAI45988.1
AC092807 Genomic DNA No translation available.
AL078459 Genomic DNA No translation available.
AL360219 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW73199.1
BC033680 mRNA Translation: AAH33680.1
BC043235 mRNA Translation: AAH43235.2
CCDSiCCDS44170.1 [O94760-2]
CCDS705.1 [O94760-1]
RefSeqiNP_001127917.1, NM_001134445.1 [O94760-2]
NP_036269.1, NM_012137.3 [O94760-1]
XP_005270767.1, XM_005270710.2 [O94760-2]
UniGeneiHs.713411

Genome annotation databases

EnsembliENST00000284031; ENSP00000284031; ENSG00000153904 [O94760-1]
ENST00000426972; ENSP00000411189; ENSG00000153904 [O94760-2]
ENST00000535924; ENSP00000439045; ENSG00000153904 [O94760-2]
GeneIDi23576
KEGGihsa:23576
UCSCiuc001dlb.4 human [O94760-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001915 mRNA Translation: BAA37117.1
BX648145 mRNA Translation: CAI45988.1
AC092807 Genomic DNA No translation available.
AL078459 Genomic DNA No translation available.
AL360219 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW73199.1
BC033680 mRNA Translation: AAH33680.1
BC043235 mRNA Translation: AAH43235.2
CCDSiCCDS44170.1 [O94760-2]
CCDS705.1 [O94760-1]
RefSeqiNP_001127917.1, NM_001134445.1 [O94760-2]
NP_036269.1, NM_012137.3 [O94760-1]
XP_005270767.1, XM_005270710.2 [O94760-2]
UniGeneiHs.713411

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JAIX-ray2.30A/B1-285[»]
2JAJX-ray2.00A/B1-285[»]
3I2EX-ray2.03A/B1-285[»]
3I4AX-ray1.90A/B1-285[»]
3P8EX-ray2.49A/B1-285[»]
3P8PX-ray2.50A/B1-285[»]
6DGEX-ray1.91A1-285[»]
ProteinModelPortaliO94760
SMRiO94760
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117114, 16 interactors
DIPiDIP-61582N
IntActiO94760, 8 interactors
STRINGi9606.ENSP00000284031

Chemistry databases

BindingDBiO94760
ChEMBLiCHEMBL6036
DrugBankiDB00155 L-Citrulline
GuidetoPHARMACOLOGYi1247

PTM databases

iPTMnetiO94760
PhosphoSitePlusiO94760
SwissPalmiO94760

Polymorphism and mutation databases

BioMutaiDDAH1

2D gel databases

REPRODUCTION-2DPAGEiIPI00220342

Proteomic databases

EPDiO94760
MaxQBiO94760
PaxDbiO94760
PeptideAtlasiO94760
PRIDEiO94760
ProteomicsDBi50422
50423 [O94760-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000284031; ENSP00000284031; ENSG00000153904 [O94760-1]
ENST00000426972; ENSP00000411189; ENSG00000153904 [O94760-2]
ENST00000535924; ENSP00000439045; ENSG00000153904 [O94760-2]
GeneIDi23576
KEGGihsa:23576
UCSCiuc001dlb.4 human [O94760-1]

Organism-specific databases

CTDi23576
DisGeNETi23576
EuPathDBiHostDB:ENSG00000153904.18
GeneCardsiDDAH1
HGNCiHGNC:2715 DDAH1
HPAiHPA006308
MIMi604743 gene
neXtProtiNX_O94760
OpenTargetsiENSG00000153904
PharmGKBiPA27185
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFS6 Eukaryota
COG1834 LUCA
GeneTreeiENSGT00390000009331
HOGENOMiHOG000161035
HOVERGENiHBG055937
InParanoidiO94760
KOiK01482
OMAiCNGIALI
OrthoDBiEOG091G0M5S
PhylomeDBiO94760
TreeFamiTF314737

Enzyme and pathway databases

BRENDAi3.5.3.18 2681
ReactomeiR-HSA-203615 eNOS activation

Miscellaneous databases

ChiTaRSiDDAH1 human
EvolutionaryTraceiO94760
GenomeRNAii23576
PROiPR:O94760
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000153904 Expressed in 230 organ(s), highest expression level in endothelial cell
CleanExiHS_DDAH1
ExpressionAtlasiO94760 baseline and differential
GenevisibleiO94760 HS

Family and domain databases

InterProiView protein in InterPro
IPR033199 DDAH/AD
IPR033197 DDAH1
PANTHERiPTHR12737 PTHR12737, 1 hit
PTHR12737:SF17 PTHR12737:SF17, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDDAH1_HUMAN
AccessioniPrimary (citable) accession number: O94760
Secondary accession number(s): Q5HYC8, Q86XK5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 167 of the entry and version 3 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 chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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