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Protein

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

Gene

DDAH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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 N(5)-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: Ensembl
  • catalytic activity Source: ProtInc
  • dimethylargininase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS00016-MONOMER.
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

HGNCiHGNC:2715. DDAH1.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • mitochondrion Source: Ensembl
Complete GO annotation...

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.

2D gel databases

REPRODUCTION-2DPAGEIPI00220342.

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.
CleanExiHS_DDAH1.
ExpressionAtlasiO94760. baseline and differential.
GenevisibleiO94760. HS.

Organism-specific databases

HPAiHPA006308.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi117114. 14 interactors.
DIPiDIP-61582N.
IntActiO94760. 2 interactors.
STRINGi9606.ENSP00000284031.

Chemistry databases

BindingDBiO94760.

Structurei

Secondary structure

1285
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 19Combined sources6
Helixi25 – 28Combined sources4
Helixi40 – 55Combined sources16
Turni56 – 58Combined sources3
Beta strandi61 – 65Combined sources5
Turni72 – 75Combined sources4
Helixi77 – 80Combined sources4
Beta strandi81 – 84Combined sources4
Beta strandi87 – 90Combined sources4
Helixi96 – 101Combined sources6
Helixi102 – 110Combined sources9
Turni111 – 113Combined sources3
Beta strandi115 – 118Combined sources4
Helixi128 – 130Combined sources3
Beta strandi131 – 133Combined sources3
Beta strandi138 – 145Combined sources8
Helixi148 – 157Combined sources10
Turni158 – 160Combined sources3
Beta strandi163 – 167Combined sources5
Helixi174 – 176Combined sources3
Beta strandi177 – 182Combined sources6
Beta strandi185 – 189Combined sources5
Helixi192 – 203Combined sources12
Beta strandi205 – 207Combined sources3
Beta strandi210 – 216Combined sources7
Helixi217 – 220Combined sources4
Beta strandi223 – 227Combined sources5
Turni228 – 230Combined sources3
Beta strandi231 – 237Combined sources7
Turni239 – 241Combined sources3
Helixi243 – 251Combined sources9
Beta strandi255 – 260Combined sources6
Helixi263 – 266Combined sources4
Turni267 – 269Combined sources3
Helixi273 – 275Combined sources3
Beta strandi277 – 279Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JAIX-ray2.30A/B2-285[»]
2JAJX-ray2.00A/B2-285[»]
3I2EX-ray2.03A/B1-285[»]
3I4AX-ray1.90A/B1-285[»]
3P8EX-ray2.49A/B1-285[»]
3P8PX-ray2.50A/B1-285[»]
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

InterProiIPR033199. DDAH/AD.
IPR033197. DDAH1.
[Graphical view]
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

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

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]
ENST00000539042; ENSP00000438604; ENSG00000153904. [O94760-1]
GeneIDi23576.
KEGGihsa:23576.
UCSCiuc001dlb.4. human. [O94760-1]

Keywords - Coding sequence diversityi

Alternative splicing

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/B2-285[»]
2JAJX-ray2.00A/B2-285[»]
3I2EX-ray2.03A/B1-285[»]
3I4AX-ray1.90A/B1-285[»]
3P8EX-ray2.49A/B1-285[»]
3P8PX-ray2.50A/B1-285[»]
ProteinModelPortaliO94760.
SMRiO94760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117114. 14 interactors.
DIPiDIP-61582N.
IntActiO94760. 2 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-2DPAGEIPI00220342.

Proteomic databases

EPDiO94760.
MaxQBiO94760.
PaxDbiO94760.
PeptideAtlasiO94760.
PRIDEiO94760.

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]
ENST00000539042; ENSP00000438604; ENSG00000153904. [O94760-1]
GeneIDi23576.
KEGGihsa:23576.
UCSCiuc001dlb.4. human. [O94760-1]

Organism-specific databases

CTDi23576.
DisGeNETi23576.
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

BioCyciZFISH:HS00016-MONOMER.
BRENDAi3.5.3.18. 2681.
ReactomeiR-HSA-203615. eNOS activation.

Miscellaneous databases

ChiTaRSiDDAH1. human.
EvolutionaryTraceiO94760.
GenomeRNAii23576.
PROiO94760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000153904.
CleanExiHS_DDAH1.
ExpressionAtlasiO94760. baseline and differential.
GenevisibleiO94760. HS.

Family and domain databases

InterProiIPR033199. DDAH/AD.
IPR033197. DDAH1.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 154 of the entry and version 3 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.