Human Gene DDAH1 (uc001dlc.3) Description and Page Index
  Description: Homo sapiens dimethylarginine dimethylaminohydrolase 1 (DDAH1), transcript variant 2, mRNA.
RefSeq Summary (NM_001134445): This gene belongs to the dimethylarginine dimethylaminohydrolase (DDAH) gene family. The encoded enzyme plays a role in nitric oxide generation by regulating cellular concentrations of methylarginines, which in turn inhibit nitric oxide synthase activity. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr1:85,784,168-86,044,046 Size: 259,879 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg19 chr1:85,787,135-85,824,524 Size: 37,390 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:85,784,168-86,044,046)mRNA (may differ from genome)Protein (182 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: DDAH1_HUMAN
DESCRIPTION: RecName: Full=N(G),N(G)-dimethylarginine dimethylaminohydrolase 1; Short=DDAH-1; Short=Dimethylarginine dimethylaminohydrolase 1; EC=3.5.3.18; AltName: Full=DDAHI; AltName: Full=Dimethylargininase-1;
FUNCTION: 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 ACTIVITY: N(omega),N(omega)-dimethyl-L-arginine + H(2)O = dimethylamine + L-citrulline.
ENZYME REGULATION: 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.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=69 uM for asymmetric dimethylarginine (ADMA); KM=54 uM for monomethyl-L-arginine (MMA); KM=3.1 uM for S-methyl-L-thiocitrulline; Vmax=356 nmol/min/mg enzyme with ADMA; Vmax=154 nmol/min/mg enzyme with NMA; pH dependence: Optimum pH is 8.5;
SUBUNIT: Monomer.
TISSUE SPECIFICITY: Detected in brain, liver, kidney and pancreas, and at low levels in skeletal muscle.
SIMILARITY: Belongs to the DDAH family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DDAH1
CDC HuGE Published Literature: DDAH1
Positive Disease Associations: Neuroblastoma , preeclampsia
Related Studies:
  1. Neuroblastoma
    , , . [PubMed 0]
  2. preeclampsia
    Akbar, F. et al. 2004, Haplotypic association of DDAH1 with susceptibility to pre-eclampsia, Molecular human reproduction. 2005 Jan;11(1):73-7. [PubMed 15501905]
    The observed haplotypic association provides the first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia susceptibility.

-  MalaCards Disease Associations
  MalaCards Gene Search: DDAH1
Diseases sorted by gene-association score: diffuse intrinsic pontine glioma (13)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 45.81 RPKM in Brain - Anterior cingulate cortex (BA24)
Total median expression: 655.15 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -161.41502-0.322 Picture PostScript Text
3' UTR -751.482967-0.253 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003198 - Amidino_trans

SCOP Domains:
55909 - Pentein

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2JAI
- X-ray MuPIT

2JAJ
- X-ray MuPIT

3I2E
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3I4A - X-ray MuPIT 3P8E - X-ray MuPIT 3P8P - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O94760
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003824 catalytic activity
GO:0016403 dimethylargininase activity
GO:0016597 amino acid binding
GO:0016787 hydrolase activity
GO:0046872 metal ion binding

Biological Process:
GO:0000052 citrulline metabolic process
GO:0003073 regulation of systemic arterial blood pressure
GO:0006525 arginine metabolic process
GO:0006527 arginine catabolic process
GO:0007263 nitric oxide mediated signal transduction
GO:0008285 negative regulation of cell proliferation
GO:0043116 negative regulation of vascular permeability
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045766 positive regulation of angiogenesis
GO:0050999 regulation of nitric-oxide synthase activity
GO:1900038 negative regulation of cellular response to hypoxia

Cellular Component:
GO:0005829 cytosol
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BX648145 - Homo sapiens mRNA; cDNA DKFZp686N2176 (from clone DKFZp686N2176).
AK098405 - Homo sapiens cDNA FLJ25539 fis, clone CBR09481.
AK304876 - Homo sapiens cDNA FLJ61209 complete cds, highly similar to NG,NG-dimethylarginine dimethylaminohydrolase 1 (EC 3.5.3.18).
BC043235 - Homo sapiens dimethylarginine dimethylaminohydrolase 1, mRNA (cDNA clone IMAGE:5295723), partial cds.
BC033680 - Homo sapiens dimethylarginine dimethylaminohydrolase 1, mRNA (cDNA clone MGC:45161 IMAGE:5189970), complete cds.
EU794605 - Homo sapiens epididymis secretory protein Li 16 (HEL-S-16) mRNA, complete cds.
AK309225 - Homo sapiens cDNA, FLJ99266.
AB001915 - Homo sapiens mRNA for NG,NG-dimethylarginine dimethylaminohydrolase, complete cds.
AK294752 - Homo sapiens cDNA FLJ54083 complete cds, highly similar to NG,NG-dimethylarginine dimethylaminohydrolase 1 (EC 3.5.3.18).
AK302531 - Homo sapiens cDNA FLJ54119 complete cds, highly similar to NG,NG-dimethylarginine dimethylaminohydrolase 1 (EC 3.5.3.18).
AK312432 - Homo sapiens cDNA, FLJ92778, Homo sapiens dimethylarginine dimethylaminohydrolase 1 (DDAH1), mRNA.
KJ893405 - Synthetic construct Homo sapiens clone ccsbBroadEn_02799 DDAH1 gene, encodes complete protein.
AK026093 - Homo sapiens cDNA: FLJ22440 fis, clone HRC09260.
BC036432 - Homo sapiens dimethylarginine dimethylaminohydrolase 1, mRNA (cDNA clone IMAGE:4813859).
AK024917 - Homo sapiens cDNA: FLJ21264 fis, clone COL01579.
AK055626 - Homo sapiens cDNA FLJ31064 fis, clone HSYRA2001138.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O94760 (Reactome details) participates in the following event(s):

R-HSA-5693373 DDAH1,2 hydrolyses ADMA to DMA and L-Cit
R-HSA-203615 eNOS activation
R-HSA-203765 eNOS activation and regulation
R-HSA-202131 Metabolism of nitric oxide
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: DDAH, DDAH1_HUMAN, NM_001134445, NP_001127917, O94760, Q5HYC8, Q86XK5
UCSC ID: uc001dlc.3
RefSeq Accession: NM_001134445
Protein: O94760 (aka DDAH1_HUMAN or DDH1_HUMAN)
CCDS: CCDS44170.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001134445.1
exon count: 7CDS single in 3' UTR: no RNA size: 4023
ORF size: 549CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 993.00frame shift in genome: no % Coverage: 99.88
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.