Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O94760 (DDAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1

Short name=DDAH-1
Short name=Dimethylarginine dimethylaminohydrolase 1
EC=3.5.3.18
Alternative name(s):
DDAHI
Dimethylargininase-1
Gene names
Name:DDAH1
Synonyms:DDAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length285 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 + H2O = dimethylamine + L-citrulline. Ref.8 Ref.12

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. Ref.8 Ref.12

Subunit structure

Monomer. Ref.12

Tissue specificity

Detected in brain, liver, kidney and pancreas, and at low levels in skeletal muscle. Ref.2

Sequence similarities

Belongs to the DDAH family.

Biophysicochemical properties

Kinetic parameters:

KM=69 µM for asymmetric dimethylarginine (ADMA) Ref.8 Ref.12

KM=54 µM for monomethyl-L-arginine (MMA)

KM=3.1 µM 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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O94760-1)

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.
Isoform 2 (identifier: O94760-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.1
Chain2 – 285284N(G),N(G)-dimethylarginine dimethylaminohydrolase 1
PRO_0000171118

Regions

Region78 – 792Substrate binding

Sites

Active site1731Proton donor Probable
Active site2741Nucleophile Ref.12
Metal binding2741Zinc By similarity
Binding site301Substrate; via carbonyl oxygen
Binding site731Substrate
Binding site981Substrate
Binding site1451Substrate
Binding site2681Substrate; via carbonyl oxygen

Amino acid modifications

Modified residue21N-acetylalanine Ref.1 Ref.9
Modified residue2221S-nitrosocysteine By similarity
Modified residue2741S-nitrosocysteine By similarity

Natural variations

Alternative sequence1 – 103103Missing in isoform 2.
VSP_043813

Experimental info

Mutagenesis301L → A: Reduces enzyme activity and affinity for asymmetric dimethylarginine about 12-fold. Ref.12
Mutagenesis781E → A: Reduces enzyme activity about 1000-fold, and affinity for asymmetric dimethylarginine about 100-fold. Ref.12
Mutagenesis2711L → G: Reduces enzyme activity about 10-fold, and affinity for asymmetric dimethylarginine about 7-fold. Ref.12

Secondary structure

.............................................................. 285
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: CD8875DF267EF39B

FASTA28531,122
        10         20         30         40         50         60 
MAGLGHPAAF GRATHAVVRA LPESLGQHAL RSAKGEEVDV ARAERQHQLY VGVLGSKLGL 

        70         80         90        100        110        120 
QVVELPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK EVDMMKEALE KLQLNIVEMK 

       130        140        150        160        170        180 
DENATLDGGD VLFTGREFFV GLSKRTNQRG AEILADTFKD YAVSTVPVAD GLHLKSFCSM 

       190        200        210        220        230        240 
AGPNLIAIGS SESAQKALKI MQQMSDHRYD KLTVPDDIAA NCIYLNIPNK GHVLLHRTPE 

       250        260        270        280 
EYPESAKVYE KLKDHMLIPV SMSELEKVDG LLTCCSVLIN KKVDS 

« Hide

Isoform 2 [UniParc].

Checksum: 0612A4D0E824A1EE
Show »

FASTA18220,189

References

« Hide 'large scale' references
[1]"Purification, cDNA cloning and expression of human NG,NG-dimethylarginine dimethylaminohydrolase."
Kimoto M., Miyatake S., Sasagawa T., Yamashita H., Okita M., Oka T., Ogawa T., Tsuji H.
Eur. J. Biochem. 258:863-868(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 2-12 AND 35-50, ABSENCE OF BOUND ZINC, ACETYLATION AT ALA-2.
Tissue: Kidney and Liver.
[2]"Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases."
Leiper J.M., Santa Maria J., Chubb A., MacAllister R.J., Charles I.G., Whitley G.S., Vallance P.
Biochem. J. 343:209-214(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Endometrial cancer.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon, Kidney, Stomach and Testis.
[7]Lubec G., Vishwanath V., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 20-31; 46-57; 112-136; 150-196; 212-230 AND 268-281, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[8]"Mechanism of 4-HNE mediated inhibition of hDDAH-1: implications in NO regulation."
Forbes S.P., Druhan L.J., Guzman J.E., Parinandi N., Zhang L., Green-Church K.B., Cardounel A.J.
Biochemistry 47:1819-1826(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Disruption of methylarginine metabolism impairs vascular homeostasis."
Leiper J., Nandi M., Torondel B., Murray-Rust J., Malaki M., O'Hara B., Rossiter S., Anthony S., Madhani M., Selwood D., Smith C., Wojciak-Stothard B., Rudiger A., Stidwill R., McDonald N.Q., Vallance P.
Nat. Med. 13:198-203(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-284 IN COMPLEXES WITH CITRULLINE AND INHIBITOR L-257.
[12]"Developing dual and specific inhibitors of dimethylarginine dimethylaminohydrolase-1 and nitric oxide synthase: toward a targeted polypharmacology to control nitric oxide."
Wang Y., Monzingo A.F., Hu S., Schaller T.H., Robertus J.D., Fast W.
Biochemistry 48:8624-8635(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH N-1-IMINOPROPYL-L-ORNITHINE, CATALYTIC ACTIVITY, ZINC-BINDING, ENZYME REGULATION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, MUTAGENESIS OF LEU-30; GLU-78 AND LEU-271, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001127917.1. NM_001134445.1.
NP_036269.1. NM_012137.3.
XP_005270766.1. XM_005270709.2.
XP_005270767.1. XM_005270710.2.
UniGeneHs.713411.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JAIX-ray2.30A/B2-284[»]
2JAJX-ray2.00A/B2-284[»]
3I2EX-ray2.03A/B1-285[»]
3I4AX-ray1.90A/B1-285[»]
3P8EX-ray2.49A/B1-285[»]
3P8PX-ray2.50A/B1-285[»]
ProteinModelPortalO94760.
SMRO94760. Positions 8-282.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117114. 4 interactions.
IntActO94760. 2 interactions.
STRING9606.ENSP00000284031.

Chemistry

BindingDBO94760.
ChEMBLCHEMBL6036.
DrugBankDB00155. L-Citrulline.

PTM databases

PhosphoSiteO94760.

2D gel databases

REPRODUCTION-2DPAGEIPI00220342.

Proteomic databases

PaxDbO94760.
PeptideAtlasO94760.
PRIDEO94760.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284031; ENSP00000284031; ENSG00000153904. [O94760-1]
ENST00000535924; ENSP00000439045; ENSG00000153904. [O94760-2]
ENST00000539042; ENSP00000438604; ENSG00000153904. [O94760-1]
GeneID23576.
KEGGhsa:23576.
UCSCuc001dlb.3. human. [O94760-1]

Organism-specific databases

CTD23576.
GeneCardsGC01M085785.
HGNCHGNC:2715. DDAH1.
HPAHPA006308.
MIM604743. gene.
neXtProtNX_O94760.
PharmGKBPA27185.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1834.
HOGENOMHOG000161035.
HOVERGENHBG055937.
InParanoidO94760.
KOK01482.
OMADDTAANC.
OrthoDBEOG73V6KV.
PhylomeDBO94760.
TreeFamTF314737.

Gene expression databases

ArrayExpressO94760.
BgeeO94760.
CleanExHS_DDAH1.
GenevestigatorO94760.

Family and domain databases

InterProIPR003198. Amidino_trans.
[Graphical view]
PfamPF02274. Amidinotransf. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDDAH1. human.
EvolutionaryTraceO94760.
GenomeRNAi23576.
NextBio46178.
PROO94760.
SOURCESearch...

Entry information

Entry nameDDAH1_HUMAN
AccessionPrimary (citable) accession number: O94760
Secondary accession number(s): Q5HYC8, Q86XK5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 130 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM