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O94760

- DDAH1_HUMAN

UniProt

O94760 - DDAH1_HUMAN

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Protein

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

Gene
DDAH1, DDAH
Organism
Homo sapiens (Human)
Status
Reviewed - 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.2 Publications

Kineticsi

  1. KM=69 µM for asymmetric dimethylarginine (ADMA)2 Publications
  2. KM=54 µM for monomethyl-L-arginine (MMA)
  3. 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 dependencei

Optimum pH is 8.5.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei30 – 301Substrate; via carbonyl oxygen
Binding sitei73 – 731Substrate
Binding sitei98 – 981Substrate
Binding sitei145 – 1451Substrate
Active sitei173 – 1731Proton donor Inferred
Binding sitei268 – 2681Substrate; via carbonyl oxygen
Active sitei274 – 2741Nucleophile1 Publication
Metal bindingi274 – 2741Zinc By similarity

GO - Molecular functioni

  1. amino acid binding Source: Ensembl
  2. catalytic activity Source: ProtInc
  3. dimethylargininase activity Source: UniProtKB
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. arginine catabolic process Source: ProtInc
  2. citrulline metabolic process Source: UniProtKB
  3. nitric oxide mediated signal transduction Source: ProtInc
  4. positive regulation of angiogenesis Source: Ensembl
  5. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  6. regulation of systemic arterial blood pressure Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

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
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:2715. DDAH1.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. mitochondrion Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi30 – 301L → A: Reduces enzyme activity and affinity for asymmetric dimethylarginine about 12-fold. 1 Publication
Mutagenesisi78 – 781E → A: Reduces enzyme activity about 1000-fold, and affinity for asymmetric dimethylarginine about 100-fold. 1 Publication
Mutagenesisi271 – 2711L → G: Reduces enzyme activity about 10-fold, and affinity for asymmetric dimethylarginine about 7-fold. 1 Publication

Organism-specific databases

PharmGKBiPA27185.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 285284N(G),N(G)-dimethylarginine dimethylaminohydrolase 1PRO_0000171118Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine2 Publications
Modified residuei222 – 2221S-nitrosocysteine By similarity
Modified residuei274 – 2741S-nitrosocysteine By similarity

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

MaxQBiO94760.
PaxDbiO94760.
PeptideAtlasiO94760.
PRIDEiO94760.

2D gel databases

REPRODUCTION-2DPAGEIPI00220342.

PTM databases

PhosphoSiteiO94760.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiO94760.
BgeeiO94760.
CleanExiHS_DDAH1.
GenevestigatoriO94760.

Organism-specific databases

HPAiHPA006308.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi117114. 4 interactions.
IntActiO94760. 2 interactions.
STRINGi9606.ENSP00000284031.

Structurei

Secondary structure

1
285
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi14 – 196
Helixi25 – 284
Helixi40 – 5516
Turni56 – 583
Beta strandi61 – 655
Turni72 – 754
Helixi77 – 804
Beta strandi81 – 844
Beta strandi87 – 904
Helixi96 – 1016
Helixi102 – 1109
Turni111 – 1133
Beta strandi115 – 1184
Helixi128 – 1303
Beta strandi131 – 1333
Beta strandi138 – 1458
Helixi148 – 15710
Turni158 – 1603
Beta strandi163 – 1675
Helixi174 – 1763
Beta strandi177 – 1826
Beta strandi185 – 1895
Helixi192 – 20312
Beta strandi205 – 2073
Beta strandi210 – 2167
Helixi217 – 2204
Beta strandi223 – 2275
Turni228 – 2303
Beta strandi231 – 2377
Turni239 – 2413
Helixi243 – 2519
Beta strandi255 – 2606
Helixi263 – 2664
Turni267 – 2693
Helixi273 – 2753
Beta strandi277 – 2793

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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. Positions 8-282.

Miscellaneous databases

EvolutionaryTraceiO94760.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni78 – 792Substrate binding

Sequence similaritiesi

Belongs to the DDAH family.

Phylogenomic databases

eggNOGiCOG1834.
HOGENOMiHOG000161035.
HOVERGENiHBG055937.
InParanoidiO94760.
KOiK01482.
OMAiKTMQQMS.
OrthoDBiEOG73V6KV.
PhylomeDBiO94760.
TreeFamiTF314737.

Family and domain databases

InterProiIPR003198. Amidino_trans.
[Graphical view]
PfamiPF02274. Amidinotransf. 1 hit.
[Graphical view]

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. Align

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

MAGLGHPAAF GRATHAVVRA LPESLGQHAL RSAKGEEVDV ARAERQHQLY    50
VGVLGSKLGL QVVELPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK 100
EVDMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG 150
AEILADTFKD YAVSTVPVAD GLHLKSFCSM AGPNLIAIGS SESAQKALKI 200
MQQMSDHRYD KLTVPDDIAA NCIYLNIPNK GHVLLHRTPE EYPESAKVYE 250
KLKDHMLIPV SMSELEKVDG LLTCCSVLIN KKVDS 285
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 103103Missing in isoform 2. VSP_043813Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_005270766.1. XM_005270709.2. [O94760-2]
XP_005270767.1. XM_005270710.2. [O94760-2]
XP_006710607.1. XM_006710544.1. [O94760-2]
UniGeneiHs.713411.

Genome annotation databases

EnsembliENST00000284031; ENSP00000284031; ENSG00000153904. [O94760-1]
ENST00000535924; ENSP00000439045; ENSG00000153904. [O94760-2]
ENST00000539042; ENSP00000438604; ENSG00000153904. [O94760-1]
GeneIDi23576.
KEGGihsa:23576.
UCSCiuc001dlb.3. human. [O94760-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS44170.1. [O94760-2 ]
CCDS705.1. [O94760-1 ]
RefSeqi NP_001127917.1. NM_001134445.1. [O94760-2 ]
NP_036269.1. NM_012137.3. [O94760-1 ]
XP_005270766.1. XM_005270709.2. [O94760-2 ]
XP_005270767.1. XM_005270710.2. [O94760-2 ]
XP_006710607.1. XM_006710544.1. [O94760-2 ]
UniGenei Hs.713411.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2JAI X-ray 2.30 A/B 2-285 [» ]
2JAJ X-ray 2.00 A/B 2-285 [» ]
3I2E X-ray 2.03 A/B 1-285 [» ]
3I4A X-ray 1.90 A/B 1-285 [» ]
3P8E X-ray 2.49 A/B 1-285 [» ]
3P8P X-ray 2.50 A/B 1-285 [» ]
ProteinModelPortali O94760.
SMRi O94760. Positions 8-282.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 117114. 4 interactions.
IntActi O94760. 2 interactions.
STRINGi 9606.ENSP00000284031.

Chemistry

BindingDBi O94760.
ChEMBLi CHEMBL6036.
DrugBanki DB00155. L-Citrulline.

PTM databases

PhosphoSitei O94760.

2D gel databases

REPRODUCTION-2DPAGE IPI00220342.

Proteomic databases

MaxQBi O94760.
PaxDbi O94760.
PeptideAtlasi O94760.
PRIDEi O94760.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000284031 ; ENSP00000284031 ; ENSG00000153904 . [O94760-1 ]
ENST00000535924 ; ENSP00000439045 ; ENSG00000153904 . [O94760-2 ]
ENST00000539042 ; ENSP00000438604 ; ENSG00000153904 . [O94760-1 ]
GeneIDi 23576.
KEGGi hsa:23576.
UCSCi uc001dlb.3. human. [O94760-1 ]

Organism-specific databases

CTDi 23576.
GeneCardsi GC01M085785.
HGNCi HGNC:2715. DDAH1.
HPAi HPA006308.
MIMi 604743. gene.
neXtProti NX_O94760.
PharmGKBi PA27185.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1834.
HOGENOMi HOG000161035.
HOVERGENi HBG055937.
InParanoidi O94760.
KOi K01482.
OMAi KTMQQMS.
OrthoDBi EOG73V6KV.
PhylomeDBi O94760.
TreeFami TF314737.

Miscellaneous databases

ChiTaRSi DDAH1. human.
EvolutionaryTracei O94760.
GenomeRNAii 23576.
NextBioi 46178.
PROi O94760.
SOURCEi Search...

Gene expression databases

ArrayExpressi O94760.
Bgeei O94760.
CleanExi HS_DDAH1.
Genevestigatori O94760.

Family and domain databases

InterProi IPR003198. Amidino_trans.
[Graphical view ]
Pfami PF02274. Amidinotransf. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. 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.

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: July 9, 2014
This is version 132 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

External Data

Dasty 3

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