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Protein

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

Gene

DDAH1

Organism
Bos taurus (Bovine)
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.1 Publication

Enzyme regulationi

Copurifies with a tightly bound zinc ion. Activated by release of zinc. His and other agents that promote the release of bound zinc ions activate the enzyme (in vitro). Inhibited by S-nitrosylation. Zinc protects the protein against S-nitrosylation.3 Publications

pH dependencei

Optimum pH is 7.8.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei30 – 301Substrate; via carbonyl oxygen
Binding sitei73 – 731Substrate
Binding sitei78 – 781Substrate
Binding sitei79 – 791Substrate
Binding sitei98 – 981Substrate
Binding sitei145 – 1451Substrate
Active sitei173 – 1731Proton donorBy similarity
Binding sitei268 – 2681Substrate; via carbonyl oxygen
Active sitei274 – 2741NucleophileBy similarity
Metal bindingi274 – 2741Zinc

GO - Molecular functioni

  • dimethylargininase activity Source: UniProtKB
  • zinc ion binding Source: MGI

GO - Biological processi

  • citrulline metabolic process Source: UniProtKB
  • nitric oxide biosynthetic process Source: MGI
  • positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  • protein nitrosylation Source: MGI
  • regulation of systemic arterial blood pressure Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.3.18. 908.
ReactomeiR-BTA-203615. eNOS activation.
SABIO-RKP56965.

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 3

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL6081.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved2 Publications
Chaini2 – 285284N(G),N(G)-dimethylarginine dimethylaminohydrolase 1PRO_0000171117Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei222 – 2221S-nitrosocysteine1 Publication
Modified residuei274 – 2741S-nitrosocysteine1 Publication

Keywords - PTMi

Acetylation, S-nitrosylation

Proteomic databases

PaxDbiP56965.
PRIDEiP56965.

Expressioni

Tissue specificityi

Widely distributed, highest concentrations found in brain, brain cortex and kidney (at protein level).1 Publication

Interactioni

Subunit structurei

Monomer.2 Publications

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000046157.

Structurei

Secondary structure

1
285
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi14 – 196Combined sources
Helixi25 – 284Combined sources
Turni30 – 323Combined sources
Beta strandi34 – 363Combined sources
Helixi40 – 5516Combined sources
Turni56 – 583Combined sources
Beta strandi61 – 655Combined sources
Turni72 – 754Combined sources
Helixi77 – 804Combined sources
Beta strandi81 – 844Combined sources
Beta strandi87 – 904Combined sources
Helixi96 – 1016Combined sources
Helixi102 – 11110Combined sources
Beta strandi115 – 1184Combined sources
Helixi128 – 1303Combined sources
Beta strandi131 – 1333Combined sources
Beta strandi135 – 14511Combined sources
Helixi148 – 15710Combined sources
Turni158 – 1603Combined sources
Beta strandi161 – 1677Combined sources
Beta strandi170 – 1734Combined sources
Helixi174 – 1763Combined sources
Beta strandi177 – 1826Combined sources
Beta strandi185 – 1895Combined sources
Helixi192 – 20413Combined sources
Beta strandi210 – 2167Combined sources
Helixi217 – 2204Combined sources
Beta strandi223 – 2275Combined sources
Turni228 – 2303Combined sources
Beta strandi231 – 2366Combined sources
Turni239 – 2413Combined sources
Helixi243 – 2497Combined sources
Beta strandi255 – 2595Combined sources
Helixi263 – 2664Combined sources
Turni267 – 2693Combined sources
Helixi273 – 2753Combined sources
Beta strandi277 – 2793Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C6ZX-ray1.20A2-285[»]
2CI1X-ray1.08A8-282[»]
2CI3X-ray1.70A2-285[»]
2CI4X-ray1.70A2-285[»]
2CI5X-ray1.79A/B2-285[»]
2CI6X-ray2.00A2-285[»]
2CI7X-ray1.60A2-285[»]
ProteinModelPortaliP56965.
SMRiP56965. Positions 8-281.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56965.

Family & Domainsi

Sequence similaritiesi

Belongs to the DDAH family.Curated

Phylogenomic databases

eggNOGiENOG410IFS6. Eukaryota.
COG1834. LUCA.
GeneTreeiENSGT00390000009331.
HOGENOMiHOG000161035.
HOVERGENiHBG055937.
InParanoidiP56965.
KOiK01482.
OMAiCNGIALI.
OrthoDBiEOG73V6KV.
TreeFamiTF314737.

Family and domain databases

InterProiIPR033199. DDAH/AD.
IPR033197. DDAH1.
[Graphical view]
PANTHERiPTHR12737. PTHR12737. 1 hit.
PTHR12737:SF17. PTHR12737:SF17. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P56965-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASLGHPATF GRATHVVVRA LPESLAQQAL RRTKGDEVDF ARAERQHQLY
60 70 80 90 100
VGVLGSKLGL QVVQLPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK
110 120 130 140 150
EADMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG
160 170 180 190 200
AEILADTFKD YAVSTVPVVD ALHLKSFCSM AGPNLIAIGS SESAQKALKI
210 220 230 240 250
MQQMSDHRYD KLTVPDDTAA NCIYLNIPSK GHVLLHRTPE EYPESAKVYE
260 270 280
KLKDHMLIPV SNSELEKVDG LLTCSSVLIN KKVDS
Length:285
Mass (Da):31,289
Last modified:January 23, 2007 - v3
Checksum:i65C5C032EE513CE5
GO

Mass spectrometryi

Molecular mass is 31199 Da from positions 2 - 285. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC149998 mRNA. Translation: AAI49999.1.
PIRiS74156.
RefSeqiNP_001095671.1. NM_001102201.2.
UniGeneiBt.104256.

Genome annotation databases

EnsembliENSBTAT00000049235; ENSBTAP00000046157; ENSBTAG00000034776.
GeneIDi537391.
KEGGibta:537391.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC149998 mRNA. Translation: AAI49999.1.
PIRiS74156.
RefSeqiNP_001095671.1. NM_001102201.2.
UniGeneiBt.104256.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2C6ZX-ray1.20A2-285[»]
2CI1X-ray1.08A8-282[»]
2CI3X-ray1.70A2-285[»]
2CI4X-ray1.70A2-285[»]
2CI5X-ray1.79A/B2-285[»]
2CI6X-ray2.00A2-285[»]
2CI7X-ray1.60A2-285[»]
ProteinModelPortaliP56965.
SMRiP56965. Positions 8-281.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000046157.

Chemistry

ChEMBLiCHEMBL6081.

Proteomic databases

PaxDbiP56965.
PRIDEiP56965.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000049235; ENSBTAP00000046157; ENSBTAG00000034776.
GeneIDi537391.
KEGGibta:537391.

Organism-specific databases

CTDi23576.

Phylogenomic databases

eggNOGiENOG410IFS6. Eukaryota.
COG1834. LUCA.
GeneTreeiENSGT00390000009331.
HOGENOMiHOG000161035.
HOVERGENiHBG055937.
InParanoidiP56965.
KOiK01482.
OMAiCNGIALI.
OrthoDBiEOG73V6KV.
TreeFamiTF314737.

Enzyme and pathway databases

BRENDAi3.5.3.18. 908.
ReactomeiR-BTA-203615. eNOS activation.
SABIO-RKP56965.

Miscellaneous databases

EvolutionaryTraceiP56965.
PROiP56965.

Family and domain databases

InterProiIPR033199. DDAH/AD.
IPR033197. DDAH1.
[Graphical view]
PANTHERiPTHR12737. PTHR12737. 1 hit.
PTHR12737:SF17. PTHR12737:SF17. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Hypothalamus.
  2. "Zn(II)-free dimethylargininase-1 (DDAH-1) is inhibited upon specific CysS-nitrosylation."
    Knipp M., Braun O., Gehrig P.M., Sack R., Vasak M.
    J. Biol. Chem. 278:3410-3416(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-285, MASS SPECTROMETRY, ACETYLATION AT ALA-2, S-NITROSYLATION AT CYS-222 AND CYS-274, ENZYME REGULATION, 3D-STRUCTURE MODELING.
    Tissue: Brain.
  3. "Characterization of dimethylargininase from bovine brain: evidence for a zinc binding site."
    Bogumil R., Knipp M., Fundel S.M., Vasak M.
    Biochemistry 37:4791-4798(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 2-12, CATALYTIC ACTIVITY, ENZYME REGULATION, ZINC BINDING, SUBUNIT, TISSUE SPECIFICITY, CIRCULAR DICHROISM.
    Tissue: Brain.
  4. "Isolation and characterization of a novel monomeric zinc- and heme-containing protein from bovine brain."
    Fundel S.M., Pountney D.L., Bogumil R., Gehrig P.M., Hasler D.W., Faller P., Vasak M.
    FEBS Lett. 395:33-38(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 46-57; 105-119 AND 180-200, CHARACTERIZATION.
    Tissue: Brain.
  5. "Structural and functional characterization of the Zn(II) site in dimethylargininase-1 (DDAH-1) from bovine brain. Zn(II) release activates DDAH-1."
    Knipp M., Charnock J.M., Garner C.D., Vasak M.
    J. Biol. Chem. 276:40449-40456(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ZINC BINDING, ENZYME REGULATION.
  6. "Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: a basis for the design of specific inhibitors."
    Frey D., Braun O., Briand C., Vasak M., Gruetter M.G.
    Structure 14:901-911(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG; INHIBITOR AND ZINC IONS.

Entry informationi

Entry nameiDDAH1_BOVIN
AccessioniPrimary (citable) accession number: P56965
Secondary accession number(s): A6QQU7, P81020
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be a heme protein, but this was later shown to be an artifact.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.