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Protein

N(G),N(G)-dimethylarginine dimethylaminohydrolase 2

Gene

DDAH2

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.1 Publication

Catalytic activityi

N(omega),N(omega)-dimethyl-L-arginine + H2O = dimethylamine + L-citrulline.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei171 – 1711Proton donorBy similarity
Active sitei276 – 2761NucleophileSequence Analysis

GO - Molecular functioni

  • amino acid binding Source: Ensembl
  • catalytic activity Source: ProtInc
  • dimethylargininase activity Source: UniProtKB

GO - Biological processi

  • arginine catabolic process Source: ProtInc
  • citrulline metabolic process Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • nitric oxide biosynthetic process Source: ProtInc
  • nitric oxide mediated signal transduction Source: ProtInc
  • positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Enzyme and pathway databases

BRENDAi3.5.3.18. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2 (EC:3.5.3.18)
Short name:
DDAH-2
Short name:
Dimethylarginine dimethylaminohydrolase 2
Alternative name(s):
DDAHII
Dimethylargininase-2
Protein G6a
S-phase protein
Gene namesi
Name:DDAH2
Synonyms:DDAH, G6A, NG30
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:2716. DDAH2.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: HPA
  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • mitochondrion Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27186.

Chemistry

DrugBankiDB00155. L-Citrulline.

Polymorphism and mutation databases

BioMutaiDDAH2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 285285N(G),N(G)-dimethylarginine dimethylaminohydrolase 2PRO_0000171121Add
BLAST

Proteomic databases

PaxDbiO95865.
PeptideAtlasiO95865.
PRIDEiO95865.

2D gel databases

REPRODUCTION-2DPAGEIPI00000760.
O95865.

PTM databases

PhosphoSiteiO95865.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO95865.
CleanExiHS_DDAH2.
ExpressionAtlasiO95865. baseline and differential.
GenevisibleiO95865. HS.

Organism-specific databases

HPAiHPA012509.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TRIP13Q156453EBI-749139,EBI-358993

Protein-protein interaction databases

BioGridi117107. 31 interactions.
IntActiO95865. 21 interactions.
MINTiMINT-5000845.
STRINGi9606.ENSP00000364943.

Structurei

3D structure databases

ProteinModelPortaliO95865.
SMRiO95865. Positions 7-279.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the DDAH family.Curated

Phylogenomic databases

eggNOGiNOG86337.
GeneTreeiENSGT00390000009331.
HOGENOMiHOG000161035.
HOVERGENiHBG055937.
InParanoidiO95865.
KOiK01482.
OMAiANCIYVR.
PhylomeDBiO95865.
TreeFamiTF314737.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

O95865-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG
60 70 80 90 100
KLRQRLGLQL LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV
110 120 130 140 150
DGVRKALQDL GLRIVEIGDE NATLDGTDVL FTGREFFVGL SKWTNHRGAE
160 170 180 190 200
IVADTFRDFA VSTVPVSGPS HLRGLCGMGG PRTVVAGSSD AAQKAVRAMA
210 220 230 240 250
VLTDHPYASL TLPDDAAADC LFLRPGLPGV PPFLLHRGGG DLPNSQEALQ
260 270 280
KLSDVTLVPV SCSELEKAGA GLSSLCLVLS TRPHS
Length:285
Mass (Da):29,644
Last modified:May 1, 1999 - v1
Checksum:iB3D9B00F29492548
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF070667 mRNA. Translation: AAD20973.1.
AJ012008 Genomic DNA. Translation: CAB46079.1.
AF087894 mRNA. Translation: AAP97193.1.
AF129756 Genomic DNA. Translation: AAD18074.1.
BA000025 Genomic DNA. Translation: BAB63377.1.
AL662899 Genomic DNA. Translation: CAI18413.1.
AL670886 Genomic DNA. Translation: CAI17820.1.
AL844216 Genomic DNA. Translation: CAM45772.1.
BX248244 Genomic DNA. Translation: CAM26098.1.
CR354443 Genomic DNA. Translation: CAQ07022.1.
CR759787 Genomic DNA. Translation: CAQ10110.1.
CR936239 Genomic DNA. Translation: CAQ08895.1.
CH471081 Genomic DNA. Translation: EAX03500.1.
BC001435 mRNA. Translation: AAH01435.1.
CCDSiCCDS4718.1.
RefSeqiNP_001289936.1. NM_001303007.1.
NP_001289937.1. NM_001303008.1.
NP_039268.1. NM_013974.2.
XP_011512750.1. XM_011514448.1.
XP_011545498.1. XM_011547196.1.
XP_011545912.1. XM_011547610.1.
XP_011546149.1. XM_011547847.1.
XP_011546318.1. XM_011548016.1.
XP_011546507.1. XM_011548205.1.
XP_011546691.1. XM_011548389.1.
UniGeneiHs.247362.

Genome annotation databases

EnsembliENST00000375787; ENSP00000364943; ENSG00000213722.
ENST00000375789; ENSP00000364945; ENSG00000213722.
ENST00000375792; ENSP00000364949; ENSG00000213722.
ENST00000383409; ENSP00000372901; ENSG00000206395.
ENST00000400062; ENSP00000382935; ENSG00000206395.
ENST00000400063; ENSP00000382936; ENSG00000206395.
ENST00000411456; ENSP00000409396; ENSG00000226634.
ENST00000413532; ENSP00000402594; ENSG00000226634.
ENST00000413655; ENSP00000412800; ENSG00000233076.
ENST00000414455; ENSP00000404342; ENSG00000225635.
ENST00000424790; ENSP00000391632; ENSG00000233076.
ENST00000426149; ENSP00000412327; ENSG00000228128.
ENST00000427126; ENSP00000395372; ENSG00000228128.
ENST00000430482; ENSP00000408148; ENSG00000227317.
ENST00000434464; ENSP00000391833; ENSG00000228128.
ENST00000437889; ENSP00000399023; ENSG00000227317.
ENST00000443533; ENSP00000389552; ENSG00000226634.
ENST00000444699; ENSP00000404851; ENSG00000225635.
ENST00000447101; ENSP00000405515; ENSG00000233076.
ENST00000451411; ENSP00000403154; ENSG00000227317.
ENST00000454138; ENSP00000399357; ENSG00000225635.
GeneIDi23564.
KEGGihsa:23564.
UCSCiuc003nwp.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF070667 mRNA. Translation: AAD20973.1.
AJ012008 Genomic DNA. Translation: CAB46079.1.
AF087894 mRNA. Translation: AAP97193.1.
AF129756 Genomic DNA. Translation: AAD18074.1.
BA000025 Genomic DNA. Translation: BAB63377.1.
AL662899 Genomic DNA. Translation: CAI18413.1.
AL670886 Genomic DNA. Translation: CAI17820.1.
AL844216 Genomic DNA. Translation: CAM45772.1.
BX248244 Genomic DNA. Translation: CAM26098.1.
CR354443 Genomic DNA. Translation: CAQ07022.1.
CR759787 Genomic DNA. Translation: CAQ10110.1.
CR936239 Genomic DNA. Translation: CAQ08895.1.
CH471081 Genomic DNA. Translation: EAX03500.1.
BC001435 mRNA. Translation: AAH01435.1.
CCDSiCCDS4718.1.
RefSeqiNP_001289936.1. NM_001303007.1.
NP_001289937.1. NM_001303008.1.
NP_039268.1. NM_013974.2.
XP_011512750.1. XM_011514448.1.
XP_011545498.1. XM_011547196.1.
XP_011545912.1. XM_011547610.1.
XP_011546149.1. XM_011547847.1.
XP_011546318.1. XM_011548016.1.
XP_011546507.1. XM_011548205.1.
XP_011546691.1. XM_011548389.1.
UniGeneiHs.247362.

3D structure databases

ProteinModelPortaliO95865.
SMRiO95865. Positions 7-279.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117107. 31 interactions.
IntActiO95865. 21 interactions.
MINTiMINT-5000845.
STRINGi9606.ENSP00000364943.

Chemistry

DrugBankiDB00155. L-Citrulline.

PTM databases

PhosphoSiteiO95865.

Polymorphism and mutation databases

BioMutaiDDAH2.

2D gel databases

REPRODUCTION-2DPAGEIPI00000760.
O95865.

Proteomic databases

PaxDbiO95865.
PeptideAtlasiO95865.
PRIDEiO95865.

Protocols and materials databases

DNASUi23564.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375787; ENSP00000364943; ENSG00000213722.
ENST00000375789; ENSP00000364945; ENSG00000213722.
ENST00000375792; ENSP00000364949; ENSG00000213722.
ENST00000383409; ENSP00000372901; ENSG00000206395.
ENST00000400062; ENSP00000382935; ENSG00000206395.
ENST00000400063; ENSP00000382936; ENSG00000206395.
ENST00000411456; ENSP00000409396; ENSG00000226634.
ENST00000413532; ENSP00000402594; ENSG00000226634.
ENST00000413655; ENSP00000412800; ENSG00000233076.
ENST00000414455; ENSP00000404342; ENSG00000225635.
ENST00000424790; ENSP00000391632; ENSG00000233076.
ENST00000426149; ENSP00000412327; ENSG00000228128.
ENST00000427126; ENSP00000395372; ENSG00000228128.
ENST00000430482; ENSP00000408148; ENSG00000227317.
ENST00000434464; ENSP00000391833; ENSG00000228128.
ENST00000437889; ENSP00000399023; ENSG00000227317.
ENST00000443533; ENSP00000389552; ENSG00000226634.
ENST00000444699; ENSP00000404851; ENSG00000225635.
ENST00000447101; ENSP00000405515; ENSG00000233076.
ENST00000451411; ENSP00000403154; ENSG00000227317.
ENST00000454138; ENSP00000399357; ENSG00000225635.
GeneIDi23564.
KEGGihsa:23564.
UCSCiuc003nwp.3. human.

Organism-specific databases

CTDi23564.
GeneCardsiGC06M031694.
GC06Mj31682.
GC06Mk31676.
GC06Ml31734.
GC06Mm31771.
GC06Mn31685.
GC06Mo31684.
HGNCiHGNC:2716. DDAH2.
HPAiHPA012509.
MIMi604744. gene.
neXtProtiNX_O95865.
PharmGKBiPA27186.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG86337.
GeneTreeiENSGT00390000009331.
HOGENOMiHOG000161035.
HOVERGENiHBG055937.
InParanoidiO95865.
KOiK01482.
OMAiANCIYVR.
PhylomeDBiO95865.
TreeFamiTF314737.

Enzyme and pathway databases

BRENDAi3.5.3.18. 2681.

Miscellaneous databases

ChiTaRSiDDAH2. human.
GenomeRNAii23564.
NextBioi46156.
PROiO95865.
SOURCEiSearch...

Gene expression databases

BgeeiO95865.
CleanExiHS_DDAH2.
ExpressionAtlasiO95865. baseline and differential.
GenevisibleiO95865. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "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], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY.
  2. "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
    Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X.
    , Gu J., Chen S.-J., Chen Z.
    Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Umbilical cord blood.
  3. "Genes encoding three new members of the leukocyte antigen 6 superfamily and a novel member of Ig superfamily, together with genes encoding the regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-kb segment of the MHC class III region."
    Ribas G., Neville M., Wixon J.L., Cheng J., Campbell R.D.
    J. Immunol. 163:278-287(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. Yu L.
    Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse."
    Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., Hood L.
    Genome Res. 13:2621-2636(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."
    Shiina S., Tamiya G., Oka A., Inoko H.
    Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "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].
    Tissue: Placenta.
  10. Lubec G., Vishwanath V., Chen W.-Q., Sun Y.
    Submitted (DEC-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 18-40; 113-134; 148-173 AND 268-285, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. "Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial protein modulating nitric oxide synthesis in normal human chondrocytes."
    Cillero-Pastor B., Mateos J., Fernandez-Lopez C., Oreiro N., Ruiz-Romero C., Blanco F.J.
    Arthritis Rheum. 64:204-212(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  13. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiDDAH2_HUMAN
AccessioniPrimary (citable) accession number: O95865
Secondary accession number(s): A2BEZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: July 22, 2015
This is version 134 of the entry and version 1 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.