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O95865

- DDAH2_HUMAN

UniProt

O95865 - DDAH2_HUMAN

Protein

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

Gene

DDAH2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 May 1999)
      Previous versions | rss
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    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

    1. amino acid binding Source: Ensembl
    2. catalytic activity Source: ProtInc
    3. dimethylargininase activity Source: UniProtKB
    4. protein binding Source: IntAct

    GO - Biological processi

    1. arginine catabolic process Source: ProtInc
    2. citrulline metabolic process Source: UniProtKB
    3. negative regulation of apoptotic process Source: UniProtKB
    4. nitric oxide biosynthetic process Source: ProtInc
    5. nitric oxide mediated signal transduction Source: ProtInc
    6. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL

    Keywords - Molecular functioni

    Hydrolase

    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: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:2716. DDAH2.

    Subcellular locationi

    Cytoplasm 1 Publication. Mitochondrion 1 Publication
    Note: Translocates from cytosol to mitochondrion upon IL-1beta stimulation in chondrocytes.

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. mitochondrion Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27186.

    PTM / Processingi

    Molecule processing

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

    Proteomic databases

    MaxQBiO95865.
    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

    ArrayExpressiO95865.
    BgeeiO95865.
    CleanExiHS_DDAH2.
    GenevestigatoriO95865.

    Organism-specific databases

    HPAiHPA012509.

    Interactioni

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi117107. 24 interactions.
    IntActiO95865. 21 interactions.
    MINTiMINT-5000845.
    STRINGi9606.ENSP00000372901.

    Structurei

    3D structure databases

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

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the DDAH family.Curated

    Phylogenomic databases

    eggNOGiNOG86337.
    HOGENOMiHOG000161035.
    HOVERGENiHBG055937.
    InParanoidiO95865.
    KOiK01482.
    OMAiALPFLLH.
    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

    MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG    50
    KLRQRLGLQL LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV 100
    DGVRKALQDL GLRIVEIGDE NATLDGTDVL FTGREFFVGL SKWTNHRGAE 150
    IVADTFRDFA VSTVPVSGPS HLRGLCGMGG PRTVVAGSSD AAQKAVRAMA 200
    VLTDHPYASL TLPDDAAADC LFLRPGLPGV PPFLLHRGGG DLPNSQEALQ 250
    KLSDVTLVPV SCSELEKAGA GLSSLCLVLS TRPHS 285
    Length:285
    Mass (Da):29,644
    Last modified:May 1, 1999 - v1
    Checksum:iB3D9B00F29492548
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_039268.1. NM_013974.1.
    XP_005249031.1. XM_005248974.2.
    XP_005272840.1. XM_005272783.2.
    XP_005274986.1. XM_005274929.2.
    XP_005275143.1. XM_005275086.2.
    XP_005275282.1. XM_005275225.2.
    XP_005275418.1. XM_005275361.2.
    XP_005275579.1. XM_005275522.2.
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS4718.1.
    RefSeqi NP_039268.1. NM_013974.1.
    XP_005249031.1. XM_005248974.2.
    XP_005272840.1. XM_005272783.2.
    XP_005274986.1. XM_005274929.2.
    XP_005275143.1. XM_005275086.2.
    XP_005275282.1. XM_005275225.2.
    XP_005275418.1. XM_005275361.2.
    XP_005275579.1. XM_005275522.2.
    UniGenei Hs.247362.

    3D structure databases

    ProteinModelPortali O95865.
    SMRi O95865. Positions 7-279.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117107. 24 interactions.
    IntActi O95865. 21 interactions.
    MINTi MINT-5000845.
    STRINGi 9606.ENSP00000372901.

    Chemistry

    DrugBanki DB00155. L-Citrulline.

    PTM databases

    PhosphoSitei O95865.

    2D gel databases

    REPRODUCTION-2DPAGE IPI00000760.
    O95865.

    Proteomic databases

    MaxQBi O95865.
    PaxDbi O95865.
    PeptideAtlasi O95865.
    PRIDEi O95865.

    Protocols and materials databases

    DNASUi 23564.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000375787 ; 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 .
    GeneIDi 23564.
    KEGGi hsa:23564.
    UCSCi uc003nwp.3. human.

    Organism-specific databases

    CTDi 23564.
    GeneCardsi GC06M031694.
    GC06Mj31682.
    GC06Mk31676.
    GC06Ml31734.
    GC06Mm31771.
    GC06Mn31685.
    GC06Mo31684.
    HGNCi HGNC:2716. DDAH2.
    HPAi HPA012509.
    MIMi 604744. gene.
    neXtProti NX_O95865.
    PharmGKBi PA27186.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG86337.
    HOGENOMi HOG000161035.
    HOVERGENi HBG055937.
    InParanoidi O95865.
    KOi K01482.
    OMAi ALPFLLH.
    PhylomeDBi O95865.
    TreeFami TF314737.

    Miscellaneous databases

    ChiTaRSi DDAH2. human.
    GenomeRNAii 23564.
    NextBioi 46156.
    PROi O95865.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95865.
    Bgeei O95865.
    CleanExi HS_DDAH2.
    Genevestigatori O95865.

    Family and domain databases

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

    Publicationsi

    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.

    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: October 1, 2014
    This is version 125 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