DDAH2_HUMAN
ID DDAH2_HUMAN Reviewed; 285 AA.
AC O95865; A2BEZ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=N(G),N(G)-dimethylarginine dimethylaminohydrolase 2;
DE Short=DDAH-2;
DE Short=Dimethylarginine dimethylaminohydrolase 2;
DE EC=3.5.3.18;
DE AltName: Full=DDAHII;
DE AltName: Full=Dimethylargininase-2;
DE AltName: Full=Protein G6a;
DE AltName: Full=S-phase protein;
GN Name=DDAH2; Synonyms=DDAH, G6A, NG30;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10493931; DOI=10.1042/bj3430209;
RA Leiper J.M., Santa Maria J., Chubb A., MacAllister R.J., Charles I.G.,
RA Whitley G.S., Vallance P.;
RT "Identification of two human dimethylarginine dimethylaminohydrolases with
RT distinct tissue distributions and homology with microbial arginine
RT deiminases.";
RL Biochem. J. 343:209-214(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10384126;
RA Ribas G., Neville M., Wixon J.L., Cheng J., Campbell R.D.;
RT "Genes encoding three new members of the leukocyte antigen 6 superfamily
RT and a novel member of Ig superfamily, together with genes encoding the
RT regulatory nuclear chloride ion channel protein (hRNCC) and an N omega-N
RT omega-dimethylarginine dimethylaminohydrolase homologue, are found in a 30-
RT kb segment of the MHC class III region.";
RL J. Immunol. 163:278-287(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yu L.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14656967; DOI=10.1101/gr.1736803;
RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D.,
RA Hood L.;
RT "Analysis of the gene-dense major histocompatibility complex class III
RT region and its comparison to mouse.";
RL Genome Res. 13:2621-2636(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 18-40; 113-134; 148-173 AND 268-285, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=21898353; DOI=10.1002/art.30652;
RA Cillero-Pastor B., Mateos J., Fernandez-Lopez C., Oreiro N.,
RA Ruiz-Romero C., Blanco F.J.;
RT "Dimethylarginine dimethylaminohydrolase 2, a newly identified
RT mitochondrial protein modulating nitric oxide synthesis in normal human
RT chondrocytes.";
RL Arthritis Rheum. 64:204-212(2012).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-
CC monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has
CC therefore a role in the regulation of nitric oxide generation.
CC {ECO:0000269|PubMed:10493931}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(omega),N(omega)-dimethyl-L-arginine = dimethylamine +
CC L-citrulline; Xref=Rhea:RHEA:17305, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57743, ChEBI:CHEBI:58040, ChEBI:CHEBI:58326; EC=3.5.3.18;
CC Evidence={ECO:0000269|PubMed:10493931};
CC -!- INTERACTION:
CC O95865; Q08043: ACTN3; NbExp=3; IntAct=EBI-749139, EBI-2880652;
CC O95865; Q9NW38: FANCL; NbExp=3; IntAct=EBI-749139, EBI-2339898;
CC O95865; Q86VF2-5: IGFN1; NbExp=3; IntAct=EBI-749139, EBI-11955401;
CC O95865; Q86UR1-2: NOXA1; NbExp=3; IntAct=EBI-749139, EBI-12025760;
CC O95865; O43741: PRKAB2; NbExp=3; IntAct=EBI-749139, EBI-1053424;
CC O95865; Q15645: TRIP13; NbExp=6; IntAct=EBI-749139, EBI-358993;
CC O95865; PRO_0000037314 [P0C6X7]: rep; Xeno; NbExp=2; IntAct=EBI-749139, EBI-25487672;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21898353}.
CC Mitochondrion {ECO:0000269|PubMed:21898353}. Note=Translocates from
CC cytosol to mitochondrion upon IL-1beta stimulation in chondrocytes.
CC -!- TISSUE SPECIFICITY: Detected in heart, placenta, lung, liver, skeletal
CC muscle, kidney and pancreas, and at very low levels in brain.
CC {ECO:0000269|PubMed:10493931}.
CC -!- SIMILARITY: Belongs to the DDAH family. {ECO:0000305}.
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DR EMBL; AF070667; AAD20973.1; -; mRNA.
DR EMBL; AJ012008; CAB46079.1; -; Genomic_DNA.
DR EMBL; AF087894; AAP97193.1; -; mRNA.
DR EMBL; AF129756; AAD18074.1; -; Genomic_DNA.
DR EMBL; BA000025; BAB63377.1; -; Genomic_DNA.
DR EMBL; AL662899; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL670886; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX248244; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR354443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR759787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR936239; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03500.1; -; Genomic_DNA.
DR EMBL; BC001435; AAH01435.1; -; mRNA.
DR CCDS; CCDS4718.1; -.
DR RefSeq; NP_001289936.1; NM_001303007.1.
DR RefSeq; NP_001289937.1; NM_001303008.1.
DR RefSeq; NP_039268.1; NM_013974.2.
DR RefSeq; XP_011512750.1; XM_011514448.2.
DR AlphaFoldDB; O95865; -.
DR SMR; O95865; -.
DR BioGRID; 117107; 68.
DR IntAct; O95865; 39.
DR MINT; O95865; -.
DR STRING; 9606.ENSP00000364945; -.
DR DrugBank; DB00155; Citrulline.
DR GlyGen; O95865; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O95865; -.
DR MetOSite; O95865; -.
DR PhosphoSitePlus; O95865; -.
DR BioMuta; DDAH2; -.
DR REPRODUCTION-2DPAGE; IPI00000760; -.
DR REPRODUCTION-2DPAGE; O95865; -.
DR EPD; O95865; -.
DR jPOST; O95865; -.
DR MassIVE; O95865; -.
DR PaxDb; O95865; -.
DR PeptideAtlas; O95865; -.
DR PRIDE; O95865; -.
DR ProteomicsDB; 51100; -.
DR Antibodypedia; 27580; 277 antibodies from 34 providers.
DR DNASU; 23564; -.
DR Ensembl; ENST00000375787.6; ENSP00000364943.2; ENSG00000213722.10.
DR Ensembl; ENST00000375789.7; ENSP00000364945.2; ENSG00000213722.10.
DR Ensembl; ENST00000375792.7; ENSP00000364949.3; ENSG00000213722.10.
DR Ensembl; ENST00000383409.6; ENSP00000372901.2; ENSG00000206395.8.
DR Ensembl; ENST00000400062.5; ENSP00000382935.1; ENSG00000206395.8.
DR Ensembl; ENST00000400063.7; ENSP00000382936.3; ENSG00000206395.8.
DR Ensembl; ENST00000411456.6; ENSP00000409396.2; ENSG00000226634.6.
DR Ensembl; ENST00000413532.5; ENSP00000402594.1; ENSG00000226634.6.
DR Ensembl; ENST00000413655.5; ENSP00000412800.1; ENSG00000233076.6.
DR Ensembl; ENST00000414455.5; ENSP00000404342.1; ENSG00000225635.7.
DR Ensembl; ENST00000416410.6; ENSP00000397466.2; ENSG00000213722.10.
DR Ensembl; ENST00000424790.5; ENSP00000391632.1; ENSG00000233076.6.
DR Ensembl; ENST00000426149.5; ENSP00000412327.1; ENSG00000228128.6.
DR Ensembl; ENST00000427126.5; ENSP00000395372.1; ENSG00000228128.6.
DR Ensembl; ENST00000430482.5; ENSP00000408148.1; ENSG00000227317.6.
DR Ensembl; ENST00000434464.6; ENSP00000391833.2; ENSG00000228128.6.
DR Ensembl; ENST00000436437.2; ENSP00000395759.2; ENSG00000213722.10.
DR Ensembl; ENST00000437889.6; ENSP00000399023.2; ENSG00000227317.6.
DR Ensembl; ENST00000443533.5; ENSP00000389552.1; ENSG00000226634.6.
DR Ensembl; ENST00000444699.5; ENSP00000404851.1; ENSG00000225635.7.
DR Ensembl; ENST00000447101.6; ENSP00000405515.2; ENSG00000233076.6.
DR Ensembl; ENST00000451411.5; ENSP00000403154.1; ENSG00000227317.6.
DR Ensembl; ENST00000454138.6; ENSP00000399357.2; ENSG00000225635.7.
DR GeneID; 23564; -.
DR KEGG; hsa:23564; -.
DR MANE-Select; ENST00000375789.7; ENSP00000364945.2; NM_001303007.2; NP_001289936.1.
DR CTD; 23564; -.
DR DisGeNET; 23564; -.
DR GeneCards; DDAH2; -.
DR HGNC; HGNC:2716; DDAH2.
DR HPA; ENSG00000213722; Low tissue specificity.
DR MIM; 604744; gene.
DR neXtProt; NX_O95865; -.
DR OpenTargets; ENSG00000213722; -.
DR PharmGKB; PA27186; -.
DR VEuPathDB; HostDB:ENSG00000213722; -.
DR eggNOG; ENOG502QW4J; Eukaryota.
DR GeneTree; ENSGT00940000160769; -.
DR InParanoid; O95865; -.
DR OMA; DIMANMC; -.
DR OrthoDB; 1469762at2759; -.
DR PhylomeDB; O95865; -.
DR TreeFam; TF314737; -.
DR BioCyc; MetaCyc:HS03493-MON; -.
DR BRENDA; 3.5.3.18; 2681.
DR PathwayCommons; O95865; -.
DR Reactome; R-HSA-203615; eNOS activation.
DR SignaLink; O95865; -.
DR BioGRID-ORCS; 23564; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; DDAH2; human.
DR GenomeRNAi; 23564; -.
DR Pharos; O95865; Tbio.
DR PRO; PR:O95865; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O95865; protein.
DR Bgee; ENSG00000213722; Expressed in ganglionic eminence and 92 other tissues.
DR ExpressionAtlas; O95865; baseline and differential.
DR Genevisible; O95865; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0016597; F:amino acid binding; IBA:GO_Central.
DR GO; GO:0003824; F:catalytic activity; TAS:ProtInc.
DR GO; GO:0016403; F:dimethylargininase activity; IDA:UniProtKB.
DR GO; GO:0006527; P:arginine catabolic process; TAS:ProtInc.
DR GO; GO:0006525; P:arginine metabolic process; IBA:GO_Central.
DR GO; GO:0000052; P:citrulline metabolic process; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; TAS:ProtInc.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
DR InterPro; IPR033199; DDAH.
DR InterPro; IPR033202; DDAH2.
DR PANTHER; PTHR12737; PTHR12737; 1.
DR PANTHER; PTHR12737:SF16; PTHR12737:SF16; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Mitochondrion;
KW Reference proteome.
FT CHAIN 1..285
FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase 2"
FT /id="PRO_0000171121"
FT ACT_SITE 171
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT ACT_SITE 276
FT /note="Nucleophile"
FT /evidence="ECO:0000255"
SQ SEQUENCE 285 AA; 29644 MW; B3D9B00F29492548 CRC64;
MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG KLRQRLGLQL
LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV DGVRKALQDL GLRIVEIGDE
NATLDGTDVL FTGREFFVGL SKWTNHRGAE IVADTFRDFA VSTVPVSGPS HLRGLCGMGG
PRTVVAGSSD AAQKAVRAMA VLTDHPYASL TLPDDAAADC LFLRPGLPGV PPFLLHRGGG
DLPNSQEALQ KLSDVTLVPV SCSELEKAGA GLSSLCLVLS TRPHS
