Full text data of DDAH2
DDAH2
(DDAH, G6A, NG30)
[Confidence: low (only semi-automatic identification from reviews)]
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2; DDAH-2; Dimethylarginine dimethylaminohydrolase 2; 3.5.3.18 (DDAHII; Dimethylargininase-2; Protein G6a; S-phase protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
N(G),N(G)-dimethylarginine dimethylaminohydrolase 2; DDAH-2; Dimethylarginine dimethylaminohydrolase 2; 3.5.3.18 (DDAHII; Dimethylargininase-2; Protein G6a; S-phase protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O95865
ID DDAH2_HUMAN Reviewed; 285 AA.
AC O95865; A2BEZ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 118.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10493931; DOI=10.1042/0264-6021:3430209;
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
RT with distinct tissue distributions and homology with microbial
RT arginine 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
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor 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
RT superfamily and a novel member of Ig superfamily, together with genes
RT encoding the regulatory nuclear chloride ion channel protein (hRNCC)
RT and an N omega-N omega-dimethylarginine dimethylaminohydrolase
RT homologue, are found in a 30-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.,
RA Campbell R.D., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 MASS
RP 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.,
RA Buerckstuemmer T., 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
RT human chondrocytes.";
RL Arthritis Rheum. 64:204-212(2012).
CC -!- FUNCTION: Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and
CC N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS.
CC Has therefore a role in the regulation of nitric oxide generation.
CC -!- CATALYTIC ACTIVITY: N(omega),N(omega)-dimethyl-L-arginine + H(2)O
CC = dimethylamine + L-citrulline.
CC -!- INTERACTION:
CC Q15645:TRIP13; NbExp=3; IntAct=EBI-749139, EBI-358993;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Note=Translocates
CC from cytosol to mitochondrion upon IL-1beta stimulation in
CC chondrocytes.
CC -!- TISSUE SPECIFICITY: Detected in heart, placenta, lung, liver,
CC skeletal muscle, kidney and pancreas, and at very low levels in
CC brain.
CC -!- SIMILARITY: Belongs to the DDAH family.
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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; CAI18413.1; -; Genomic_DNA.
DR EMBL; AL670886; CAI17820.1; -; Genomic_DNA.
DR EMBL; AL844216; CAM45772.1; -; Genomic_DNA.
DR EMBL; BX248244; CAM26098.1; -; Genomic_DNA.
DR EMBL; CR354443; CAQ07022.1; -; Genomic_DNA.
DR EMBL; CR759787; CAQ10110.1; -; Genomic_DNA.
DR EMBL; CR936239; CAQ08895.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03500.1; -; Genomic_DNA.
DR EMBL; BC001435; AAH01435.1; -; mRNA.
DR RefSeq; NP_039268.1; NM_013974.1.
DR RefSeq; XP_005249031.1; XM_005248974.1.
DR RefSeq; XP_005249032.1; XM_005248975.1.
DR RefSeq; XP_005272840.1; XM_005272783.1.
DR RefSeq; XP_005272841.1; XM_005272784.1.
DR RefSeq; XP_005274986.1; XM_005274929.1.
DR RefSeq; XP_005274987.1; XM_005274930.1.
DR RefSeq; XP_005275143.1; XM_005275086.1.
DR RefSeq; XP_005275144.1; XM_005275087.1.
DR RefSeq; XP_005275282.1; XM_005275225.1.
DR RefSeq; XP_005275283.1; XM_005275226.1.
DR RefSeq; XP_005275418.1; XM_005275361.1.
DR RefSeq; XP_005275419.1; XM_005275362.1.
DR RefSeq; XP_005275579.1; XM_005275522.1.
DR RefSeq; XP_005275580.1; XM_005275523.1.
DR UniGene; Hs.247362; -.
DR ProteinModelPortal; O95865; -.
DR SMR; O95865; 7-279.
DR IntAct; O95865; 21.
DR MINT; MINT-5000845; -.
DR STRING; 9606.ENSP00000372901; -.
DR DrugBank; DB00155; L-Citrulline.
DR PhosphoSite; O95865; -.
DR REPRODUCTION-2DPAGE; IPI00000760; -.
DR REPRODUCTION-2DPAGE; O95865; -.
DR PaxDb; O95865; -.
DR PeptideAtlas; O95865; -.
DR PRIDE; O95865; -.
DR DNASU; 23564; -.
DR Ensembl; ENST00000375787; ENSP00000364943; ENSG00000213722.
DR Ensembl; ENST00000375789; ENSP00000364945; ENSG00000213722.
DR Ensembl; ENST00000375792; ENSP00000364949; ENSG00000213722.
DR Ensembl; ENST00000383409; ENSP00000372901; ENSG00000206395.
DR Ensembl; ENST00000400062; ENSP00000382935; ENSG00000206395.
DR Ensembl; ENST00000400063; ENSP00000382936; ENSG00000206395.
DR Ensembl; ENST00000411456; ENSP00000409396; ENSG00000226634.
DR Ensembl; ENST00000413532; ENSP00000402594; ENSG00000226634.
DR Ensembl; ENST00000413655; ENSP00000412800; ENSG00000233076.
DR Ensembl; ENST00000414455; ENSP00000404342; ENSG00000225635.
DR Ensembl; ENST00000424790; ENSP00000391632; ENSG00000233076.
DR Ensembl; ENST00000426149; ENSP00000412327; ENSG00000228128.
DR Ensembl; ENST00000427126; ENSP00000395372; ENSG00000228128.
DR Ensembl; ENST00000430482; ENSP00000408148; ENSG00000227317.
DR Ensembl; ENST00000434464; ENSP00000391833; ENSG00000228128.
DR Ensembl; ENST00000437889; ENSP00000399023; ENSG00000227317.
DR Ensembl; ENST00000443533; ENSP00000389552; ENSG00000226634.
DR Ensembl; ENST00000444699; ENSP00000404851; ENSG00000225635.
DR Ensembl; ENST00000447101; ENSP00000405515; ENSG00000233076.
DR Ensembl; ENST00000451411; ENSP00000403154; ENSG00000227317.
DR Ensembl; ENST00000454138; ENSP00000399357; ENSG00000225635.
DR GeneID; 23564; -.
DR KEGG; hsa:23564; -.
DR UCSC; uc003nwp.3; human.
DR CTD; 23564; -.
DR GeneCards; GC06M031694; -.
DR GeneCards; GC06Mj31682; -.
DR GeneCards; GC06Mk31676; -.
DR GeneCards; GC06Ml31734; -.
DR GeneCards; GC06Mm31771; -.
DR GeneCards; GC06Mn31685; -.
DR GeneCards; GC06Mo31684; -.
DR HGNC; HGNC:2716; DDAH2.
DR HPA; HPA012509; -.
DR MIM; 604744; gene.
DR neXtProt; NX_O95865; -.
DR PharmGKB; PA27186; -.
DR eggNOG; NOG86337; -.
DR HOGENOM; HOG000161035; -.
DR HOVERGEN; HBG055937; -.
DR InParanoid; O95865; -.
DR KO; K01482; -.
DR OMA; ALPFLLH; -.
DR PhylomeDB; O95865; -.
DR ChiTaRS; DDAH2; human.
DR GenomeRNAi; 23564; -.
DR NextBio; 46156; -.
DR PRO; PR:O95865; -.
DR ArrayExpress; O95865; -.
DR Bgee; O95865; -.
DR CleanEx; HS_DDAH2; -.
DR Genevestigator; O95865; -.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl.
DR GO; GO:0016403; F:dimethylargininase activity; IDA:UniProtKB.
DR GO; GO:0006527; P:arginine catabolic process; TAS:ProtInc.
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 InterPro; IPR003198; Amidino_trans.
DR Pfam; PF02274; Amidinotransf; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Mitochondrion; Reference proteome.
FT CHAIN 1 285 N(G),N(G)-dimethylarginine
FT dimethylaminohydrolase 2.
FT /FTId=PRO_0000171121.
FT ACT_SITE 171 171 Proton donor (By similarity).
FT ACT_SITE 276 276 Nucleophile (Potential).
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
//
ID DDAH2_HUMAN Reviewed; 285 AA.
AC O95865; A2BEZ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 118.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10493931; DOI=10.1042/0264-6021:3430209;
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
RT with distinct tissue distributions and homology with microbial
RT arginine 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
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor 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
RT superfamily and a novel member of Ig superfamily, together with genes
RT encoding the regulatory nuclear chloride ion channel protein (hRNCC)
RT and an N omega-N omega-dimethylarginine dimethylaminohydrolase
RT homologue, are found in a 30-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.,
RA Campbell R.D., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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 MASS
RP 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.,
RA Buerckstuemmer T., 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
RT human chondrocytes.";
RL Arthritis Rheum. 64:204-212(2012).
CC -!- FUNCTION: Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and
CC N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS.
CC Has therefore a role in the regulation of nitric oxide generation.
CC -!- CATALYTIC ACTIVITY: N(omega),N(omega)-dimethyl-L-arginine + H(2)O
CC = dimethylamine + L-citrulline.
CC -!- INTERACTION:
CC Q15645:TRIP13; NbExp=3; IntAct=EBI-749139, EBI-358993;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Note=Translocates
CC from cytosol to mitochondrion upon IL-1beta stimulation in
CC chondrocytes.
CC -!- TISSUE SPECIFICITY: Detected in heart, placenta, lung, liver,
CC skeletal muscle, kidney and pancreas, and at very low levels in
CC brain.
CC -!- SIMILARITY: Belongs to the DDAH family.
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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; CAI18413.1; -; Genomic_DNA.
DR EMBL; AL670886; CAI17820.1; -; Genomic_DNA.
DR EMBL; AL844216; CAM45772.1; -; Genomic_DNA.
DR EMBL; BX248244; CAM26098.1; -; Genomic_DNA.
DR EMBL; CR354443; CAQ07022.1; -; Genomic_DNA.
DR EMBL; CR759787; CAQ10110.1; -; Genomic_DNA.
DR EMBL; CR936239; CAQ08895.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03500.1; -; Genomic_DNA.
DR EMBL; BC001435; AAH01435.1; -; mRNA.
DR RefSeq; NP_039268.1; NM_013974.1.
DR RefSeq; XP_005249031.1; XM_005248974.1.
DR RefSeq; XP_005249032.1; XM_005248975.1.
DR RefSeq; XP_005272840.1; XM_005272783.1.
DR RefSeq; XP_005272841.1; XM_005272784.1.
DR RefSeq; XP_005274986.1; XM_005274929.1.
DR RefSeq; XP_005274987.1; XM_005274930.1.
DR RefSeq; XP_005275143.1; XM_005275086.1.
DR RefSeq; XP_005275144.1; XM_005275087.1.
DR RefSeq; XP_005275282.1; XM_005275225.1.
DR RefSeq; XP_005275283.1; XM_005275226.1.
DR RefSeq; XP_005275418.1; XM_005275361.1.
DR RefSeq; XP_005275419.1; XM_005275362.1.
DR RefSeq; XP_005275579.1; XM_005275522.1.
DR RefSeq; XP_005275580.1; XM_005275523.1.
DR UniGene; Hs.247362; -.
DR ProteinModelPortal; O95865; -.
DR SMR; O95865; 7-279.
DR IntAct; O95865; 21.
DR MINT; MINT-5000845; -.
DR STRING; 9606.ENSP00000372901; -.
DR DrugBank; DB00155; L-Citrulline.
DR PhosphoSite; O95865; -.
DR REPRODUCTION-2DPAGE; IPI00000760; -.
DR REPRODUCTION-2DPAGE; O95865; -.
DR PaxDb; O95865; -.
DR PeptideAtlas; O95865; -.
DR PRIDE; O95865; -.
DR DNASU; 23564; -.
DR Ensembl; ENST00000375787; ENSP00000364943; ENSG00000213722.
DR Ensembl; ENST00000375789; ENSP00000364945; ENSG00000213722.
DR Ensembl; ENST00000375792; ENSP00000364949; ENSG00000213722.
DR Ensembl; ENST00000383409; ENSP00000372901; ENSG00000206395.
DR Ensembl; ENST00000400062; ENSP00000382935; ENSG00000206395.
DR Ensembl; ENST00000400063; ENSP00000382936; ENSG00000206395.
DR Ensembl; ENST00000411456; ENSP00000409396; ENSG00000226634.
DR Ensembl; ENST00000413532; ENSP00000402594; ENSG00000226634.
DR Ensembl; ENST00000413655; ENSP00000412800; ENSG00000233076.
DR Ensembl; ENST00000414455; ENSP00000404342; ENSG00000225635.
DR Ensembl; ENST00000424790; ENSP00000391632; ENSG00000233076.
DR Ensembl; ENST00000426149; ENSP00000412327; ENSG00000228128.
DR Ensembl; ENST00000427126; ENSP00000395372; ENSG00000228128.
DR Ensembl; ENST00000430482; ENSP00000408148; ENSG00000227317.
DR Ensembl; ENST00000434464; ENSP00000391833; ENSG00000228128.
DR Ensembl; ENST00000437889; ENSP00000399023; ENSG00000227317.
DR Ensembl; ENST00000443533; ENSP00000389552; ENSG00000226634.
DR Ensembl; ENST00000444699; ENSP00000404851; ENSG00000225635.
DR Ensembl; ENST00000447101; ENSP00000405515; ENSG00000233076.
DR Ensembl; ENST00000451411; ENSP00000403154; ENSG00000227317.
DR Ensembl; ENST00000454138; ENSP00000399357; ENSG00000225635.
DR GeneID; 23564; -.
DR KEGG; hsa:23564; -.
DR UCSC; uc003nwp.3; human.
DR CTD; 23564; -.
DR GeneCards; GC06M031694; -.
DR GeneCards; GC06Mj31682; -.
DR GeneCards; GC06Mk31676; -.
DR GeneCards; GC06Ml31734; -.
DR GeneCards; GC06Mm31771; -.
DR GeneCards; GC06Mn31685; -.
DR GeneCards; GC06Mo31684; -.
DR HGNC; HGNC:2716; DDAH2.
DR HPA; HPA012509; -.
DR MIM; 604744; gene.
DR neXtProt; NX_O95865; -.
DR PharmGKB; PA27186; -.
DR eggNOG; NOG86337; -.
DR HOGENOM; HOG000161035; -.
DR HOVERGEN; HBG055937; -.
DR InParanoid; O95865; -.
DR KO; K01482; -.
DR OMA; ALPFLLH; -.
DR PhylomeDB; O95865; -.
DR ChiTaRS; DDAH2; human.
DR GenomeRNAi; 23564; -.
DR NextBio; 46156; -.
DR PRO; PR:O95865; -.
DR ArrayExpress; O95865; -.
DR Bgee; O95865; -.
DR CleanEx; HS_DDAH2; -.
DR Genevestigator; O95865; -.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016597; F:amino acid binding; IEA:Ensembl.
DR GO; GO:0016403; F:dimethylargininase activity; IDA:UniProtKB.
DR GO; GO:0006527; P:arginine catabolic process; TAS:ProtInc.
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 InterPro; IPR003198; Amidino_trans.
DR Pfam; PF02274; Amidinotransf; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Mitochondrion; Reference proteome.
FT CHAIN 1 285 N(G),N(G)-dimethylarginine
FT dimethylaminohydrolase 2.
FT /FTId=PRO_0000171121.
FT ACT_SITE 171 171 Proton donor (By similarity).
FT ACT_SITE 276 276 Nucleophile (Potential).
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
//
MIM
604744
*RECORD*
*FIELD* NO
604744
*FIELD* TI
*604744 DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 2; DDAH2
*FIELD* TX
DESCRIPTION
Dimethylarginine dimethylaminohydrolase (DDAH; EC 3.5.3.18) regulates
read morecellular methylarginine concentrations, which in turn inhibit nitric
oxide synthase (see 163731) activity.
CLONING
Leiper et al. (1999) isolated a cDNA encoding DDAHI (604743) and, by
screening a database of translated open reading frames with the deduced
DDAHI peptide sequence, identified DDAHII. Both DDAHI and DDAHII cDNAs
encode 285-amino acid proteins. The DDAHII amino acid sequence shares
98% identity with that of its mouse homolog and 62% identity with the
sequence of DDAHI. Northern blot analysis detected a 2.0-kb DDAHII
transcript expressed at highest levels in heart, kidney, and placenta.
By RNA dot blot analysis, Tran et al. (2000) determined that DDAH2
expression predominates in more highly vascularized tissues and in
immune tissues, while DDAH1 expression predominates in tissues that also
express the neuronal isoform of NOS (163731).
GENE FUNCTION
Leiper et al. (1999) expressed a histidine-tagged DDAHII clone in E.
coli and assayed the cell lysate for DDAH activity. Recombinant DDAHII
metabolized ADMA and L-NMMA, but not SDMA or L-arginine, demonstrating
that DDAHII is a functional homolog of DDAHI.
By overexpression in human and murine endothelial cells, Smith et al.
(2003) determined that DDAH2 reduced the secretion of ADMA, increased
VEGF mRNA expression, and enhanced tube formation by cells grown in a
3-dimensional medium. A DDAH inhibitor reduced tube formation in human
umbilical vein endothelial cells.
GENE STRUCTURE
Genomic sequence analysis by Tran et al. (2000) indicated that DDAH2
contains 8 exons with 3 transcription start sites that generate
alternatively spliced transcripts.
MAPPING
Tran et al. (2000) mapped the DDAH2 gene to 6p21.3 by radiation hybrid
and FISH analysis.
*FIELD* RF
1. Leiper, J. M,; Santa Maria, J.; Chubb, A.; MacAllister, R. J.;
Charles, I. G.; Whitley, G. S.; Vallance, P.: Identification of two
human dimethylarginine dimethylaminohydrolases with distinct tissue
distributions and homology with microbial arginine deiminases. Biochem.
J. 343: 209-214, 1999.
2. Smith, C. L.; Birdsey, G. M.; Anthony, S.; Arrigoni, F. I.; Leiper,
J. M.; Vallance, P.: Dimethylarginine dimethylaminohydrolase activity
modulates ADMA levels, VEGF expression, and cell phenotype. Biochem.
Biophys. Res. Commun. 308: 984-989, 2003.
3. Tran, C. T. L.; Fox, M. F.; Vallance, P.; Leiper, J. M.: Chromosomal
localization, gene structure, and expression pattern of DDAH1: comparison
with DDAH2 and implications for evolutionary origins. Genomics 68:
101-105, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 2/4/2005
Paul J. Converse - updated: 10/31/2000
*FIELD* CD
Stefanie A. Nelson: 3/27/2000
*FIELD* ED
alopez: 06/11/2008
mgross: 2/4/2005
mgross: 10/31/2000
alopez: 3/27/2000
*RECORD*
*FIELD* NO
604744
*FIELD* TI
*604744 DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 2; DDAH2
*FIELD* TX
DESCRIPTION
Dimethylarginine dimethylaminohydrolase (DDAH; EC 3.5.3.18) regulates
read morecellular methylarginine concentrations, which in turn inhibit nitric
oxide synthase (see 163731) activity.
CLONING
Leiper et al. (1999) isolated a cDNA encoding DDAHI (604743) and, by
screening a database of translated open reading frames with the deduced
DDAHI peptide sequence, identified DDAHII. Both DDAHI and DDAHII cDNAs
encode 285-amino acid proteins. The DDAHII amino acid sequence shares
98% identity with that of its mouse homolog and 62% identity with the
sequence of DDAHI. Northern blot analysis detected a 2.0-kb DDAHII
transcript expressed at highest levels in heart, kidney, and placenta.
By RNA dot blot analysis, Tran et al. (2000) determined that DDAH2
expression predominates in more highly vascularized tissues and in
immune tissues, while DDAH1 expression predominates in tissues that also
express the neuronal isoform of NOS (163731).
GENE FUNCTION
Leiper et al. (1999) expressed a histidine-tagged DDAHII clone in E.
coli and assayed the cell lysate for DDAH activity. Recombinant DDAHII
metabolized ADMA and L-NMMA, but not SDMA or L-arginine, demonstrating
that DDAHII is a functional homolog of DDAHI.
By overexpression in human and murine endothelial cells, Smith et al.
(2003) determined that DDAH2 reduced the secretion of ADMA, increased
VEGF mRNA expression, and enhanced tube formation by cells grown in a
3-dimensional medium. A DDAH inhibitor reduced tube formation in human
umbilical vein endothelial cells.
GENE STRUCTURE
Genomic sequence analysis by Tran et al. (2000) indicated that DDAH2
contains 8 exons with 3 transcription start sites that generate
alternatively spliced transcripts.
MAPPING
Tran et al. (2000) mapped the DDAH2 gene to 6p21.3 by radiation hybrid
and FISH analysis.
*FIELD* RF
1. Leiper, J. M,; Santa Maria, J.; Chubb, A.; MacAllister, R. J.;
Charles, I. G.; Whitley, G. S.; Vallance, P.: Identification of two
human dimethylarginine dimethylaminohydrolases with distinct tissue
distributions and homology with microbial arginine deiminases. Biochem.
J. 343: 209-214, 1999.
2. Smith, C. L.; Birdsey, G. M.; Anthony, S.; Arrigoni, F. I.; Leiper,
J. M.; Vallance, P.: Dimethylarginine dimethylaminohydrolase activity
modulates ADMA levels, VEGF expression, and cell phenotype. Biochem.
Biophys. Res. Commun. 308: 984-989, 2003.
3. Tran, C. T. L.; Fox, M. F.; Vallance, P.; Leiper, J. M.: Chromosomal
localization, gene structure, and expression pattern of DDAH1: comparison
with DDAH2 and implications for evolutionary origins. Genomics 68:
101-105, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 2/4/2005
Paul J. Converse - updated: 10/31/2000
*FIELD* CD
Stefanie A. Nelson: 3/27/2000
*FIELD* ED
alopez: 06/11/2008
mgross: 2/4/2005
mgross: 10/31/2000
alopez: 3/27/2000