ID DDAH1_HUMAN Reviewed; 285 AA. AC O94760; Q5HYC8; Q86XK5; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 195. DE RecName: Full=N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 {ECO:0000305}; DE Short=DDAH-1; DE Short=Dimethylarginine dimethylaminohydrolase 1; DE EC=3.5.3.18 {ECO:0000269|PubMed:18171027, ECO:0000269|PubMed:19663506, ECO:0000269|PubMed:21493890, ECO:0000269|PubMed:37296100}; DE AltName: Full=DDAHI; DE AltName: Full=Dimethylargininase-1; GN Name=DDAH1 {ECO:0000312|HGNC:HGNC:2715}; Synonyms=DDAH; 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] (ISOFORM 1), PROTEIN SEQUENCE OF 2-12 AND 35-50, RP ABSENCE OF BOUND ZINC, AND ACETYLATION AT ALA-2. RC TISSUE=Kidney, and Liver; RX PubMed=9874257; DOI=10.1046/j.1432-1327.1998.2580863.x; RA Kimoto M., Miyatake S., Sasagawa T., Yamashita H., Okita M., Oka T., RA Ogawa T., Tsuji H.; RT "Purification, cDNA cloning and expression of human NG,NG-dimethylarginine RT dimethylaminohydrolase."; RL Eur. J. Biochem. 258:863-868(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Endometrial cancer; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, Kidney, Stomach, and Testis; 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 [7] RP PROTEIN SEQUENCE OF 20-31; 46-57; 112-136; 150-196; 212-230 AND 268-281, RP AND IDENTIFICATION 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 [8] RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION BY MASS RP SPECTROMETRY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION. RX PubMed=18171027; DOI=10.1021/bi701659n; RA Forbes S.P., Druhan L.J., Guzman J.E., Parinandi N., Zhang L., RA Green-Church K.B., Cardounel A.J.; RT "Mechanism of 4-HNE mediated inhibition of hDDAH-1: implications in NO RT regulation."; RL Biochemistry 47:1819-1826(2008). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=21493890; DOI=10.1161/atvbaha.110.222638; RA Hu X., Atzler D., Xu X., Zhang P., Guo H., Lu Z., Fassett J., RA Schwedhelm E., Boeger R.H., Bache R.J., Chen Y.; RT "Dimethylarginine dimethylaminohydrolase-1 is the critical enzyme for RT degrading the cardiovascular risk factor asymmetrical dimethylarginine."; RL Arterioscler. Thromb. Vasc. Biol. 31:1540-1546(2011). 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 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). RN [13] RP FUNCTION. RX PubMed=37296100; DOI=10.1038/s41467-023-38467-9; RA Ragavan V.N., Nair P.C., Jarzebska N., Angom R.S., Ruta L., Bianconi E., RA Grottelli S., Tararova N.D., Ryazanskiy D., Lentz S.R., Tommasi S., RA Martens-Lobenhoffer J., Suzuki-Yamamoto T., Kimoto M., Rubets E., Chau S., RA Chen Y., Hu X., Bernhardt N., Spieth P.M., Weiss N., Bornstein S.R., RA Mukhopadhyay D., Bode-Boeger S.M., Maas R., Wang Y., Macchiarulo A., RA Mangoni A.A., Cellini B., Rodionov R.N.; RT "A multicentric consortium study demonstrates that dimethylarginine RT dimethylaminohydrolase 2 is not a dimethylarginine RT dimethylaminohydrolase."; RL Nat. Commun. 14:3392-3392(2023). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-284 IN COMPLEXES WITH CITRULLINE RP AND INHIBITOR L-257. RX PubMed=17273169; DOI=10.1038/nm1543; RA Leiper J., Nandi M., Torondel B., Murray-Rust J., Malaki M., O'Hara B., RA Rossiter S., Anthony S., Madhani M., Selwood D., Smith C., RA Wojciak-Stothard B., Rudiger A., Stidwill R., McDonald N.Q., Vallance P.; RT "Disruption of methylarginine metabolism impairs vascular homeostasis."; RL Nat. Med. 13:198-203(2007). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH RP N-1-IMINOPROPYL-L-ORNITHINE, CATALYTIC ACTIVITY, ZINC-BINDING, ACTIVITY RP REGULATION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, RP MUTAGENESIS OF LEU-30; GLU-78 AND LEU-271, IDENTIFICATION BY MASS RP SPECTROMETRY, AND FUNCTION. RX PubMed=19663506; DOI=10.1021/bi9007098; RA Wang Y., Monzingo A.F., Hu S., Schaller T.H., Robertus J.D., Fast W.; RT "Developing dual and specific inhibitors of dimethylarginine RT dimethylaminohydrolase-1 and nitric oxide synthase: toward a targeted RT polypharmacology to control nitric oxide."; RL Biochemistry 48:8624-8635(2009). 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:18171027, ECO:0000269|PubMed:19663506, CC ECO:0000269|PubMed:21493890, ECO:0000269|PubMed:37296100}. 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:18171027, ECO:0000269|PubMed:19663506, CC ECO:0000269|PubMed:21493890, ECO:0000269|PubMed:37296100}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17306; CC Evidence={ECO:0000305|PubMed:19663506}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N(omega)-methyl-L-arginine = L-citrulline + methylamine; CC Xref=Rhea:RHEA:25173, ChEBI:CHEBI:15377, ChEBI:CHEBI:57743, CC ChEBI:CHEBI:59338, ChEBI:CHEBI:114953; EC=3.5.3.18; CC Evidence={ECO:0000269|PubMed:18171027, ECO:0000269|PubMed:19663506}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25174; CC Evidence={ECO:0000305|PubMed:19663506}; CC -!- ACTIVITY REGULATION: Inhibited by zinc ions (By similarity). Enzyme CC purified in the absence of 1,10-phenanthroline contains on average 0.4 CC zinc atoms per subunit. Inhibited by 4-hydroxy-nonenal through the CC formation of a covalent adduct with His-173. Competitively inhibited by CC N(5)-iminopropyl-ornithine. {ECO:0000250, ECO:0000269|PubMed:18171027, CC ECO:0000269|PubMed:19663506}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=69 uM for asymmetric dimethylarginine (ADMA) CC {ECO:0000269|PubMed:18171027, ECO:0000269|PubMed:19663506}; CC KM=54 uM for monomethyl-L-arginine (MMA) CC {ECO:0000269|PubMed:18171027, ECO:0000269|PubMed:19663506}; CC KM=3.1 uM for S-methyl-L-thiocitrulline {ECO:0000269|PubMed:18171027, CC ECO:0000269|PubMed:19663506}; CC Vmax=356 nmol/min/mg enzyme with ADMA {ECO:0000269|PubMed:18171027, CC ECO:0000269|PubMed:19663506}; CC Vmax=154 nmol/min/mg enzyme with NMA {ECO:0000269|PubMed:18171027, CC ECO:0000269|PubMed:19663506}; CC pH dependence: CC Optimum pH is 8.5. {ECO:0000269|PubMed:18171027, CC ECO:0000269|PubMed:19663506}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:19663506}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O94760-1; Sequence=Displayed; CC Name=2; CC IsoId=O94760-2; Sequence=VSP_043813; CC -!- TISSUE SPECIFICITY: Detected in brain, liver, kidney and pancreas, and CC at low levels in skeletal muscle. {ECO:0000269|PubMed:10493931}. CC -!- SIMILARITY: Belongs to the DDAH family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB001915; BAA37117.1; -; mRNA. DR EMBL; BX648145; CAI45988.1; -; mRNA. DR EMBL; AC092807; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL078459; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL360219; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471097; EAW73199.1; -; Genomic_DNA. DR EMBL; BC033680; AAH33680.1; -; mRNA. DR EMBL; BC043235; AAH43235.2; -; mRNA. DR CCDS; CCDS44170.1; -. [O94760-2] DR CCDS; CCDS705.1; -. [O94760-1] DR RefSeq; NP_001127917.1; NM_001134445.1. [O94760-2] DR RefSeq; NP_036269.1; NM_012137.3. [O94760-1] DR RefSeq; XP_005270767.1; XM_005270710.2. [O94760-2] DR PDB; 2JAI; X-ray; 2.30 A; A/B=1-285. DR PDB; 2JAJ; X-ray; 2.00 A; A/B=1-285. DR PDB; 3I2E; X-ray; 2.03 A; A/B=1-285. DR PDB; 3I4A; X-ray; 1.90 A; A/B=1-285. DR PDB; 3P8E; X-ray; 2.49 A; A/B=1-285. DR PDB; 3P8P; X-ray; 2.50 A; A/B=1-285. DR PDB; 6DGE; X-ray; 1.91 A; A=1-285. DR PDB; 6SZP; X-ray; 1.76 A; A=1-285. DR PDB; 6SZQ; X-ray; 2.41 A; A/B/C/D/E/F=1-285. DR PDB; 7ULU; X-ray; 2.20 A; A/B=1-285. DR PDB; 7ULV; X-ray; 2.37 A; A/B/C/D/E/F=1-285. DR PDB; 7ULX; X-ray; 1.71 A; A/B=1-285. DR PDB; 7USZ; X-ray; 1.65 A; A/B=2-285. DR PDB; 7UT0; X-ray; 1.68 A; A/B=2-285. DR PDBsum; 2JAI; -. DR PDBsum; 2JAJ; -. DR PDBsum; 3I2E; -. DR PDBsum; 3I4A; -. DR PDBsum; 3P8E; -. DR PDBsum; 3P8P; -. DR PDBsum; 6DGE; -. DR PDBsum; 6SZP; -. DR PDBsum; 6SZQ; -. DR PDBsum; 7ULU; -. DR PDBsum; 7ULV; -. DR PDBsum; 7ULX; -. DR PDBsum; 7USZ; -. DR PDBsum; 7UT0; -. DR AlphaFoldDB; O94760; -. DR SMR; O94760; -. DR BioGRID; 117114; 49. DR DIP; DIP-61582N; -. DR IntAct; O94760; 15. DR STRING; 9606.ENSP00000284031; -. DR BindingDB; O94760; -. DR ChEMBL; CHEMBL6036; -. DR DrugBank; DB00155; Citrulline. DR DrugBank; DB05351; Dexlansoprazole. DR DrugBank; DB00736; Esomeprazole. DR DrugBank; DB00213; Pantoprazole. DR GuidetoPHARMACOLOGY; 1247; -. DR GlyGen; O94760; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O94760; -. DR PhosphoSitePlus; O94760; -. DR SwissPalm; O94760; -. DR BioMuta; DDAH1; -. DR REPRODUCTION-2DPAGE; IPI00220342; -. DR EPD; O94760; -. DR jPOST; O94760; -. DR MassIVE; O94760; -. DR MaxQB; O94760; -. DR PaxDb; 9606-ENSP00000284031; -. DR PeptideAtlas; O94760; -. DR ProteomicsDB; 50422; -. [O94760-1] DR ProteomicsDB; 50423; -. [O94760-2] DR Pumba; O94760; -. DR Antibodypedia; 1588; 348 antibodies from 35 providers. DR DNASU; 23576; -. DR Ensembl; ENST00000284031.13; ENSP00000284031.8; ENSG00000153904.21. [O94760-1] DR Ensembl; ENST00000426972.8; ENSP00000411189.4; ENSG00000153904.21. [O94760-2] DR GeneID; 23576; -. DR KEGG; hsa:23576; -. DR MANE-Select; ENST00000284031.13; ENSP00000284031.8; NM_012137.4; NP_036269.1. DR UCSC; uc001dlb.4; human. [O94760-1] DR AGR; HGNC:2715; -. DR CTD; 23576; -. DR DisGeNET; 23576; -. DR GeneCards; DDAH1; -. DR HGNC; HGNC:2715; DDAH1. DR HPA; ENSG00000153904; Tissue enhanced (kidney). DR MIM; 604743; gene. DR neXtProt; NX_O94760; -. DR OpenTargets; ENSG00000153904; -. DR PharmGKB; PA27185; -. DR VEuPathDB; HostDB:ENSG00000153904; -. DR eggNOG; ENOG502QWPA; Eukaryota. DR GeneTree; ENSGT00940000157892; -. DR HOGENOM; CLU_115111_0_0_1; -. DR InParanoid; O94760; -. DR OMA; HRYTHAI; -. DR OrthoDB; 315054at2759; -. DR PhylomeDB; O94760; -. DR TreeFam; TF314737; -. DR BioCyc; MetaCyc:HS00016-MONOMER; -. DR BRENDA; 3.5.3.18; 2681. DR PathwayCommons; O94760; -. DR Reactome; R-HSA-203615; eNOS activation. DR SignaLink; O94760; -. DR BioGRID-ORCS; 23576; 17 hits in 1152 CRISPR screens. DR ChiTaRS; DDAH1; human. DR EvolutionaryTrace; O94760; -. DR GenomeRNAi; 23576; -. DR Pharos; O94760; Tchem. DR PRO; PR:O94760; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O94760; Protein. DR Bgee; ENSG00000153904; Expressed in endothelial cell and 207 other cell types or tissues. DR ExpressionAtlas; O94760; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. 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:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL. DR GO; GO:0006525; P:arginine metabolic process; IBA:GO_Central. DR GO; GO:0000052; P:citrulline metabolic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; IDA:BHF-UCL. DR GO; GO:0043116; P:negative regulation of vascular permeability; IDA:BHF-UCL. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; TAS:ProtInc. DR GO; GO:0046209; P:nitric oxide metabolic process; TAS:Reactome. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:BHF-UCL. DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; ISS:BHF-UCL. DR InterPro; IPR033199; DDAH-like. DR PANTHER; PTHR12737; DIMETHYLARGININE DIMETHYLAMINOHYDROLASE; 1. DR PANTHER; PTHR12737:SF17; N(G),N(G)-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 1; 1. DR Pfam; PF19420; DDAH_eukar; 1. DR SUPFAM; SSF55909; Pentein; 1. DR Genevisible; O94760; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Hydrolase; Metal-binding; Reference proteome; S-nitrosylation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9874257, FT ECO:0007744|PubMed:19413330" FT CHAIN 2..285 FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase 1" FT /id="PRO_0000171118" FT ACT_SITE 173 FT /note="Proton donor" FT /evidence="ECO:0000305|PubMed:19663506" FT ACT_SITE 274 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:19663506" FT BINDING 30 FT /ligand="substrate" FT BINDING 73 FT /ligand="substrate" FT BINDING 78..79 FT /ligand="substrate" FT BINDING 98 FT /ligand="substrate" FT BINDING 145 FT /ligand="substrate" FT BINDING 268 FT /ligand="substrate" FT BINDING 274 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|PubMed:9874257, FT ECO:0007744|PubMed:19413330" FT MOD_RES 222 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P56965" FT MOD_RES 274 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:P56965" FT VAR_SEQ 1..103 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_043813" FT MUTAGEN 30 FT /note="L->A: Reduces enzyme activity and affinity for FT asymmetric dimethylarginine about 12-fold." FT /evidence="ECO:0000269|PubMed:19663506" FT MUTAGEN 78 FT /note="E->A: Reduces enzyme activity about 1000-fold, and FT affinity for asymmetric dimethylarginine about 100-fold." FT /evidence="ECO:0000269|PubMed:19663506" FT MUTAGEN 271 FT /note="L->G: Reduces enzyme activity about 10-fold, and FT affinity for asymmetric dimethylarginine about 7-fold." FT /evidence="ECO:0000269|PubMed:19663506" FT HELIX 2..4 FT /evidence="ECO:0007829|PDB:7UT0" FT STRAND 14..19 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 25..28 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 40..54 FT /evidence="ECO:0007829|PDB:7USZ" FT TURN 55..58 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 61..65 FT /evidence="ECO:0007829|PDB:7USZ" FT TURN 72..75 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 77..80 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 81..84 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 87..90 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 96..101 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 102..111 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 135..142 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 148..157 FT /evidence="ECO:0007829|PDB:7USZ" FT TURN 158..160 FT /evidence="ECO:0007829|PDB:6SZP" FT STRAND 161..167 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 174..176 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 177..182 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 185..189 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 192..204 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:7UT0" FT STRAND 210..216 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 217..220 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 223..227 FT /evidence="ECO:0007829|PDB:7USZ" FT TURN 228..230 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 231..236 FT /evidence="ECO:0007829|PDB:7USZ" FT TURN 239..241 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 243..249 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 265..268 FT /evidence="ECO:0007829|PDB:7USZ" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:7USZ" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:7USZ" SQ SEQUENCE 285 AA; 31122 MW; CD8875DF267EF39B CRC64; MAGLGHPAAF GRATHAVVRA LPESLGQHAL RSAKGEEVDV ARAERQHQLY VGVLGSKLGL QVVELPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK EVDMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG AEILADTFKD YAVSTVPVAD GLHLKSFCSM AGPNLIAIGS SESAQKALKI MQQMSDHRYD KLTVPDDIAA NCIYLNIPNK GHVLLHRTPE EYPESAKVYE KLKDHMLIPV SMSELEKVDG LLTCCSVLIN KKVDS //