ID DDAH1_RAT Reviewed; 285 AA. AC O08557; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 154. DE RecName: Full=N(G),N(G)-dimethylarginine dimethylaminohydrolase 1; DE Short=DDAH-1; DE Short=Dimethylarginine dimethylaminohydrolase 1; DE EC=3.5.3.18; DE AltName: Full=DDAHI; DE AltName: Full=Dimethylargininase-1; GN Name=Ddah1; Synonyms=Ddah; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND ACETYLATION AT RP ALA-2. RC STRAIN=Wistar; TISSUE=Kidney; RX PubMed=9003431; DOI=10.1016/s0167-4838(96)00196-3; RA Kimoto M., Sasakawa T., Tsuji H., Miyatake S., Oka T., Nio N., Ogawa T.; RT "Cloning and sequencing of cDNA encoding NG,NG-dimethylarginine RT dimethylaminohydrolase from rat kidney."; RL Biochim. Biophys. Acta 1337:6-10(1997). RN [2] RP PROTEIN SEQUENCE OF 46-57; 112-136 AND 160-175, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord; RA Lubec G., Afjehi-Sadat L., Chen W.-Q.; RL Submitted (APR-2007) to UniProtKB. RN [3] RP FUNCTION, ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RX PubMed=16632550; DOI=10.1152/ajpheart.00066.2006; RA Billecke S.S., Kitzmiller L.A., Northrup J.J., Whitesall S.E., Kimoto M., RA Hinz A.V., D'Alecy L.G.; RT "Contribution of whole blood to the control of plasma asymmetrical RT dimethylarginine."; RL Am. J. Physiol. 291:H1788-H1796(2006). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-33, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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:16632550}. 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 -!- 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:0000250|UniProtKB:O94760}; CC -!- ACTIVITY REGULATION: Inhibited by zinc ions. CC {ECO:0000269|PubMed:16632550}. CC -!- SUBUNIT: Monomer. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Detected in red blood cells (at protein level). CC Widely distributed, high amounts found in kidney, brain, aorta and CC pancreas. {ECO:0000269|PubMed:16632550}. 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; D86041; BAA18993.1; -; mRNA. DR RefSeq; NP_071633.1; NM_022297.2. DR AlphaFoldDB; O08557; -. DR SMR; O08557; -. DR IntAct; O08557; 1. DR STRING; 10116.ENSRNOP00000044971; -. DR BindingDB; O08557; -. DR ChEMBL; CHEMBL4196; -. DR iPTMnet; O08557; -. DR PhosphoSitePlus; O08557; -. DR SwissPalm; O08557; -. DR jPOST; O08557; -. DR PaxDb; 10116-ENSRNOP00000044971; -. DR Ensembl; ENSRNOT00000045016.5; ENSRNOP00000044971.3; ENSRNOG00000014613.8. DR Ensembl; ENSRNOT00055042787; ENSRNOP00055034943; ENSRNOG00055024828. DR Ensembl; ENSRNOT00060001034; ENSRNOP00060000339; ENSRNOG00060000840. DR Ensembl; ENSRNOT00065020806; ENSRNOP00065016012; ENSRNOG00065012752. DR GeneID; 64157; -. DR KEGG; rno:64157; -. DR AGR; RGD:70968; -. DR CTD; 23576; -. DR RGD; 70968; Ddah1. DR eggNOG; ENOG502QWPA; Eukaryota. DR GeneTree; ENSGT00940000157892; -. DR HOGENOM; CLU_067923_0_0_1; -. DR InParanoid; O08557; -. DR OMA; HRYTHAI; -. DR OrthoDB; 315054at2759; -. DR PhylomeDB; O08557; -. DR BRENDA; 3.5.3.18; 5301. DR Reactome; R-RNO-203615; eNOS activation. DR SABIO-RK; O08557; -. DR PRO; PR:O08557; -. DR Proteomes; UP000002494; Chromosome 2. DR Bgee; ENSRNOG00000014613; Expressed in adult mammalian kidney and 19 other cell types or tissues. DR GO; GO:0016597; F:amino acid binding; IDA:RGD. DR GO; GO:0016403; F:dimethylargininase activity; IDA:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006527; P:arginine catabolic process; ISO:RGD. DR GO; GO:0006525; P:arginine metabolic process; IDA:RGD. DR GO; GO:0000052; P:citrulline metabolic process; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD. DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; ISO:RGD. DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:RGD. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:RGD. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:RGD. DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; ISO:RGD. 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; O08557; RN. PE 1: Evidence at protein level; KW Acetylation; Direct protein sequencing; Hydrolase; Metal-binding; KW Phosphoprotein; Reference proteome; S-nitrosylation; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9003431" FT CHAIN 2..285 FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase 1" FT /id="PRO_0000171120" FT ACT_SITE 173 FT /note="Proton donor" FT /evidence="ECO:0000250" FT ACT_SITE 274 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT BINDING 30 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 73 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 78 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 79 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 145 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 268 FT /ligand="substrate" FT /evidence="ECO:0000250" 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:9003431" FT MOD_RES 33 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" 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" SQ SEQUENCE 285 AA; 31426 MW; 9FE8DF56E37A7E4A CRC64; MAGLSHPSVF GRATHAVVRA PPESLCRHAL RRSQGEEVDF ARAERQHQLY VGVLGSKLGL QVVQLPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK EVDMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG AEILADTFKD YAVSTVPVAD SLHLKSFCSM AGPNLIAIGS SESAQKALKI MQQMSDHRYD KLTVPDDMAA NCIYLNIPSK GHVLLHRTPE EYPESAKVYE KLKDHLLIPV SNSEMEKVDG LLTCCSVFIN KKTDS //