DDAH1_RAT
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 03-AUG-2022, entry version 148.
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 -!- 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}.
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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; O08557; -.
DR PRIDE; O08557; -.
DR Ensembl; ENSRNOT00000045016; ENSRNOP00000044971; ENSRNOG00000014613.
DR GeneID; 64157; -.
DR KEGG; rno:64157; -.
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; 1469762at2759; -.
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 tissues.
DR Genevisible; O08557; RN.
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.
DR InterPro; IPR033197; DDAH1.
DR PANTHER; PTHR12737; PTHR12737; 1.
DR PANTHER; PTHR12737:SF17; PTHR12737:SF17; 1.
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
