ID DDAH1_BOVIN Reviewed; 285 AA.
AC P56965; A6QQU7; P81020;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 24-JAN-2024, entry version 143.
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;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 2-285, MASS SPECTROMETRY, ACETYLATION AT ALA-2,
RP S-NITROSYLATION AT CYS-222 AND CYS-274, ACTIVITY REGULATION, AND
RP 3D-STRUCTURE MODELING.
RC TISSUE=Brain;
RX PubMed=12441345; DOI=10.1074/jbc.m209088200;
RA Knipp M., Braun O., Gehrig P.M., Sack R., Vasak M.;
RT "Zn(II)-free dimethylargininase-1 (DDAH-1) is inhibited upon specific CysS-
RT nitrosylation.";
RL J. Biol. Chem. 278:3410-3416(2003).
RN [3]
RP PROTEIN SEQUENCE OF 2-12, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ZINC
RP BINDING, SUBUNIT, TISSUE SPECIFICITY, AND CIRCULAR DICHROISM.
RC TISSUE=Brain;
RX PubMed=9537995; DOI=10.1021/bi972312t;
RA Bogumil R., Knipp M., Fundel S.M., Vasak M.;
RT "Characterization of dimethylargininase from bovine brain: evidence for a
RT zinc binding site.";
RL Biochemistry 37:4791-4798(1998).
RN [4]
RP PROTEIN SEQUENCE OF 46-57; 105-119 AND 180-200, AND CHARACTERIZATION.
RC TISSUE=Brain;
RX PubMed=8849684; DOI=10.1016/0014-5793(96)00997-0;
RA Fundel S.M., Pountney D.L., Bogumil R., Gehrig P.M., Hasler D.W.,
RA Faller P., Vasak M.;
RT "Isolation and characterization of a novel monomeric zinc- and heme-
RT containing protein from bovine brain.";
RL FEBS Lett. 395:33-38(1996).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, ZINC BINDING, AND ACTIVITY REGULATION.
RX PubMed=11546769; DOI=10.1074/jbc.m104056200;
RA Knipp M., Charnock J.M., Garner C.D., Vasak M.;
RT "Structural and functional characterization of the Zn(II) site in
RT dimethylargininase-1 (DDAH-1) from bovine brain. Zn(II) release activates
RT DDAH-1.";
RL J. Biol. Chem. 276:40449-40456(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG;
RP INHIBITOR AND ZINC IONS.
RX PubMed=16698551; DOI=10.1016/j.str.2006.03.006;
RA Frey D., Braun O., Briand C., Vasak M., Gruetter M.G.;
RT "Structure of the mammalian NOS regulator dimethylarginine
RT dimethylaminohydrolase: a basis for the design of specific inhibitors.";
RL Structure 14:901-911(2006).
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 -!- 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:9537995};
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:9537995};
CC -!- ACTIVITY REGULATION: Copurifies with a tightly bound zinc ion.
CC Activated by release of zinc. His and other agents that promote the
CC release of bound zinc ions activate the enzyme (in vitro). Inhibited by
CC S-nitrosylation. Zinc protects the protein against S-nitrosylation.
CC {ECO:0000269|PubMed:11546769, ECO:0000269|PubMed:12441345,
CC ECO:0000269|PubMed:9537995}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.8. {ECO:0000269|PubMed:11546769};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:16698551,
CC ECO:0000269|PubMed:9537995}.
CC -!- TISSUE SPECIFICITY: Widely distributed, highest concentrations found in
CC brain, brain cortex and kidney (at protein level).
CC {ECO:0000269|PubMed:9537995}.
CC -!- MASS SPECTROMETRY: Mass=31199; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12441345};
CC -!- SIMILARITY: Belongs to the DDAH family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a heme protein, but this was
CC later shown to be an artifact. {ECO:0000305|PubMed:8849684}.
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DR EMBL; BC149998; AAI49999.1; -; mRNA.
DR PIR; S74156; S74156.
DR RefSeq; NP_001095671.1; NM_001102201.2.
DR PDB; 2C6Z; X-ray; 1.20 A; A=2-285.
DR PDB; 2CI1; X-ray; 1.08 A; A=8-282.
DR PDB; 2CI3; X-ray; 1.70 A; A=2-285.
DR PDB; 2CI4; X-ray; 1.70 A; A=2-285.
DR PDB; 2CI5; X-ray; 1.79 A; A/B=2-285.
DR PDB; 2CI6; X-ray; 2.00 A; A=2-285.
DR PDB; 2CI7; X-ray; 1.60 A; A=2-285.
DR PDBsum; 2C6Z; -.
DR PDBsum; 2CI1; -.
DR PDBsum; 2CI3; -.
DR PDBsum; 2CI4; -.
DR PDBsum; 2CI5; -.
DR PDBsum; 2CI6; -.
DR PDBsum; 2CI7; -.
DR AlphaFoldDB; P56965; -.
DR SMR; P56965; -.
DR BioGRID; 193961; 1.
DR STRING; 9913.ENSBTAP00000046157; -.
DR ChEMBL; CHEMBL6081; -.
DR iPTMnet; P56965; -.
DR PaxDb; 9913-ENSBTAP00000046157; -.
DR PeptideAtlas; P56965; -.
DR Ensembl; ENSBTAT00000049235.4; ENSBTAP00000046157.3; ENSBTAG00000034776.4.
DR GeneID; 537391; -.
DR KEGG; bta:537391; -.
DR CTD; 23576; -.
DR VEuPathDB; HostDB:ENSBTAG00000034776; -.
DR VGNC; VGNC:27939; DDAH1.
DR eggNOG; ENOG502QWPA; Eukaryota.
DR GeneTree; ENSGT00940000157892; -.
DR HOGENOM; CLU_067923_0_0_1; -.
DR InParanoid; P56965; -.
DR OMA; HRYTHAI; -.
DR OrthoDB; 315054at2759; -.
DR TreeFam; TF314737; -.
DR BRENDA; 3.5.3.18; 908.
DR Reactome; R-BTA-203615; eNOS activation.
DR SABIO-RK; P56965; -.
DR EvolutionaryTrace; P56965; -.
DR PRO; PR:P56965; -.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000034776; Expressed in temporal cortex and 99 other cell types or tissues.
DR GO; GO:0016597; F:amino acid binding; IBA:GO_Central.
DR GO; GO:0016403; F:dimethylargininase activity; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IDA:MGI.
DR GO; GO:0006527; P:arginine catabolic process; IEA:Ensembl.
DR GO; GO:0006525; P:arginine metabolic process; IBA:GO_Central.
DR GO; GO:0000052; P:citrulline metabolic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IEA:Ensembl.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0017014; P:protein nitrosylation; IDA:MGI.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IEA:Ensembl.
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; PF02274; ADI; 1.
DR SUPFAM; SSF55909; Pentein; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Hydrolase;
KW Metal-binding; Reference proteome; S-nitrosylation; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12441345,
FT ECO:0000269|PubMed:9537995"
FT CHAIN 2..285
FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase 1"
FT /id="PRO_0000171117"
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 BINDING 73
FT /ligand="substrate"
FT BINDING 78
FT /ligand="substrate"
FT BINDING 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 MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:12441345"
FT MOD_RES 222
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:12441345"
FT MOD_RES 274
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:12441345"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 25..28
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:2CI4"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:2CI4"
FT HELIX 40..55
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 72..75
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 96..101
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 135..145
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 148..157
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:2CI7"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 177..182
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 192..204
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 210..216
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 228..230
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:2CI1"
FT STRAND 255..259
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:2CI1"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:2CI1"
FT HELIX 273..275
FT /evidence="ECO:0007829|PDB:2C6Z"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2CI1"
SQ SEQUENCE 285 AA; 31289 MW; 65C5C032EE513CE5 CRC64;
MASLGHPATF GRATHVVVRA LPESLAQQAL RRTKGDEVDF ARAERQHQLY VGVLGSKLGL
QVVQLPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK EADMMKEALE KLQLNIVEMK
DENATLDGGD VLFTGREFFV GLSKRTNQRG AEILADTFKD YAVSTVPVVD ALHLKSFCSM
AGPNLIAIGS SESAQKALKI MQQMSDHRYD KLTVPDDTAA NCIYLNIPSK GHVLLHRTPE
EYPESAKVYE KLKDHMLIPV SNSELEKVDG LLTCSSVLIN KKVDS
//
