DDAH1_MOUSE
ID DDAH1_MOUSE Reviewed; 285 AA.
AC Q9CWS0; Q3UF65;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 153.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, and Sympathetic ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [3]
RP PROTEIN SEQUENCE OF 33-42; 121-136; 160-175; 212-230; 238-247 AND 268-281,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus;
RA Lubec G., Klug S., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:17273169}.
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. {ECO:0000250}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in skeletal muscle, lung, heart and brain
CC (at protein level). Detected in liver, kidney and lung.
CC {ECO:0000269|PubMed:17273169}.
CC -!- DISRUPTION PHENOTYPE: Death at embryonic stages. Heterozygous mice show
CC no visible phenotype, but have higher than normal tissue and plasma
CC levels of asymmetric dimethylarginine (ADMA). They have increased mean
CC arterial blood pressure and systemic vascular resistance, and decreased
CC cardiac output and heart rate, probably due to reduced levels of nitric
CC oxide (NO). {ECO:0000269|PubMed:17273169}.
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; AK010430; BAB26932.1; -; mRNA.
DR EMBL; AK143507; BAE25405.1; -; mRNA.
DR EMBL; AK148907; BAE28696.1; -; mRNA.
DR EMBL; BC034505; AAH34505.1; -; mRNA.
DR CCDS; CCDS17896.1; -.
DR RefSeq; NP_081269.1; NM_026993.3.
DR AlphaFoldDB; Q9CWS0; -.
DR SMR; Q9CWS0; -.
DR BioGRID; 213300; 2.
DR IntAct; Q9CWS0; 3.
DR MINT; Q9CWS0; -.
DR STRING; 10090.ENSMUSP00000029845; -.
DR ChEMBL; CHEMBL3988621; -.
DR iPTMnet; Q9CWS0; -.
DR PhosphoSitePlus; Q9CWS0; -.
DR SwissPalm; Q9CWS0; -.
DR REPRODUCTION-2DPAGE; Q9CWS0; -.
DR CPTAC; non-CPTAC-3418; -.
DR jPOST; Q9CWS0; -.
DR MaxQB; Q9CWS0; -.
DR PaxDb; Q9CWS0; -.
DR PeptideAtlas; Q9CWS0; -.
DR PRIDE; Q9CWS0; -.
DR ProteomicsDB; 279842; -.
DR Antibodypedia; 1588; 309 antibodies from 35 providers.
DR DNASU; 69219; -.
DR Ensembl; ENSMUST00000029845; ENSMUSP00000029845; ENSMUSG00000028194.
DR GeneID; 69219; -.
DR KEGG; mmu:69219; -.
DR UCSC; uc008rqr.2; mouse.
DR CTD; 23576; -.
DR MGI; MGI:1916469; Ddah1.
DR VEuPathDB; HostDB:ENSMUSG00000028194; -.
DR eggNOG; ENOG502QWPA; Eukaryota.
DR GeneTree; ENSGT00940000157892; -.
DR HOGENOM; CLU_067923_0_0_1; -.
DR InParanoid; Q9CWS0; -.
DR OMA; HRYTHAI; -.
DR OrthoDB; 1469762at2759; -.
DR PhylomeDB; Q9CWS0; -.
DR TreeFam; TF314737; -.
DR BRENDA; 3.5.3.18; 3474.
DR Reactome; R-MMU-203615; eNOS activation.
DR BioGRID-ORCS; 69219; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Ddah1; mouse.
DR PRO; PR:Q9CWS0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9CWS0; protein.
DR Bgee; ENSMUSG00000028194; Expressed in ventricular zone and 229 other tissues.
DR ExpressionAtlas; Q9CWS0; baseline and differential.
DR Genevisible; Q9CWS0; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0016403; F:dimethylargininase activity; IMP:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006527; P:arginine catabolic process; ISO:MGI.
DR GO; GO:0006525; P:arginine metabolic process; ISO:MGI.
DR GO; GO:0000052; P:citrulline metabolic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1900038; P:negative regulation of cellular response to hypoxia; ISO:MGI.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:MGI.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0017014; P:protein nitrosylation; ISO:MGI.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IMP:BHF-UCL.
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:0000250|UniProtKB:P56965"
FT CHAIN 2..285
FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase 1"
FT /id="PRO_0000171119"
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:0000250|UniProtKB:P56965"
FT MOD_RES 33
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08557"
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; 31381 MW; 290B8DDF5AAE7928 CRC64;
MAGLGHPSAF GRATHAVVRA PPESLCRHAL RRSQGEEVDF ARAERQHELY VGVLGSKLGL
QVVQLPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK EVDMMKEALE KLQLNIVEMK
DENATLDGGD VLFTGREFFV GLSKRTNQRG AEILADTFKD YAVSTVPVAD SLHLKSFCSM
AGPNLIAIGS SESAQKALKI MQQMSDHRYD KLTVPDDMAA NCIYLNIPSK GHVLLHRTPE
EYPESAKVYE KLKDHLLIPV SNSEMEKVDG LLTCCSVFIN KKIDS
