ID   DDAH2_RAT               Reviewed;         285 AA.
AC   Q6MG60;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 126.
DE   RecName: Full=Putative hydrolase DDAH2;
DE            EC=3.-.-.- {ECO:0000250|UniProtKB:O95865};
DE   AltName: Full=DDAHII;
DE   AltName: Full=Inactive N(G),N(G)-dimethylarginine dimethylaminohydrolase 2;
DE            Short=DDAH-2;
DE            Short=Inactive dimethylarginine dimethylaminohydrolase 2;
GN   Name=Ddah2;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15060004; DOI=10.1101/gr.1987704;
RA   Hurt P., Walter L., Sudbrak R., Klages S., Mueller I., Shiina T., Inoko H.,
RA   Lehrach H., Guenther E., Reinhardt R., Himmelbauer H.;
RT   "The genomic sequence and comparative analysis of the rat major
RT   histocompatibility complex.";
RL   Genome Res. 14:631-639(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary, and Thymus;
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 106-142; 148-173; 183-194 AND 268-285, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA   Lubec G., Afjehi-Sadat L., Chen W.-Q., Kang S.U.;
RL   Submitted (JUL-2007) to UniProtKB.
CC   -!- FUNCTION: Putative hydrolase with unknown substrate. Does not hydrolyze
CC       N(G),N(G)-dimethyl-L-arginine (ADMA) which acts as an inhibitor of NOS
CC       (By similarity). In endothelial cells, induces expression of vascular
CC       endothelial growth factor (VEGF) via phosphorylation of the
CC       transcription factor SP1 by PKA in a process that is independent of NO
CC       and NO synthase. Similarly, enhances pancreatic insulin secretion
CC       through SP1-mediated transcriptional up-regulation of
CC       secretagogin/SCGN, an insulin vesicle docking protein (By similarity).
CC       Upon viral infection, relocates to mitochondria where it promotes
CC       mitochondrial fission through activation of DNM1L leading to the
CC       inhibition of innate response activation mediated by MAVS (By
CC       similarity). {ECO:0000250|UniProtKB:O95865,
CC       ECO:0000250|UniProtKB:Q99LD8}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95865}.
CC       Mitochondrion {ECO:0000250|UniProtKB:O95865}. Note=Translocates from
CC       cytosol to mitochondrion upon IL1B stimulation in chondrocytes.
CC       {ECO:0000250|UniProtKB:O95865}.
CC   -!- PTM: Phosphorylated by TBK1. Phosphorylation inhibits the translocation
CC       into the mitochondrion upon Sendai viral infection.
CC       {ECO:0000250|UniProtKB:O95865}.
CC   -!- SIMILARITY: Belongs to the DDAH family. {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be a dimethylarginine
CC       dimethylaminohydrolase (with EC:3.5.3.18) able to hydrolyze N(G),N(G)-
CC       dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) (By
CC       similarity). However, a recent multicentre study has shown that DDAH2
CC       does not have dimethylarginine dimethylaminohydrolase activity by using
CC       different approaches (By similarity). {ECO:0000250|UniProtKB:O95865}.
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DR   EMBL; BX883045; CAE83986.1; -; Genomic_DNA.
DR   EMBL; BC086443; AAH86443.1; -; mRNA.
DR   EMBL; BC097930; AAH97930.1; -; mRNA.
DR   RefSeq; NP_001159408.1; NM_001165936.1.
DR   RefSeq; NP_997697.1; NM_212532.2.
DR   AlphaFoldDB; Q6MG60; -.
DR   SMR; Q6MG60; -.
DR   BioGRID; 254630; 1.
DR   IntAct; Q6MG60; 1.
DR   STRING; 10116.ENSRNOP00000001118; -.
DR   iPTMnet; Q6MG60; -.
DR   PhosphoSitePlus; Q6MG60; -.
DR   SwissPalm; Q6MG60; -.
DR   jPOST; Q6MG60; -.
DR   PaxDb; 10116-ENSRNOP00000001118; -.
DR   Ensembl; ENSRNOT00000088251.2; ENSRNOP00000069121.1; ENSRNOG00000000842.6.
DR   Ensembl; ENSRNOT00055012017; ENSRNOP00055009521; ENSRNOG00055007228.
DR   Ensembl; ENSRNOT00060007344; ENSRNOP00060005574; ENSRNOG00060004372.
DR   Ensembl; ENSRNOT00065055326; ENSRNOP00065045516; ENSRNOG00065032128.
DR   GeneID; 294239; -.
DR   KEGG; rno:294239; -.
DR   UCSC; RGD:1302955; rat.
DR   AGR; RGD:1302955; -.
DR   CTD; 23564; -.
DR   RGD; 1302955; Ddah2.
DR   VEuPathDB; HostDB:ENSRNOG00000029682; -.
DR   eggNOG; ENOG502QW4J; Eukaryota.
DR   GeneTree; ENSGT00940000160769; -.
DR   InParanoid; Q6MG60; -.
DR   OMA; CPYGRFT; -.
DR   OrthoDB; 315054at2759; -.
DR   PhylomeDB; Q6MG60; -.
DR   TreeFam; TF314737; -.
DR   BRENDA; 3.5.3.18; 5301.
DR   PRO; PR:Q6MG60; -.
DR   Proteomes; UP000002494; Chromosome 20.
DR   Bgee; ENSRNOG00000000842; Expressed in heart and 20 other cell types or tissues.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0016597; F:amino acid binding; IBA:GO_Central.
DR   GO; GO:0016403; F:dimethylargininase activity; IBA:GO_Central.
DR   GO; GO:0006525; P:arginine metabolic process; IBA:GO_Central.
DR   GO; GO:0000052; P:citrulline metabolic process; IBA:GO_Central.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IBA:GO_Central.
DR   InterPro; IPR033199; DDAH-like.
DR   PANTHER; PTHR12737; DIMETHYLARGININE DIMETHYLAMINOHYDROLASE; 1.
DR   PANTHER; PTHR12737:SF16; N(G),N(G)-DIMETHYLARGININE DIMETHYLAMINOHYDROLASE 2; 1.
DR   SUPFAM; SSF55909; Pentein; 1.
DR   Genevisible; Q6MG60; RN.
PE   1: Evidence at protein level;
KW   Cytoplasm; Direct protein sequencing; Hydrolase; Mitochondrion;
KW   Reference proteome.
FT   CHAIN           1..285
FT                   /note="Putative hydrolase DDAH2"
FT                   /id="PRO_0000270760"
FT   ACT_SITE        171
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        276
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   285 AA;  29688 MW;  C28D60FF20CEAEFF CRC64;
     MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG KLRQRLGLQL
     LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV DGVRKALQDL GLRIVEMGDE
     NATLDGTDVL FTGREFFVGL SKWTNHRGAE IVADTFRDFA VSTVPVSGAS HLRGLCGMGG
     PRTVVAGSSE AAQKAVRAMA ALTDHPYASL TLPDDAASDC LFLRPGLPGT TPFLLHRGGG
     DLPNSQEALQ KLSDVTLVPV SCSELEKVGA GLSSLCLVLS TRPHC
//