N(G),N(G)-dimethylarginine dimethylaminohydrolase 2 (DDAH2)
The protein contains 285 amino acids for an estimated molecular weight of 29644 Da.
Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Arginine catabolic process
Arginine metabolic process
Citrulline metabolic process
Negative regulation of apoptotic process
Nitric oxide biosynthetic process
Nitric oxide mediated signal transduction
Positive regulation of nitric oxide biosynthetic process
Regulation of nitric-oxide synthase activity
The reference OMIM entry for this protein is 604744
Dimethylarginine dimethylaminohydrolase 2; ddah2
DESCRIPTION
Dimethylarginine dimethylaminohydrolase (DDAH; EC 3.5.3.18) regulates cellular methylarginine concentrations, which in turn inhibit nitric oxide synthase (see 163731) activity.CLONING
Leiper et al. (1999) isolated a cDNA encoding DDAHI (604743) and, by screening a database of translated open reading frames with the deduced DDAHI peptide sequence, identified DDAHII. Both DDAHI and DDAHII cDNAs encode 285-amino acid proteins. The DDAHII amino acid sequence shares 98% identity with that of its mouse homolog and 62% identity with the sequence of DDAHI. Northern blot analysis detected a 2.0-kb DDAHII transcript expressed at highest levels in heart, kidney, and placenta. By RNA dot blot analysis, Tran et al. (2000) determined that DDAH2 expression predominates in more highly vascularized tissues and in immune tissues, while DDAH1 expression predominates in tissues that also express the neuronal isoform of NOS (163731).GENE FUNCTION
Leiper et al. (1999) expressed a histidine-tagged DDAHII clone in E. coli and assayed the cell lysate for DDAH activity. Recombinant DDAHII metabolized ADMA and L-NMMA, but not SDMA or L-arginine, demonstrating that DDAHII is a functional homolog of DDAHI. By overexpression in human and murine endothelial cells, Smith et al. (2003) determined that DDAH2 reduced the secretion of ADMA, increased VEGF mRNA expression, and enhanced tube formation by cells grown in a 3-dimensional medium. A DDAH inhibitor reduced tube formation in human umbilical vein endothelial cells.GENE STRUCTURE
Genomic sequence analysis by Tran et al. (2000) indicated that DDAH2 contains 8 exons with 3 transcription start sites that generate alternatively spliced transcripts.MAPPING
Tran et al. (2000) mapped the DDAH2 gene to 6p21.3 by radiation hybrid and FISH analysis. ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604744 was added.