DDAH2
DDAH2 (DDAH family member 2, ADMA-independent; also G6A or DDAHII) is a putative hydrolase of the DDAH family. It acts in endothelial and pancreatic signalling and in the mitochondrial response to viral infection. Browse Assay Genie's current range of DDAH2 research reagents below, or read on for the biology behind the target.
DDAH2 is annotated as a putative hydrolase with an unknown substrate. Unlike what its family name suggests, it does not hydrolyse N(G),N(G)-dimethyl-L-arginine (ADMA), the inhibitor of nitric oxide synthase (NOS). Its documented activities are therefore signalling roles. In endothelial cells, DDAH2 induces expression of vascular endothelial growth factor (VEGF) through phosphorylation of the transcription factor SP1 by PKA, a process independent of nitric oxide and NO synthase.
The same SP1-mediated mechanism operates in the pancreas. DDAH2 enhances insulin secretion by up-regulating transcription of secretagogin (SCGN), an insulin vesicle docking protein. After viral infection, the protein relocates to mitochondria, where it promotes mitochondrial fission through activation of DNM1L. This inhibits the innate response activation mediated by MAVS. The protein is found in the cytoplasm and the mitochondrion.
The DDAH2 gene belongs to the DDAH family and encodes a dimethylarginine dimethylaminohydrolase; its previous name was dimethylarginine dimethylaminohydrolase 2. NCBI describes the enzyme as functioning in nitric oxide generation by regulating cellular concentrations of methylarginines, which inhibit NOS activity, although the UniProt annotation indicates ADMA is not a substrate of DDAH2. Alternative splicing produces multiple transcript variants. Mouse and rat both carry a Ddah2 ortholog, and DDAH1 is the related family member.
DDAH2 induces VEGF expression in endothelial cells through PKA-mediated phosphorylation of SP1, independently of NO and NO synthase.
DDAH2 enhances pancreatic insulin secretion by SP1-mediated up-regulation of secretagogin, an insulin vesicle docking protein.
On viral infection DDAH2 moves to mitochondria and promotes DNM1L-dependent fission, which inhibits MAVS-mediated innate response activation.
The DDAH family is linked to methylarginine regulation of NOS activity, making DDAH2 relevant when separating NO-dependent from NO-independent effects.
DDAH2 is a putative hydrolase with unknown substrate. It induces VEGF expression in endothelial cells via PKA phosphorylation of SP1, enhances insulin secretion through secretagogin up-regulation, and after viral infection promotes mitochondrial fission via DNM1L, inhibiting MAVS-mediated innate responses.
The HGNC name is DDAH family member 2, ADMA-independent. Aliases and previous symbols include G6A and DDAHII, and the previous name was dimethylarginine dimethylaminohydrolase 2. UniProt lists the protein as putative hydrolase DDAH2. NCBI notes alternative splicing yields multiple transcript variants.
UniProt states DDAH2 does not hydrolyse ADMA, the NOS inhibitor, despite its family membership and the NCBI description of a role in methylarginine regulation. Mouse and rat each have a Ddah2 ortholog. Check the datasheet of any product for its validated reactivity.
Other DDAH family members and related targets in nitric oxide and endothelial signalling with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O95865; product specifications from Assay Genie datasheets.