Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase MESH1

HDDC3 (also known as MESH1) is a guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase that catalyzes the hydrolysis of ppGpp, a nucleotide alarmone central to bacterial and archaeal starvation responses (UniProt: Q8N4P3). The protein is a small 179-amino acid enzyme with a molecular mass of approximately 20 kDa. Its presence and activity in human cells suggest conserved metabolic signaling functions, though detailed mechanistic roles in mammalian physiology remain poorly characterized.

HDDC3 is expressed as a human protein, but UniProt records no curated disease associations in its primary annotation (UniProt: Q8N4P3). Its normal tissue distribution and pathway context are not extensively documented in the current database.

In Alzheimer's Disease, HDDC3 shows modest upregulation in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.41 (Chaparral AD proteomics). This elevation was detected via TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) from human post-mortem brain, suggesting a potential role in AD-associated cellular stress responses or metabolic dysregulation, though the biological significance of this modest increase requires further investigation.