biostudies-literatureWarmack RADivision of Molecular and Cellular BiosciencesUniversity of California, Los AngelesNational Institute of General Medical SciencesNIGMS NIH HHSLife Extension Foundation, Inc.Division of Graduate Education879-894https://www.ebi.ac.uk/biostudies/studies/S-EPMC9875861biostudies-literatureUnknown61(10)The spontaneous l-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-l-isoaspartyl (d-aspartyl) <i>O</i>-methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which l-isoaspartate-damaged proteins are recognized and proteolytically degraded. Herein, we describe the protein-l-isoaspartate <i>O</i>-methyltransferase domain-containing protein 1 (PCMTD1) as a putative E3 ubiquitin ligase substrate adaptor protein. The N-terminal domain of PCMTD1 contains l-isoaspartate and <i>S</i>-adenosylmethionine (AdoMet) binding motifs similar to those in PCMT1. This protein also has a C-terminal domain containing suppressor of cytokBiochemistryHuman Protein-l-isoaspartate <i>O</i>-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins.PMC9875861T32 GM136614DGE-1650604T32 GM007185R35 GM139539GM007185R35GM139539MCB-1714569Warmack RALowenson JDPeluso EOng JYPang EZTorres JZClarke SGfalseHuman Protein-l-isoaspartate <i>O</i>-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins.The spontaneous l-isoaspartate protein modification has been observed to negatively affect protein function. However, this modification can be reversed in many proteins in reactions initiated by the protein-l-isoaspartyl (d-aspartyl) <i>O</i>-methyltransferase (PCMT1). It has been hypothesized that an additional mechanism exists in which l-isoaspartate-damaged proteins are recognized and proteolytically degraded. Herein, we describe the protein-l-isoaspartate <i>O</i>-methyltransferase domain-containing protein 1 (PCMTD1) as a putative E3 ubiquitin ligase substrate adaptor protein. The N-terminal domain of PCMTD1 contains l-isoaspartate and <i>S</i>-adenosylmethionine (AdoMet) binding motifs similar to those in PCMT1. This protein also has a C-terminal domain containing suppressor of cytok2022-01-01T00:00:00Z2022 May2025-04-04T08:06:40.465Z2025-04-04T08:06:40.465ZS-EPMC98758613548688110.1021/acs.biochem.2c00130