Entry created on 1 July 2019 (Revision 1.0) Annotator: Bálint Mészáros
Basic protein information
Accession P29590-12
Common name PML
Gene PML
Organism Homo sapiens
Uniprot name Isoform PML-12 of Protein PML
Basic LLPS information
Organelle PML body
Type of experimental evidence
Protein region(s) mediating LLPS
1
-
585
Only full-length protein studied
Based on the experimental results of the following publication: 17081985
Molecular features viewer
PDB structures
Extended LLPS information
Functional description
PML nuclear bodies (NBs) are nuclear structures that have been implicated in processes such as transcriptional regulation, genome stability, response to viral infection, apoptosis, and tumor suppression. Unlike other, more specialized subnuclear structures such as Cajal and Polycomb group bodies, PML-NBs are functionally promiscuous and have been implicated in the regulation of diverse cellular functions. PML-NBs are dynamic structures that favour the sequestration and release of proteins, mediate their post-translational modifications and promote specific nuclear events in response to various cellular stresses. Post-translational modification (especially SUMOylation) of both the PML scaffold and clients can regulate client recruitment to PML NBs. Phosphorylation of the Daxx SUMO interacting motif increases its affinity for SUMO-1 and, presumably, SUMOylated PML. Several results illustrate how SUMOylation of PML and SUMOylation or phosphorylation of clients can regulate the composition of PML NBs through modulating scaffold–client interactions. PML is the only protein that has been found to be essential for the formation of the NBs; and these structures do not form in PML null cells, although PML add back fully rescues their formation (PMID:17081985, PMID:17928811, PMID:30099028).
Literature supporting the LLPS: 17081985, 10806494, 29599493, 17928811, 29723661, 27211601, 25355412, 24637324, 30099028
Functional class of membraneless organelle: activation/nucleation/signal amplification/bioreactor; protective storage/reservoir
Binding partners (at biological protein concentrations)
1) SUMO-1 (most probably needed for LLPS)
Type of RNA(s) required/used for the LLPS at biological protein concentrations
RNA not required.
Molecular interaction types contributing to LLPS
coiled-coil formation (PMID:24637324) discrete oligomerization (PMID:25355412)
Determinants of phase separation and droplet properties
1) protein concentration of SUMO-1 2) modification state (SUMOylation) 3) arsenic concentration
Membrane cluster No
Partner-dependent Yes
RNA-dependent No
PTM required No
Domain-motif interactions Yes
Discrete oligomerization Yes
Regulation and disease
Post-translational modifications affecting LLPS
Position Residue PTM Effect Reference Modifying enzyme Notes
Isoforms known to affect LLPS
Isoform Effect Reference
All known isoforms containing sequence changes in the LLPS region(s)
Position type Isoform names from UniProt
Disease mutations affecting LLPS
Mutation dbSNP Disease OMIM Effect Reference Notes
Experimental information
Experimental techniques applied to prove/investigate LLPS
In in vivo experiments, human PML and human GFP-tagged SUMO-1 was knocked-in to PML deficient mouse embryonic fibroblasts and confocal immunofluorescence analysis was performed following protein localization and co-localization with SUMO-1. These cells contained 10–20 PML NBs per cell nucleus of heterogeneous sizes (particle size and count), and PML was found to completely colocalize with GFP-SUMO-1, as evidenced by immunofluorescence microscopy. PML with the induced mutation of the SUMO binding motif still formed NBs, however with aberrant morphologies, and with reduced particle size and count compared to those formed by wild type PML in the nucleus; yet mutant PML still colocalized with GFP-SUMO-1 in agreement with the notion that it can still be SUMOylated. These results show that the PML SUMO binding motif and an intact RING domain (physsical interaction between the two) are required for PML-NB formation (PMID:17081985).
Experimental observations supporting the liquid material state of the condensate
morphological traits (PMID:17081985)