Entry created on 1 July 2019 (Revision 1.0) Annotator: Rita Pancsa; Orsolya Kovács
Basic protein information
Accession P05205
Common name HP1a
Gene SU(VAR)205
Organism Drosophila melanogaster
Uniprot name Heterochromatin protein 1
Basic LLPS information
Organelle heterochromatin
Type of experimental evidence
Protein region(s) mediating LLPS
1
-
206
Only full-length protein studied
Based on the experimental results of the following publication: 28636597
Molecular features viewer
PDB structures
View on PDBe
Extended LLPS information
Functional description
Constitutive heterochromatin is an important component of eukaryotic genomest hat has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. The formation of heterochromatin domains is mediated by phase separation. Drosophila HP1a protein undergoes liquid-liquid demixing in vitro, and nucleates into foci that display liquid proprties during the first stages of heterochromatin domain formation in early Drosophila embryos. HP1a is required for heterochromatin domain integrity and compartmentalization. In D. melanogaster post-fertilization nuclear cycles 11-14 HP1a droplets appear in early interphase and dissolve at the onset of mitotic prophase. The integrity of mature heterochromatin domains relies on weak hydrophobic interactions (responsible for LLPS) and also, dimerization and interactions with non-histone binding partners contribute to HP1a immobilization. Thus mature chromatin domains consist of both immobile (static) and mobile(liquid) HP1a compartments (PMID:28636597).
Literature supporting the LLPS: 28636597
Functional class of membraneless organelle: protective storage/reservoir
Binding partners (at biological protein concentrations)
N/A
Type of RNA(s) required/used for the LLPS at biological protein concentrations
RNA not required.
Molecular interaction types contributing to LLPS
discrete oligomerization (PMID:28636597)
Determinants of phase separation and droplet properties
1) temperature 2) salt concentration 3) protein concentration of HP1a
Membrane cluster No
Partner-dependent No
RNA-dependent No
PTM required No
Domain-motif interactions No
Discrete oligomerization No
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
Among high protein concentrations and low levels of salt purified Drosophila HP1a protein solutions spontaneously demixed to form droplets at 22 °C in vitro (particle size and count by microscopy) that reversibly dissolved at 37 °C with change in temperature. High-resolution 4D analysis using lattice light-sheet microscopy revealed that GFP-HP1a (fusion protein) is initially diffuse, then forms highly spherical foci (protein localization) that grow, frequently fuse together, and dissolve (morphology) at the onset of mitotic prophase in vivo. HP1a is needed for compartmentalization of heterochromatin in vivo, since after depleting (RNAi) it from cultured Drosophila S2 cells GFP–HP4 lost coordinated movement and became dispersed throughout the nucleus (protein localization) (PMID:28636597).
Experimental observations supporting the liquid material state of the condensate
temperature-dependence (PMID:28636597) reversibility of formation and dissolution (PMID:28636597) morphological traits (PMID:28636597) dynamic movement/reorganization of molecules within the droplet (PMID:28636597) sensitivity to 1,6-hexanediol (PMID:28636597)