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IID00727
 UniprotQ15910
ProteinHistone-lysine N-methyltransferase EZH2
GeneEZH2
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
 Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
746
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 1-182,211-385,421-746 Hetero tetramer : IID00530Complex,IID00725Complex,Q92833
 Evidence X-RAY 5ls6 A Reference
       Region 5ls6 A 1-9 disorder
       Region 5ls6 A 10-182 order
       Region 5ls6 A 211-216 order
       Region 5ls6 A 217-219 disorder
       Region 5ls6 A 220-249 order
       Region 5ls6 A 250-256 disorder
       Region 5ls6 A 257-345 order
       Region 5ls6 A 346-385 disorder
       Region 5ls6 A 421-421 disorder
       Region 5ls6 A 422-480 order
       Region 5ls6 A 481-515 disorder
       Region 5ls6 A 516-728 order
       Region 5ls6 A 729-746 disorder
Seq 1-182,211-385,421-746 Hetero tetramer : IID00530Complex,IID00725Complex,Q92833
 Evidence X-RAY 5ls6 J Reference
       Region 5ls6 J 1-9 disorder
       Region 5ls6 J 10-182 order
       Region 5ls6 J 211-216 order
       Region 5ls6 J 217-219 disorder
       Region 5ls6 J 220-249 order
       Region 5ls6 J 250-256 disorder
       Region 5ls6 J 257-345 order
       Region 5ls6 J 346-385 disorder
       Region 5ls6 J 421-421 disorder
       Region 5ls6 J 422-480 order
       Region 5ls6 J 481-515 disorder
       Region 5ls6 J 516-728 order
       Region 5ls6 J 729-746 disorder
Seq 1-182,211-385,421-746 Hetero tetramer : IID00530Complex,IID00725Complex,Q92833
 Evidence X-RAY 5ls6 G Reference
       Region 5ls6 G 1-9 disorder
       Region 5ls6 G 10-182 order
       Region 5ls6 G 211-216 order
       Region 5ls6 G 217-219 disorder
       Region 5ls6 G 220-249 order
       Region 5ls6 G 250-256 disorder
       Region 5ls6 G 257-345 order
       Region 5ls6 G 346-385 disorder
       Region 5ls6 G 421-421 disorder
       Region 5ls6 G 422-480 order
       Region 5ls6 G 481-515 disorder
       Region 5ls6 G 516-730 order
       Region 5ls6 G 731-746 disorder
Seq 1-182,211-385,421-746 Hetero tetramer : IID00530Complex,IID00725Complex,Q92833
 Evidence X-RAY 5ls6 D Reference
       Region 5ls6 D 1-9 disorder
       Region 5ls6 D 10-182 order
       Region 5ls6 D 211-216 order
       Region 5ls6 D 217-219 disorder
       Region 5ls6 D 220-249 order
       Region 5ls6 D 250-256 disorder
       Region 5ls6 D 257-345 order
       Region 5ls6 D 346-385 disorder
       Region 5ls6 D 421-421 disorder
       Region 5ls6 D 422-480 order
       Region 5ls6 D 481-515 disorder
       Region 5ls6 D 516-728 order
       Region 5ls6 D 729-746 disorder
Seq 1-746 Hetero pentamer : IID00062Complex,IID00530Complex,IID00725Complex,Q92833
 Evidence X-RAY 5hyn Q Reference
       Region 5hyn Q 1-11 disorder
       Region 5hyn Q 12-180 order
       Region 5hyn Q 181-218 disorder
       Region 5hyn Q 219-248 order
       Region 5hyn Q 249-258 disorder
       Region 5hyn Q 259-345 order
       Region 5hyn Q 346-424 disorder
       Region 5hyn Q 425-478 order
       Region 5hyn Q 479-514 disorder
       Region 5hyn Q 515-739 order
       Region 5hyn Q 740-746 disorder
 Evidence X-RAY 5hyn K Reference
       Region 5hyn K 1-9 disorder
       Region 5hyn K 10-181 order
       Region 5hyn K 182-218 disorder
       Region 5hyn K 219-247 order
       Region 5hyn K 248-259 disorder
       Region 5hyn K 260-345 order
       Region 5hyn K 346-422 disorder
       Region 5hyn K 423-479 order
       Region 5hyn K 480-514 disorder
       Region 5hyn K 515-732 order
       Region 5hyn K 733-746 disorder
 Evidence X-RAY 5hyn F Reference
       Region 5hyn F 1-9 disorder
       Region 5hyn F 10-181 order
       Region 5hyn F 182-218 disorder
       Region 5hyn F 219-248 order
       Region 5hyn F 249-258 disorder
       Region 5hyn F 259-345 order
       Region 5hyn F 346-423 disorder
       Region 5hyn F 424-478 order
       Region 5hyn F 479-515 disorder
       Region 5hyn F 516-739 order
       Region 5hyn F 740-746 disorder
 Evidence X-RAY 5hyn A Reference
       Region 5hyn A 1-9 disorder
       Region 5hyn A 10-182 order
       Region 5hyn A 183-210 disorder
       Region 5hyn A 211-216 order
       Region 5hyn A 217-219 disorder
       Region 5hyn A 220-249 order
       Region 5hyn A 250-256 disorder
       Region 5hyn A 257-345 order
       Region 5hyn A 346-421 disorder
       Region 5hyn A 422-479 order
       Region 5hyn A 480-515 disorder
       Region 5hyn A 516-740 order
       Region 5hyn A 741-746 disorder
Seq 39-68 Hetero dimer : IID00530Complex
 Evidence X-RAY 5wuk B Reference
       Region 5wuk B 41-68 order
 Evidence X-RAY 5u62 D Reference
       Region 5u62 D 39-40 disorder
       Region 5u62 D 41-68 order
 Evidence X-RAY 5u62 C Reference
       Region 5u62 C 39-42 disorder
       Region 5u62 C 43-68 order
 Evidence X-RAY 5u5t D Reference
       Region 5u5t D 39-40 disorder
       Region 5u5t D 41-68 order
 Evidence X-RAY 5u5t C Reference
       Region 5u5t C 39-42 disorder
       Region 5u5t C 43-68 order
 Evidence X-RAY 5h25 D Reference
       Region 5h25 D 40-68 order
 Evidence X-RAY 5h25 C Reference
       Region 5h25 C 40-68 order
 Evidence X-RAY 5h24 D Reference
       Region 5h24 D 40-68 order
 Evidence X-RAY 5h24 C Reference
       Region 5h24 C 40-68 order
 Evidence X-RAY 5h19 B Reference
       Region 5h19 B 40-68 order
 Evidence X-RAY 5h17 B Reference
       Region 5h17 B 40-66 order
       Region 5h17 B 67-68 disorder
 Evidence X-RAY 5h15 D Reference
       Region 5h15 D 40-68 order
 Evidence X-RAY 5h15 C Reference
       Region 5h15 C 40-68 order
 Evidence X-RAY 5h14 C Reference
       Region 5h14 C 40-68 order
 Evidence X-RAY 5h14 D Reference
       Region 5h14 D 40-68 order
 Evidence X-RAY 5gsa D Reference
       Region 5gsa D 40-68 order
 Evidence X-RAY 5gsa C Reference
       Region 5gsa C 40-68 order
Seq 429-487,511-531,533-746 Hetero trimer : G1KPH4,IID00530Complex,IID00725Complex
 Evidence X-RAY 5ij8 B This entry is Anolis carolinensis EZH2 (G1KPH4). Reference
       Region 5ij8 B 429-432 disorder
       Region 5ij8 B 433-472 order
       Region 5ij8 B 473-487 disorder
       Region 5ij8 B 511-516 disorder
       Region 5ij8 B 517-531 order
       Region 5ij8 B 533-733 order
       Region 5ij8 B 734-746 disorder
Seq 429-487,511-746 Hetero trimer : G1KPH4,IID00530Complex,IID00725Complex
 Evidence X-RAY 5ij7 B This entry is Anolis carolinensis EZH2 (G1KPH4). Reference
       Region 5ij7 B 429-429 disorder
       Region 5ij7 B 430-472 order
       Region 5ij7 B 473-487 disorder
       Region 5ij7 B 511-516 disorder
       Region 5ij7 B 517-733 order
       Region 5ij7 B 734-746 disorder
Seq 429-487,511-746 Hetero trimer : G1KPH4,IID00530Complex,IID00725Complex
 Evidence X-RAY 5ij7 A This entry is Anolis carolinensis EZH2 (G1KPH4). Reference
       Region 5ij7 A 429-431 disorder
       Region 5ij7 A 432-472 order
       Region 5ij7 A 473-487 disorder
       Region 5ij7 A 511-516 disorder
       Region 5ij7 A 517-733 order
       Region 5ij7 A 734-746 disorder
Seq 429-487,511-531,533-746 Hetero trimer : G1KPH4,IID00530Complex,IID00725Complex
 Evidence X-RAY 5ij8 A This entry is Anolis carolinensis EZH2 (G1KPH4). Reference
       Region 5ij8 A 429-431 disorder
       Region 5ij8 A 432-472 order
       Region 5ij8 A 473-487 disorder
       Region 5ij8 A 511-516 disorder
       Region 5ij8 A 517-531 order
       Region 5ij8 A 533-733 order
       Region 5ij8 A 734-746 disorder
Seq 520-746 Monomer :
 Evidence X-RAY 4mi0 A Reference
       Region 4mi0 A 520-657 order
       Region 4mi0 A 658-659 disorder
       Region 4mi0 A 660-729 order
       Region 4mi0 A 730-746 disorder
 Evidence X-RAY 4mi5 A Reference
       Region 4mi5 A 521-592 order
       Region 4mi5 A 593-598 disorder
       Region 4mi5 A 599-731 order
       Region 4mi5 A 732-746 disorder
SeqProS possible 125-163 This region corresponds to SRM, shown to be disordered in a basal state in yeast EZH2(G0SDW4) (PubMed=28008038) Hetero pentamer : IID00062Complex,IID00530Complex,IID00725Complex,Q92833
       Region 5hyn A 10-182 order
       Region 5hyn F 10-181 order
       Region 5hyn K 10-181 order
       Region 5hyn Q 12-180 order
Seqphosphorylation
    21-21 Phosphoserine; by PKB/AKT1
    76-76 Phosphoserine
    339-339 Phosphothreonine
    345-345 Phosphothreonine; by CDK1 and CDK2
    363-363 Phosphoserine
    366-366 Phosphoserine
    367-367 Phosphothreonine
    487-487 Phosphothreonine
 
Prediction
NeProc
Disorder 1-10,185-217,253-266,323-326,337-424,482-503,742-746
Order 11-184,218-252,267-322,327-336,425-476,504-741
ProS 189-193,200-212,253-266,323-326,337-424,482-503,742-746
AlphaFold
Disorder 1-10,71-78,139-140,160-165,183-217,250-258,309-317,339-428,475-515,728-746
Order 11-70,79-138,141-159,166-182,218-249,259-308,318-338,429-474,516-727
Pfam Hmmer
PF00856 606-733 1e-53
SEG 183-192 ,238-252 ,349-366 ,385-409
Function
Function in SwissProt
Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.
Biological Process
Diagram with PDB data
EZH2/EED/SUZ12/H3C1/JARID2Structure of Human Polycomb Repressive Complex 2 (PRC2) with oncogenic histone H3K27M peptide
See also
Diagram with PDB data
SUZ12/RBBP4/PHF19/JARID2Crystal Structure of a SUZ12-RBBP4-PHF19-JARID2 Heterotetrameric Complex