Q15022 · SUZ12_HUMAN
- ProteinPolycomb protein SUZ12
- GeneSUZ12
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids739 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:15231737, PubMed:15385962, PubMed:16618801, PubMed:17344414, PubMed:18285464, PubMed:28229514, PubMed:29499137, PubMed:31959557).
The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464).
Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557).
The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464).
Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557).
Miscellaneous
Under hypoxic conditions, the precursor SUZ12 RNA undergoes regulated trans-splicing with the JAZF1 RNA, resulting in a chimeric isoform which may be protective against apoptosis. The chimeric transcript is characterized by JAZF1 exons 1-3 joined to SUZ12 exon 2-16. The chimeric transcript is expressed primarily in the endometrium from late secretory and early proliferative phases of the menstrual cycle, but not in normal myometrium at any phase of the cycle. Its expression is slightly induced by low levels of progesterone, but suppressed by both estrogen and high levels of progesterone (PubMed:18772439).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 93-94 | Breakpoint for translocation to form JAZF1-SUZ12 oncogene | ||||
Sequence: PT |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePolycomb protein SUZ12
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ15022
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to chromatin as part of the PRC2 complex.
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Imagawa-Matsumoto syndrome (IMMAS)
- Note
- DescriptionAn autosomal dominant syndrome characterized by generalized overgrowth, dysmorphic features, musculoskeletal abnormalities, developmental delay and intellectual disability. Some patients have genitourinary and structural brain abnormalities.
- See alsoMIM:618786
Natural variants in IMMAS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_083817 | 535 | R>Q | in IMMAS; uncertain significance; dbSNP:rs1909934091 | |
VAR_083818 | 599 | Q>H | in IMMAS; dbSNP:rs1567840381 | |
VAR_083819 | 603 | F>L | in IMMAS; dbSNP:rs1598192095 | |
VAR_078318 | 610 | E>V | in IMMAS; decreased trimethylation of 'Lys-27' of histone H3; no effect on interaction with EZH2; dbSNP:rs1131692177 | |
VAR_083820 | 654-739 | missing | in IMMAS |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 86 | Fails to interact with JARID2; when associated with A-90. | ||||
Sequence: F → A | ||||||
Mutagenesis | 90 | Fails to interact with JARID2; when associated with A-86. | ||||
Sequence: F → A | ||||||
Mutagenesis | 195-197 | Fails to form a PRC2.1 dimer. Reduced H3K27me3 enrichment on PRC2 target genes. | ||||
Sequence: KRK → DDD | ||||||
Mutagenesis | 196 | Fails to form a PRC2.1 dimer. | ||||
Sequence: R → A | ||||||
Natural variant | VAR_028100 | 216 | in dbSNP:rs17339444 | |||
Sequence: N → I | ||||||
Mutagenesis | 334 | Fails to interact with PHF19. The PRC2.1 dimer forms but is unstable. | ||||
Sequence: W → A | ||||||
Mutagenesis | 518 | No effect on interaction with PHF19. The PRC2.1 dimer forms but is unstable. | ||||
Sequence: G → W | ||||||
Natural variant | VAR_083817 | 535 | in IMMAS; uncertain significance; dbSNP:rs1909934091 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_083818 | 599 | in IMMAS; dbSNP:rs1567840381 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_083819 | 603 | in IMMAS; dbSNP:rs1598192095 | |||
Sequence: F → L | ||||||
Natural variant | VAR_078318 | 610 | in IMMAS; decreased trimethylation of 'Lys-27' of histone H3; no effect on interaction with EZH2; dbSNP:rs1131692177 | |||
Sequence: E → V | ||||||
Natural variant | VAR_083820 | 654-739 | in IMMAS | |||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 576 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue, cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000047057 | 1-739 | UniProt | Polycomb protein SUZ12 | |||
Sequence: MAPQKHGGGGGGGSGPSAGSGGGGFGGSAAVAAATASGGKSGGGSCGGGGSYSASSSSSAAAAAGAAVLPVKKPKMEHVQADHELFLQAFEKPTQIYRFLRTRNLIAPIFLHRTLTYMSHRNSRTNIKRKTFKVDDMLSKVEKMKGEQESHSLSAHLQLTFTGFFHKNDKPSPNSENEQNSVTLEVLLVKVCHKKRKDVSCPIRQVPTGKKQVPLNPDLNQTKPGNFPSLAVSSNEFEPSNSHMVKSYSLLFRVTRPGRREFNGMINGETNENIDVNEELPARRKRNREDGEKTFVAQMTVFDKNRRLQLLDGEYEVAMQEMEECPISKKRATWETILDGKRLPPFETFSQGPTLQFTLRWTGETNDKSTAPIAKPLATRNSESLHQENKPGSVKPTQTIAVKESLTTDLQTRKEKDTPNENRQKLRIFYQFLYNNNTRQQTEARDDLHCPWCTLNCRKLYSLLKHLKLCHSRFIFNYVYHPKGARIDVSINECYDGSYAGNPQDIHRQPGFAFSRNGPVKRTPITHILVCRPKRTKASMSEFLESEDGEVEQQRTYSSGHNRLYFHSDTCLPLRPQEMEVDSEDEKDPEWLREKTITQIEEFSDVNEGEKEVMKLWNLHVMKHGFIADNQMNHACMLFVENYGQKIIKKNLCRNFMLHLVSMHDFNLISIMSIDKAVTKLREMQQKLEKGESASPANEEITEEQNGTANGFSEINSKEKALETDSVSGVSKQSKKQKL | |||||||
Modified residue (large scale data) | 17 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 20 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 37 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 72 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Cross-link | 73 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) | ||||
Sequence: K | |||||||
Cross-link | 75 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate | ||||
Sequence: K | |||||||
Cross-link | 75 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Cross-link | 223 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 382 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 384 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 390 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 539 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 541 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 541 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 546 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 546 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 583 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 583 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 693 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 695 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 726 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 726 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 728 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Sumoylated, probably by PIAS2.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Overexpressed in breast and colon cancer.
Induction
Expression is induced by E2F1, E2F2 and E2F3.
Developmental stage
Expressed at low levels in quiescent cells. Expression rises at the G1/S phase transition.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of the PRC2 complex, which consists of the core subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16224021, PubMed:18285464, PubMed:19026781, PubMed:29499137, PubMed:31959557).
Within the complex, interacts (via C2H2 zinc finger domain) with JARID2 and EPOP; JARID2 and EPOP compete for SUZ12 binding (PubMed:29499137).
Also interacts with AEBP2 and PHF19 (PubMed:29499137).
Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (PubMed:29499137).
Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (PubMed:31959557).
The minimum components required for methyltransferase activity of the PRC2/EZH2 complex are EED, EZH2 and SUZ12 (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464).
The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit (PubMed:15684044, PubMed:18285464).
Interacts with WDR77 (PubMed:16712789).
Interacts with histone H1 (PubMed:16431907).
Interacts with CDYL (PubMed:22009739).
Interacts with BMAL1 (By similarity).
Interacts with EZHIP (via C-terminal region) (PubMed:30923826).
Interacts with ARMC12 (PubMed:30026490).
Within the complex, interacts (via C2H2 zinc finger domain) with JARID2 and EPOP; JARID2 and EPOP compete for SUZ12 binding (PubMed:29499137).
Also interacts with AEBP2 and PHF19 (PubMed:29499137).
Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (PubMed:29499137).
Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (PubMed:31959557).
The minimum components required for methyltransferase activity of the PRC2/EZH2 complex are EED, EZH2 and SUZ12 (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464).
The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit (PubMed:15684044, PubMed:18285464).
Interacts with WDR77 (PubMed:16712789).
Interacts with histone H1 (PubMed:16431907).
Interacts with CDYL (PubMed:22009739).
Interacts with BMAL1 (By similarity).
Interacts with EZHIP (via C-terminal region) (PubMed:30923826).
Interacts with ARMC12 (PubMed:30026490).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q15022 | EED O75530 | 12 | EBI-1264675, EBI-923794 | |
BINARY | Q15022 | EZH2 Q15910 | 31 | EBI-1264675, EBI-530054 | |
BINARY | Q15022 | HDAC3 O15379 | 7 | EBI-1264675, EBI-607682 | |
BINARY | Q15022 | JARID2 Q92833-1 | 7 | EBI-1264675, EBI-15825247 | |
BINARY | Q15022 | PML-RAR Q15156 | 6 | EBI-1264675, EBI-867256 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-23 | Disordered | ||||
Sequence: MAPQKHGGGGGGGSGPSAGSGGG | ||||||
Region | 79-106 | Interaction with JARID2 and EPOP | ||||
Sequence: VQADHELFLQAFEKPTQIYRFLRTRNLI | ||||||
Region | 146-363 | Interaction with AEBP2 and PHF19 | ||||
Sequence: GEQESHSLSAHLQLTFTGFFHKNDKPSPNSENEQNSVTLEVLLVKVCHKKRKDVSCPIRQVPTGKKQVPLNPDLNQTKPGNFPSLAVSSNEFEPSNSHMVKSYSLLFRVTRPGRREFNGMINGETNENIDVNEELPARRKRNREDGEKTFVAQMTVFDKNRRLQLLDGEYEVAMQEMEECPISKKRATWETILDGKRLPPFETFSQGPTLQFTLRWTG | ||||||
Region | 378-399 | Disordered | ||||
Sequence: ATRNSESLHQENKPGSVKPTQT | ||||||
Zinc finger | 448-471 | C2H2-type | ||||
Sequence: LHCPWCTLNCRKLYSLLKHLKLCH | ||||||
Region | 563-639 | VEFS-box | ||||
Sequence: RLYFHSDTCLPLRPQEMEVDSEDEKDPEWLREKTITQIEEFSDVNEGEKEVMKLWNLHVMKHGFIADNQMNHACMLF | ||||||
Region | 687-739 | Disordered | ||||
Sequence: KLEKGESASPANEEITEEQNGTANGFSEINSKEKALETDSVSGVSKQSKKQKL | ||||||
Compositional bias | 698-739 | Polar residues | ||||
Sequence: NEEITEEQNGTANGFSEINSKEKALETDSVSGVSKQSKKQKL |
Sequence similarities
Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length739
- Mass (Da)83,055
- Last updated2006-10-17 v3
- ChecksumA8830EBC3FD38D56
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
J3QQW9 | J3QQW9_HUMAN | SUZ12 | 716 |
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 698-739 | Polar residues | ||||
Sequence: NEEITEEQNGTANGFSEINSKEKALETDSVSGVSKQSKKQKL |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D63881 EMBL· GenBank· DDBJ | BAA09931.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC015704 EMBL· GenBank· DDBJ | AAH15704.1 EMBL· GenBank· DDBJ | mRNA |