UniProt functional annotation for Q15022



	UniProt functional annotation for Q15022

UniProt code: Q15022.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, 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). {ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15099518, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}.

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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, PubMed:15684044, PubMed:16224021, PubMed:19026781, PubMed:18285464, 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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, 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 ARNTL/BMAL1 (By similarity). Interacts with EZHIP (via C-terminal region) (PubMed:30923826). {ECO:0000250|UniProtKB:Q80U70, ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15099518, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:16224021, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:16712789, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:22009739, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:30923826, ECO:0000269|PubMed:31959557}.

Subcellular location: Nucleus {ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}. Note=Localizes to chromatin as part of the PRC2 complex. {ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}.

Tissue specificity: Overexpressed in breast and colon cancer. {ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15684044}.

Developmental stage: Expressed at low levels in quiescent cells. Expression rises at the G1/S phase transition. {ECO:0000269|PubMed:15385962}.

Induction: Expression is induced by E2F1, E2F2 and E2F3. {ECO:0000269|PubMed:11564866, ECO:0000269|PubMed:14532106}.

Ptm: Sumoylated, probably by PIAS2. {ECO:0000269|PubMed:18628979}.

Disease: Note=A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. {ECO:0000269|PubMed:11371647}.

Disease: Imagawa-Matsumoto syndrome (IMMAS) [MIM:618786]: An autosomal dominant syndrome characterized by generalized overgrowth, dysmorphic features, musculoskeletal abnormalities, developmental delay and intellectual disability. Some patients have genitourinary and structural brain abnormalities. {ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:30019515, ECO:0000269|PubMed:31736240}. Note=The disease is caused by variants affecting the gene represented in this entry.

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). {ECO:0000305|PubMed:18772439}.

Similarity: Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family. {ECO:0000305}.

Sequence caution: Sequence=BAA09931.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, 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). {ECO:0000269\|PubMed:12351676, ECO:0000269\|PubMed:12435631, ECO:0000269\|PubMed:15099518, ECO:0000269\|PubMed:15225548, ECO:0000269\|PubMed:15231737, ECO:0000269\|PubMed:15385962, ECO:0000269\|PubMed:15684044, ECO:0000269\|PubMed:16431907, ECO:0000269\|PubMed:16618801, ECO:0000269\|PubMed:17200670, ECO:0000269\|PubMed:17344414, ECO:0000269\|PubMed:18086877, ECO:0000269\|PubMed:18285464, ECO:0000269\|PubMed:28229514, ECO:0000269\|PubMed:29499137, ECO:0000269\|PubMed:31959557}.


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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, PubMed:15684044, PubMed:16224021, PubMed:19026781, PubMed:18285464, 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:12435631, PubMed:12351676, PubMed:15385962, PubMed:15099518, PubMed:15225548, 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 ARNTL/BMAL1 (By similarity). Interacts with EZHIP (via C-terminal region) (PubMed:30923826). {ECO:0000250\|UniProtKB:Q80U70, ECO:0000269\|PubMed:12351676, ECO:0000269\|PubMed:12435631, ECO:0000269\|PubMed:15099518, ECO:0000269\|PubMed:15225548, ECO:0000269\|PubMed:15385962, ECO:0000269\|PubMed:15684044, ECO:0000269\|PubMed:16224021, ECO:0000269\|PubMed:16431907, ECO:0000269\|PubMed:16712789, ECO:0000269\|PubMed:18086877, ECO:0000269\|PubMed:18285464, ECO:0000269\|PubMed:19026781, ECO:0000269\|PubMed:22009739, ECO:0000269\|PubMed:29499137, ECO:0000269\|PubMed:30923826, ECO:0000269\|PubMed:31959557}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:15231737, ECO:0000269\|PubMed:29499137, ECO:0000269\|PubMed:31959557}. Note=Localizes to chromatin as part of the PRC2 complex. {ECO:0000269\|PubMed:29499137, ECO:0000269\|PubMed:31959557}.
Tissue specificity:		Overexpressed in breast and colon cancer. {ECO:0000269\|PubMed:15231737, ECO:0000269\|PubMed:15684044}.
Developmental stage:		Expressed at low levels in quiescent cells. Expression rises at the G1/S phase transition. {ECO:0000269\|PubMed:15385962}.
Induction:		Expression is induced by E2F1, E2F2 and E2F3. {ECO:0000269\|PubMed:11564866, ECO:0000269\|PubMed:14532106}.
Ptm:		Sumoylated, probably by PIAS2. {ECO:0000269\|PubMed:18628979}.
Disease:		Note=A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. {ECO:0000269\|PubMed:11371647}.
Disease:		Imagawa-Matsumoto syndrome (IMMAS) [MIM:618786]: An autosomal dominant syndrome characterized by generalized overgrowth, dysmorphic features, musculoskeletal abnormalities, developmental delay and intellectual disability. Some patients have genitourinary and structural brain abnormalities. {ECO:0000269\|PubMed:28229514, ECO:0000269\|PubMed:30019515, ECO:0000269\|PubMed:31736240}. Note=The disease is caused by variants affecting the gene represented in this entry.
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). {ECO:0000305\|PubMed:18772439}.
Similarity:		Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family. {ECO:0000305}.
Sequence caution:		Sequence=BAA09931.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};