UniProt functional annotation for O75530



	UniProt functional annotation for O75530

UniProt code: O75530.

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/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. 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 and CDKN2A. {ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:20974918, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:9584199}.

Subunit: Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. Interacts with CDYL. Interacts with ARNTL/BMAL1. Interacts with KMT2A/MLL1 (By similarity). {ECO:0000250|UniProtKB:Q921E6, ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:11158321, ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:20974918, ECO:0000269|PubMed:22009739, ECO:0000269|PubMed:9584199, ECO:0000269|PubMed:9765275}.

Subunit: (Microbial infection) May interact with the MA protein of HIV- 1. {ECO:0000269|PubMed:9880543}.

Subcellular location: Nucleus. Chromosome. Note=Transiently colocalizes with XIST at inactive X chromosomes.

Tissue specificity: Expressed in brain, colon, heart, kidney, liver, lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta, prostate, spleen, small intestine, testis, thymus and uterus. Appears to be overexpressed in breast and colon cancer. {ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:9584199, ECO:0000269|PubMed:9765275, ECO:0000269|PubMed:9806832, ECO:0000269|PubMed:9880543}.

Developmental stage: Expression peaks at the G1/S phase boundary. {ECO:0000269|PubMed:14532106}.

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

Domain: The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365. {ECO:0000269|PubMed:20974918}.

Ptm: Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines. {ECO:0000269|PubMed:20974918}.

Disease: Cohen-Gibson syndrome (COGIS) [MIM:617561]: An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability. {ECO:0000269|PubMed:25787343, ECO:0000269|PubMed:27193220, ECO:0000269|PubMed:27868325, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:28475857}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the WD repeat ESC family. {ECO:0000305}.

Sequence caution: Sequence=AAC23685.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAC68675.1; Type=Erroneous initiation; Note=Truncated 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/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. 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 and CDKN2A. {ECO:0000269\|PubMed:10581039, ECO:0000269\|PubMed:14532106, ECO:0000269\|PubMed:15225548, ECO:0000269\|PubMed:15231737, ECO:0000269\|PubMed:15385962, ECO:0000269\|PubMed:16357870, ECO:0000269\|PubMed:18285464, ECO:0000269\|PubMed:20974918, ECO:0000269\|PubMed:28229514, ECO:0000269\|PubMed:9584199}.


Subunit:		Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. Interacts with CDYL. Interacts with ARNTL/BMAL1. Interacts with KMT2A/MLL1 (By similarity). {ECO:0000250\|UniProtKB:Q921E6, ECO:0000269\|PubMed:10581039, ECO:0000269\|PubMed:11158321, ECO:0000269\|PubMed:12351676, ECO:0000269\|PubMed:12435631, ECO:0000269\|PubMed:15385962, ECO:0000269\|PubMed:16357870, ECO:0000269\|PubMed:16431907, ECO:0000269\|PubMed:18086877, ECO:0000269\|PubMed:18285464, ECO:0000269\|PubMed:19026781, ECO:0000269\|PubMed:20974918, ECO:0000269\|PubMed:22009739, ECO:0000269\|PubMed:9584199, ECO:0000269\|PubMed:9765275}.
Subunit:		(Microbial infection) May interact with the MA protein of HIV- 1. {ECO:0000269\|PubMed:9880543}.
Subcellular location:		Nucleus. Chromosome. Note=Transiently colocalizes with XIST at inactive X chromosomes.
Tissue specificity:		Expressed in brain, colon, heart, kidney, liver, lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta, prostate, spleen, small intestine, testis, thymus and uterus. Appears to be overexpressed in breast and colon cancer. {ECO:0000269\|PubMed:15684044, ECO:0000269\|PubMed:9584199, ECO:0000269\|PubMed:9765275, ECO:0000269\|PubMed:9806832, ECO:0000269\|PubMed:9880543}.
Developmental stage:		Expression peaks at the G1/S phase boundary. {ECO:0000269\|PubMed:14532106}.
Induction:		Expression is induced by E2F1, E2F2 and E2F3. {ECO:0000269\|PubMed:14532106}.
Domain:		The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365. {ECO:0000269\|PubMed:20974918}.
Ptm:		Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines. {ECO:0000269\|PubMed:20974918}.
Disease:		Cohen-Gibson syndrome (COGIS) [MIM:617561]: An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability. {ECO:0000269\|PubMed:25787343, ECO:0000269\|PubMed:27193220, ECO:0000269\|PubMed:27868325, ECO:0000269\|PubMed:28229514, ECO:0000269\|PubMed:28475857}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the WD repeat ESC family. {ECO:0000305}.
Sequence caution:		Sequence=AAC23685.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=AAC68675.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};