UniProt functional annotation for Q921E6



	UniProt functional annotation for Q921E6

UniProt code: Q921E6.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED- EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain. {ECO:0000250|UniProtKB:O75530, ECO:0000269|PubMed:11479595, ECO:0000269|PubMed:12370779, ECO:0000269|PubMed:12627233, ECO:0000269|PubMed:12649488, ECO:0000269|PubMed:12689588, ECO:0000269|PubMed:15516932, ECO:0000269|PubMed:15916951, ECO:0000269|PubMed:16415857, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17259173, ECO:0000269|PubMed:17997413, ECO:0000269|PubMed:18201968, ECO:0000269|PubMed:9234727, ECO:0000269|PubMed:9742080}.

Subunit: Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). 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 (By similarity). Interacts with HDAC, HDAC2, histone H1 and YY1 (By similarity). May interact with ITGA4, ITGAE and ITGB7 (By similarity). Interacts with CDYL (By similarity). Interacts with EZH2. Interacts with KMT2A/MLL1 in adult brain. Interacts with ARNTL/BMAL1. {ECO:0000250|UniProtKB:O75530, ECO:0000269|PubMed:16224021, ECO:0000269|PubMed:17259173, ECO:0000269|PubMed:17937919, ECO:0000269|PubMed:17997413, ECO:0000269|PubMed:19026780, ECO:0000269|PubMed:20144788, ECO:0000269|PubMed:23970558, ECO:0000269|PubMed:9742080}.

Subcellular location: Nucleus. Chromosome. Note=Localizes to the inactive X chromosome in cells of the early embryo and in stem cells of the extraembryonic trophectoderm lineage. Recruitment to the inactive X-chromosome requires XIST.

Tissue specificity: Expressed in brain, heart, kidney, liver, lung, muscle, ovary, spleen and testis. Expressed throughout the brain. {ECO:0000269|PubMed:17259173, ECO:0000269|PubMed:8805699, ECO:0000269|PubMed:9234727}.

Developmental stage: Maternally expressed. Expressed from 5.5 dpc, and expression remains high throughout development. Expression decreases during differentiation of embryonic stem cells (ES cells). Expression increases in prostate during prostate tumor development. {ECO:0000269|PubMed:12689588, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:8805699}.

Induction: Induced in embryonic stem cells (ES cells) by STAT3 and POU5F1. {ECO:0000269|PubMed:18201968}.

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 (By similarity). {ECO:0000250}.

Ptm: Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines (By similarity). {ECO:0000250}.

Miscellaneous: Mice homozygous for a null allele of this protein (Pro- 196) exhibit disrupted anterior posterior patterning of the primitive streak during gastrulation and reduced numbers of trophoblast giant cells. Mice homozygous for a hypomorphic allele of this protein (Asn- 193) exhibit posterior transformations along the axial skeleton and altered patterns of Hox gene expression.

Miscellaneous: [Isoform 2]: Translation initiates from a non-canonical start codon (GUG). {ECO:0000305}.

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

Sequence caution: Sequence=AAB38319.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAC53302.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH12966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED- EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain. {ECO:0000250\|UniProtKB:O75530, ECO:0000269\|PubMed:11479595, ECO:0000269\|PubMed:12370779, ECO:0000269\|PubMed:12627233, ECO:0000269\|PubMed:12649488, ECO:0000269\|PubMed:12689588, ECO:0000269\|PubMed:15516932, ECO:0000269\|PubMed:15916951, ECO:0000269\|PubMed:16415857, ECO:0000269\|PubMed:16618801, ECO:0000269\|PubMed:17259173, ECO:0000269\|PubMed:17997413, ECO:0000269\|PubMed:18201968, ECO:0000269\|PubMed:9234727, ECO:0000269\|PubMed:9742080}.


Subunit:		Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). 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 (By similarity). Interacts with HDAC, HDAC2, histone H1 and YY1 (By similarity). May interact with ITGA4, ITGAE and ITGB7 (By similarity). Interacts with CDYL (By similarity). Interacts with EZH2. Interacts with KMT2A/MLL1 in adult brain. Interacts with ARNTL/BMAL1. {ECO:0000250\|UniProtKB:O75530, ECO:0000269\|PubMed:16224021, ECO:0000269\|PubMed:17259173, ECO:0000269\|PubMed:17937919, ECO:0000269\|PubMed:17997413, ECO:0000269\|PubMed:19026780, ECO:0000269\|PubMed:20144788, ECO:0000269\|PubMed:23970558, ECO:0000269\|PubMed:9742080}.
Subcellular location:		Nucleus. Chromosome. Note=Localizes to the inactive X chromosome in cells of the early embryo and in stem cells of the extraembryonic trophectoderm lineage. Recruitment to the inactive X-chromosome requires XIST.
Tissue specificity:		Expressed in brain, heart, kidney, liver, lung, muscle, ovary, spleen and testis. Expressed throughout the brain. {ECO:0000269\|PubMed:17259173, ECO:0000269\|PubMed:8805699, ECO:0000269\|PubMed:9234727}.
Developmental stage:		Maternally expressed. Expressed from 5.5 dpc, and expression remains high throughout development. Expression decreases during differentiation of embryonic stem cells (ES cells). Expression increases in prostate during prostate tumor development. {ECO:0000269\|PubMed:12689588, ECO:0000269\|PubMed:15684044, ECO:0000269\|PubMed:8805699}.
Induction:		Induced in embryonic stem cells (ES cells) by STAT3 and POU5F1. {ECO:0000269\|PubMed:18201968}.
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 (By similarity). {ECO:0000250}.
Ptm:		Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines (By similarity). {ECO:0000250}.
Miscellaneous:		Mice homozygous for a null allele of this protein (Pro- 196) exhibit disrupted anterior posterior patterning of the primitive streak during gastrulation and reduced numbers of trophoblast giant cells. Mice homozygous for a hypomorphic allele of this protein (Asn- 193) exhibit posterior transformations along the axial skeleton and altered patterns of Hox gene expression.
Miscellaneous:		[Isoform 2]: Translation initiates from a non-canonical start codon (GUG). {ECO:0000305}.
Similarity:		Belongs to the WD repeat ESC family. {ECO:0000305}.
Sequence caution:		Sequence=AAB38319.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAC53302.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=AAH12966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};