UniProt functional annotation for Q9UMN6



	UniProt functional annotation for Q9UMN6

UniProt code: Q9UMN6.

Organism: Homo sapiens (Human).

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

Function: Histone methyltransferase that methylates 'Lys-4' of histone H3 (PubMed:17707229). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:17707229). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250|UniProtKB:O08550, ECO:0000269|PubMed:17707229}.

Catalytic activity: Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA- COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354; Evidence={ECO:0000269|PubMed:17707229};

Subunit: Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and POLR2B via MEN1. Interacts with NFE2. Interacts with KDM6B. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653, PubMed:18840606). Interacts (via MBM motif) with MEN1 (PubMed:22327296). {ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:17825402, ECO:0000269|PubMed:18840606, ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22665483}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q03164}.

Tissue specificity: Widely expressed. Highest levels in testis. Also found in brain with higher expression in the cerebellum than in any other region, bone marrow, heart, muscle, kidney, placenta, spleen, thymus, prostate, ovary, intestine, colon, peripheral blood lymphocytes and pancreas. Often amplified in pancreatic carcinomas. {ECO:0000269|PubMed:27992417}.

Domain: The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. {ECO:0000269|PubMed:29276034}.

Disease: Dystonia 28, childhood-onset (DYT28) [MIM:617284]: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT28 is an autosomal dominant, progressive form characterized by onset in the first decade of life and variable severity. Dystonia begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region. {ECO:0000269|PubMed:27839873, ECO:0000269|PubMed:27992417}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.

Sequence caution: Sequence=AAD26113.1; Type=Miscellaneous discrepancy; Note=Probably cloning artifact.; 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:		Histone methyltransferase that methylates 'Lys-4' of histone H3 (PubMed:17707229). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:17707229). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (PubMed:17707229). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (By similarity). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (By similarity). {ECO:0000250\|UniProtKB:O08550, ECO:0000269\|PubMed:17707229}.


Catalytic activity:		Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA- COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354; Evidence={ECO:0000269\|PubMed:17707229};
Subunit:		Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and POLR2B via MEN1. Interacts with NFE2. Interacts with KDM6B. Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653, PubMed:18840606). Interacts (via MBM motif) with MEN1 (PubMed:22327296). {ECO:0000269\|PubMed:14992727, ECO:0000269\|PubMed:17707229, ECO:0000269\|PubMed:17825402, ECO:0000269\|PubMed:18840606, ECO:0000269\|PubMed:22266653, ECO:0000269\|PubMed:22327296, ECO:0000269\|PubMed:22665483}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:Q03164}.
Tissue specificity:		Widely expressed. Highest levels in testis. Also found in brain with higher expression in the cerebellum than in any other region, bone marrow, heart, muscle, kidney, placenta, spleen, thymus, prostate, ovary, intestine, colon, peripheral blood lymphocytes and pancreas. Often amplified in pancreatic carcinomas. {ECO:0000269\|PubMed:27992417}.
Domain:		The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. {ECO:0000269\|PubMed:29276034}.
Disease:		Dystonia 28, childhood-onset (DYT28) [MIM:617284]: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT28 is an autosomal dominant, progressive form characterized by onset in the first decade of life and variable severity. Dystonia begins focally in the lower limbs, resulting in gait difficulties, with later progression to other body regions, including the upper limbs, neck, and orofacial region. {ECO:0000269\|PubMed:27839873, ECO:0000269\|PubMed:27992417}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00190}.
Sequence caution:		Sequence=AAD26113.1; Type=Miscellaneous discrepancy; Note=Probably cloning artifact.; Evidence={ECO:0000305};