UniProt functional annotation for Q6ZMT4



	UniProt functional annotation for Q6ZMT4

UniProt code: Q6ZMT4.

Organism: Homo sapiens (Human).

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

Function: Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate. {ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20194436, ECO:0000269|PubMed:20622853}.

Cofactor: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20194436}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20194436};

Biophysicochemical properties: Kinetic parameters: KM=1.2 uM for histone H3 H3K9Me2 {ECO:0000269|PubMed:20023638};

Subcellular location: Nucleus.

Domain: The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2. {ECO:0000269|PubMed:20023638}.

Domain: The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2. {ECO:0000269|PubMed:20023638}.

Miscellaneous: [Isoform 2]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.

Similarity: Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily. {ECO:0000305}.

Sequence caution: Sequence=BAD18641.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=EAL24032.1; Type=Erroneous gene model prediction; 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 demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate. {ECO:0000269\|PubMed:20023638, ECO:0000269\|PubMed:20194436, ECO:0000269\|PubMed:20622853}.


Cofactor:		Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000269\|PubMed:20023638, ECO:0000269\|PubMed:20194436}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269\|PubMed:20023638, ECO:0000269\|PubMed:20194436};
Biophysicochemical properties:		Kinetic parameters: KM=1.2 uM for histone H3 H3K9Me2 {ECO:0000269\|PubMed:20023638};
Subcellular location:		Nucleus.
Domain:		The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2. {ECO:0000269\|PubMed:20023638}.
Domain:		The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2. {ECO:0000269\|PubMed:20023638}.
Miscellaneous:		[Isoform 2]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.
Similarity:		Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily. {ECO:0000305}.
Sequence caution:		Sequence=BAD18641.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=EAL24032.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};