UniProt functional annotation for Q9NQR1



	UniProt functional annotation for Q9NQR1

UniProt code: Q9NQR1.

Organism: Homo sapiens (Human).

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

Function: Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF- beta response regulation and a positive role in cell migration. {ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:16517599, ECO:0000269|PubMed:17707234, ECO:0000269|PubMed:23478445}.

Catalytic activity: Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361; Evidence={ECO:0000255|PROSITE-ProRule:PRU00904, ECO:0000269|PubMed:12086618, ECO:0000269|PubMed:12121615, ECO:0000269|PubMed:15964846};

Catalytic activity: Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000305};

Subunit: Interacts with L3MBTL1. Isoform 2 interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A- mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner. {ECO:0000269|PubMed:15933069, ECO:0000269|PubMed:15933070, ECO:0000269|PubMed:18408754, ECO:0000269|PubMed:23468428}.

Subcellular location: Nucleus. Chromosome. Note=Specifically localizes to mitotic chromosomes. Colocalized with SIRT2 at mitotic foci. Associates with chromosomes during mitosis; association is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin.

Developmental stage: Not detected during G1 phase. First detected during S through G2 phases, and peaks during mitosis (at protein level). {ECO:0000269|PubMed:12208845}.

Induction: By HCFC1 C-terminal chain, independently of HCFC1 N-terminal chain. Transiently induced by TGF-beta and during the cell cycle. {ECO:0000269|PubMed:15200950, ECO:0000269|PubMed:23478445}.

Domain: Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.

Ptm: Acetylated at Lys-172; does not change methyltransferase activity. Deacetylated at Lys-172 by SIRT2; does not change methyltransferase activity. {ECO:0000269|PubMed:23468428}.

Ptm: Ubiquitinated and degraded by the DCX(DTL) complex. {ECO:0000305|PubMed:23478445}.

Similarity: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily. {ECO:0000255|PROSITE-ProRule:PRU00904}.

Sequence caution: Sequence=AAL40879.1; 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:		Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF- beta response regulation and a positive role in cell migration. {ECO:0000269\|PubMed:12086618, ECO:0000269\|PubMed:12121615, ECO:0000269\|PubMed:15200950, ECO:0000269\|PubMed:15933069, ECO:0000269\|PubMed:15933070, ECO:0000269\|PubMed:16517599, ECO:0000269\|PubMed:17707234, ECO:0000269\|PubMed:23478445}.


Catalytic activity:		Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00904, ECO:0000269\|PubMed:12086618, ECO:0000269\|PubMed:12121615, ECO:0000269\|PubMed:15964846};
Catalytic activity:		Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; Evidence={ECO:0000305};
Subunit:		Interacts with L3MBTL1. Isoform 2 interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A- mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner. {ECO:0000269\|PubMed:15933069, ECO:0000269\|PubMed:15933070, ECO:0000269\|PubMed:18408754, ECO:0000269\|PubMed:23468428}.
Subcellular location:		Nucleus. Chromosome. Note=Specifically localizes to mitotic chromosomes. Colocalized with SIRT2 at mitotic foci. Associates with chromosomes during mitosis; association is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Associates with silent chromatin on euchromatic arms. Not associated with constitutive heterochromatin.
Developmental stage:		Not detected during G1 phase. First detected during S through G2 phases, and peaks during mitosis (at protein level). {ECO:0000269\|PubMed:12208845}.
Induction:		By HCFC1 C-terminal chain, independently of HCFC1 N-terminal chain. Transiently induced by TGF-beta and during the cell cycle. {ECO:0000269\|PubMed:15200950, ECO:0000269\|PubMed:23478445}.
Domain:		Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.
Ptm:		Acetylated at Lys-172; does not change methyltransferase activity. Deacetylated at Lys-172 by SIRT2; does not change methyltransferase activity. {ECO:0000269\|PubMed:23468428}.
Ptm:		Ubiquitinated and degraded by the DCX(DTL) complex. {ECO:0000305\|PubMed:23478445}.
Similarity:		Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00904}.
Sequence caution:		Sequence=AAL40879.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};