UniProt functional annotation for Q8NHM5



	UniProt functional annotation for Q8NHM5

UniProt code: Q8NHM5.

Organism: Homo sapiens (Human).

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

Function: Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}.

Catalytic activity: Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(36)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:42032, Rhea:RHEA-COMP:9785, Rhea:RHEA- COMP:9787, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031, ChEBI:CHEBI:61976; EC=1.14.11.27; Evidence={ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:26237645};

Cofactor: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9Y2K7};

Activity regulation: Histone demethylase activity is inhibited by fumarate. {ECO:0000269|PubMed:26237645}.

Subunit: Interacts with SKP1, forming heterodimers (PubMed:27568929). The heterodimeric KDM2B-SKP1 complex interacts with the PCGF1-BCORL1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (PubMed:27568929). Directly interacts with CUL1. The SKP1-KDM2B complex interacts with UBB (PubMed:30033217). {ECO:0000269|PubMed:27568929, ECO:0000269|PubMed:30033217, ECO:0000305}.

Subcellular location: Nucleus, nucleolus {ECO:0000269|PubMed:17994099}. Nucleus {ECO:0000269|PubMed:26237645}. Chromosome {ECO:0000269|PubMed:26237645}.

Domain: The LRR repeats are required for the interaction with the PCGF1-BCORL1 heterodimeric complex. {ECO:0000269|PubMed:27568929}.

Domain: The JmjC domain mediates demethylation activity (PubMed:17994099). It is also required for repression of ribosomal RNA genes (PubMed:17994099). {ECO:0000269|PubMed:17994099}.

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

Domain: The F-box domain mediates interaction with UBB. {ECO:0000269|PubMed:30033217}.

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

Sequence caution: Sequence=AAH08735.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB55112.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB55301.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC11159.1; Type=Erroneous initiation; 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 that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269\|PubMed:16362057, ECO:0000269\|PubMed:17994099, ECO:0000269\|PubMed:26237645, ECO:0000305}.


Catalytic activity:		Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(36)-[histone H3] + 2 succinate; Xref=Rhea:RHEA:42032, Rhea:RHEA-COMP:9785, Rhea:RHEA- COMP:9787, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031, ChEBI:CHEBI:61976; EC=1.14.11.27; Evidence={ECO:0000269\|PubMed:16362057, ECO:0000269\|PubMed:26237645};
Cofactor:		Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250\|UniProtKB:Q9Y2K7};
Activity regulation:		Histone demethylase activity is inhibited by fumarate. {ECO:0000269\|PubMed:26237645}.
Subunit:		Interacts with SKP1, forming heterodimers (PubMed:27568929). The heterodimeric KDM2B-SKP1 complex interacts with the PCGF1-BCORL1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (PubMed:27568929). Directly interacts with CUL1. The SKP1-KDM2B complex interacts with UBB (PubMed:30033217). {ECO:0000269\|PubMed:27568929, ECO:0000269\|PubMed:30033217, ECO:0000305}.
Subcellular location:		Nucleus, nucleolus {ECO:0000269\|PubMed:17994099}. Nucleus {ECO:0000269\|PubMed:26237645}. Chromosome {ECO:0000269\|PubMed:26237645}.
Domain:		The LRR repeats are required for the interaction with the PCGF1-BCORL1 heterodimeric complex. {ECO:0000269\|PubMed:27568929}.
Domain:		The JmjC domain mediates demethylation activity (PubMed:17994099). It is also required for repression of ribosomal RNA genes (PubMed:17994099). {ECO:0000269\|PubMed:17994099}.
Domain:		The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. {ECO:0000269\|PubMed:29276034}.
Domain:		The F-box domain mediates interaction with UBB. {ECO:0000269\|PubMed:30033217}.
Similarity:		Belongs to the JHDM1 histone demethylase family. {ECO:0000305}.
Sequence caution:		Sequence=AAH08735.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB55112.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB55301.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC11159.1; Type=Erroneous initiation; Evidence={ECO:0000305};