UniProt functional annotation for Q12830



	UniProt functional annotation for Q12830

UniProt code: Q12830.

Organism: Homo sapiens (Human).

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

Function: Histone-binding component of NURF (nucleosome-remodeling factor), a complex which catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin. Specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. May also regulate transcription through direct binding to DNA or transcription factors.

Subunit: Interacts with MAZ. Interacts with KEAP1. Part of the nucleosome-remodeling factor (NURF) complex which consists of SMARCA1; BPTF; RBBP4 and RBBP7. Interacts with histone H3K4me3 and to a lesser extent with histone H3-K4Me2. {ECO:0000269|PubMed:10727212, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:16728976, ECO:0000269|PubMed:16728978, ECO:0000269|PubMed:18042461}.

Subcellular location: Cytoplasm. Nucleus. Note=In brains of Alzheimer disease patients, present in a subset of amyloid-containing plaques.

Tissue specificity: Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level). {ECO:0000269|PubMed:10662542, ECO:0000269|PubMed:10727212, ECO:0000269|PubMed:7621746, ECO:0000269|PubMed:9225734}.

Developmental stage: Abundantly expressed in the fetal brain. Present throughout the gray and white matter of the developing spinal cord at 18-22 gestational weeks. Expressed at low levels in adult brain and spinal cord and reexpressed in neurodegenerative diseases (at protein level). {ECO:0000269|PubMed:9225734}.

Domain: The second PHD-type zinc finger mediates binding to histone H3K4Me3. Has specificity for trimethyllysine; introducing a mutation in the Tyr-2876 residue can induce binding to dimethyllysine. {ECO:0000269|PubMed:18042461}.

Ptm: Phosphorylation enhances DNA-binding. {ECO:0000269|PubMed:10403843}.

Ptm: Highly susceptible to proteolysis.

Disease: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) [MIM:617755]: An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet. {ECO:0000269|PubMed:28942966}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the PBTF family. {ECO:0000305}.

Sequence caution: Sequence=AAA97522.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAA97522.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305}; Sequence=BAA89208.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors in the N-terminal part.; 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-binding component of NURF (nucleosome-remodeling factor), a complex which catalyzes ATP-dependent nucleosome sliding and facilitates transcription of chromatin. Specifically recognizes H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of virtually all active genes. May also regulate transcription through direct binding to DNA or transcription factors.


Subunit:		Interacts with MAZ. Interacts with KEAP1. Part of the nucleosome-remodeling factor (NURF) complex which consists of SMARCA1; BPTF; RBBP4 and RBBP7. Interacts with histone H3K4me3 and to a lesser extent with histone H3-K4Me2. {ECO:0000269\|PubMed:10727212, ECO:0000269\|PubMed:14609955, ECO:0000269\|PubMed:15379550, ECO:0000269\|PubMed:16728976, ECO:0000269\|PubMed:16728978, ECO:0000269\|PubMed:18042461}.
Subcellular location:		Cytoplasm. Nucleus. Note=In brains of Alzheimer disease patients, present in a subset of amyloid-containing plaques.
Tissue specificity:		Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level). {ECO:0000269\|PubMed:10662542, ECO:0000269\|PubMed:10727212, ECO:0000269\|PubMed:7621746, ECO:0000269\|PubMed:9225734}.
Developmental stage:		Abundantly expressed in the fetal brain. Present throughout the gray and white matter of the developing spinal cord at 18-22 gestational weeks. Expressed at low levels in adult brain and spinal cord and reexpressed in neurodegenerative diseases (at protein level). {ECO:0000269\|PubMed:9225734}.
Domain:		The second PHD-type zinc finger mediates binding to histone H3K4Me3. Has specificity for trimethyllysine; introducing a mutation in the Tyr-2876 residue can induce binding to dimethyllysine. {ECO:0000269\|PubMed:18042461}.
Ptm:		Phosphorylation enhances DNA-binding. {ECO:0000269\|PubMed:10403843}.
Ptm:		Highly susceptible to proteolysis.
Disease:		Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) [MIM:617755]: An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet. {ECO:0000269\|PubMed:28942966}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the PBTF family. {ECO:0000305}.
Sequence caution:		Sequence=AAA97522.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAA97522.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305}; Sequence=BAA89208.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors in the N-terminal part.; Evidence={ECO:0000305};