UniProt functional annotation for O43791



	UniProt functional annotation for O43791

UniProt code: O43791.

Organism: Homo sapiens (Human).

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

Function: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420). {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:32109420}.

Pathway: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:32109420}.

Subunit: Interacts with GLI2 and GLI3 (By similarity). Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX. {ECO:0000250, ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15240113, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832}.

Subcellular location: Nucleus {ECO:0000269|PubMed:22085717}. Nucleus speckle {ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:9414087}.

Tissue specificity: Widely expressed. {ECO:0000269|PubMed:9414087}.

Domain: The BTB (POZ) domain mediates dimerization and interaction with CUL3. {ECO:0000269|PubMed:19818708}.

Domain: The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1. {ECO:0000269|PubMed:19818708}.

Disease: Nabais Sa-de Vries syndrome 1 (NSDVS1) [MIM:618828]: An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show congenital microcephaly and dysmorphic facial features, including round face, small palpebral fissures, highly arched eyebrows, and short nose. {ECO:0000269|PubMed:32109420}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Nabais Sa-de Vries syndrome 2 (NSDVS2) [MIM:618829]: An autosomal dominant disorder characterized by global developmental delay apparent from birth, impaired intellectual development, speech delay, dysmorphic facial features, and additional anomalies including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities. {ECO:0000269|PubMed:32109420}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

Miscellaneous: Antigen recognized by serum from scleroderma patient.

Similarity: Belongs to the Tdpoz family. {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:		Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (PubMed:32109420). {ECO:0000269\|PubMed:14528312, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16524876, ECO:0000269\|PubMed:19818708, ECO:0000269\|PubMed:22085717, ECO:0000269\|PubMed:22632832, ECO:0000269\|PubMed:32109420}.


Pathway:		Protein modification; protein ubiquitination. {ECO:0000269\|PubMed:14528312, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16524876, ECO:0000269\|PubMed:19818708, ECO:0000269\|PubMed:22085717, ECO:0000269\|PubMed:22632832, ECO:0000269\|PubMed:32109420}.
Subunit:		Interacts with GLI2 and GLI3 (By similarity). Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX. {ECO:0000250, ECO:0000269\|PubMed:14528312, ECO:0000269\|PubMed:15240113, ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:16524876, ECO:0000269\|PubMed:19818708, ECO:0000269\|PubMed:22085717, ECO:0000269\|PubMed:22632832}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:22085717}. Nucleus speckle {ECO:0000269\|PubMed:15897469, ECO:0000269\|PubMed:9414087}.
Tissue specificity:		Widely expressed. {ECO:0000269\|PubMed:9414087}.
Domain:		The BTB (POZ) domain mediates dimerization and interaction with CUL3. {ECO:0000269\|PubMed:19818708}.
Domain:		The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1. {ECO:0000269\|PubMed:19818708}.
Disease:		Nabais Sa-de Vries syndrome 1 (NSDVS1) [MIM:618828]: An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show congenital microcephaly and dysmorphic facial features, including round face, small palpebral fissures, highly arched eyebrows, and short nose. {ECO:0000269\|PubMed:32109420}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Nabais Sa-de Vries syndrome 2 (NSDVS2) [MIM:618829]: An autosomal dominant disorder characterized by global developmental delay apparent from birth, impaired intellectual development, speech delay, dysmorphic facial features, and additional anomalies including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities. {ECO:0000269\|PubMed:32109420}. Note=The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.
Miscellaneous:		Antigen recognized by serum from scleroderma patient.
Similarity:		Belongs to the Tdpoz family. {ECO:0000305}.