Polyglutamine(Q) tract binding protein-1 (PQBP-1) is a transcription repressor that associates with polyglutamine tract-containing transcription regulators and causative genes for neurodegenerative disorders. Hepta- and di-amino acid repeat sequences rich in polar residues are essential for PQBP-1 to interact with polyglutamine tract-containing proteins (i.e. huntingtin, androgen receptor and Brain-2). PQBP-1 contains a WWP/WW domain that binds proline-rich motifs and a C2 domain that can influence Ca2+-dependent phospholipid signaling. PQBP-1 localizes to the nucleus and is present in neurons throughout the brain, with abundant levels in hippocampus, cerebellar cortex and olfactory bulb. The human PQBP-1 gene maps to chromosome Xp11.23.
Function:
May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner. Can activate transcription directly or via association with the transcription machinery. May be involved in ATXN1 mutant-induced cell death. The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit.
Subunit:
nteracts with POU3F2/Brn-2, ATXN1, TXNL4A, HTT and AR.Interaction with ATXN1 correlates positively with the length of thepolyglutamine tract. Interacts with RNA polymerase II large subunitin a phosphorylation-dependent manner. Forms a ternary complex withATXN1 mutant and phosphorylated RNA polymerase II.
Subcellular Location:
Nucleus. Co-localized with POU3F2. Co-localized with ATXN1 in nuclear inclusion bodies.
Tissue Specificity:
Widely expressed with high level in heart, skeletal muscle, pancreas, spleen, thymus, prostate, ovary, small intestine and peripheral blood leukocytes.
DISEASE:
Defects in PQBP1 are the cause of Renpenning syndrome 1 (RENS1) [MIM:309500]; also known as Sutherland-Haan X-linked mental retardation syndrome (SHS) or X-linked mental retardation syndromes MRXS3/MRXS8/MRX55. The clinical features are mental retardation, microcephaly, short stature, and small testes. The craniofacies tends to be narrow and tall with upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. RENS1 is more frequently in males than in females where little or no expression is found.
Similarity:
Contains 1 WW domain.
SWISS:
O60828
Gene ID:
10084
Database links:
Entrez Gene: 10084 Human
Entrez Gene: 54633 Mouse
Omim: 300463 Human
SwissProt: O60828 Human
SwissProt: Q91VJ5 Mouse
Unigene: 534384 Human
Unigene: 14616 Mouse
|
|
