Protein: Tetratricopeptide repeat protein 5 (TPR repeat protein 5) (Stress-responsive activator of p300) (Protein Strap) (Q8N0Z6)
Organism: Homo sapiens (Human)
Function: Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair. In non-stress conditions, interacts with cofactor JMY in the cytoplasm which prevents JMY's actin nucleation activity and ability to activate the Arp2/3 complex. Acts as a negative regulator of nutrient stress-induced autophagy by preventing JMY's interaction with MAP1LC3B, thereby preventing autophagosome formation (By similarity). Involves in tubulin autoregulation by promoting its degradation in response to excess soluble tubulin. To do so, associates with the active ribosome near the ribosome exit tunnel and with nascent tubulin polypeptides early during their translation, triggering tubulin mRNA-targeted degradation. Following DNA damage, phosphorylated by DNA damage responsive protein kinases ATM and CHEK2, leading to its nuclear accumulation and stability. Nuclear TTC5/STRAP promotes the assembly of a stress-responsive p53/TP53 coactivator complex, which includes the coactivators JMY and p300, thereby increasing p53/TP53-dependent transcription and apoptosis. Also recruits arginine methyltransferase PRMT5 to p53/TP53 when DNA is damaged, allowing PRMT5 to methylate p53/TP53. In DNA stress conditions, also prevents p53/TP53 degradation by E3 ubiquitin ligase MDM2 (By similarity). Upon heat-shock stress, forms a chromatin-associated complex with heat-shock factor 1 HSF1 and p300/EP300 to stimulate heat-shock-responsive transcription, thereby increasing cell survival. Mitochondrial TTC5/STRAP interacts with ATP synthase subunit beta ATP5F1B which decreased ATP synthase activity and lowers mitochondrial ATP production, thereby regulating cellular respiration and mitochondrial-dependent apoptosis. Mitochondrial TTC5/STRAP also regulates p53/TP53-mediated apoptosis (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q99LG4}. Cytoplasm {ECO:0000269|PubMed:31727855}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q99LG4}. Mitochondrion matrix {ECO:0000250|UniProtKB:Q99LG4}. Note=Phosphorylation at Ser-203 results in nuclear localization, while unphosphorylated protein localizes to the cytoplasm. Nuclear localization may be necessary for DNA damage-dependent stabilization of the protein. {ECO:0000250|UniProtKB:Q99LG4}.
Interaction partners:
- Histone acetyltransferase p300
- Junction-mediating and -regulatory protein
- Large ribosomal subunit protein uL10
- Tubulin beta chain
- Large ribosomal subunit protein uL6
- Large ribosomal subunit protein uL23
- Large ribosomal subunit protein uL5
- Large ribosomal subunit protein uL13
- Large ribosomal subunit protein uL18
- Large ribosomal subunit protein uL14
Sequence:
MMADEEEEVKPILQKLQELVDQLYSFRDCYFETHSVEDAGRKQQDVQKEMEKTLQQMEEVVGSVQGKAQVLMLTGKALNVTPDYSPKAEELLSKAVKLEPELVEAWNQLGEVYWKKGDVAAAHTCFSGALTHCRNKVSLQNLSMVLRQLRTDTEDEHSHHVMDSVRQAKLAVQMDVHDGRSWYILGNSYLSLYFSTGQNPKISQQALSAYAQAEKVDRKASSNPDLHLNRATLHKYEESYGEALEGFSRAAALDPAWPEPRQREQQLLEFLDRLTSLLESKGKVKTKKLQSMLGSLRPAHLGPCSDGHYQSASGQKVTLELKPLSTLQPGVNSGAVILGKVVFSLTTEEKVPFTFGLVDSDGPCYAVMVYNIVQSWGVLIGDSVAIPEPNLRLHRIQHKGKDYSFSSVRVETPLLLVVNGKPQGSSSQAVATVASRPQCE