TTC5
entrez
91875
canonical
uniprot
Q8N0Z6
canonical
ensembl
ENSG00000136319
resolver
ensembl
ENSG00000291781
resolver
ensp
ENSP00000258821
resolver
ensp
ENSP00000517308
resolver
enst
ENST00000258821
resolver
enst
ENST00000708730
resolver
genesymbol
TTC5
resolver
hgnc
HGNC:19274
resolver
uniprot
A8MQ18
resolver
uniprot
Q86T04
resolver
uniprot
Q96HF9
resolver
uniprot_entry
Q86T04_HUMAN
resolver
uniprot_entry
TTC5_HUMAN
resolver
uniprot_sec
A8MQ18
resolver
uniprot_sec
Q96HF9
resolver
amino_acid_sequence
MMADEEEEVKPILQKLQELVDQLYSFRDCYFETHSVEDAGRKQQDVQKEMEKTLQQMEEVVGSVQGKAQVLMLTGKALNVTPDYSPKAEELLSKAVKLEPELVEAWNQLGEVYWKKGDVAAAHTCFSGALTHCRNKVSLQNLSMVLRQLRTDTEDEHSHHVMDSVRQAKLAVQMDVHDGRSWYILGNSYLSLYFSTGQNPKISQQALSAYAQAEKVDRKASSNPDLHLNRATLHKYEESYGEALEGFSRAAALDPAWPEPRQREQQLLEFLDRLTSLLESKGKVKTKKLQSMLGSLRPAHLGPCSDGHYQSASGQKVTLELKPLSTLQPGVNSGAVILGKVVFSLTTEEKVPFTFGLVDSDGPCYAVMVYNIVQSWGVLIGDSVAIPEPNLRLHRIQHKGKDYSFSSVRVETPLLLVVNGKPQGSSSQAVATVASRPQCE
uniprot
proteins
disease_involvement
DISEASE: Neurodevelopmental disorder with cerebral atrophy and variable facial dysmorphism (NEDCAFD) [MIM:619244]: An autosomal recessive disorder characterized by global developmental delay apparent from birth, moderate-to-severe intellectual disability, poor or absent speech, and hypotonia. Most patients have variable dysmorphic facial features. Brain imaging shows corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, and cerebral atrophy. {ECO:0000269|PubMed:32439809}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair (PubMed:18451878, PubMed:31727855). 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 (PubMed:31727855). 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 (PubMed:31727855). 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 (PubMed:18451878). 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). {ECO:0000250|UniProtKB:Q99LG4, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:31727855}.
uniprot
proteins
mass_dalton
48928
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="D->A: No change in interaction with N-terminal MREI motif of beta-tubulin nascent chain."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 147; /note="R->A: Loss of interaction with N-terminal MREI motif of beta-tubulin nascent chain. Loss of interaction with 28S rRNA of ribosome-coding tubulin. Loss of tubulin autoregulation and accurate mitosis."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 225; /note="D->A: Partial loss of interaction with N-terminal MREI motif of beta-tubulin nascent chain. Loss of interaction with N-terminal MREI motif of beta-tubulin nascent chain; when associated with A-259."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 254; /note="D->A: No change in interaction with 28S rRNA of ribosome-coding tubulin."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 259; /note="E->A: Partial loss of interaction with N-terminal MREI motif of beta-tubulin nascent chain. Loss of interaction with N-terminal MREI motif of beta-tubulin nascent chain; when associated with D-225."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 285; /note="K->E: Loss of interaction with 28S rRNA of ribosome-coding tubulin, when associated with E-287. No change in interaction with N-terminal MREI motif of beta-tubulin nascent chain, when associated with E-287. Loss of tubulin autoregulation and accurate mitosis, when associated with E-287."; /evidence="ECO:0000269|PubMed:31727855"; MUTAGEN 287; /note="K->E: Loss of interaction with 28S rRNA of ribosome-coding tubulin, when associated with E-285. No change in interaction with N-terminal MREI motif of beta-tubulin nascent chain, when associated with E-285. Loss of tubulin autoregulation and accurate mitosis, when associated with E-285."; /evidence="ECO:0000269|PubMed:31727855
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by ATM kinase induces nuclear accumulation while interfering with nuclear export, and phosphorylation by CHEK2 kinase enhances nuclear stability. {ECO:0000250|UniProtKB:Q99LG4}.
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18451878
uniprot
proteins
pubmed
19011621
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22362889
uniprot
proteins
pubmed
31727855
uniprot
proteins
pubmed
32439809
uniprot
proteins
sequence_length
440
uniprot
proteins
subcellular_location
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}.
uniprot
proteins