TTC5_BOVIN
ID TTC5_BOVIN Reviewed; 440 AA.
AC Q0P5H9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 19-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Tetratricopeptide repeat protein 5 {ECO:0000250|UniProtKB:Q8N0Z6};
DE Short=TPR repeat protein 5 {ECO:0000250|UniProtKB:Q8N0Z6};
DE AltName: Full=Stress-responsive activator of p300 {ECO:0000250|UniProtKB:Q99LG4};
DE Short=Protein Strap {ECO:0000250|UniProtKB:Q99LG4};
GN Name=TTC5;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal pons;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Cofactor involved in the regulation of various cellular
CC mechanisms such as actin regulation, autophagy, chromatin regulation
CC and DNA repair. In physiological conditions, interacts with cofactor
CC JMY in the cytoplasm which prevents JMY's actin nucleation activity and
CC ability to activate the Arp2/3 complex. Acts as a negative regulator of
CC nutrient stress-induced autophagy by inhibiting JMY's interaction with
CC MAP1LC3B, thereby preventing autophagosome formation (By similarity).
CC Involves in tubulin autoregulation by promoting its degradation in
CC response to excess soluble tubulin. To do so, associates with the
CC active ribosome near the ribosome exit tunnel and with nascent tubulin
CC polypeptides early during their translation, triggering tubulin mRNA-
CC targeted degradation (By similarity). Following DNA damage,
CC phosphorylated by DNA damage responsive protein kinases ATM and CHEK2,
CC leading to its nuclear accumulation and stability. Nuclear TTC5/STRAP
CC promotes the assembly of a stress-responsive p53/TP53 coactivator
CC complex, which includes the coactivators JMY and p300, thereby
CC increasing p53/TP53-dependent transcription and apoptosis. Also
CC recruits arginine methyltransferase PRMT5 to p53/TP53 when DNA is
CC damaged, allowing PRMT5 to methylate p53/TP53. In DNA stress
CC conditions, also prevents p53/TP53 degradation by E3 ubiquitin ligase
CC MDM2. Upon heat-shock stress, forms a chromatin-associated complex with
CC heat-shock factor 1 HSF1 and p300/EP300 to stimulate heat-shock-
CC responsive transcription, thereby increasing cell survival.
CC Mitochondrial TTC5/STRAP interacts with ATP synthase subunit beta
CC ATP5F1B which decreased ATP synthase activity and lowers mitochondrial
CC ATP production, thereby regulating cellular respiration and
CC mitochondrial-dependent apoptosis. Mitochondrial TTC5/STRAP also
CC regulates p53/TP53-mediated apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q8N0Z6, ECO:0000250|UniProtKB:Q99LG4}.
CC -!- SUBUNIT: Interacts with JMY and p300/EP300; the interaction occurs in
CC the nucleus and augments the association between JMY and p300/EP300 in
CC response to DNA damage. Interacts with PRMT5; the interaction is DNA
CC damage-dependent and promotes PRMT5 interaction with p53/TP53 and
CC subsequent methylation. Forms a complex with HSF1 and p300/EP300; these
CC interactions augment chromatin-bound HSF1 and p300/EP300 histone
CC acetyltransferase activity, resulting in enhanced heat-shock-responsive
CC transcription. Interacts with JMY; the interaction occurs in the
CC cytoplasm and results in the inhibition of JYM's nucleation activity
CC (By similarity). Interacts with ribosome-coding tubulin (via 60S
CC subunit 28S rRNA and protein uL24/RPL26) and the N-terminal of nascent
CC tubulin polypeptide (via alpha-tubulin MREC motif and beta-tubulin MREI
CC motif); these interactions result in tubulin mRNA-targeted degradation
CC (By similarity). Interacts with ATP5F1B; the interaction occurs in the
CC mitochondria and results in ATP production decrease. Interacts with
CC p53/TP53; the interaction occurs in the mitochondria and results in
CC increased apoptosis (By similarity). {ECO:0000250|UniProtKB:Q8N0Z6,
CC ECO:0000250|UniProtKB:Q99LG4}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99LG4}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q99LG4}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q99LG4}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q99LG4}. Note=Phosphorylation at Ser-203 results
CC in nuclear localization, while unphosphorylated protein localizes to
CC the cytoplasm. Nuclear localization may be necessary for DNA damage-
CC dependent stabilization of the protein. {ECO:0000250|UniProtKB:Q99LG4}.
CC -!- DOMAIN: The tetratricopep-repeat (TPR) motifs may function as protein
CC interaction domains. {ECO:0000250|UniProtKB:Q99LG4}.
CC -!- PTM: Phosphorylation by ATM kinase induces nuclear accumulation while
CC interfering with nuclear export, and phosphorylation by CHEK2 kinase
CC enhances nuclear stability. {ECO:0000250|UniProtKB:Q99LG4}.
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DR EMBL; BC120007; AAI20008.1; -; mRNA.
DR RefSeq; NP_001068932.1; NM_001075464.2.
DR AlphaFoldDB; Q0P5H9; -.
DR SMR; Q0P5H9; -.
DR STRING; 9913.ENSBTAP00000036097; -.
DR PaxDb; Q0P5H9; -.
DR PRIDE; Q0P5H9; -.
DR Ensembl; ENSBTAT00000036235; ENSBTAP00000036097; ENSBTAG00000009372.
DR GeneID; 510757; -.
DR KEGG; bta:510757; -.
DR CTD; 91875; -.
DR VEuPathDB; HostDB:ENSBTAG00000009372; -.
DR VGNC; VGNC:36479; TTC5.
DR eggNOG; ENOG502QQ6C; Eukaryota.
DR GeneTree; ENSGT00390000006227; -.
DR HOGENOM; CLU_026886_2_1_1; -.
DR InParanoid; Q0P5H9; -.
DR OMA; DECKGYE; -.
DR OrthoDB; 633153at2759; -.
DR TreeFam; TF316804; -.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000009372; Expressed in oocyte and 107 other tissues.
DR ExpressionAtlas; Q0P5H9; baseline and differential.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0043022; F:ribosome binding; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 2.40.50.550; -; 1.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR032076; TTC5_OB.
DR InterPro; IPR038645; TTC5_OB_sf.
DR Pfam; PF16669; TTC5_OB; 1.
DR SMART; SM00028; TPR; 2.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50005; TPR; 2.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 2: Evidence at transcript level;
KW Cytoplasm; Cytoplasmic vesicle; DNA damage; DNA repair; Mitochondrion;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..440
FT /note="Tetratricopeptide repeat protein 5"
FT /id="PRO_0000324615"
FT REPEAT 7..61
FT /note="TPR 1"
FT REPEAT 68..98
FT /note="TPR 2"
FT REPEAT 103..130
FT /note="TPR 3"
FT REPEAT 136..174
FT /note="TPR 4"
FT REPEAT 179..216
FT /note="TPR 5"
FT REPEAT 224..253
FT /note="TPR 6"
FT REGION 285..287
FT /note="Mediates interaction with 28S rRNA of ribosome-
FT coding tubulin"
FT /evidence="ECO:0000250|UniProtKB:Q8N0Z6"
FT MOTIF 13..24
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q99LG4"
FT SITE 147
FT /note="Mediates interaction with N-terminal MREI motif of
FT beta-tubulin nascent chain"
FT /evidence="ECO:0000250|UniProtKB:Q8N0Z6"
FT SITE 225
FT /note="Mediates interaction with N-terminal MREI motif of
FT beta-tubulin nascent chain"
FT /evidence="ECO:0000250|UniProtKB:Q8N0Z6"
FT SITE 259
FT /note="Mediates interaction with N-terminal MREI motif of
FT beta-tubulin nascent chain"
FT /evidence="ECO:0000250|UniProtKB:Q8N0Z6"
FT MOD_RES 203
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000250|UniProtKB:Q99LG4"
FT MOD_RES 221
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000250|UniProtKB:Q99LG4"
SQ SEQUENCE 440 AA; 48918 MW; 9F099946DE2A77EC CRC64;
MMAVEEEEVK EVLQKLQELV DQLYSFRECY FETHSVDDAG RKQQDVREEM EKTLQQMEEV
VGSVQGNAQV LMLTGKALNV TPDYSPKAEE LLSKAVKLEP KLVEAWNQLG EVYWKKGDVA
AAHTCFSGAL THCKNKVSLQ NLSMVLRQLR TDSGDEHSRH VMDSVRQAKL AVQMDILDGR
SWYILGNAYL SLYFNTGQNP KISQQALSAY AQAEKVDRTA SSNPDLHLNR ATLHKYEENY
GEALEGFSRA AALDPAWPEP WQREQQLLDF LTRLTSFLES KGKVKTKKLQ SMLGNLRPAH
LGPCGDGRYQ SASGQKVTLE RKPLNALQPG VNSGAVVLGK VVFSLTTEEK VPFTFGLVDS
DGPCYAVMVY NMVQSWGVLI GDSVAIPEPN LRLHRIQHKG KDYSFSSVRV ETPLLLVVNG
KPQGSSSQAA ATVASRPQCE
