TTC5_HUMAN
ID TTC5_HUMAN Reviewed; 440 AA.
AC Q8N0Z6; A8MQ18; Q96HF9;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Tetratricopeptide repeat protein 5 {ECO:0000303|PubMed:31727855};
DE Short=TPR repeat protein 5 {ECO:0000303|PubMed:31727855};
DE AltName: Full=Stress-responsive activator of p300 {ECO:0000303|PubMed:22362889};
DE Short=Protein Strap {ECO:0000303|PubMed:22362889};
GN Name=TTC5 {ECO:0000312|HGNC:HGNC:19274};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-47.
RC TISSUE=Embryo;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-47.
RC TISSUE=Eye, Pancreas, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH HSF1 AND EP300, AND INDUCTION.
RX PubMed=18451878; DOI=10.1038/embor.2008.70;
RA Xu D., Zalmas L.P., La Thangue N.B.;
RT "A transcription cofactor required for the heat-shock response.";
RL EMBO Rep. 9:662-669(2008).
RN [5]
RP INTERACTION WITH PRMT5.
RX PubMed=19011621; DOI=10.1038/ncb1802;
RA Jansson M., Durant S.T., Cho E.C., Sheahan S., Edelmann M., Kessler B.,
RA La Thangue N.B.;
RT "Arginine methylation regulates the p53 response.";
RL Nat. Cell Biol. 10:1431-1439(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 261-424, AND TPR REPEATS.
RX PubMed=22362889; DOI=10.1073/pnas.1113731109;
RA Adams C.J., Pike A.C., Maniam S., Sharpe T.D., Coutts A.S., Knapp S.,
RA La Thangue N.B., Bullock A.N.;
RT "The p53 cofactor Strap exhibits an unexpected TPR motif and
RT oligonucleotide-binding (OB)-fold structure.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3778-3783(2012).
RN [8] {ECO:0007744|PDB:6T59}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.11 ANGSTROMS), FUNCTION, INTERACTION
RP WITH RIBOSOME 60S SUBUNIT AND TUBULIN, SUBCELLULAR LOCATION, REGION, AND
RP MUTAGENESIS OF ASP-83; ARG-147; ASP-225; ASP-254; GLU-259; LYS-285 AND
RP LYS-287.
RX PubMed=31727855; DOI=10.1126/science.aaz4352;
RA Lin Z., Gasic I., Chandrasekaran V., Peters N., Shao S., Mitchison T.J.,
RA Hegde R.S.;
RT "TTC5 mediates autoregulation of tubulin via mRNA degradation.";
RL Science 367:100-104(2020).
RN [9]
RP INVOLVEMENT IN NEDCAFD, VARIANTS NEDCAFD CYS-210; VAL-231; 263-ARG--GLU-440
RP DEL AND 395-ARG--GLU-440 DEL, AND CHARACTERIZATION OF VARIANT NEDCAFD
RP 395-ARG--GLU-440 DEL.
RX PubMed=32439809; DOI=10.1136/jmedgenet-2020-106849;
RA Rasheed A., Gumus E., Zaki M., Johnson K., Manzoor H., LaForce G., Ross D.,
RA McEvoy-Venneri J., Stanley V., Lee S., Virani A., Ben-Omran T.,
RA Gleeson J.G., Naz S., Schaffer A.;
RT "Bi-allelic TTC5 variants cause delayed developmental milestones and
RT intellectual disability.";
RL J. Med. Genet. 58:237-246(2021).
CC -!- FUNCTION: Cofactor involved in the regulation of various cellular
CC mechanisms such as actin regulation, autophagy, chromatin regulation
CC and DNA repair (PubMed:18451878, PubMed:31727855). In non-stress
CC conditions, interacts with cofactor JMY in the cytoplasm which prevents
CC JMY's actin nucleation activity and ability to activate the Arp2/3
CC complex. Acts as a negative regulator of nutrient stress-induced
CC autophagy by preventing JMY's interaction with MAP1LC3B, thereby
CC preventing autophagosome formation (By similarity). Involves in tubulin
CC autoregulation by promoting its degradation in response to excess
CC soluble tubulin (PubMed:31727855). To do so, associates with the active
CC ribosome near the ribosome exit tunnel and with nascent tubulin
CC polypeptides early during their translation, triggering tubulin mRNA-
CC targeted degradation (PubMed:31727855). 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 (By similarity). Upon heat-shock stress, forms a chromatin-
CC associated complex with heat-shock factor 1 HSF1 and p300/EP300 to
CC stimulate heat-shock-responsive transcription, thereby increasing cell
CC survival (PubMed:18451878). Mitochondrial TTC5/STRAP interacts with ATP
CC synthase subunit beta ATP5F1B which decreased ATP synthase activity and
CC lowers mitochondrial ATP production, thereby regulating cellular
CC respiration and mitochondrial-dependent apoptosis. Mitochondrial
CC TTC5/STRAP also regulates p53/TP53-mediated apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q99LG4, ECO:0000269|PubMed:18451878,
CC ECO:0000269|PubMed:31727855}.
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 (By similarity). Forms a complex with HSF1 and
CC p300/EP300; these interactions augment chromatin-bound HSF1 and
CC p300/EP300 histone acetyltransferase activity, resulting in enhanced
CC heat-shock-responsive transcription (PubMed:18451878). Interacts with
CC PRMT5; the interaction is DNA damage-dependent and promotes PRMT5
CC interaction with p53/TP53 and subsequent methylation (PubMed:19011621).
CC Interacts with JMY; the interaction occurs in the cytoplasm and results
CC in the inhibition of JYM's nucleation activity (By similarity).
CC Interacts with ribosome-coding tubulin (via 60S subunit 28S rRNA and
CC protein uL24/RPL26) and the N-terminal of nascent tubulin polypeptide
CC (via alpha-tubulin MREC motif and beta-tubulin MREI motif); these
CC interactions result in tubulin mRNA-targeted degradation
CC (PubMed:31727855). Interacts with ATP5F1B; the interaction occurs in
CC the 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:Q99LG4,
CC ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:19011621,
CC ECO:0000269|PubMed:31727855}.
CC -!- INTERACTION:
CC Q8N0Z6; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-9526213, EBI-1383687;
CC Q8N0Z6; Q13554: CAMK2B; NbExp=3; IntAct=EBI-9526213, EBI-1058722;
CC Q8N0Z6; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-9526213, EBI-11523526;
CC Q8N0Z6; Q13557: CAMK2D; NbExp=4; IntAct=EBI-9526213, EBI-351018;
CC Q8N0Z6; Q13557-8: CAMK2D; NbExp=3; IntAct=EBI-9526213, EBI-11534483;
CC Q8N0Z6; Q13555-5: CAMK2G; NbExp=3; IntAct=EBI-9526213, EBI-12020154;
CC Q8N0Z6; Q6NZI2: CAVIN1; NbExp=3; IntAct=EBI-9526213, EBI-2559016;
CC Q8N0Z6; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-9526213, EBI-742054;
CC Q8N0Z6; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-9526213, EBI-11163335;
CC Q8N0Z6; Q7Z353: HDX; NbExp=3; IntAct=EBI-9526213, EBI-1052734;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q99LG4}. Cytoplasm
CC {ECO:0000269|PubMed:31727855}. 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 -!- INDUCTION: Induced upon heat-shock stress (at protein level).
CC {ECO:0000269|PubMed:18451878}.
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}.
CC -!- DISEASE: Neurodevelopmental disorder with cerebral atrophy and variable
CC facial dysmorphism (NEDCAFD) [MIM:619244]: An autosomal recessive
CC disorder characterized by global developmental delay apparent from
CC birth, moderate-to-severe intellectual disability, poor or absent
CC speech, and hypotonia. Most patients have variable dysmorphic facial
CC features. Brain imaging shows corpus callosum agenesis, mild
CC ventriculomegaly, simplified gyral pattern, and cerebral atrophy.
CC {ECO:0000269|PubMed:32439809}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AK074553; BAC11056.1; -; mRNA.
DR EMBL; AL356019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008647; AAH08647.1; -; mRNA.
DR EMBL; BC030822; AAH30822.1; -; mRNA.
DR EMBL; BC053538; AAH53538.1; -; mRNA.
DR CCDS; CCDS9546.1; -.
DR RefSeq; NP_612385.2; NM_138376.2.
DR PDB; 2XVS; X-ray; 1.80 A; A=261-424.
DR PDB; 6T59; EM; 3.11 A; TT=1-440.
DR PDB; 7QWS; EM; 3.40 A; K=1-440.
DR PDBsum; 2XVS; -.
DR PDBsum; 6T59; -.
DR PDBsum; 7QWS; -.
DR AlphaFoldDB; Q8N0Z6; -.
DR SMR; Q8N0Z6; -.
DR BioGRID; 124889; 54.
DR IntAct; Q8N0Z6; 27.
DR MINT; Q8N0Z6; -.
DR STRING; 9606.ENSP00000258821; -.
DR GlyGen; Q8N0Z6; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8N0Z6; -.
DR PhosphoSitePlus; Q8N0Z6; -.
DR BioMuta; TTC5; -.
DR DMDM; 229462802; -.
DR EPD; Q8N0Z6; -.
DR jPOST; Q8N0Z6; -.
DR MassIVE; Q8N0Z6; -.
DR MaxQB; Q8N0Z6; -.
DR PaxDb; Q8N0Z6; -.
DR PeptideAtlas; Q8N0Z6; -.
DR PRIDE; Q8N0Z6; -.
DR ProteomicsDB; 71493; -.
DR Antibodypedia; 6802; 140 antibodies from 27 providers.
DR DNASU; 91875; -.
DR Ensembl; ENST00000258821.8; ENSP00000258821.3; ENSG00000136319.12.
DR GeneID; 91875; -.
DR KEGG; hsa:91875; -.
DR MANE-Select; ENST00000258821.8; ENSP00000258821.3; NM_138376.3; NP_612385.2.
DR UCSC; uc001vwt.5; human.
DR CTD; 91875; -.
DR DisGeNET; 91875; -.
DR GeneCards; TTC5; -.
DR HGNC; HGNC:19274; TTC5.
DR HPA; ENSG00000136319; Low tissue specificity.
DR MalaCards; TTC5; -.
DR MIM; 619014; gene.
DR MIM; 619244; phenotype.
DR neXtProt; NX_Q8N0Z6; -.
DR OpenTargets; ENSG00000136319; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA134919164; -.
DR VEuPathDB; HostDB:ENSG00000136319; -.
DR eggNOG; ENOG502QQ6C; Eukaryota.
DR GeneTree; ENSGT00390000006227; -.
DR HOGENOM; CLU_026886_2_1_1; -.
DR InParanoid; Q8N0Z6; -.
DR OMA; DECKGYE; -.
DR OrthoDB; 633153at2759; -.
DR PhylomeDB; Q8N0Z6; -.
DR TreeFam; TF316804; -.
DR PathwayCommons; Q8N0Z6; -.
DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR SignaLink; Q8N0Z6; -.
DR SIGNOR; Q8N0Z6; -.
DR BioGRID-ORCS; 91875; 20 hits in 1080 CRISPR screens.
DR ChiTaRS; TTC5; human.
DR EvolutionaryTrace; Q8N0Z6; -.
DR GenomeRNAi; 91875; -.
DR Pharos; Q8N0Z6; Tbio.
DR PRO; PR:Q8N0Z6; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8N0Z6; protein.
DR Bgee; ENSG00000136319; Expressed in secondary oocyte and 152 other tissues.
DR ExpressionAtlas; Q8N0Z6; baseline and differential.
DR Genevisible; Q8N0Z6; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA: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; IDA:HPA.
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; IMP:UniProtKB.
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; IMP:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Cytoplasmic vesicle; Disease variant; DNA damage;
KW DNA repair; Intellectual disability; Mitochondrion; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..440
FT /note="Tetratricopeptide repeat protein 5"
FT /id="PRO_0000106381"
FT REPEAT 7..61
FT /note="TPR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REPEAT 68..98
FT /note="TPR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REPEAT 103..130
FT /note="TPR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REPEAT 136..174
FT /note="TPR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REPEAT 179..216
FT /note="TPR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REPEAT 224..253
FT /note="TPR 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00339,
FT ECO:0000269|PubMed:22362889"
FT REGION 285..287
FT /note="Mediates interaction with 28S rRNA of ribosome-
FT coding tubulin"
FT /evidence="ECO:0000269|PubMed:31727855,
FT ECO:0007744|PDB:6T59"
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:0000269|PubMed:31727855,
FT ECO:0007744|PDB:6T59"
FT SITE 225
FT /note="Mediates interaction with N-terminal MREI motif of
FT beta-tubulin nascent chain"
FT /evidence="ECO:0000269|PubMed:31727855,
FT ECO:0007744|PDB:6T59"
FT SITE 259
FT /note="Mediates interaction with N-terminal MREI motif of
FT beta-tubulin nascent chain"
FT /evidence="ECO:0000269|PubMed:31727855,
FT ECO:0007744|PDB:6T59"
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"
FT VARIANT 14
FT /note="Q -> H (in dbSNP:rs34675160)"
FT /id="VAR_034131"
FT VARIANT 47
FT /note="Q -> R (in dbSNP:rs3742945)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_055293"
FT VARIANT 210
FT /note="Y -> C (in NEDCAFD; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32439809"
FT /id="VAR_085226"
FT VARIANT 231
FT /note="A -> V (in NEDCAFD; unknown pathological
FT significance; dbSNP:rs749799203)"
FT /evidence="ECO:0000269|PubMed:32439809"
FT /id="VAR_085227"
FT VARIANT 263..440
FT /note="Missing (in NEDCAFD; likely pathogenic)"
FT /evidence="ECO:0000269|PubMed:32439809"
FT /id="VAR_085228"
FT VARIANT 395..440
FT /note="Missing (in NEDCAFD; likely pathogenic; decreased
FT TTC5 transcript levels)"
FT /evidence="ECO:0000269|PubMed:32439809"
FT /id="VAR_085229"
FT MUTAGEN 83
FT /note="D->A: No change in interaction with N-terminal MREI
FT motif of beta-tubulin nascent chain."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 147
FT /note="R->A: Loss of interaction with N-terminal MREI motif
FT of beta-tubulin nascent chain. Loss of interaction with 28S
FT rRNA of ribosome-coding tubulin. Loss of tubulin
FT autoregulation and accurate mitosis."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 225
FT /note="D->A: Partial loss of interaction with N-terminal
FT MREI motif of beta-tubulin nascent chain. Loss of
FT interaction with N-terminal MREI motif of beta-tubulin
FT nascent chain; when associated with A-259."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 254
FT /note="D->A: No change in interaction with 28S rRNA of
FT ribosome-coding tubulin."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 259
FT /note="E->A: Partial loss of interaction with N-terminal
FT MREI motif of beta-tubulin nascent chain. Loss of
FT interaction with N-terminal MREI motif of beta-tubulin
FT nascent chain; when associated with D-225."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 285
FT /note="K->E: Loss of interaction with 28S rRNA of ribosome-
FT coding tubulin, when associated with E-287. No change in
FT interaction with N-terminal MREI motif of beta-tubulin
FT nascent chain, when associated with E-287. Loss of tubulin
FT autoregulation and accurate mitosis, when associated with
FT E-287."
FT /evidence="ECO:0000269|PubMed:31727855"
FT MUTAGEN 287
FT /note="K->E: Loss of interaction with 28S rRNA of ribosome-
FT coding tubulin, when associated with E-285. No change in
FT interaction with N-terminal MREI motif of beta-tubulin
FT nascent chain, when associated with E-285. Loss of tubulin
FT autoregulation and accurate mitosis, when associated with
FT E-285."
FT /evidence="ECO:0000269|PubMed:31727855"
FT HELIX 262..280
FT /evidence="ECO:0007829|PDB:2XVS"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:2XVS"
FT HELIX 286..294
FT /evidence="ECO:0007829|PDB:2XVS"
FT HELIX 298..304
FT /evidence="ECO:0007829|PDB:2XVS"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 352..362
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 365..369
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 383..388
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 390..398
FT /evidence="ECO:0007829|PDB:2XVS"
FT STRAND 401..411
FT /evidence="ECO:0007829|PDB:2XVS"
FT HELIX 413..415
FT /evidence="ECO:0007829|PDB:2XVS"
SQ SEQUENCE 440 AA; 48928 MW; DB4505A217811BD0 CRC64;
MMADEEEEVK PILQKLQELV DQLYSFRDCY FETHSVEDAG RKQQDVQKEM EKTLQQMEEV
VGSVQGKAQV LMLTGKALNV TPDYSPKAEE LLSKAVKLEP ELVEAWNQLG EVYWKKGDVA
AAHTCFSGAL THCRNKVSLQ NLSMVLRQLR TDTEDEHSHH VMDSVRQAKL AVQMDVHDGR
SWYILGNSYL SLYFSTGQNP KISQQALSAY AQAEKVDRKA SSNPDLHLNR ATLHKYEESY
GEALEGFSRA AALDPAWPEP RQREQQLLEF LDRLTSLLES KGKVKTKKLQ SMLGSLRPAH
LGPCSDGHYQ SASGQKVTLE LKPLSTLQPG VNSGAVILGK VVFSLTTEEK VPFTFGLVDS
DGPCYAVMVY NIVQSWGVLI GDSVAIPEPN LRLHRIQHKG KDYSFSSVRV ETPLLLVVNG
KPQGSSSQAV ATVASRPQCE
