TBCD_HUMAN
ID TBCD_HUMAN Reviewed; 1192 AA.
AC Q9BTW9; O95458; Q7L8K1; Q8IXP6; Q8NAX0; Q8WYH4; Q96E74; Q9UF82; Q9UG46;
AC Q9Y2J3;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Tubulin-specific chaperone D;
DE AltName: Full=Beta-tubulin cofactor D;
DE Short=tfcD;
DE AltName: Full=SSD-1;
DE AltName: Full=Tubulin-folding cofactor D;
GN Name=TBCD; Synonyms=KIAA0988, SSD1, TFCD; ORFNames=PP1096;
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 [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11110777; DOI=10.1161/01.res.87.12.1188;
RA Schubert A., Cattaruzza M., Hecker M., Darmer D., Holtz J., Morawietz H.;
RT "Shear stress-dependent regulation of the human beta-tubulin folding
RT cofactor D gene.";
RL Circ. Res. 87:1188-1194(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [4]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Kidney;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 143-1192 (ISOFORM 1).
RC TISSUE=Testis, and Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT THR-617.
RC TISSUE=Brain, Colon, and Muscle;
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 [9]
RP FUNCTION.
RX PubMed=10722852; DOI=10.1016/s0014-5793(00)01293-x;
RA Martin L., Fanarraga M.L., Aloria K., Zabala J.C.;
RT "Tubulin folding cofactor D is a microtubule destabilizing protein.";
RL FEBS Lett. 470:93-95(2000).
RN [10]
RP FUNCTION, INTERACTION WITH BETA TUBULIN AND ARL2, AND ABSENCE OF
RP INTERACTION WITH ARL3; ARL4A AND ARL4D.
RX PubMed=10831612; DOI=10.1083/jcb.149.5.1087;
RA Bhamidipati A., Lewis S.A., Cowan N.J.;
RT "ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of
RT tubulin-folding cofactor D with native tubulin.";
RL J. Cell Biol. 149:1087-1096(2000).
RN [11]
RP FUNCTION.
RX PubMed=11847227; DOI=10.1074/jbc.m200128200;
RA Bartolini F., Bhamidipati A., Thomas S., Schwahn U., Lewis S.A.,
RA Cowan N.J.;
RT "Functional overlap between retinitis pigmentosa 2 protein and the tubulin-
RT specific chaperone cofactor C.";
RL J. Biol. Chem. 277:14629-14634(2002).
RN [12]
RP FUNCTION.
RX PubMed=20740604; DOI=10.1002/cm.20480;
RA Tian G., Thomas S., Cowan N.J.;
RT "Effect of TBCD and its regulatory interactor Arl2 on tubulin and
RT microtubule integrity.";
RL Cytoskeleton 67:706-714(2010).
RN [13]
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 [14]
RP FUNCTION, INTERACTION WITH ARL2; TBCE AND BETA TUBULIN, INVOLVEMENT IN
RP PEBAT, VARIANTS PEBAT ARG-387; CYS-772; THR-921; ARG-937 AND LEU-1122, AND
RP CHARACTERIZATION OF VARIANTS PEBAT ARG-387; CYS-772; THR-921; ARG-937 AND
RP LEU-1122.
RX PubMed=27666374; DOI=10.1016/j.ajhg.2016.08.005;
RA Miyake N., Fukai R., Ohba C., Chihara T., Miura M., Shimizu H., Kakita A.,
RA Imagawa E., Shiina M., Ogata K., Okuno-Yuguchi J., Fueki N., Ogiso Y.,
RA Suzumura H., Watabe Y., Imataka G., Leong H.Y., Fattal-Valevski A.,
RA Kramer U., Miyatake S., Kato M., Okamoto N., Sato Y., Mitsuhashi S.,
RA Nishino I., Kaneko N., Nishiyama A., Tamura T., Mizuguchi T., Nakashima M.,
RA Tanaka F., Saitsu H., Matsumoto N.;
RT "Biallelic TBCD mutations cause early-onset neurodegenerative
RT encephalopathy.";
RL Am. J. Hum. Genet. 99:950-961(2016).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BETA TUBULIN, INVOLVEMENT
RP IN PEBAT, VARIANTS PEBAT ARG-229; MET-374; GLN-377; THR-626; MET-994;
RP MET-1105 AND LEU-1122, AND CHARACTERIZATION OF VARIANTS PEBAT MET-374;
RP GLN-377; THR-626 AND LEU-1122.
RX PubMed=27666370; DOI=10.1016/j.ajhg.2016.08.003;
RA Flex E., Niceta M., Cecchetti S., Thiffault I., Au M.G., Capuano A.,
RA Piermarini E., Ivanova A.A., Francis J.W., Chillemi G., Chandramouli B.,
RA Carpentieri G., Haaxma C.A., Ciolfi A., Pizzi S., Douglas G.V., Levine K.,
RA Sferra A., Dentici M.L., Pfundt R.R., Le Pichon J.B., Farrow E., Baas F.,
RA Piemonte F., Dallapiccola B., Graham J.M. Jr., Saunders C.J., Bertini E.,
RA Kahn R.A., Koolen D.A., Tartaglia M.;
RT "Biallelic mutations in TBCD, encoding the tubulin folding cofactor D,
RT perturb microtubule dynamics and cause early-onset encephalopathy.";
RL Am. J. Hum. Genet. 99:962-973(2016).
RN [16]
RP FUNCTION, VARIANTS PEBAT THR-475 AND VAL-586, AND CHARACTERIZATION OF
RP VARIANTS PEBAT THR-475 AND VAL-586.
RX PubMed=28158450; DOI=10.1093/hmg/ddw292;
RA Edvardson S., Tian G., Cullen H., Vanyai H., Ngo L., Bhat S., Aran A.,
RA Daana M., Da'amseh N., Abu-Libdeh B., Cowan N.J., Heng J., Elpeleg O.;
RT "Infantile neurodegenerative disorder associated with mutations in TBCD, an
RT essential gene in the tubulin heterodimer assembly pathway.";
RL Hum. Mol. Genet. 25:4635-4648(2016).
RN [17]
RP VARIANTS PEBAT THR-475; VAL-586 AND ARG-937.
RX PubMed=27807845; DOI=10.1111/cge.12914;
RA Pode-Shakked B., Barash H., Ziv L., Gripp K.W., Flex E., Barel O.,
RA Carvalho K.S., Scavina M., Chillemi G., Niceta M., Eyal E., Kol N.,
RA Ben-Zeev B., Bar-Yosef O., Marek-Yagel D., Bertini E., Duker A.L.,
RA Anikster Y., Tartaglia M., Raas-Rothschild A.;
RT "Microcephaly, intractable seizures and developmental delay caused by
RT biallelic variants in TBCD: further delineation of a new chaperone-mediated
RT tubulinopathy.";
RL Clin. Genet. 91:725-738(2017).
CC -!- FUNCTION: Tubulin-folding protein implicated in the first step of the
CC tubulin folding pathway and required for tubulin complex assembly.
CC Involved in the regulation of microtubule polymerization or
CC depolymerization, it modulates microtubule dynamics by capturing GTP-
CC bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is
CC regulated via its interaction with ARL2. Acts as a GTPase-activating
CC protein (GAP) for ARL2. Induces microtubule disruption in absence of
CC ARL2. Increases degradation of beta tubulin, when overexpressed in
CC polarized cells. Promotes epithelial cell detachment, a process
CC antagonized by ARL2. Induces tight adherens and tight junctions
CC disassembly at the lateral cell membrane (PubMed:10722852,
CC PubMed:10831612, PubMed:11847227, PubMed:20740604, PubMed:27666370,
CC PubMed:28158450). Required for correct assembly and maintenance of the
CC mitotic spindle, and proper progression of mitosis (PubMed:27666370).
CC Involved in neuron morphogenesis (PubMed:27666374).
CC {ECO:0000269|PubMed:10722852, ECO:0000269|PubMed:10831612,
CC ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:20740604,
CC ECO:0000269|PubMed:27666370, ECO:0000269|PubMed:27666374,
CC ECO:0000269|PubMed:28158450}.
CC -!- SUBUNIT: Found in a complex with at least ARL2, PPP2CB, PPP2R1A,
CC PPP2R2A, PPP2R5E and TBCD. Interacts with PPP2CB (By similarity). Part
CC of a supercomplex made of cofactors A to E. Cofactors A and D function
CC by capturing and stabilizing tubulin in a quasi-native conformation.
CC Cofactor E binds to the cofactor D-tubulin complex; interaction with
CC cofactor C then causes the release of tubulin polypeptides that are
CC committed to the native state (PubMed:10831612). Interacts with ARL2;
CC interaction is enhanced with the GDP-bound form of ARL2
CC (PubMed:10831612, PubMed:27666374). Does not interact with ARL3, ARL4A
CC and ARL4D (PubMed:10831612). Interacts with beta tubulin
CC (PubMed:10831612, PubMed:27666370, PubMed:27666374). Interacts with
CC TBCE (PubMed:27666374). {ECO:0000250|UniProtKB:Q28205,
CC ECO:0000269|PubMed:10831612, ECO:0000269|PubMed:27666370,
CC ECO:0000269|PubMed:27666374}.
CC -!- INTERACTION:
CC Q9BTW9; Q96AP0: ACD; NbExp=2; IntAct=EBI-356005, EBI-717666;
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q28205}. Lateral cell membrane
CC {ECO:0000250|UniProtKB:Q28205}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q28205}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:Q28205}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:27666370}.
CC Note=Localized in cell-cell contacts. {ECO:0000250|UniProtKB:Q28205}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q9BTW9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BTW9-2; Sequence=VSP_017210;
CC Name=3;
CC IsoId=Q9BTW9-3; Sequence=VSP_017211, VSP_017215, VSP_017213,
CC VSP_017214;
CC Name=4;
CC IsoId=Q9BTW9-4; Sequence=VSP_017217, VSP_017218;
CC Name=5;
CC IsoId=Q9BTW9-5; Sequence=VSP_017212, VSP_017216;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10231032, ECO:0000269|PubMed:11110777}.
CC -!- INDUCTION: Down-regulated by shear stress.
CC {ECO:0000269|PubMed:11110777}.
CC -!- DISEASE: Encephalopathy, progressive, early-onset, with brain atrophy
CC and thin corpus callosum (PEBAT) [MIM:617193]: An autosomal recessive
CC disease with neurodevelopmental and neurodegenerative features. PEBAT
CC is characterized by early-onset cortical atrophy, hypomyelination,
CC microcephaly, thin corpus callosum, delayed psychomotor development,
CC developmental regression, intellectual disability, seizures, optic
CC atrophy, muscle weakness and atrophy, spastic quadriplegia, and
CC respiratory insufficiency due to hypotonia.
CC {ECO:0000269|PubMed:27666370, ECO:0000269|PubMed:27666374,
CC ECO:0000269|PubMed:27807845, ECO:0000269|PubMed:28158450}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the TBCD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH39654.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA76832.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ006417; CAA07022.1; -; mRNA.
DR EMBL; AF193042; AAG22470.1; -; mRNA.
DR EMBL; AB023205; BAA76832.2; ALT_INIT; mRNA.
DR EMBL; AK091959; BAC03777.1; -; mRNA.
DR EMBL; AL133562; CAB63716.1; -; mRNA.
DR EMBL; AL096745; CAB62532.2; -; mRNA.
DR EMBL; AC024361; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087222; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC130371; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003094; AAH03094.1; -; mRNA.
DR EMBL; BC012824; AAH12824.2; -; mRNA.
DR EMBL; BC039654; AAH39654.1; ALT_INIT; mRNA.
DR CCDS; CCDS45818.1; -. [Q9BTW9-1]
DR PIR; T12548; T12548.
DR PIR; T43482; T43482.
DR RefSeq; NP_005984.3; NM_005993.4. [Q9BTW9-1]
DR AlphaFoldDB; Q9BTW9; -.
DR BioGRID; 112767; 123.
DR CORUM; Q9BTW9; -.
DR IntAct; Q9BTW9; 31.
DR MINT; Q9BTW9; -.
DR STRING; 9606.ENSP00000347719; -.
DR GlyGen; Q9BTW9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BTW9; -.
DR MetOSite; Q9BTW9; -.
DR PhosphoSitePlus; Q9BTW9; -.
DR SwissPalm; Q9BTW9; -.
DR BioMuta; TBCD; -.
DR DMDM; 296452924; -.
DR EPD; Q9BTW9; -.
DR jPOST; Q9BTW9; -.
DR MassIVE; Q9BTW9; -.
DR MaxQB; Q9BTW9; -.
DR PaxDb; Q9BTW9; -.
DR PeptideAtlas; Q9BTW9; -.
DR PRIDE; Q9BTW9; -.
DR ProteomicsDB; 79016; -. [Q9BTW9-1]
DR ProteomicsDB; 79017; -. [Q9BTW9-2]
DR ProteomicsDB; 79018; -. [Q9BTW9-3]
DR ProteomicsDB; 79019; -. [Q9BTW9-4]
DR ProteomicsDB; 79020; -. [Q9BTW9-5]
DR Antibodypedia; 33047; 79 antibodies from 20 providers.
DR DNASU; 6904; -.
DR Ensembl; ENST00000355528.9; ENSP00000347719.4; ENSG00000141556.22. [Q9BTW9-1]
DR GeneID; 6904; -.
DR KEGG; hsa:6904; -.
DR MANE-Select; ENST00000355528.9; ENSP00000347719.4; NM_005993.5; NP_005984.3.
DR UCSC; uc002kfz.4; human. [Q9BTW9-1]
DR CTD; 6904; -.
DR DisGeNET; 6904; -.
DR GeneCards; TBCD; -.
DR HGNC; HGNC:11581; TBCD.
DR HPA; ENSG00000141556; Low tissue specificity.
DR MalaCards; TBCD; -.
DR MIM; 604649; gene.
DR MIM; 617193; phenotype.
DR neXtProt; NX_Q9BTW9; -.
DR OpenTargets; ENSG00000141556; -.
DR Orphanet; 496641; Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome.
DR PharmGKB; PA36345; -.
DR VEuPathDB; HostDB:ENSG00000141556; -.
DR eggNOG; KOG1943; Eukaryota.
DR GeneTree; ENSGT00390000017103; -.
DR HOGENOM; CLU_003043_0_0_1; -.
DR InParanoid; Q9BTW9; -.
DR OMA; EPHEAWH; -.
DR OrthoDB; 79003at2759; -.
DR PhylomeDB; Q9BTW9; -.
DR TreeFam; TF105754; -.
DR PathwayCommons; Q9BTW9; -.
DR Reactome; R-HSA-389977; Post-chaperonin tubulin folding pathway.
DR SignaLink; Q9BTW9; -.
DR BioGRID-ORCS; 6904; 687 hits in 1078 CRISPR screens.
DR ChiTaRS; TBCD; human.
DR GeneWiki; TBCD; -.
DR GenomeRNAi; 6904; -.
DR Pharos; Q9BTW9; Tbio.
DR PRO; PR:Q9BTW9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9BTW9; protein.
DR Bgee; ENSG00000141556; Expressed in right lobe of thyroid gland and 91 other tissues.
DR ExpressionAtlas; Q9BTW9; baseline and differential.
DR Genevisible; Q9BTW9; HS.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; TAS:ProtInc.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0034333; P:adherens junction assembly; ISS:UniProtKB.
DR GO; GO:0070830; P:bicellular tight junction assembly; ISS:UniProtKB.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IMP:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IDA:UniProtKB.
DR GO; GO:0007023; P:post-chaperonin tubulin folding pathway; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; IDA:UniProtKB.
DR GO; GO:0007021; P:tubulin complex assembly; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 2.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR033162; TBCD.
DR InterPro; IPR022577; Tubulin_specific_chaperoneD_C.
DR PANTHER; PTHR12658; PTHR12658; 1.
DR Pfam; PF12612; TFCD_C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell junction; Cell membrane; Chaperone; Cytoplasm;
KW Cytoskeleton; Disease variant; GTPase activation; Membrane;
KW Neurodegeneration; Reference proteome; Repeat; Tight junction.
FT CHAIN 1..1192
FT /note="Tubulin-specific chaperone D"
FT /id="PRO_0000080049"
FT REPEAT 361..399
FT /note="HEAT 1"
FT REPEAT 557..594
FT /note="HEAT 2"
FT REPEAT 596..632
FT /note="HEAT 3"
FT VAR_SEQ 1..1008
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15498874"
FT /id="VSP_017210"
FT VAR_SEQ 1..546
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017211"
FT VAR_SEQ 62..78
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_017212"
FT VAR_SEQ 547..549
FT /note="LVI -> MFN (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017215"
FT VAR_SEQ 662..697
FT /note="LYDRQLYRGLGGQLMRQAVCVLIEKLSLSKMPFRGD -> PCICSWGLMSPE
FT SKAEFCVCVCRISLGRQCVHLSGL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017213"
FT VAR_SEQ 698..1192
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017214"
FT VAR_SEQ 739..1156
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_017216"
FT VAR_SEQ 1094
FT /note="V -> VDFPSATLVCVGTVQMYAHTHLRLGAPGPHCAHGSAMPR (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:11110777"
FT /id="VSP_017217"
FT VAR_SEQ 1182..1192
FT /note="RPQLVPQPGAC -> SPTWCPAWCLLKPVLEPIPHPCLVRMSCS (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:11110777"
FT /id="VSP_017218"
FT VARIANT 229
FT /note="L -> R (in PEBAT; dbSNP:rs778417127)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077968"
FT VARIANT 374
FT /note="T -> M (in PEBAT; severely decreased interaction
FT with beta tubulin; does not affect localization to
FT centrosome; dbSNP:rs953299085)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077969"
FT VARIANT 377
FT /note="R -> Q (in PEBAT; decreased protein abundance;
FT severely decreased interaction with beta tubulin; does not
FT affect localization to centrosome; dbSNP:rs764085684)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077970"
FT VARIANT 387
FT /note="M -> R (in PEBAT; decreased function in neuron
FT morphogenesis; severely decreased interaction with ARL2;
FT decreased interaction with TBCE; decreased interaction with
FT beta tubulin; dbSNP:rs886041086)"
FT /evidence="ECO:0000269|PubMed:27666374"
FT /id="VAR_077971"
FT VARIANT 475
FT /note="A -> T (in PEBAT; decreased function in tubulin
FT complex assembly; increased protein degradation;
FT dbSNP:rs775014444)"
FT /evidence="ECO:0000269|PubMed:27807845,
FT ECO:0000269|PubMed:28158450"
FT /id="VAR_077972"
FT VARIANT 586
FT /note="A -> V (in PEBAT; decreased function in tubulin
FT complex assembly; dbSNP:rs1567999844)"
FT /evidence="ECO:0000269|PubMed:27807845,
FT ECO:0000269|PubMed:28158450"
FT /id="VAR_077973"
FT VARIANT 617
FT /note="M -> T (in dbSNP:rs2292971)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_057264"
FT VARIANT 626
FT /note="A -> T (in PEBAT; decreased protein abundance; does
FT not affect localization to centrosome; dbSNP:rs749225304)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077974"
FT VARIANT 772
FT /note="R -> C (in PEBAT; decreased function in neuron
FT morphogenesis; decreased interaction with ARL2; decreased
FT interaction with TBCE; decreased interaction with beta
FT tubulin; dbSNP:rs181969865)"
FT /evidence="ECO:0000269|PubMed:27666374"
FT /id="VAR_077975"
FT VARIANT 921
FT /note="A -> T (in PEBAT; decreased interaction with ARL2;
FT decreased interaction with TBCE; decreased interaction with
FT beta tubulin; dbSNP:rs886041085)"
FT /evidence="ECO:0000269|PubMed:27666374"
FT /id="VAR_077976"
FT VARIANT 923
FT /note="S -> N (in dbSNP:rs3214033)"
FT /id="VAR_057265"
FT VARIANT 937
FT /note="P -> R (in PEBAT; decreased interaction with TBCE;
FT decreased interaction with beta tubulin; does not affect
FT interaction with ARL2; dbSNP:rs886041087)"
FT /evidence="ECO:0000269|PubMed:27666374,
FT ECO:0000269|PubMed:27807845"
FT /id="VAR_077977"
FT VARIANT 943
FT /note="G -> V (in dbSNP:rs8072406)"
FT /id="VAR_057266"
FT VARIANT 994
FT /note="T -> M (in PEBAT; unknown pathological significance;
FT dbSNP:rs867484272)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077978"
FT VARIANT 1105
FT /note="V -> M (in PEBAT; unknown pathological significance;
FT dbSNP:rs764003906)"
FT /evidence="ECO:0000269|PubMed:27666370"
FT /id="VAR_077979"
FT VARIANT 1122
FT /note="P -> L (in PEBAT; severely decreased protein
FT abundance; does not affect localization to centrosome;
FT decreased interaction with ARL2; decreased interaction with
FT TBCE; decreased interaction with beta tubulin;
FT dbSNP:rs755177846)"
FT /evidence="ECO:0000269|PubMed:27666370,
FT ECO:0000269|PubMed:27666374"
FT /id="VAR_077980"
FT VARIANT 1185
FT /note="L -> P (in dbSNP:rs2292969)"
FT /id="VAR_057267"
FT CONFLICT 31
FT /note="G -> S (in Ref. 1; CAA07022)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="W -> C (in Ref. 3; BAA76832)"
FT /evidence="ECO:0000305"
FT CONFLICT 799..801
FT /note="RAV -> GAL (in Ref. 1; CAA07022)"
FT /evidence="ECO:0000305"
FT CONFLICT 985
FT /note="G -> R (in Ref. 1; CAA07022)"
FT /evidence="ECO:0000305"
FT CONFLICT 1068
FT /note="A -> S (in Ref. 8; AAH12824)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075
FT /note="C -> V (in Ref. 1; CAA07022)"
FT /evidence="ECO:0000305"
FT CONFLICT 1097
FT /note="E -> G (in Ref. 1; CAA07022, 3; BAA76832 and 8;
FT AAH03094)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1192 AA; 132600 MW; C46BE2048A5FEBC2 CRC64;
MALSDEPAAG GPEEEAEDET LAFGAALEAF GESAETRALL GRLREVHGGG AEREVALERF
RVIMDKYQEQ PHLLDPHLEW MMNLLLDIVQ DQTSPASLVH LAFKFLYIIT KVRGYKTFLR
LFPHEVADVE PVLDLVTIQN PKDHEAWETR YMLLLWLSVT CLIPFDFSRL DGNLLTQPGQ
ARMSIMDRIL QIAESYLIVS DKARDAAAVL VSRFITRPDV KQSKMAEFLD WSLCNLARSS
FQTMQGVITM DGTLQALAQI FKHGKREDCL PYAATVLRCL DGCRLPESNQ TLLRKLGVKL
VQRLGLTFLK PKVAAWRYQR GCRSLAANLQ LLTQGQSEQK PLILTEDDDE DDDVPEGVER
VIEQLLVGLK DKDTVVRWSA AKGIGRMAGR LPRALADDVV GSVLDCFSFQ ETDKAWHGGC
LALAELGRRG LLLPSRLVDV VAVILKALTY DEKRGACSVG TNVRDAACYV CWAFARAYEP
QELKPFVTAI SSALVIAAVF DRDINCRRAA SAAFQENVGR QGTFPHGIDI LTTADYFAVG
NRSNCFLVIS VFIAGFPEYT QPMIDHLVTM KISHWDGVIR ELAARALHNL AQQAPEFSAT
QVFPRLLSMT LSPDLHMRHG SILACAEVAY ALYKLAAQEN RPVTDHLDEQ AVQGLKQIHQ
QLYDRQLYRG LGGQLMRQAV CVLIEKLSLS KMPFRGDTVI DGWQWLINDT LRHLHLISSH
SRQQMKDAAV SALAALCSEY YMKEPGEADP AIQEELITQY LAELRNPEEM TRCGFSLALG
ALPGFLLKGR LQQVLTGLRA VTHTSPEDVS FAESRRDGLK AIARICQTVG VKAGAPDEAV
CGENVSQIYC ALLGCMDDYT TDSRGDVGTW VRKAAMTSLM DLTLLLARSQ PELIEAHTCE
RIMCCVAQQA SEKIDRFRAH AASVFLTLLH FDSPPIPHVP HRGELEKLFP RSDVASVNWS
APSQAFPRIT QLLGLPTYRY HVLLGLVVSL GGLTESTIRH STQSLFEYMK GIQSDPQALG
SFSGTLLQIF EDNLLNERVS VPLLKTLDHV LTHGCFDIFT TEEDHPFAVK LLALCKKEIK
NSKDIQKLLS GIAVFCEMVQ FPGDVRRQAL LQLCLLLCHR FPLIRKTTAS QVYETLLTYS
DVVGADVLDE VVTVLSDTAW DAELAVVREQ RNRLCDLLGV PRPQLVPQPG AC
