TBB3_HUMAN
ID TBB3_HUMAN Reviewed; 450 AA.
AC Q13509; A8K854; Q9BTZ0; Q9BW10;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Tubulin beta-3 chain;
DE AltName: Full=Tubulin beta-4 chain;
DE AltName: Full=Tubulin beta-III;
GN Name=TUBB3; Synonyms=TUBB4;
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 1).
RX PubMed=9473684; DOI=10.1016/s0167-4781(97)00168-1;
RA Ranganathan S., Dexter D.W., Benetatos C.A., Hudes G.R.;
RT "Cloning and sequencing of human betaIII-tubulin cDNA: induction of betaIII
RT isotype in human prostate carcinoma cells by acute exposure to
RT antimicrotubule agents.";
RL Biochim. Biophys. Acta 1395:237-245(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Mammary cancer;
RA Banerjee A.;
RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, and Esophagus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [7]
RP PROTEIN SEQUENCE OF 63-77; 104-121; 242-251; 163-174 AND 381-390, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14736079; DOI=10.1177/088307380301801205;
RA Katsetos C.D., Legido A., Perentes E., Mork S.J.;
RT "Class III beta-tubulin isotype: a key cytoskeletal protein at the
RT crossroads of developmental neurobiology and tumor neuropathology.";
RL J. Child Neurol. 18:851-866(2003).
RN [9]
RP ERRATUM OF PUBMED:14736079.
RA Katsetos C.D., Legido A., Perentes E., Mork S.J.;
RL J. Child Neurol. 19:531-531(2004).
RN [10]
RP PHOSPHORYLATION AT SER-172 BY CDK1.
RX PubMed=16371510; DOI=10.1091/mbc.e05-07-0621;
RA Fourest-Lieuvin A., Peris L., Gache V., Garcia-Saez I., Juillan-Binard C.,
RA Lantez V., Job D.;
RT "Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-
RT dependent kinase Cdk1.";
RL Mol. Biol. Cell 17:1041-1050(2006).
RN [11]
RP GLYCYLATION.
RX PubMed=19524510; DOI=10.1016/j.cell.2009.05.020;
RA Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M., Levilliers N.,
RA Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J., Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [12]
RP FUNCTION, VARIANTS CFEOM3A GLN-62; CYS-262; HIS-262; THR-302; CYS-380;
RP LYS-410; HIS-417 AND ASN-417, AND CHARACTERIZATION OF VARIANTS CFEOM3A
RP GLN-62; CYS-262; HIS-262; THR-302; CYS-380 AND LYS-410.
RX PubMed=20074521; DOI=10.1016/j.cell.2009.12.011;
RA Tischfield M.A., Baris H.N., Wu C., Rudolph G., Van Maldergem L., He W.,
RA Chan W.M., Andrews C., Demer J.L., Robertson R.L., Mackey D.A.,
RA Ruddle J.B., Bird T.D., Gottlob I., Pieh C., Traboulsi E.I., Pomeroy S.L.,
RA Hunter D.G., Soul J.S., Newlin A., Sabol L.J., Doherty E.J.,
RA de Uzcategui C.E., de Uzcategui N., Collins M.L., Sener E.C., Wabbels B.,
RA Hellebrand H., Meitinger T., de Berardinis T., Magli A., Schiavi C.,
RA Pastore-Trossello M., Koc F., Wong A.M., Levin A.V., Geraghty M.T.,
RA Descartes M., Flaherty M., Jamieson R.V., Moller H.U., Meuthen I.,
RA Callen D.F., Kerwin J., Lindsay S., Meindl A., Gupta M.L. Jr., Pellman D.,
RA Engle E.C.;
RT "Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions,
RT and axon guidance.";
RL Cell 140:74-87(2010).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=20191564; DOI=10.1002/cm.20436;
RA Leandro-Garcia L.J., Leskela S., Landa I., Montero-Conde C.,
RA Lopez-Jimenez E., Leton R., Cascon A., Robledo M., Rodriguez-Antona C.;
RT "Tumoral and tissue-specific expression of the major human beta-tubulin
RT isotypes.";
RL Cytoskeleton 67:214-223(2010).
RN [14]
RP INTERACTION WITH NLRP5.
RX PubMed=24374158; DOI=10.1016/j.ydbio.2013.12.025;
RA Kim B., Zhang X., Kan R., Cohen R., Mukai C., Travis A.J., Coonrod S.A.;
RT "The role of MATER in endoplasmic reticulum distribution and calcium
RT homeostasis in mouse oocytes.";
RL Dev. Biol. 386:331-339(2014).
RN [15]
RP GLUTAMYLATION.
RX PubMed=26875866; DOI=10.1016/j.cell.2016.01.019;
RA Valenstein M.L., Roll-Mecak A.;
RT "Graded control of microtubule severing by tubulin glutamylation.";
RL Cell 164:911-921(2016).
RN [16]
RP FUNCTION, AND INTERACTION WITH UNC5C.
RX PubMed=28483977; DOI=10.1523/jneurosci.2617-16.2017;
RA Shao Q., Yang T., Huang H., Alarmanazi F., Liu G.;
RT "Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates
RT Netrin-1 Repulsion.";
RL J. Neurosci. 37:5620-5633(2017).
RN [17]
RP INTERACTION WITH DPYSL5.
RX PubMed=33894126; DOI=10.1016/j.ajhg.2021.04.004;
RA Jeanne M., Demory H., Moutal A., Vuillaume M.L., Blesson S., Thepault R.A.,
RA Marouillat S., Halewa J., Maas S.M., Motazacker M.M., Mancini G.M.S.,
RA van Slegtenhorst M.A., Andreou A., Cox H., Vogt J., Laufman J.,
RA Kostandyan N., Babikyan D., Hancarova M., Bendova S., Sedlacek Z.,
RA Aldinger K.A., Sherr E.H., Argilli E., England E.M., Audebert-Bellanger S.,
RA Bonneau D., Colin E., Denomme-Pichon A.S., Gilbert-Dussardier B.,
RA Isidor B., Kuery S., Odent S., Redon R., Khanna R., Dobyns W.B.,
RA Bezieau S., Honnorat J., Lohkamp B., Toutain A., Laumonnier F.;
RT "Missense variants in DPYSL5 cause a neurodevelopmental disorder with
RT corpus callosum agenesis and cerebellar abnormalities.";
RL Am. J. Hum. Genet. 108:951-961(2021).
RN [18]
RP VARIANTS CDCBM1 MET-178; LYS-205; VAL-302 AND VAL-323, AND CHARACTERIZATION
RP OF VARIANTS CDCBM1 MET-178; LYS-205; VAL-302 AND VAL-323.
RX PubMed=20829227; DOI=10.1093/hmg/ddq377;
RA Poirier K., Saillour Y., Bahi-Buisson N., Jaglin X.H., Fallet-Bianco C.,
RA Nabbout R., Castelnau-Ptakhine L., Roubertie A., Attie-Bitach T.,
RA Desguerre I., Genevieve D., Barnerias C., Keren B., Lebrun N., Boddaert N.,
RA Encha-Razavi F., Chelly J.;
RT "Mutations in the neuronal ss-tubulin subunit TUBB3 result in malformation
RT of cortical development and neuronal migration defects.";
RL Hum. Mol. Genet. 19:4462-4473(2010).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. It binds
CC two moles of GTP, one at an exchangeable site on the beta chain and one
CC at a non-exchangeable site on the alpha chain. TUBB3 plays a critical
CC role in proper axon guidance and maintenance. Binding of NTN1/Netrin-1
CC to its receptor UNC5C might cause dissociation of UNC5C from
CC polymerized TUBB3 in microtubules and thereby lead to increased
CC microtubule dynamics and axon repulsion (PubMed:28483977). Plays a role
CC in dorsal root ganglion axon projection towards the spinal cord
CC (PubMed:28483977). {ECO:0000269|PubMed:20074521,
CC ECO:0000269|PubMed:28483977}.
CC -!- SUBUNIT: Dimer of alpha and beta chains. A typical microtubule is a
CC hollow water-filled tube with an outer diameter of 25 nm and an inner
CC diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to
CC form protofilaments running lengthwise along the microtubule wall with
CC the beta-tubulin subunit facing the microtubule plus end conferring a
CC structural polarity. Microtubules usually have 13 protofilaments but
CC different protofilament numbers can be found in some organisms and
CC specialized cells. Interacts with UNC5C (via cytoplasmic domain); this
CC interaction is decreased by NTN1/Netrin-1 (PubMed:28483977). Interacts
CC with NLRP5/MATER at cytoskeleton microtubules (PubMed:24374158).
CC Interacts with DPYSL5 (PubMed:33894126). {ECO:0000269|PubMed:24374158,
CC ECO:0000269|PubMed:28483977, ECO:0000269|PubMed:33894126}.
CC -!- INTERACTION:
CC Q13509; P54274: TERF1; NbExp=2; IntAct=EBI-350989, EBI-710997;
CC Q13509; P68363: TUBA1B; NbExp=3; IntAct=EBI-350989, EBI-487083;
CC Q13509; O95185: UNC5C; NbExp=2; IntAct=EBI-350989, EBI-11343380;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9ERD7}. Cell projection, growth cone
CC {ECO:0000250|UniProtKB:Q9ERD7}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q9ERD7}. Cell projection, filopodium
CC {ECO:0000250|UniProtKB:Q9ERD7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13509-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13509-2; Sequence=VSP_054659;
CC -!- TISSUE SPECIFICITY: Expression is primarily restricted to central and
CC peripheral nervous system. Greatly increased expression in most
CC cancerous tissues. {ECO:0000269|PubMed:14736079,
CC ECO:0000269|PubMed:20191564}.
CC -!- DOMAIN: The highly acidic C-terminal region may bind cations such as
CC calcium.
CC -!- DOMAIN: The MREI motif is common among all beta-tubulin isoforms and
CC may be critical for tubulin autoregulation.
CC {ECO:0000250|UniProtKB:P07437}.
CC -!- PTM: Some glutamate residues at the C-terminus are polyglutamylated,
CC resulting in polyglutamate chains on the gamma-carboxyl group
CC (PubMed:26875866). Polyglutamylation plays a key role in microtubule
CC severing by spastin (SPAST). SPAST preferentially recognizes and acts
CC on microtubules decorated with short polyglutamate tails: severing
CC activity by SPAST increases as the number of glutamates per tubulin
CC rises from one to eight, but decreases beyond this glutamylation
CC threshold (PubMed:26875866). Glutamylation is also involved in cilia
CC motility (By similarity). {ECO:0000250|UniProtKB:P99024,
CC ECO:0000269|PubMed:26875866}.
CC -!- PTM: Some glutamate residues at the C-terminus are monoglycylated but
CC not polyglycylated due to the absence of functional TTLL10 in human.
CC Monoglycylation is mainly limited to tubulin incorporated into cilia
CC and flagella axonemes, which is required for their stability and
CC maintenance. Flagella glycylation controls sperm motility. Both
CC polyglutamylation and monoglycylation can coexist on the same protein
CC on adjacent residues, and lowering glycylation levels increases
CC polyglutamylation, and reciprocally. {ECO:0000250|UniProtKB:P07437,
CC ECO:0000305|PubMed:19524510}.
CC -!- PTM: Phosphorylated on Ser-172 by CDK1 during the cell cycle, from
CC metaphase to telophase, but not in interphase. This phosphorylation
CC inhibits tubulin incorporation into microtubules.
CC {ECO:0000269|PubMed:16371510}.
CC -!- DISEASE: Fibrosis of extraocular muscles, congenital, 3A (CFEOM3A)
CC [MIM:600638]: A congenital ocular motility disorder marked by
CC restrictive ophthalmoplegia affecting extraocular muscles innervated by
CC the oculomotor and/or trochlear nerves. It is clinically characterized
CC by anchoring of the eyes in downward gaze, ptosis, and backward tilt of
CC the head. Congenital fibrosis of extraocular muscles type 3 presents as
CC a non-progressive, autosomal dominant disorder with variable
CC expression. Patients may be bilaterally or unilaterally affected, and
CC their oculo-motility defects range from complete ophthalmoplegia (with
CC the eyes fixed in a hypo- and exotropic position), to mild asymptomatic
CC restrictions of ocular movement. Ptosis, refractive error, amblyopia,
CC and compensatory head positions are associated with the more severe
CC forms of the disorder. In some cases, the ocular phenotype is
CC accompanied by additional features including developmental delay,
CC corpus callosum agenesis, basal ganglia dysmorphism, facial weakness,
CC polyneuropathy. {ECO:0000269|PubMed:20074521}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Cortical dysplasia, complex, with other brain malformations 1
CC (CDCBM1) [MIM:614039]: A disorder of aberrant neuronal migration and
CC disturbed axonal guidance. Affected individuals have mild to severe
CC intellectual disability, strabismus, axial hypotonia, and spasticity.
CC Brain imaging shows variable malformations of cortical development,
CC including polymicrogyria, gyral disorganization, and fusion of the
CC basal ganglia, as well as thin corpus callosum, hypoplastic brainstem,
CC and dysplastic cerebellar vermis. Extraocular muscles are not involved.
CC {ECO:0000269|PubMed:20829227}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tubulin family. {ECO:0000305}.
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DR EMBL; U47634; AAC52035.1; -; mRNA.
DR EMBL; AF427491; AAL28094.1; -; mRNA.
DR EMBL; AK122757; BAG53710.1; -; mRNA.
DR EMBL; AK292219; BAF84908.1; -; mRNA.
DR EMBL; AC092143; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471184; EAW66674.1; -; Genomic_DNA.
DR EMBL; BC000748; AAH00748.1; -; mRNA.
DR EMBL; BC003021; AAH03021.2; -; mRNA.
DR CCDS; CCDS10988.1; -. [Q13509-1]
DR CCDS; CCDS56012.1; -. [Q13509-2]
DR RefSeq; NP_001184110.1; NM_001197181.1. [Q13509-2]
DR RefSeq; NP_006077.2; NM_006086.3. [Q13509-1]
DR PDB; 5IJ0; EM; 3.80 A; B=1-426.
DR PDB; 5IJ9; EM; 3.70 A; B=1-426.
DR PDB; 5JCO; EM; 4.00 A; C/D/I/J/K/L=1-426.
DR PDB; 6E7B; EM; 3.50 A; B=1-426.
DR PDB; 6S8L; X-ray; 1.80 A; B=1-450.
DR PDB; 6WSL; EM; 3.10 A; B/F=1-450.
DR PDB; 7LXB; EM; 3.26 A; B/D/F/H/J/L/N/P=1-450.
DR PDB; 7M18; EM; 3.38 A; B/D/F/H/J/L/N/P=1-450.
DR PDB; 7M20; EM; 3.84 A; B/D/F/H/J/L/N/P/R=1-450.
DR PDB; 7PJF; X-ray; 1.86 A; B=1-450.
DR PDB; 7SJ7; EM; 3.80 A; B/D/F/G/H/I=1-450.
DR PDB; 7SJ8; EM; 3.60 A; B/D/F/G/H/I=1-450.
DR PDB; 7SJ9; EM; 3.80 A; B/D/F/G/H/I=1-450.
DR PDB; 7SJA; EM; 3.80 A; B/D/F/G/H/I=1-450.
DR PDBsum; 5IJ0; -.
DR PDBsum; 5IJ9; -.
DR PDBsum; 5JCO; -.
DR PDBsum; 6E7B; -.
DR PDBsum; 6S8L; -.
DR PDBsum; 6WSL; -.
DR PDBsum; 7LXB; -.
DR PDBsum; 7M18; -.
DR PDBsum; 7M20; -.
DR PDBsum; 7PJF; -.
DR PDBsum; 7SJ7; -.
DR PDBsum; 7SJ8; -.
DR PDBsum; 7SJ9; -.
DR PDBsum; 7SJA; -.
DR AlphaFoldDB; Q13509; -.
DR SMR; Q13509; -.
DR BioGRID; 115654; 407.
DR CORUM; Q13509; -.
DR DIP; DIP-31505N; -.
DR IntAct; Q13509; 270.
DR MINT; Q13509; -.
DR STRING; 9606.ENSP00000320295; -.
DR BindingDB; Q13509; -.
DR ChEMBL; CHEMBL2597; -.
DR DrugBank; DB05147; CYT997.
DR DrugBank; DB01873; Epothilone D.
DR DrugBank; DB04845; Ixabepilone.
DR DrugBank; DB03010; Patupilone.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR DrugBank; DB06042; ZEN-012.
DR DrugCentral; Q13509; -.
DR GuidetoPHARMACOLOGY; 2752; -.
DR GlyGen; Q13509; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13509; -.
DR MetOSite; Q13509; -.
DR PhosphoSitePlus; Q13509; -.
DR SwissPalm; Q13509; -.
DR BioMuta; TUBB3; -.
DR DMDM; 20455526; -.
DR OGP; Q13509; -.
DR EPD; Q13509; -.
DR jPOST; Q13509; -.
DR MassIVE; Q13509; -.
DR MaxQB; Q13509; -.
DR PaxDb; Q13509; -.
DR PeptideAtlas; Q13509; -.
DR PRIDE; Q13509; -.
DR ProteomicsDB; 1874; -.
DR ProteomicsDB; 59510; -. [Q13509-1]
DR TopDownProteomics; Q13509-1; -. [Q13509-1]
DR ABCD; Q13509; 1 sequenced antibody.
DR Antibodypedia; 54822; 1122 antibodies from 45 providers.
DR DNASU; 10381; -.
DR Ensembl; ENST00000315491.12; ENSP00000320295.7; ENSG00000258947.8. [Q13509-1]
DR Ensembl; ENST00000554444.5; ENSP00000451617.1; ENSG00000258947.8. [Q13509-2]
DR GeneID; 10381; -.
DR KEGG; hsa:10381; -.
DR MANE-Select; ENST00000315491.12; ENSP00000320295.7; NM_006086.4; NP_006077.2.
DR UCSC; uc002fph.2; human. [Q13509-1]
DR CTD; 10381; -.
DR DisGeNET; 10381; -.
DR GeneCards; TUBB3; -.
DR GeneReviews; TUBB3; -.
DR HGNC; HGNC:20772; TUBB3.
DR HPA; ENSG00000258947; Tissue enriched (brain).
DR MalaCards; TUBB3; -.
DR MIM; 600638; phenotype.
DR MIM; 602661; gene.
DR MIM; 614039; phenotype.
DR neXtProt; NX_Q13509; -.
DR OpenTargets; ENSG00000258947; -.
DR Orphanet; 45358; Congenital fibrosis of extraocular muscles.
DR Orphanet; 300570; Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation.
DR Orphanet; 467166; Tubulinopathy-associated dysgyria.
DR PharmGKB; PA134953867; -.
DR VEuPathDB; HostDB:ENSG00000258947; -.
DR eggNOG; KOG1375; Eukaryota.
DR GeneTree; ENSGT00940000159115; -.
DR HOGENOM; CLU_015718_0_0_1; -.
DR InParanoid; Q13509; -.
DR OMA; ACHHARA; -.
DR PhylomeDB; Q13509; -.
DR TreeFam; TF300298; -.
DR PathwayCommons; Q13509; -.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR Reactome; R-HSA-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
DR Reactome; R-HSA-190861; Gap junction assembly.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-389957; Prefoldin mediated transfer of substrate to CCT/TriC.
DR Reactome; R-HSA-389960; Formation of tubulin folding intermediates by CCT/TriC.
DR Reactome; R-HSA-389977; Post-chaperonin tubulin folding pathway.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5617833; Cilium Assembly.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-6807878; COPI-mediated anterograde transport.
DR Reactome; R-HSA-6811434; COPI-dependent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR Reactome; R-HSA-9619483; Activation of AMPK downstream of NMDARs.
DR Reactome; R-HSA-9646399; Aggrephagy.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR Reactome; R-HSA-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III.
DR Reactome; R-HSA-983189; Kinesins.
DR SignaLink; Q13509; -.
DR SIGNOR; Q13509; -.
DR BioGRID-ORCS; 10381; 93 hits in 1082 CRISPR screens.
DR ChiTaRS; TUBB3; human.
DR GeneWiki; TUBB3; -.
DR GenomeRNAi; 10381; -.
DR Pharos; Q13509; Tclin.
DR PRO; PR:Q13509; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q13509; protein.
DR Bgee; ENSG00000258947; Expressed in cortical plate and 97 other tissues.
DR ExpressionAtlas; Q13509; baseline and differential.
DR Genevisible; Q13509; HS.
DR GO; GO:0030424; C:axon; ISS:ARUK-UCL.
DR GO; GO:0071944; C:cell periphery; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:1990890; F:netrin receptor binding; IPI:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR GO; GO:1990791; P:dorsal root ganglion development; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007017; P:microtubule-based process; IEA:InterPro.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
DR Gene3D; 1.10.287.600; -; 1.
DR Gene3D; 3.30.1330.20; -; 1.
DR Gene3D; 3.40.50.1440; -; 1.
DR InterPro; IPR013838; Beta-tubulin_BS.
DR InterPro; IPR002453; Beta_tubulin.
DR InterPro; IPR008280; Tub_FtsZ_C.
DR InterPro; IPR000217; Tubulin.
DR InterPro; IPR037103; Tubulin/FtsZ-like_C.
DR InterPro; IPR018316; Tubulin/FtsZ_2-layer-sand-dom.
DR InterPro; IPR036525; Tubulin/FtsZ_GTPase_sf.
DR InterPro; IPR023123; Tubulin_C.
DR InterPro; IPR017975; Tubulin_CS.
DR InterPro; IPR003008; Tubulin_FtsZ_GTPase.
DR PANTHER; PTHR11588; PTHR11588; 1.
DR Pfam; PF00091; Tubulin; 1.
DR Pfam; PF03953; Tubulin_C; 1.
DR PRINTS; PR01163; BETATUBULIN.
DR PRINTS; PR01161; TUBULIN.
DR SMART; SM00864; Tubulin; 1.
DR SMART; SM00865; Tubulin_C; 1.
DR SUPFAM; SSF52490; SSF52490; 1.
DR SUPFAM; SSF55307; SSF55307; 1.
DR PROSITE; PS00227; TUBULIN; 1.
DR PROSITE; PS00228; TUBULIN_B_AUTOREG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell projection; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Disease variant; GTP-binding;
KW Isopeptide bond; Microtubule; Nucleotide-binding; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..450
FT /note="Tubulin beta-3 chain"
FT /id="PRO_0000048250"
FT REGION 425..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1..4
FT /note="MREI motif"
FT /evidence="ECO:0000250|UniProtKB:P07437"
FT COMPBIAS 431..450
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 140..146
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT MOD_RES 172
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:16371510"
FT MOD_RES 438
FT /note="5-glutamyl polyglutamate"
FT /evidence="ECO:0000250|UniProtKB:Q2T9S0"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2T9S0"
FT VAR_SEQ 1..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054659"
FT VARIANT 62
FT /note="R -> Q (in CFEOM3A; affects heterodimers formation;
FT results in increased stability and reduced dynamics of
FT microtubules; dbSNP:rs864321714)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062758"
FT VARIANT 178
FT /note="T -> M (in CDCBM1; can form tubulin heterodimers
FT that are properly incorporated into microtubules; the
FT microtubules are less stable than wild-type;
FT dbSNP:rs747480526)"
FT /evidence="ECO:0000269|PubMed:20829227"
FT /id="VAR_066206"
FT VARIANT 205
FT /note="E -> K (in CDCBM1; does not form tubulin
FT heterodimers; patient fibroblasts show no major alterations
FT in the microtubule network, but the microtubules are less
FT stable than wild-type; dbSNP:rs878853257)"
FT /evidence="ECO:0000269|PubMed:20829227"
FT /id="VAR_066207"
FT VARIANT 262
FT /note="R -> C (in CFEOM3A; affects heterodimers formation;
FT affects microtubules polymerization and depolymerization
FT rates; dbSNP:rs267607162)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062759"
FT VARIANT 262
FT /note="R -> H (in CFEOM3A; severe phenotype with congenital
FT facial weakness, congenital wrist and finger contractures;
FT affects microtubules polymerization and depolymerization
FT rates; dbSNP:rs864321716)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062760"
FT VARIANT 302
FT /note="A -> T (in CFEOM3A; affects heterodimers formation;
FT results in increased stability and reduced dynamics of
FT microtubules; dbSNP:rs267607163)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062761"
FT VARIANT 302
FT /note="A -> V (in CDCBM1; does not form tubulin
FT heterodimers; dbSNP:rs878853258)"
FT /evidence="ECO:0000269|PubMed:20829227"
FT /id="VAR_066208"
FT VARIANT 323
FT /note="M -> V (in CDCBM1; reduced heterodimers formation;
FT dbSNP:rs878853256)"
FT /evidence="ECO:0000269|PubMed:20829227"
FT /id="VAR_066209"
FT VARIANT 380
FT /note="R -> C (in CFEOM3A; affects heterodimers formation;
FT results in increased stability and reduced dynamics of
FT microtubules; dbSNP:rs864321717)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062762"
FT VARIANT 410
FT /note="E -> K (in CFEOM3A; severe phenotype with congenital
FT facial weakness; lower extremity weakness and sensory loss
FT in the second to third decade of life in one patient;
FT affects microtubules polymerization and depolymerization
FT rates; dbSNP:rs267607165)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062763"
FT VARIANT 417
FT /note="D -> H (in CFEOM3A; severe phenotype with congenital
FT facial weakness, congenital wrist and finger contractures;
FT dbSNP:rs267607164)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062764"
FT VARIANT 417
FT /note="D -> N (in CFEOM3A; some patients with lower
FT extremity weakness and sensory loss in the second to third
FT decade of life; also found in patients without CFEOM3A who
FT developed polyneuropathy; dbSNP:rs267607164)"
FT /evidence="ECO:0000269|PubMed:20074521"
FT /id="VAR_062765"
FT CONFLICT 275
FT /note="A -> R (in Ref. 1; AAC52035)"
FT /evidence="ECO:0000305"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 10..28
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:7M18"
FT HELIX 42..45
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 47..49
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:6WSL"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 63..69
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 101..106
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 108..125
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 132..142
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 143..158
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:6S8L"
FT TURN 173..175
FT /evidence="ECO:0007829|PDB:7PJF"
FT HELIX 181..195
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 197..203
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 204..213
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 222..241
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:7PJF"
FT HELIX 250..257
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:7LXB"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:6WSL"
FT TURN 279..283
FT /evidence="ECO:0007829|PDB:6WSL"
FT HELIX 286..294
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 299..302
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 305..307
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 310..320
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 323..335
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 343..347
FT /evidence="ECO:0007829|PDB:7LXB"
FT STRAND 349..356
FT /evidence="ECO:0007829|PDB:6S8L"
FT STRAND 364..371
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 375..390
FT /evidence="ECO:0007829|PDB:6S8L"
FT TURN 391..394
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 395..399
FT /evidence="ECO:0007829|PDB:6S8L"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:6S8L"
FT HELIX 405..427
FT /evidence="ECO:0007829|PDB:6S8L"
SQ SEQUENCE 450 AA; 50433 MW; 4B9CDE7DBA102949 CRC64;
MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPSGNYVGDS DLQLERISVY YNEASSHKYV
PRAILVDLEP GTMDSVRSGA FGHLFRPDNF IFGQSGAGNN WAKGHYTEGA ELVDSVLDVV
RKECENCDCL QGFQLTHSLG GGTGSGMGTL LISKVREEYP DRIMNTFSVV PSPKVSDTVV
EPYNATLSIH QLVENTDETY CIDNEALYDI CFRTLKLATP TYGDLNHLVS ATMSGVTTSL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTARGSQQ YRALTVPELT QQMFDAKNMM
AACDPRHGRY LTVATVFRGR MSMKEVDEQM LAIQSKNSSY FVEWIPNNVK VAVCDIPPRG
LKMSSTFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS
EYQQYQDATA EEEGEMYEDD EEESEAQGPK
