Full text data of TUBB
TUBB
(TUBB5)
[Confidence: high (present in two of the MS resources)]
Tubulin beta chain (Tubulin beta-5 chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Tubulin beta chain (Tubulin beta-5 chain)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00011654
IPI00011654 Tubulin beta-1 chain Tubulin beta-1 chain membrane n/a n/a n/a n/a n/a n/a n/a n/a 8 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton match also tubulin beta 5 chain found at its expected molecular weight found at molecular weight
IPI00011654 Tubulin beta-1 chain Tubulin beta-1 chain membrane n/a n/a n/a n/a n/a n/a n/a n/a 8 n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoskeleton match also tubulin beta 5 chain found at its expected molecular weight found at molecular weight
UniProt
P07437
ID TBB5_HUMAN Reviewed; 444 AA.
AC P07437; P05218; Q8WUC1; Q9CY33;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-DEC-2004, sequence version 2.
DT 22-JAN-2014, entry version 165.
DE RecName: Full=Tubulin beta chain;
DE AltName: Full=Tubulin beta-5 chain;
GN Name=TUBB; Synonyms=TUBB5; ORFNames=OK/SW-cl.56;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6688039; DOI=10.1016/0092-8674(83)90429-4;
RA Lee M.G.-S., Lewis S.A., Wilde C.D., Cowan N.J.;
RT "Evolutionary history of a multigene family: an expressed human beta-
RT tubulin gene and three processed pseudogenes.";
RL Cell 33:477-487(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6865944;
RA Hall J.L., Dudley L., Dobner P.R., Lewis S.A., Cowan N.J.;
RT "Identification of two human beta-tubulin isotypes.";
RL Mol. Cell. Biol. 3:854-862(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=11504633; DOI=10.1016/S0968-0896(01)00103-1;
RA Crabtree D.V., Ojima I., Geng X., Adler A.J.;
RT "Tubulins in the primate retina: evidence that xanthophylls may be
RT endogenous ligands for the paclitaxel-binding site.";
RL Bioorg. Med. Chem. 9:1967-1976(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H.;
RT "Genome diversity in HLA: a new strategy for detection of genetic
RT polymorphisms in expressed genes within the HLA class III and class I
RT regions.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Lung, Muscle, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-19; 47-77; 104-174; 242-276; 283-297; 310-359
RP AND 363-390, METHYLATION AT ARG-318, AND MASS SPECTROMETRY.
RC TISSUE=Foreskin fibroblast, and Mammary carcinoma;
RA Bienvenut W.V., Campbell A., Ozanne B.W., Lourenco F., Olson M.F.;
RL Submitted (DEC-2009) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 3-19; 47-58; 63-77; 104-121; 163-174; 242-251;
RP 253-276; 283-297; 310-318; 325-336 AND 381-390, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [12]
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.,
RA Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J.,
RA Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-58, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
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.,
RA Rodriguez-Antona C.;
RT "Tumoral and tissue-specific expression of the major human beta-
RT tubulin isotypes.";
RL Cytoskeleton 67:214-223(2010).
RN [15]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [16]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. It
CC binds two moles of GTP, one at an exchangeable site on the beta
CC chain and one at a non-exchangeable site on the alpha chain.
CC -!- SUBUNIT: May interact with RNABP10 (By similarity). Interacts with
CC MX1 (By similarity). Dimer of alpha and beta chains. A typical
CC microtubule is a hollow water-filled tube with an outer diameter
CC of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers
CC associate head-to-tail to form protofilaments running lengthwise
CC along the microtubule wall with the beta-tubulin subunit facing
CC the microtubule plus end conferring a structural polarity.
CC Microtubules usually have 13 protofilaments but different
CC protofilament numbers can be found in some organisms and
CC specialized cells. Interacts with PIFO.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC spleen, thymus and immature brain.
CC -!- DOMAIN: The highly acidic C-terminal region may bind cations such
CC as calcium.
CC -!- PTM: Some glutamate residues at the C-terminus are
CC polyglutamylated. This modification occurs exclusively on
CC glutamate residues and results in polyglutamate chains on the
CC gamma-carboxyl group. Also monoglycylated but not polyglycylated
CC due to the absence of functional TTLL10 in human. Monoglycylation
CC is mainly limited to tubulin incorporated into axonemes (cilia and
CC flagella) whereas glutamylation is prevalent in neuronal cells,
CC centrioles, axonemes, and the mitotic spindle. Both modifications
CC can coexist on the same protein on adjacent residues, and lowering
CC glycylation levels increases polyglutamylation, and reciprocally.
CC The precise function of such modifications is still unclear but
CC they regulate the assembly and dynamics of axonemal microtubules
CC (Probable).
CC -!- SIMILARITY: Belongs to the tubulin family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tubulin entry;
CC URL="http://en.wikipedia.org/wiki/Tubulin";
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DR EMBL; J00314; AAB59507.1; -; Genomic_DNA.
DR EMBL; AF141349; AAD33873.1; -; mRNA.
DR EMBL; AF070561; AAC28642.1; -; mRNA.
DR EMBL; AF070593; AAC28650.1; -; mRNA.
DR EMBL; AF070600; AAC28654.1; -; mRNA.
DR EMBL; BA000025; BAB63321.1; -; Genomic_DNA.
DR EMBL; AB088100; BAC54932.1; -; Genomic_DNA.
DR EMBL; AB062393; BAB93480.1; -; mRNA.
DR EMBL; BC001938; AAH01938.1; -; mRNA.
DR EMBL; BC002347; AAH02347.1; -; mRNA.
DR EMBL; BC005838; AAH05838.1; -; mRNA.
DR EMBL; BC007605; AAH07605.1; -; mRNA.
DR EMBL; BC013374; AAH13374.1; -; mRNA.
DR EMBL; BC019924; AAH19924.1; -; mRNA.
DR EMBL; BC020946; AAH20946.1; -; mRNA.
DR EMBL; BC021909; AAH21909.1; -; mRNA.
DR EMBL; BC070326; AAH70326.1; -; mRNA.
DR PIR; A26561; A26561.
DR RefSeq; NP_821133.1; NM_178014.2.
DR UniGene; Hs.636480; -.
DR PDB; 3QNZ; X-ray; 2.20 A; C=429-438.
DR PDB; 3QO0; X-ray; 2.30 A; C=422-441.
DR PDBsum; 3QNZ; -.
DR PDBsum; 3QO0; -.
DR ProteinModelPortal; P07437; -.
DR SMR; P07437; 2-427.
DR IntAct; P07437; 69.
DR MINT; MINT-1146393; -.
DR STRING; 9606.ENSP00000410071; -.
DR BindingDB; P07437; -.
DR ChEMBL; CHEMBL5444; -.
DR DrugBank; DB01394; Colchicine.
DR DrugBank; DB00570; Vinblastine.
DR DrugBank; DB00541; Vincristine.
DR DrugBank; DB00361; Vinorelbine.
DR PhosphoSite; P07437; -.
DR DMDM; 56757569; -.
DR OGP; P07437; -.
DR REPRODUCTION-2DPAGE; P07437; -.
DR SWISS-2DPAGE; P07437; -.
DR UCD-2DPAGE; P07437; -.
DR PaxDb; P07437; -.
DR PRIDE; P07437; -.
DR Ensembl; ENST00000327892; ENSP00000339001; ENSG00000196230.
DR Ensembl; ENST00000383564; ENSP00000373058; ENSG00000183311.
DR Ensembl; ENST00000419792; ENSP00000401317; ENSG00000235067.
DR Ensembl; ENST00000421473; ENSP00000399155; ENSG00000224156.
DR Ensembl; ENST00000422650; ENSP00000400663; ENSG00000229684.
DR Ensembl; ENST00000422674; ENSP00000406811; ENSG00000227739.
DR Ensembl; ENST00000432462; ENSP00000410829; ENSG00000232421.
DR Ensembl; ENST00000436628; ENSP00000410071; ENSG00000232575.
DR GeneID; 203068; -.
DR KEGG; hsa:203068; -.
DR UCSC; uc003nrl.3; human.
DR CTD; 203068; -.
DR GeneCards; GC06P030687; -.
DR GeneCards; GC06Pi30696; -.
DR GeneCards; GC06Pj30677; -.
DR GeneCards; GC06Pk30678; -.
DR GeneCards; GC06Pl30732; -.
DR GeneCards; GC06Pm30766; -.
DR GeneCards; GC06Pn30677; -.
DR GeneCards; GC06Po30679; -.
DR HGNC; HGNC:20778; TUBB.
DR HPA; CAB005417; -.
DR HPA; CAB012406; -.
DR HPA; HPA043640; -.
DR HPA; HPA046280; -.
DR MIM; 191130; gene.
DR neXtProt; NX_P07437; -.
DR PharmGKB; PA358; -.
DR eggNOG; COG5023; -.
DR HOVERGEN; HBG000089; -.
DR InParanoid; P07437; -.
DR KO; K07375; -.
DR OMA; ELDYEDE; -.
DR PhylomeDB; P07437; -.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; TUBB; human.
DR GeneWiki; TUBB; -.
DR GenomeRNAi; 203068; -.
DR NextBio; 90324; -.
DR PRO; PR:P07437; -.
DR ArrayExpress; P07437; -.
DR Bgee; P07437; -.
DR CleanEx; HS_TUBB; -.
DR Genevestigator; P07437; -.
DR GO; GO:0044297; C:cell body; IDA:DFLAT.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:DFLAT.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IEA:Ensembl.
DR GO; GO:0005198; F:structural molecule activity; TAS:BHF-UCL.
DR GO; GO:0051301; P:cell division; TAS:BHF-UCL.
DR GO; GO:0006928; P:cellular component movement; TAS:UniProtKB.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; TAS:BHF-UCL.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007017; P:microtubule-based process; TAS:BHF-UCL.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; NAS:UniProtKB.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051225; P:spindle assembly; IEA:Ensembl.
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; IPR018316; Tubulin/FtsZ_2-layer-sand-dom.
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; Acetylation; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; GTP-binding; Isopeptide bond; Methylation;
KW Microtubule; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1 444 Tubulin beta chain.
FT /FTId=PRO_0000048243.
FT NP_BIND 140 146 GTP (Potential).
FT MOD_RES 58 58 N6-acetyllysine; alternate.
FT MOD_RES 172 172 Phosphoserine; by CDK1 (By similarity).
FT MOD_RES 318 318 Omega-N-methylarginine.
FT CROSSLNK 58 58 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT CROSSLNK 324 324 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CONFLICT 216 216 K -> R (in Ref. 1 and 2).
FT CONFLICT 231 231 A -> G (in Ref. 1 and 2).
FT CONFLICT 234 235 SG -> EC (in Ref. 1 and 2).
FT CONFLICT 288 288 E -> D (in Ref. 1 and 2).
FT CONFLICT 298 298 N -> D (in Ref. 8; AAH20946).
SQ SEQUENCE 444 AA; 49671 MW; 1E6CD0A36773A103 CRC64;
MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLDRISVY YNEATGGKYV
PRAILVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN WAKGHYTEGA ELVDSVLDVV
RKEAESCDCL QGFQLTHSLG GGTGSGMGTL LISKIREEYP DRIMNTFSVV PSPKVSDTVV
EPYNATLSVH QLVENTDETY CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQVFDAKNMM
AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LNVQNKNSSY FVEWIPNNVK TAVCDIPPRG
LKMAVTFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS
EYQQYQDATA EEEEDFGEEA EEEA
//
ID TBB5_HUMAN Reviewed; 444 AA.
AC P07437; P05218; Q8WUC1; Q9CY33;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-DEC-2004, sequence version 2.
DT 22-JAN-2014, entry version 165.
DE RecName: Full=Tubulin beta chain;
DE AltName: Full=Tubulin beta-5 chain;
GN Name=TUBB; Synonyms=TUBB5; ORFNames=OK/SW-cl.56;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6688039; DOI=10.1016/0092-8674(83)90429-4;
RA Lee M.G.-S., Lewis S.A., Wilde C.D., Cowan N.J.;
RT "Evolutionary history of a multigene family: an expressed human beta-
RT tubulin gene and three processed pseudogenes.";
RL Cell 33:477-487(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6865944;
RA Hall J.L., Dudley L., Dobner P.R., Lewis S.A., Cowan N.J.;
RT "Identification of two human beta-tubulin isotypes.";
RL Mol. Cell. Biol. 3:854-862(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=11504633; DOI=10.1016/S0968-0896(01)00103-1;
RA Crabtree D.V., Ojima I., Geng X., Adler A.J.;
RT "Tubulins in the primate retina: evidence that xanthophylls may be
RT endogenous ligands for the paclitaxel-binding site.";
RL Bioorg. Med. Chem. 9:1967-1976(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Yu W., Gibbs R.A.;
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Shiina T., Ota M., Katsuyama Y., Hashimoto N., Inoko H.;
RT "Genome diversity in HLA: a new strategy for detection of genetic
RT polymorphisms in expressed genes within the HLA class III and class I
RT regions.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, Lung, Muscle, and Placenta;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1-19; 47-77; 104-174; 242-276; 283-297; 310-359
RP AND 363-390, METHYLATION AT ARG-318, AND MASS SPECTROMETRY.
RC TISSUE=Foreskin fibroblast, and Mammary carcinoma;
RA Bienvenut W.V., Campbell A., Ozanne B.W., Lourenco F., Olson M.F.;
RL Submitted (DEC-2009) to UniProtKB.
RN [10]
RP PROTEIN SEQUENCE OF 3-19; 47-58; 63-77; 104-121; 163-174; 242-251;
RP 253-276; 283-297; 310-318; 325-336 AND 381-390, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [12]
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.,
RA Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J.,
RA Janke C.;
RT "Evolutionary divergence of enzymatic mechanisms for posttranslational
RT polyglycylation.";
RL Cell 137:1076-1087(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-58, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
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.,
RA Rodriguez-Antona C.;
RT "Tumoral and tissue-specific expression of the major human beta-
RT tubulin isotypes.";
RL Cytoskeleton 67:214-223(2010).
RN [15]
RP INTERACTION WITH PIFO.
RX PubMed=20643351; DOI=10.1016/j.devcel.2010.06.005;
RA Kinzel D., Boldt K., Davis E.E., Burtscher I., Trumbach D., Diplas B.,
RA Attie-Bitach T., Wurst W., Katsanis N., Ueffing M., Lickert H.;
RT "Pitchfork regulates primary cilia disassembly and left-right
RT asymmetry.";
RL Dev. Cell 19:66-77(2010).
RN [16]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Tubulin is the major constituent of microtubules. It
CC binds two moles of GTP, one at an exchangeable site on the beta
CC chain and one at a non-exchangeable site on the alpha chain.
CC -!- SUBUNIT: May interact with RNABP10 (By similarity). Interacts with
CC MX1 (By similarity). Dimer of alpha and beta chains. A typical
CC microtubule is a hollow water-filled tube with an outer diameter
CC of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers
CC associate head-to-tail to form protofilaments running lengthwise
CC along the microtubule wall with the beta-tubulin subunit facing
CC the microtubule plus end conferring a structural polarity.
CC Microtubules usually have 13 protofilaments but different
CC protofilament numbers can be found in some organisms and
CC specialized cells. Interacts with PIFO.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC spleen, thymus and immature brain.
CC -!- DOMAIN: The highly acidic C-terminal region may bind cations such
CC as calcium.
CC -!- PTM: Some glutamate residues at the C-terminus are
CC polyglutamylated. This modification occurs exclusively on
CC glutamate residues and results in polyglutamate chains on the
CC gamma-carboxyl group. Also monoglycylated but not polyglycylated
CC due to the absence of functional TTLL10 in human. Monoglycylation
CC is mainly limited to tubulin incorporated into axonemes (cilia and
CC flagella) whereas glutamylation is prevalent in neuronal cells,
CC centrioles, axonemes, and the mitotic spindle. Both modifications
CC can coexist on the same protein on adjacent residues, and lowering
CC glycylation levels increases polyglutamylation, and reciprocally.
CC The precise function of such modifications is still unclear but
CC they regulate the assembly and dynamics of axonemal microtubules
CC (Probable).
CC -!- SIMILARITY: Belongs to the tubulin family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tubulin entry;
CC URL="http://en.wikipedia.org/wiki/Tubulin";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; J00314; AAB59507.1; -; Genomic_DNA.
DR EMBL; AF141349; AAD33873.1; -; mRNA.
DR EMBL; AF070561; AAC28642.1; -; mRNA.
DR EMBL; AF070593; AAC28650.1; -; mRNA.
DR EMBL; AF070600; AAC28654.1; -; mRNA.
DR EMBL; BA000025; BAB63321.1; -; Genomic_DNA.
DR EMBL; AB088100; BAC54932.1; -; Genomic_DNA.
DR EMBL; AB062393; BAB93480.1; -; mRNA.
DR EMBL; BC001938; AAH01938.1; -; mRNA.
DR EMBL; BC002347; AAH02347.1; -; mRNA.
DR EMBL; BC005838; AAH05838.1; -; mRNA.
DR EMBL; BC007605; AAH07605.1; -; mRNA.
DR EMBL; BC013374; AAH13374.1; -; mRNA.
DR EMBL; BC019924; AAH19924.1; -; mRNA.
DR EMBL; BC020946; AAH20946.1; -; mRNA.
DR EMBL; BC021909; AAH21909.1; -; mRNA.
DR EMBL; BC070326; AAH70326.1; -; mRNA.
DR PIR; A26561; A26561.
DR RefSeq; NP_821133.1; NM_178014.2.
DR UniGene; Hs.636480; -.
DR PDB; 3QNZ; X-ray; 2.20 A; C=429-438.
DR PDB; 3QO0; X-ray; 2.30 A; C=422-441.
DR PDBsum; 3QNZ; -.
DR PDBsum; 3QO0; -.
DR ProteinModelPortal; P07437; -.
DR SMR; P07437; 2-427.
DR IntAct; P07437; 69.
DR MINT; MINT-1146393; -.
DR STRING; 9606.ENSP00000410071; -.
DR BindingDB; P07437; -.
DR ChEMBL; CHEMBL5444; -.
DR DrugBank; DB01394; Colchicine.
DR DrugBank; DB00570; Vinblastine.
DR DrugBank; DB00541; Vincristine.
DR DrugBank; DB00361; Vinorelbine.
DR PhosphoSite; P07437; -.
DR DMDM; 56757569; -.
DR OGP; P07437; -.
DR REPRODUCTION-2DPAGE; P07437; -.
DR SWISS-2DPAGE; P07437; -.
DR UCD-2DPAGE; P07437; -.
DR PaxDb; P07437; -.
DR PRIDE; P07437; -.
DR Ensembl; ENST00000327892; ENSP00000339001; ENSG00000196230.
DR Ensembl; ENST00000383564; ENSP00000373058; ENSG00000183311.
DR Ensembl; ENST00000419792; ENSP00000401317; ENSG00000235067.
DR Ensembl; ENST00000421473; ENSP00000399155; ENSG00000224156.
DR Ensembl; ENST00000422650; ENSP00000400663; ENSG00000229684.
DR Ensembl; ENST00000422674; ENSP00000406811; ENSG00000227739.
DR Ensembl; ENST00000432462; ENSP00000410829; ENSG00000232421.
DR Ensembl; ENST00000436628; ENSP00000410071; ENSG00000232575.
DR GeneID; 203068; -.
DR KEGG; hsa:203068; -.
DR UCSC; uc003nrl.3; human.
DR CTD; 203068; -.
DR GeneCards; GC06P030687; -.
DR GeneCards; GC06Pi30696; -.
DR GeneCards; GC06Pj30677; -.
DR GeneCards; GC06Pk30678; -.
DR GeneCards; GC06Pl30732; -.
DR GeneCards; GC06Pm30766; -.
DR GeneCards; GC06Pn30677; -.
DR GeneCards; GC06Po30679; -.
DR HGNC; HGNC:20778; TUBB.
DR HPA; CAB005417; -.
DR HPA; CAB012406; -.
DR HPA; HPA043640; -.
DR HPA; HPA046280; -.
DR MIM; 191130; gene.
DR neXtProt; NX_P07437; -.
DR PharmGKB; PA358; -.
DR eggNOG; COG5023; -.
DR HOVERGEN; HBG000089; -.
DR InParanoid; P07437; -.
DR KO; K07375; -.
DR OMA; ELDYEDE; -.
DR PhylomeDB; P07437; -.
DR Reactome; REACT_115566; Cell Cycle.
DR ChiTaRS; TUBB; human.
DR GeneWiki; TUBB; -.
DR GenomeRNAi; 203068; -.
DR NextBio; 90324; -.
DR PRO; PR:P07437; -.
DR ArrayExpress; P07437; -.
DR Bgee; P07437; -.
DR CleanEx; HS_TUBB; -.
DR Genevestigator; P07437; -.
DR GO; GO:0044297; C:cell body; IDA:DFLAT.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:DFLAT.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IEA:Ensembl.
DR GO; GO:0005198; F:structural molecule activity; TAS:BHF-UCL.
DR GO; GO:0051301; P:cell division; TAS:BHF-UCL.
DR GO; GO:0006928; P:cellular component movement; TAS:UniProtKB.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; TAS:BHF-UCL.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome.
DR GO; GO:0007017; P:microtubule-based process; TAS:BHF-UCL.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; NAS:UniProtKB.
DR GO; GO:0051258; P:protein polymerization; IEA:InterPro.
DR GO; GO:0051225; P:spindle assembly; IEA:Ensembl.
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; IPR018316; Tubulin/FtsZ_2-layer-sand-dom.
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; Acetylation; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; GTP-binding; Isopeptide bond; Methylation;
KW Microtubule; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1 444 Tubulin beta chain.
FT /FTId=PRO_0000048243.
FT NP_BIND 140 146 GTP (Potential).
FT MOD_RES 58 58 N6-acetyllysine; alternate.
FT MOD_RES 172 172 Phosphoserine; by CDK1 (By similarity).
FT MOD_RES 318 318 Omega-N-methylarginine.
FT CROSSLNK 58 58 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT CROSSLNK 324 324 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT CONFLICT 216 216 K -> R (in Ref. 1 and 2).
FT CONFLICT 231 231 A -> G (in Ref. 1 and 2).
FT CONFLICT 234 235 SG -> EC (in Ref. 1 and 2).
FT CONFLICT 288 288 E -> D (in Ref. 1 and 2).
FT CONFLICT 298 298 N -> D (in Ref. 8; AAH20946).
SQ SEQUENCE 444 AA; 49671 MW; 1E6CD0A36773A103 CRC64;
MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLDRISVY YNEATGGKYV
PRAILVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN WAKGHYTEGA ELVDSVLDVV
RKEAESCDCL QGFQLTHSLG GGTGSGMGTL LISKIREEYP DRIMNTFSVV PSPKVSDTVV
EPYNATLSVH QLVENTDETY CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQVFDAKNMM
AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LNVQNKNSSY FVEWIPNNVK TAVCDIPPRG
LKMAVTFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS
EYQQYQDATA EEEEDFGEEA EEEA
//
MIM
191130
*RECORD*
*FIELD* NO
191130
*FIELD* TI
*191130 TUBULIN, BETA; TUBB
;;TUBULIN, BETA, CLASS I;;
M40
*FIELD* TX
CLONING
Cowan et al. (1981) identified presumed tubulin pseudogenes, and Wilde
read moreet al. (1982) presented evidence that one such gene was derived from its
corresponding mRNA. Wilde et al. (1982) described the structure of 2
pseudogenes. One had no introns but had a polyadenylate signal and an
oligoadenylate trait at its 3-prime end. It may have originated by
reverse transcription of a processed messenger RNA followed by
reintegration of the complementary DNA copy into the genome. Cleveland
and Sullivan (1985) stated that in the human and rat genomes a few
authentic tubulin genes are present 'amid a sea of pseudogenes.' Many of
these are 'retroposons': they lack all intervening sequences, have a
long coded poly(A) tract at the 3-prime end, and have a 10- to
15-basepair direct repeat in the 5-prime and 3-prime flanking DNA.
Isolation of cDNA clones indicate the existence of 2 functional
alpha-tubulin genes and 3 functional beta-tubulin genes in man. There
may be more.
Crabtree et al. (2001) cloned beta-tubulin, which they designated
beta-Ib tubulin, from a human retina cDNA library.
Using database analysis, Leandro-Garcia et al. (2010) identified 8 major
beta-tubulins, including TUBB. Quantitative RT-PCR showed variable TUBB
expression in all 21 normal human tissues examined, with highest
expression in thymus, followed by brain, heart, and ovary, and lowest
expression in testis and prostate. TUBB was the major tubulin-beta
isotype in ovary, lymph node, thymus, and fetal liver. Abnormal TUBB
expressed was detected in several tumor tissues compared with their
normal counterparts.
GENE FAMILY
Microtubules are constituent parts of a diverse variety of eukaryotic
cell structures, e.g., the mitotic apparatus, cilia, flagella, and
elements of the cytoskeleton. They consist principally of 2 soluble
proteins, alpha- and beta-tubulin, each with a molecular weight of about
55,000. They are transcribed from different genes. Using chicken alpha-
and beta-tubulin cDNA, Cleveland et al. (1980) concluded that human DNA
contains about 14 copies per genome of alpha- and beta-tubulin genes.
There is much evidence for evolutionary conservation of the tubulins.
See 602660 for additional background.
Based on Southern blot analysis with a chicken beta-tubulin probe, Lee
et al. (1983) stated that beta-tubulin in humans is coded by a large
gene family with 15 to 20 members. One subfamily, identified by using
the 3-prime untranslated region of a beta-tubulin gene as a probe to
screen genomic libraries, consists of an expressed gene, designated M40,
and 3 processed pseudogenes. Two alternative polyadenylation sites cause
the M40 gene to be expressed as 2 mRNAs, 1.8 and 2.6 kb. Two of the
pseudogenes are derived from the shorter mRNA, and the third is derived
from the 2.6 kb mRNA.
GENE STRUCTURE
Crabtree et al. (2001) determined that the TUBB gene contains 4 exons.
MAPPING
With gene clones in somatic cell hybrids, Floyd-Smith et al. (1985)
found that the M40 gene is situated on chromosome 6 in the segment
6pter-6p21. Of the pseudogenes, 1 was found to be on chromosome 8 and 1
on chromosome 13. Volz et al. (1994) determined that the TUBB gene is
located in the HLA class I region at 6p21.3 by study of a panel of
deletion mutant cell lines and radiation-reduced hybrids containing
fragments of chromosome 6. A long-range restriction map, generated by
rotating field gel electrophoresis, showed that TUBB maps to a segment
170 to 370 kb telomeric of HLA-C (142840) and proximal to HLA-E
(143010).
- Linkage to Immotile Cilia Syndrome
Bianchi et al. (1992) presented evidence suggesting the involvement of
an HLA-linked gene in the immotile cilia syndrome (ICS; 244400). They
also had suggestive evidence of linkage between this form of ICS and the
TUBB locus. Thus, TUBB is a candidate gene for the microtubule
dysfunction that occurs in the immotile cilia syndrome.
BIOCHEMICAL FEATURES
- Crystal Structure
Ravelli et al. (2004) determined the crystal structure, at 3.5-angstrom
resolution, of tubulin in complex with colchicine and with the
stathmin-like domain of RB3 (RB3-SLD). It shows the interaction of 2
tubulin heterodimers in a curved complex capped by the SLD
amino-terminal domain, which prevents the incorporation of the complexed
tubulin into microtubules. A comparison with the structure of tubulin in
protofilaments showed changes in the subunits of tubulin as it switches
from its straight conformation to a curved one. These changes correlated
with the loss of lateral contacts and provided a rationale for the rapid
microtubule depolymerization characteristic of dynamic instability.
Moreover, Ravelli et al. (2004) concluded that the structure of the
tubulin-colchicine complex sheds light on the mechanism of colchicine's
activity; they demonstrated that colchicine binds at a location where it
prevents curved tubulin from adopting a straight structure, which
inhibits assembly.
Wang and Nogales (2005) presented 2 structures corresponding to the
start and end points in the microtubule polymerization and hydrolysis
cycles that illustrated the consequences of nucleotide state on
longitudinal and lateral assembly. In the absence of depolymerizers,
GDP-bound tubulin showed distinctive intra-dimer and inter-dimer
interactions and thus distinguished the GTP and GDP interfaces. A
cold-stable tubulin polymer with the nonhydrolysable GTP analog GMPCPP,
containing semiconserved lateral interactions, supported a model in
which the straightening of longitudinal interfaces happens sequentially,
starting with a conformational change after GTP binding that straightens
the dimer enough for the formation of lateral contacts into a nontubular
intermediate. Closure into a microtubule does not require GTP
hydrolysis.
GENE FUNCTION
Yen et al. (1988) described a mechanism of autoregulation of the
stability of tubulin mRNA by the intracellular concentration of tubulin
heterodimers. Transfection experiments using gene constructs prepared by
site-directed mutagenesis demonstrated that the recognition element for
autoregulated RNA instability is the amino-terminal tetrapeptide encoded
by the gene.
Smith et al. (2009) showed that mutant huntingtin (613004), disrupted
intracellular transport and insulin secretion by direct interference
with microtubular beta-tubulin. Mutant huntingtin impaired
glucose-stimulated insulin secretion in insulin-producing beta cells,
without altering stored levels of insulin. Mutant huntingtin also
retarded post-Golgi transport, and the speed of insulin vesicle
trafficking was reduced. There was an enhanced and aberrant interaction
between mutant huntingtin and beta-tubulin, implying the underlying
mechanism of impaired intracellular transport. Smith et al. (2009)
proposed a novel pathogenetic process by which mutant huntingtin may
disrupt hormone exocytosis from beta cells and possibly impair vesicular
transport in any cell that expresses the pathogenic protein.
MOLECULAR GENETICS
Monzo et al. (1999) examined constitutional genomic DNA and paired tumor
DNA from 43 Spanish and 6 American stage IIIb or IV nonsmall cell lung
cancer patients who had been treated with paclitaxel. They identified
mutations in the TUBB gene in 16 patients (33%; 95% CI, 20.7-45.3%); 1
mutation was in exon 1 and the remainder were in exon 4. None of the
patients with TUBB mutations had an objective response to chemotherapy,
whereas 13 of 33 (39.4%; 95% CI, 22.8-56%; p = 0.01) patients without
mutations had complete or partial responses. Median survival was 3
months for the 16 patients with TUBB mutations and 10 months for the 33
patients without mutations (p = 0.0001). Monzo et al. (1999) concluded
that TUBB gene mutations are a strong predictor of response to
paclitaxel and that these mutations may represent a novel mechanism of
resistance.
Using direct sequence analysis following RT-PCR, Tsurutani et al. (2002)
examined exon 4 of the TUBB gene for mutations in 20 lung cancer cell
lines and in 22 specimens from Japanese lung cancer patients. Three
silent mutations were detected, 2 of which were found to be
polymorphisms present in normal tissue. Tsurutani et al. (2002)
concluded that TUBB gene mutations might not play a major role in the
mechanism of resistance to paclitaxel in Japanese lung cancer patients.
Using exonic primers, de Castro et al. (2003) analyzed exon 4 of the
TUBB gene in tumor specimens from 15 patients with stage IIIB and IV
nonsmall cell lung cancer. They found gene sequence alterations in 13
patients (87%); however, all alterations disappeared when sequenced with
intronic primers. De Castro et al. (2003) concluded that point mutations
demonstrated with exonic but not intronic primers are probably due to
beta-tubulin pseudogenes present in advanced nonsmall cell lung cancer
specimens, and that this may account for discrepancies in published
results.
*FIELD* SA
Floyd-Smith et al. (1986); Lewis and Cowan (1990); Wilde et al. (1982)
*FIELD* RF
1. Bianchi, E.; Savasta, S.; Calligaro, A.; Beluffi, G.; Poggi, P.;
Tinelli, M.; Mevio, E.; Martinetti, M.: HLA haplotype segregation
and ultrastructural study in familial immotile-cilia syndrome. Hum.
Genet. 89: 270-274, 1992.
2. Cleveland, D. W.; Lopata, M. A.; MacDonald, R. J.; Cowan, N. J.;
Rutter, W. J.; Kirschner, M. W.: Number and evolutionary conservation
of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes
using specific cloned cDNA probes. Cell 20: 95-105, 1980.
3. Cleveland, D. W.; Sullivan, K. F.: Molecular biology and genetics
of tubulin. Ann. Rev. Biochem. 54: 331-365, 1985.
4. Cowan, N. J.; Wilde, C. D.; Chow, L. T.; Wefald, F. C.: Structural
variation among human beta-tubulin genes. Proc. Nat. Acad. Sci. 78:
4877-4881, 1981.
5. Crabtree, D. V.; Ojima, I.; Geng, X.; Adler, A. J.: Tubulins in
the primate retina: evidence that xanthophylls may be endogenous ligands
for the paclitaxel-binding site. Bioorganic Medicinal Chemistry 9:
1967-1976, 2001.
6. de Castro, J.; Belda-Iniesta, C.; Cejas, P.; Casado, E.; Fresno
Vara, J. A.; Hardisson, D.; Sanchez, J. J.; Feliu, J.; Ordonez, A.;
Nistal, M.; Gonzalez-Baron, M.: New insights in beta-tubulin sequence
analysis in non-small cell lung cancer. Lung Cancer 41: 41-48, 2003.
7. Floyd-Smith, G. A.; de Martinville, B.; Francke, U.: A beta-tubulin
expressed gene M40 (TUBB) is located on human chromosome 6 and two
related pseudogenes are located on chromosomes 8 (TUBBP1) and 13 (TUBBP2).
(Abstract) Cytogenet. Cell Genet. 40: 629, 1985.
8. Floyd-Smith, G. A.; de Martinville, B.; Francke, U.: An expressed
beta-tubulin gene, TUBB, is located on the short arm of human chromosome
6 and two related sequences are dispersed on chromosomes 8 and 13. Exp.
Cell Res. 163: 539-548, 1986.
9. Leandro-Garcia, L. J.; Leskela, S.; Landa, I.; Montero-Conde, C.;
Lopez-Jimenez, E.; Leton, R.; Cascon, A.; Robledo, M.; Rodriguez-Antona,
C.: Tumoral and tissue-specific expression of the major human beta-tubulin
isotypes. Cytoskeleton 67: 214-223, 2010.
10. Lee, M. G.-S.; Lewis, S. A.; Wilde, C. D.; Cowan, N. J.: Evolutionary
history of a multigene family: an expressed human beta-tubulin gene
and three processed pseudogenes. Cell 33: 477-487, 1983.
11. Lewis, S. A.; Cowan, N. J.: Tubulin genes: structure, expression,
and regulation.In: Avila, J. (ed.): Microtubule proteins. Boca
Raton: CRC Press, Inc. 1990. Pp. 37-66.
12. Monzo, M.; Rosell, R.; Sanchez, J. J.; Lee, J. S.; O'Brate, A.;
Gonzalez-Larriba, J. L.; Alberola, V.; Lorenzo, J. C.; Nunez, L.;
Ro, J. Y.; Martin, C.: Paclitaxel resistance in non-small-cell lung
cancer associated with beta-tubulin gene mutations. J. Clin. Oncol. 17:
1786-1793, 1999.
13. Ravelli, R. B. G.; Gigant, B.; Curmi, P. A.; Jourdain, I.; Lachkar,
S.; Sobel, A.; Knossow, M.: Insight into tubulin regulation from
a complex with colchicine and a stathmin-like domain. Nature 428:
198-202, 2004.
14. Smith, R.; Bacos, K.; Fedele, V.; Soulet, D.; Walz, H. A.; Obermuller,
S.; Lindqvist, A.; Bjorkqvist, M.; Klein, P.; Onnerfjord, P.; Brundin,
P.; Mulder, H.; Li, J.-Y.: Mutant huntingtin interacts with beta-tubulin
and disrupts vesicular transport and insulin secretion. Hum. Molec.
Genet. 18: 3942-3954, 2009.
15. Tsurutani, J.; Komiya, T.; Uejima, H.; Tada, H.; Syunichi, N.;
Oka, M.; Kohno, S.; Fukuoka, M.; Nakagawa, K.: Mutational analysis
of the beta-tubulin gene in lung cancer. Lung Cancer 35: 11-16,
2002.
16. Volz, A.; Weiss, E.; Trowsdale, J.; Ziegler, A.: Presence of
an expressed beta-tubulin gene (TUBB) in the HLA class I region may
provide the genetic basis for HLA-linked microtubule dysfunction. Hum.
Genet. 93: 42-46, 1994.
17. Wang, H.-W.; Nogales, E.: Nucleotide-dependent bending flexibility
of tubulin regulates microtubule assembly. Nature 435: 911-915,
2005.
18. Wilde, C. D.; Crowther, C. E.; Cowan, N. J.: Diverse mechanisms
in the generation of human beta-tubulin pseudogenes. Science 217:
549-552, 1982.
19. Wilde, C. D.; Crowther, C. E.; Cripe, T. P.; Lee, M. G.-S.; Cowan,
N. J.: Evidence that a human beta-tubulin pseudogene is derived from
its corresponding mRNA. Nature 297: 83-84, 1982.
20. Yen, T. J.; Machlin, P. S.; Cleveland, D. W.: Autoregulated instability
of beta-tubulin mRNAs by recognition of the nascent amino terminus
of beta-tubulin. Nature 334: 580-585, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 2/28/2013
George E. Tiller - updated: 8/6/2010
Ada Hamosh - updated: 9/7/2005
Marla J. F. O'Neill - updated: 1/12/2005
Patricia A. Hartz - updated: 12/21/2004
Ada Hamosh - updated: 3/9/2004
Rebekah S. Rasooly - updated: 5/27/1998
*FIELD* CD
Victor A. McKusick: 6/23/1986
*FIELD* ED
mgross: 02/28/2013
mgross: 2/28/2013
wwang: 8/11/2010
terry: 8/6/2010
terry: 5/26/2010
alopez: 9/14/2005
terry: 9/7/2005
carol: 1/18/2005
carol: 1/13/2005
terry: 1/12/2005
mgross: 1/12/2005
terry: 12/21/2004
alopez: 3/10/2004
terry: 3/9/2004
alopez: 6/5/2003
tkritzer: 3/5/2003
carol: 2/11/1999
alopez: 5/27/1998
mark: 4/23/1996
warfield: 4/14/1994
carol: 3/18/1994
carol: 5/14/1993
supermim: 3/16/1992
carol: 8/7/1991
supermim: 3/20/1990
*RECORD*
*FIELD* NO
191130
*FIELD* TI
*191130 TUBULIN, BETA; TUBB
;;TUBULIN, BETA, CLASS I;;
M40
*FIELD* TX
CLONING
Cowan et al. (1981) identified presumed tubulin pseudogenes, and Wilde
read moreet al. (1982) presented evidence that one such gene was derived from its
corresponding mRNA. Wilde et al. (1982) described the structure of 2
pseudogenes. One had no introns but had a polyadenylate signal and an
oligoadenylate trait at its 3-prime end. It may have originated by
reverse transcription of a processed messenger RNA followed by
reintegration of the complementary DNA copy into the genome. Cleveland
and Sullivan (1985) stated that in the human and rat genomes a few
authentic tubulin genes are present 'amid a sea of pseudogenes.' Many of
these are 'retroposons': they lack all intervening sequences, have a
long coded poly(A) tract at the 3-prime end, and have a 10- to
15-basepair direct repeat in the 5-prime and 3-prime flanking DNA.
Isolation of cDNA clones indicate the existence of 2 functional
alpha-tubulin genes and 3 functional beta-tubulin genes in man. There
may be more.
Crabtree et al. (2001) cloned beta-tubulin, which they designated
beta-Ib tubulin, from a human retina cDNA library.
Using database analysis, Leandro-Garcia et al. (2010) identified 8 major
beta-tubulins, including TUBB. Quantitative RT-PCR showed variable TUBB
expression in all 21 normal human tissues examined, with highest
expression in thymus, followed by brain, heart, and ovary, and lowest
expression in testis and prostate. TUBB was the major tubulin-beta
isotype in ovary, lymph node, thymus, and fetal liver. Abnormal TUBB
expressed was detected in several tumor tissues compared with their
normal counterparts.
GENE FAMILY
Microtubules are constituent parts of a diverse variety of eukaryotic
cell structures, e.g., the mitotic apparatus, cilia, flagella, and
elements of the cytoskeleton. They consist principally of 2 soluble
proteins, alpha- and beta-tubulin, each with a molecular weight of about
55,000. They are transcribed from different genes. Using chicken alpha-
and beta-tubulin cDNA, Cleveland et al. (1980) concluded that human DNA
contains about 14 copies per genome of alpha- and beta-tubulin genes.
There is much evidence for evolutionary conservation of the tubulins.
See 602660 for additional background.
Based on Southern blot analysis with a chicken beta-tubulin probe, Lee
et al. (1983) stated that beta-tubulin in humans is coded by a large
gene family with 15 to 20 members. One subfamily, identified by using
the 3-prime untranslated region of a beta-tubulin gene as a probe to
screen genomic libraries, consists of an expressed gene, designated M40,
and 3 processed pseudogenes. Two alternative polyadenylation sites cause
the M40 gene to be expressed as 2 mRNAs, 1.8 and 2.6 kb. Two of the
pseudogenes are derived from the shorter mRNA, and the third is derived
from the 2.6 kb mRNA.
GENE STRUCTURE
Crabtree et al. (2001) determined that the TUBB gene contains 4 exons.
MAPPING
With gene clones in somatic cell hybrids, Floyd-Smith et al. (1985)
found that the M40 gene is situated on chromosome 6 in the segment
6pter-6p21. Of the pseudogenes, 1 was found to be on chromosome 8 and 1
on chromosome 13. Volz et al. (1994) determined that the TUBB gene is
located in the HLA class I region at 6p21.3 by study of a panel of
deletion mutant cell lines and radiation-reduced hybrids containing
fragments of chromosome 6. A long-range restriction map, generated by
rotating field gel electrophoresis, showed that TUBB maps to a segment
170 to 370 kb telomeric of HLA-C (142840) and proximal to HLA-E
(143010).
- Linkage to Immotile Cilia Syndrome
Bianchi et al. (1992) presented evidence suggesting the involvement of
an HLA-linked gene in the immotile cilia syndrome (ICS; 244400). They
also had suggestive evidence of linkage between this form of ICS and the
TUBB locus. Thus, TUBB is a candidate gene for the microtubule
dysfunction that occurs in the immotile cilia syndrome.
BIOCHEMICAL FEATURES
- Crystal Structure
Ravelli et al. (2004) determined the crystal structure, at 3.5-angstrom
resolution, of tubulin in complex with colchicine and with the
stathmin-like domain of RB3 (RB3-SLD). It shows the interaction of 2
tubulin heterodimers in a curved complex capped by the SLD
amino-terminal domain, which prevents the incorporation of the complexed
tubulin into microtubules. A comparison with the structure of tubulin in
protofilaments showed changes in the subunits of tubulin as it switches
from its straight conformation to a curved one. These changes correlated
with the loss of lateral contacts and provided a rationale for the rapid
microtubule depolymerization characteristic of dynamic instability.
Moreover, Ravelli et al. (2004) concluded that the structure of the
tubulin-colchicine complex sheds light on the mechanism of colchicine's
activity; they demonstrated that colchicine binds at a location where it
prevents curved tubulin from adopting a straight structure, which
inhibits assembly.
Wang and Nogales (2005) presented 2 structures corresponding to the
start and end points in the microtubule polymerization and hydrolysis
cycles that illustrated the consequences of nucleotide state on
longitudinal and lateral assembly. In the absence of depolymerizers,
GDP-bound tubulin showed distinctive intra-dimer and inter-dimer
interactions and thus distinguished the GTP and GDP interfaces. A
cold-stable tubulin polymer with the nonhydrolysable GTP analog GMPCPP,
containing semiconserved lateral interactions, supported a model in
which the straightening of longitudinal interfaces happens sequentially,
starting with a conformational change after GTP binding that straightens
the dimer enough for the formation of lateral contacts into a nontubular
intermediate. Closure into a microtubule does not require GTP
hydrolysis.
GENE FUNCTION
Yen et al. (1988) described a mechanism of autoregulation of the
stability of tubulin mRNA by the intracellular concentration of tubulin
heterodimers. Transfection experiments using gene constructs prepared by
site-directed mutagenesis demonstrated that the recognition element for
autoregulated RNA instability is the amino-terminal tetrapeptide encoded
by the gene.
Smith et al. (2009) showed that mutant huntingtin (613004), disrupted
intracellular transport and insulin secretion by direct interference
with microtubular beta-tubulin. Mutant huntingtin impaired
glucose-stimulated insulin secretion in insulin-producing beta cells,
without altering stored levels of insulin. Mutant huntingtin also
retarded post-Golgi transport, and the speed of insulin vesicle
trafficking was reduced. There was an enhanced and aberrant interaction
between mutant huntingtin and beta-tubulin, implying the underlying
mechanism of impaired intracellular transport. Smith et al. (2009)
proposed a novel pathogenetic process by which mutant huntingtin may
disrupt hormone exocytosis from beta cells and possibly impair vesicular
transport in any cell that expresses the pathogenic protein.
MOLECULAR GENETICS
Monzo et al. (1999) examined constitutional genomic DNA and paired tumor
DNA from 43 Spanish and 6 American stage IIIb or IV nonsmall cell lung
cancer patients who had been treated with paclitaxel. They identified
mutations in the TUBB gene in 16 patients (33%; 95% CI, 20.7-45.3%); 1
mutation was in exon 1 and the remainder were in exon 4. None of the
patients with TUBB mutations had an objective response to chemotherapy,
whereas 13 of 33 (39.4%; 95% CI, 22.8-56%; p = 0.01) patients without
mutations had complete or partial responses. Median survival was 3
months for the 16 patients with TUBB mutations and 10 months for the 33
patients without mutations (p = 0.0001). Monzo et al. (1999) concluded
that TUBB gene mutations are a strong predictor of response to
paclitaxel and that these mutations may represent a novel mechanism of
resistance.
Using direct sequence analysis following RT-PCR, Tsurutani et al. (2002)
examined exon 4 of the TUBB gene for mutations in 20 lung cancer cell
lines and in 22 specimens from Japanese lung cancer patients. Three
silent mutations were detected, 2 of which were found to be
polymorphisms present in normal tissue. Tsurutani et al. (2002)
concluded that TUBB gene mutations might not play a major role in the
mechanism of resistance to paclitaxel in Japanese lung cancer patients.
Using exonic primers, de Castro et al. (2003) analyzed exon 4 of the
TUBB gene in tumor specimens from 15 patients with stage IIIB and IV
nonsmall cell lung cancer. They found gene sequence alterations in 13
patients (87%); however, all alterations disappeared when sequenced with
intronic primers. De Castro et al. (2003) concluded that point mutations
demonstrated with exonic but not intronic primers are probably due to
beta-tubulin pseudogenes present in advanced nonsmall cell lung cancer
specimens, and that this may account for discrepancies in published
results.
*FIELD* SA
Floyd-Smith et al. (1986); Lewis and Cowan (1990); Wilde et al. (1982)
*FIELD* RF
1. Bianchi, E.; Savasta, S.; Calligaro, A.; Beluffi, G.; Poggi, P.;
Tinelli, M.; Mevio, E.; Martinetti, M.: HLA haplotype segregation
and ultrastructural study in familial immotile-cilia syndrome. Hum.
Genet. 89: 270-274, 1992.
2. Cleveland, D. W.; Lopata, M. A.; MacDonald, R. J.; Cowan, N. J.;
Rutter, W. J.; Kirschner, M. W.: Number and evolutionary conservation
of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes
using specific cloned cDNA probes. Cell 20: 95-105, 1980.
3. Cleveland, D. W.; Sullivan, K. F.: Molecular biology and genetics
of tubulin. Ann. Rev. Biochem. 54: 331-365, 1985.
4. Cowan, N. J.; Wilde, C. D.; Chow, L. T.; Wefald, F. C.: Structural
variation among human beta-tubulin genes. Proc. Nat. Acad. Sci. 78:
4877-4881, 1981.
5. Crabtree, D. V.; Ojima, I.; Geng, X.; Adler, A. J.: Tubulins in
the primate retina: evidence that xanthophylls may be endogenous ligands
for the paclitaxel-binding site. Bioorganic Medicinal Chemistry 9:
1967-1976, 2001.
6. de Castro, J.; Belda-Iniesta, C.; Cejas, P.; Casado, E.; Fresno
Vara, J. A.; Hardisson, D.; Sanchez, J. J.; Feliu, J.; Ordonez, A.;
Nistal, M.; Gonzalez-Baron, M.: New insights in beta-tubulin sequence
analysis in non-small cell lung cancer. Lung Cancer 41: 41-48, 2003.
7. Floyd-Smith, G. A.; de Martinville, B.; Francke, U.: A beta-tubulin
expressed gene M40 (TUBB) is located on human chromosome 6 and two
related pseudogenes are located on chromosomes 8 (TUBBP1) and 13 (TUBBP2).
(Abstract) Cytogenet. Cell Genet. 40: 629, 1985.
8. Floyd-Smith, G. A.; de Martinville, B.; Francke, U.: An expressed
beta-tubulin gene, TUBB, is located on the short arm of human chromosome
6 and two related sequences are dispersed on chromosomes 8 and 13. Exp.
Cell Res. 163: 539-548, 1986.
9. Leandro-Garcia, L. J.; Leskela, S.; Landa, I.; Montero-Conde, C.;
Lopez-Jimenez, E.; Leton, R.; Cascon, A.; Robledo, M.; Rodriguez-Antona,
C.: Tumoral and tissue-specific expression of the major human beta-tubulin
isotypes. Cytoskeleton 67: 214-223, 2010.
10. Lee, M. G.-S.; Lewis, S. A.; Wilde, C. D.; Cowan, N. J.: Evolutionary
history of a multigene family: an expressed human beta-tubulin gene
and three processed pseudogenes. Cell 33: 477-487, 1983.
11. Lewis, S. A.; Cowan, N. J.: Tubulin genes: structure, expression,
and regulation.In: Avila, J. (ed.): Microtubule proteins. Boca
Raton: CRC Press, Inc. 1990. Pp. 37-66.
12. Monzo, M.; Rosell, R.; Sanchez, J. J.; Lee, J. S.; O'Brate, A.;
Gonzalez-Larriba, J. L.; Alberola, V.; Lorenzo, J. C.; Nunez, L.;
Ro, J. Y.; Martin, C.: Paclitaxel resistance in non-small-cell lung
cancer associated with beta-tubulin gene mutations. J. Clin. Oncol. 17:
1786-1793, 1999.
13. Ravelli, R. B. G.; Gigant, B.; Curmi, P. A.; Jourdain, I.; Lachkar,
S.; Sobel, A.; Knossow, M.: Insight into tubulin regulation from
a complex with colchicine and a stathmin-like domain. Nature 428:
198-202, 2004.
14. Smith, R.; Bacos, K.; Fedele, V.; Soulet, D.; Walz, H. A.; Obermuller,
S.; Lindqvist, A.; Bjorkqvist, M.; Klein, P.; Onnerfjord, P.; Brundin,
P.; Mulder, H.; Li, J.-Y.: Mutant huntingtin interacts with beta-tubulin
and disrupts vesicular transport and insulin secretion. Hum. Molec.
Genet. 18: 3942-3954, 2009.
15. Tsurutani, J.; Komiya, T.; Uejima, H.; Tada, H.; Syunichi, N.;
Oka, M.; Kohno, S.; Fukuoka, M.; Nakagawa, K.: Mutational analysis
of the beta-tubulin gene in lung cancer. Lung Cancer 35: 11-16,
2002.
16. Volz, A.; Weiss, E.; Trowsdale, J.; Ziegler, A.: Presence of
an expressed beta-tubulin gene (TUBB) in the HLA class I region may
provide the genetic basis for HLA-linked microtubule dysfunction. Hum.
Genet. 93: 42-46, 1994.
17. Wang, H.-W.; Nogales, E.: Nucleotide-dependent bending flexibility
of tubulin regulates microtubule assembly. Nature 435: 911-915,
2005.
18. Wilde, C. D.; Crowther, C. E.; Cowan, N. J.: Diverse mechanisms
in the generation of human beta-tubulin pseudogenes. Science 217:
549-552, 1982.
19. Wilde, C. D.; Crowther, C. E.; Cripe, T. P.; Lee, M. G.-S.; Cowan,
N. J.: Evidence that a human beta-tubulin pseudogene is derived from
its corresponding mRNA. Nature 297: 83-84, 1982.
20. Yen, T. J.; Machlin, P. S.; Cleveland, D. W.: Autoregulated instability
of beta-tubulin mRNAs by recognition of the nascent amino terminus
of beta-tubulin. Nature 334: 580-585, 1988.
*FIELD* CN
Patricia A. Hartz - updated: 2/28/2013
George E. Tiller - updated: 8/6/2010
Ada Hamosh - updated: 9/7/2005
Marla J. F. O'Neill - updated: 1/12/2005
Patricia A. Hartz - updated: 12/21/2004
Ada Hamosh - updated: 3/9/2004
Rebekah S. Rasooly - updated: 5/27/1998
*FIELD* CD
Victor A. McKusick: 6/23/1986
*FIELD* ED
mgross: 02/28/2013
mgross: 2/28/2013
wwang: 8/11/2010
terry: 8/6/2010
terry: 5/26/2010
alopez: 9/14/2005
terry: 9/7/2005
carol: 1/18/2005
carol: 1/13/2005
terry: 1/12/2005
mgross: 1/12/2005
terry: 12/21/2004
alopez: 3/10/2004
terry: 3/9/2004
alopez: 6/5/2003
tkritzer: 3/5/2003
carol: 2/11/1999
alopez: 5/27/1998
mark: 4/23/1996
warfield: 4/14/1994
carol: 3/18/1994
carol: 5/14/1993
supermim: 3/16/1992
carol: 8/7/1991
supermim: 3/20/1990