TBB1_HUMAN
ID TBB1_HUMAN Reviewed; 451 AA.
AC Q9H4B7;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Tubulin beta-1 chain;
GN Name=TUBB1;
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].
RA Gross C., Kussmann S., Hehr A., Hansmann I., Schlote D.;
RT "Mapping and characterization of the human TUBB1 gene.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 38-46 AND 263-281.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [5]
RP PHOSPHORYLATION AT SER-172.
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 [6]
RP INTERACTION WITH RANBP10.
RX PubMed=18347012; DOI=10.1074/jbc.m709397200;
RA Schulze H., Dose M., Korpal M., Meyer I., Italiano J.E. Jr.,
RA Shivdasani R.A.;
RT "RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates
RT noncentrosomal microtubules.";
RL J. Biol. Chem. 283:14109-14119(2008).
RN [7]
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 [8]
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 [9]
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 [10]
RP VARIANT PRO-43.
RX PubMed=15956286; DOI=10.1182/blood-2005-02-0723;
RA Freson K., De Vos R., Wittevrongel C., Thys C., Defoor J., Vanhees L.,
RA Vermylen J., Peerlinck K., Van Geet C.;
RT "The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular
RT disease in men by modulating platelet function and structure.";
RL Blood 106:2356-2362(2005).
RN [11]
RP VARIANTS PRO-43 AND HIS-307, VARIANT MAD-TUBB1 TRP-318, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18849486; DOI=10.1182/blood-2008-06-162610;
RA Kunishima S., Kobayashi R., Itoh T.J., Hamaguchi M., Saito H.;
RT "Mutation of the beta1-tubulin gene associated with congenital
RT macrothrombocytopenia affecting microtubule assembly.";
RL Blood 113:458-461(2009).
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 (By similarity).
CC {ECO:0000250}.
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 RANBP10.
CC {ECO:0000269|PubMed:18347012}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:18849486}.
CC -!- TISSUE SPECIFICITY: Hematopoietic cell-specific. Major isotype in
CC leukocytes, where it represents 50% of all beta-tubulins.
CC {ECO:0000269|PubMed:20191564}.
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: Macrothrombocytopenia, autosomal dominant, TUBB1-related (MAD-
CC TUBB1) [MIM:613112]: A congenital blood disorder characterized by
CC increased platelet size and decreased number of circulating platelets.
CC {ECO:0000269|PubMed:18849486}. 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; AJ292757; CAC16605.1; -; mRNA.
DR EMBL; AL109840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033679; AAH33679.1; -; mRNA.
DR CCDS; CCDS13475.1; -.
DR RefSeq; NP_110400.1; NM_030773.3.
DR AlphaFoldDB; Q9H4B7; -.
DR SMR; Q9H4B7; -.
DR BioGRID; 123347; 133.
DR CORUM; Q9H4B7; -.
DR DIP; DIP-42487N; -.
DR IntAct; Q9H4B7; 85.
DR MINT; Q9H4B7; -.
DR STRING; 9606.ENSP00000217133; -.
DR BindingDB; Q9H4B7; -.
DR ChEMBL; CHEMBL1915; -.
DR DrugBank; DB06772; Cabazitaxel.
DR DrugBank; DB05147; CYT997.
DR DrugBank; DB01248; Docetaxel.
DR DrugBank; DB01873; Epothilone D.
DR DrugBank; DB08871; Eribulin.
DR DrugBank; DB12334; Milataxel.
DR DrugBank; DB01229; Paclitaxel.
DR DrugBank; DB03010; Patupilone.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR DrugBank; DB00309; Vindesine.
DR DrugBank; DB06042; ZEN-012.
DR DrugCentral; Q9H4B7; -.
DR TCDB; 8.A.173.1.2; the tubulin (tubulin) family.
DR iPTMnet; Q9H4B7; -.
DR PhosphoSitePlus; Q9H4B7; -.
DR BioMuta; TUBB1; -.
DR DMDM; 62903515; -.
DR OGP; Q9H4B7; -.
DR EPD; Q9H4B7; -.
DR jPOST; Q9H4B7; -.
DR MassIVE; Q9H4B7; -.
DR MaxQB; Q9H4B7; -.
DR PaxDb; Q9H4B7; -.
DR PeptideAtlas; Q9H4B7; -.
DR PRIDE; Q9H4B7; -.
DR ProteomicsDB; 80819; -.
DR TopDownProteomics; Q9H4B7; -.
DR ABCD; Q9H4B7; 3 sequenced antibodies.
DR Antibodypedia; 3801; 494 antibodies from 35 providers.
DR DNASU; 81027; -.
DR Ensembl; ENST00000217133.2; ENSP00000217133.1; ENSG00000101162.4.
DR GeneID; 81027; -.
DR KEGG; hsa:81027; -.
DR MANE-Select; ENST00000217133.2; ENSP00000217133.1; NM_030773.4; NP_110400.1.
DR UCSC; uc002yak.3; human.
DR CTD; 81027; -.
DR DisGeNET; 81027; -.
DR GeneCards; TUBB1; -.
DR HGNC; HGNC:16257; TUBB1.
DR HPA; ENSG00000101162; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; TUBB1; -.
DR MIM; 612901; gene.
DR MIM; 613112; phenotype.
DR neXtProt; NX_Q9H4B7; -.
DR OpenTargets; ENSG00000101162; -.
DR Orphanet; 140957; Autosomal dominant macrothrombocytopenia.
DR PharmGKB; PA38100; -.
DR VEuPathDB; HostDB:ENSG00000101162; -.
DR eggNOG; KOG1375; Eukaryota.
DR GeneTree; ENSGT00940000159809; -.
DR HOGENOM; CLU_015718_1_1_1; -.
DR InParanoid; Q9H4B7; -.
DR OMA; NTDACFC; -.
DR OrthoDB; 962471at2759; -.
DR PhylomeDB; Q9H4B7; -.
DR TreeFam; TF300298; -.
DR PathwayCommons; Q9H4B7; -.
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; Q9H4B7; -.
DR SIGNOR; Q9H4B7; -.
DR BioGRID-ORCS; 81027; 32 hits in 1083 CRISPR screens.
DR ChiTaRS; TUBB1; human.
DR GeneWiki; TUBB1; -.
DR GenomeRNAi; 81027; -.
DR Pharos; Q9H4B7; Tclin.
DR PRO; PR:Q9H4B7; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H4B7; protein.
DR Bgee; ENSG00000101162; Expressed in monocyte and 101 other tissues.
DR Genevisible; Q9H4B7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0072686; C:mitotic spindle; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007017; P:microtubule-based process; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central.
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; 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 Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease variant;
KW GTP-binding; Isopeptide bond; Microtubule; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..451
FT /note="Tubulin beta-1 chain"
FT /id="PRO_0000048242"
FT REGION 432..451
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 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 440
FT /note="5-glutamyl polyglutamate"
FT /evidence="ECO:0000250|UniProtKB:Q2T9S0"
FT VARIANT 43
FT /note="Q -> H (in dbSNP:rs415064)"
FT /id="VAR_034542"
FT VARIANT 43
FT /note="Q -> P (in dbSNP:rs463312)"
FT /evidence="ECO:0000269|PubMed:15956286,
FT ECO:0000269|PubMed:18849486"
FT /id="VAR_034543"
FT VARIANT 274
FT /note="T -> M (in dbSNP:rs35565630)"
FT /id="VAR_052671"
FT VARIANT 307
FT /note="R -> H (in dbSNP:rs6070697)"
FT /evidence="ECO:0000269|PubMed:18849486"
FT /id="VAR_052672"
FT VARIANT 318
FT /note="R -> W (in MAD-TUBB1; dbSNP:rs121918555)"
FT /evidence="ECO:0000269|PubMed:18849486"
FT /id="VAR_063411"
SQ SEQUENCE 451 AA; 50327 MW; 6A3E5208C1C89AE4 CRC64;
MREIVHIQIG QCGNQIGAKF WEMIGEEHGI DLAGSDRGAS ALQLERISVY YNEAYGRKYV
PRAVLVDLEP GTMDSIRSSK LGALFQPDSF VHGNSGAGNN WAKGHYTEGA ELIENVLEVV
RHESESCDCL QGFQIVHSLG GGTGSGMGTL LMNKIREEYP DRIMNSFSVM PSPKVSDTVV
EPYNAVLSIH QLIENADACF CIDNEALYDI CFRTLKLTTP TYGDLNHLVS LTMSGITTSL
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTAQGSQQ YRALSVAELT QQMFDARNTM
AACDLRRGRY LTVACIFRGK MSTKEVDQQL LSVQTRNSSC FVEWIPNNVK VAVCDIPPRG
LSMAATFIGN NTAIQEIFNR VSEHFSAMFK RKAFVHWYTS EGMDINEFGE AENNIHDLVS
EYQQFQDAKA VLEEDEEVTE EAEMEPEDKG H
