ID TBB4A_MOUSE Reviewed; 444 AA. AC Q9D6F9; Q62364; Q80Y54; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 3. DT 24-JAN-2024, entry version 182. DE RecName: Full=Tubulin beta-4A chain; DE AltName: Full=Tubulin beta-4 chain; GN Name=Tubb4a; Synonyms=Tubb4; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Hippocampus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain, and Olfactory epithelium; 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 [3] RP PROTEIN SEQUENCE OF 3-19; 47-77; 104-121; 163-174; 242-276; 283-297; RP 310-318; 321-359; 363-379 AND 381-390, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC STRAIN=C57BL/6J; TISSUE=Brain, and Hippocampus; RA Lubec G., Klug S., Kang S.U.; RL Submitted (MAR-2007) to UniProtKB. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 66-444. RX PubMed=3839797; DOI=10.1083/jcb.101.3.852; RA Lewis S.A., Lee M.G.-S., Cowan N.J.; RT "Five mouse tubulin isotypes and their regulated expression during RT development."; RL J. Cell Biol. 101:852-861(1985). RN [5] RP GLUTAMYLATION. RX PubMed=15890843; DOI=10.1126/science.1113010; RA Janke C., Rogowski K., Wloga D., Regnard C., Kajava A.V., Strub J.-M., RA Temurak N., van Dijk J., Boucher D., van Dorsselaer A., Suryavanshi S., RA Gaertig J., Edde B.; RT "Tubulin polyglutamylase enzymes are members of the TTL domain protein RT family."; RL Science 308:1758-1762(2005). RN [6] 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Lung, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP GLYCYLATION, AND GLUTAMYLATION. RX PubMed=23897886; DOI=10.1083/jcb.201305041; RA Bosch Grau M., Gonzalez Curto G., Rocha C., Magiera M.M., Marques Sousa P., RA Giordano T., Spassky N., Janke C.; RT "Tubulin glycylases and glutamylases have distinct functions in RT stabilization and motility of ependymal cilia."; RL J. Cell Biol. 202:441-451(2013). RN [9] RP GLYCYLATION. RX PubMed=33414192; DOI=10.1126/science.abd4914; RA Gadadhar S., Alvarez Viar G., Hansen J.N., Gong A., Kostarev A., RA Ialy-Radio C., Leboucher S., Whitfield M., Ziyyat A., Toure A., Alvarez L., RA Pigino G., Janke C.; RT "Tubulin glycylation controls axonemal dynein activity, flagellar beat, and RT male fertility."; RL Science 371:0-0(2021). CC -!- FUNCTION: Tubulin is the major constituent of microtubules, a cylinder CC consisting of laterally associated linear protofilaments composed of CC alpha- and beta-tubulin heterodimers. Microtubules grow by the addition CC of GTP-tubulin dimers to the microtubule end, where a stabilizing cap CC forms. Below the cap, tubulin dimers are in GDP-bound state, owing to CC GTPase activity of alpha-tubulin. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P68363}; 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. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. 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 polyglycylated, CC resulting in polyglycine chains on the gamma-carboxyl group. CC Glycylation is mainly limited to tubulin incorporated into axonemes CC (cilia and flagella) whereas glutamylation is prevalent in neuronal CC cells, centrioles, axonemes, and the mitotic spindle. Both CC modifications can coexist on the same protein on adjacent residues, and CC lowering polyglycylation levels increases polyglutamylation, and CC reciprocally. Cilia and flagella glycylation is required for their CC stability and maintenance. Flagella glycylation controls sperm motility CC (PubMed:33414192). {ECO:0000269|PubMed:19524510, CC ECO:0000269|PubMed:23897886, ECO:0000269|PubMed:33414192}. CC -!- PTM: Some glutamate residues at the C-terminus are polyglutamylated, CC resulting in polyglutamate chains on the gamma-carboxyl group CC (PubMed:15890843). 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 (By similarity). Glutamylation is also involved in cilia CC motility (PubMed:23897886). {ECO:0000250|UniProtKB:Q71U36, CC ECO:0000269|PubMed:15890843, ECO:0000269|PubMed:23897886}. 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:0000250|UniProtKB:P04350}. CC -!- SIMILARITY: Belongs to the tubulin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK013717; BAB28967.1; -; mRNA. DR EMBL; BC049112; AAH49112.1; -; mRNA. DR EMBL; BC054831; AAH54831.1; -; mRNA. DR EMBL; M28730; AAA40509.1; -; mRNA. DR CCDS; CCDS28925.1; -. DR RefSeq; NP_033477.2; NM_009451.3. DR AlphaFoldDB; Q9D6F9; -. DR SMR; Q9D6F9; -. DR BioGRID; 204380; 32. DR IntAct; Q9D6F9; 13. DR MINT; Q9D6F9; -. DR STRING; 10090.ENSMUSP00000071135; -. DR CarbonylDB; Q9D6F9; -. DR GlyGen; Q9D6F9; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9D6F9; -. DR MetOSite; Q9D6F9; -. DR PhosphoSitePlus; Q9D6F9; -. DR SwissPalm; Q9D6F9; -. DR REPRODUCTION-2DPAGE; IPI00109073; -. DR REPRODUCTION-2DPAGE; Q9D6F9; -. DR EPD; Q9D6F9; -. DR jPOST; Q9D6F9; -. DR MaxQB; Q9D6F9; -. DR PaxDb; 10090-ENSMUSP00000071135; -. DR PeptideAtlas; Q9D6F9; -. DR ProteomicsDB; 262946; -. DR Pumba; Q9D6F9; -. DR TopDownProteomics; Q9D6F9; -. DR Antibodypedia; 4387; 253 antibodies from 21 providers. DR DNASU; 22153; -. DR Ensembl; ENSMUST00000071135.6; ENSMUSP00000071135.6; ENSMUSG00000062591.6. DR GeneID; 22153; -. DR KEGG; mmu:22153; -. DR UCSC; uc008dea.1; mouse. DR AGR; MGI:107848; -. DR CTD; 10382; -. DR MGI; MGI:107848; Tubb4a. DR VEuPathDB; HostDB:ENSMUSG00000062591; -. DR eggNOG; KOG1375; Eukaryota. DR GeneTree; ENSGT00940000161972; -. DR HOGENOM; CLU_015718_1_1_1; -. DR InParanoid; Q9D6F9; -. DR OMA; CFPAGGN; -. DR OrthoDB; 3124041at2759; -. DR PhylomeDB; Q9D6F9; -. DR TreeFam; TF300298; -. DR Reactome; R-MMU-190840; Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane. DR Reactome; R-MMU-2132295; MHC class II antigen presentation. DR Reactome; R-MMU-2467813; Separation of Sister Chromatids. DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion. DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes. DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes. DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome. DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes. DR Reactome; R-MMU-437239; Recycling pathway of L1. DR Reactome; R-MMU-5610787; Hedgehog 'off' state. DR Reactome; R-MMU-5617833; Cilium Assembly. DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane. DR Reactome; R-MMU-5620924; Intraflagellar transport. DR Reactome; R-MMU-5626467; RHO GTPases activate IQGAPs. DR Reactome; R-MMU-5663220; RHO GTPases Activate Formins. DR Reactome; R-MMU-6807878; COPI-mediated anterograde transport. DR Reactome; R-MMU-6811434; COPI-dependent Golgi-to-ER retrograde traffic. DR Reactome; R-MMU-6811436; COPI-independent Golgi-to-ER retrograde traffic. DR Reactome; R-MMU-68877; Mitotic Prometaphase. DR Reactome; R-MMU-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint. DR Reactome; R-MMU-8854518; AURKA Activation by TPX2. DR Reactome; R-MMU-8955332; Carboxyterminal post-translational modifications of tubulin. DR Reactome; R-MMU-9646399; Aggrephagy. DR Reactome; R-MMU-9648025; EML4 and NUDC in mitotic spindle formation. DR Reactome; R-MMU-9668328; Sealing of the nuclear envelope (NE) by ESCRT-III. DR Reactome; R-MMU-983189; Kinesins. DR Reactome; R-MMU-9833482; PKR-mediated signaling. DR BioGRID-ORCS; 22153; 4 hits in 76 CRISPR screens. DR ChiTaRS; Tubb4a; mouse. DR PRO; PR:Q9D6F9; -. DR Proteomes; UP000000589; Chromosome 17. DR RNAct; Q9D6F9; Protein. DR Bgee; ENSMUSG00000062591; Expressed in primary visual cortex and 170 other cell types or tissues. DR GO; GO:0005930; C:axoneme; ISO:MGI. DR GO; GO:0042995; C:cell projection; IDA:MGI. DR GO; GO:0005929; C:cilium; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0045171; C:intercellular bridge; ISO:MGI. DR GO; GO:0033269; C:internode region of axon; IDA:MGI. DR GO; GO:0005874; C:microtubule; ISO:MGI. DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI. DR GO; GO:0072686; C:mitotic spindle; ISO:MGI. DR GO; GO:0043209; C:myelin sheath; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; IDA:MGI. DR GO; GO:0005509; F:calcium ion binding; ISO:MGI. DR GO; GO:0005525; F:GTP binding; IBA:GO_Central. DR GO; GO:0003924; F:GTPase activity; IEA:InterPro. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central. DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IBA:GO_Central. DR GO; GO:0000278; P:mitotic cell cycle; IBA:GO_Central. DR GO; GO:0031115; P:negative regulation of microtubule polymerization; ISO:MGI. DR CDD; cd02187; beta_tubulin; 1. DR Gene3D; 1.10.287.600; Helix hairpin bin; 1. DR Gene3D; 3.30.1330.20; Tubulin/FtsZ, C-terminal domain; 1. DR Gene3D; 3.40.50.1440; Tubulin/FtsZ, GTPase domain; 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; TUBULIN; 1. DR PANTHER; PTHR11588:SF253; TUBULIN BETA-4A CHAIN; 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; SSF55307; Tubulin C-terminal domain-like; 1. DR SUPFAM; SSF52490; Tubulin nucleotide-binding domain-like; 1. DR PROSITE; PS00227; TUBULIN; 1. DR PROSITE; PS00228; TUBULIN_B_AUTOREG; 1. DR Genevisible; Q9D6F9; MM. PE 1: Evidence at protein level; KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; GTP-binding; Isopeptide bond; Magnesium; KW Metal-binding; Microtubule; Nucleotide-binding; Phosphoprotein; KW Reference proteome. FT CHAIN 1..444 FT /note="Tubulin beta-4A chain" FT /id="PRO_0000048254" FT MOTIF 1..4 FT /note="MREI motif" FT /evidence="ECO:0000250|UniProtKB:P07437" FT BINDING 11 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 69 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P68363" FT BINDING 69 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P68363" FT BINDING 138 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 142 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 143 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 144 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 204 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT BINDING 226 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:Q13509" FT MOD_RES 172 FT /note="Phosphoserine; by CDK1" FT /evidence="ECO:0000250|UniProtKB:P04350" FT MOD_RES 436 FT /note="5-glutamyl polyglutamate" FT /evidence="ECO:0000250|UniProtKB:Q2T9S0" FT CONFLICT 73 FT /note="M -> I (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 111 FT /note="E -> Q (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="F -> L (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 293 FT /note="M -> V (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 303 FT /note="C -> S (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 351 FT /note="T -> A (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 400 FT /note="G -> A (in Ref. 4; AAA40509)" FT /evidence="ECO:0000305" FT CONFLICT 427 FT /note="D -> G (in Ref. 1; BAB28967)" FT /evidence="ECO:0000305" SQ SEQUENCE 444 AA; 49586 MW; F7429D057C11A3F5 CRC64; MREIVHLQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLERINVY YNEATGGNYV PRAVLVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN WAKGHYTEGA ELVDAVLDVV RKEAESCDCL QGFQLTHSLG GGTGSGMGTL LISKIREEFP DRIMNTFSVV PSPKVSDTVV EPYNATLSVH QLVENTDETY CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQMFDAKNMM AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LSVQSKNSSY FVEWIPNNVK TAVCDIPPRG LKMAATFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS EYQQYQDATA EEGEFEEEAE EEVA //