TBA4A_HUMAN
ID TBA4A_HUMAN Reviewed; 448 AA.
AC P68366; A8MUB1; B3KNQ6; P05215;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Tubulin alpha-4A chain;
DE AltName: Full=Alpha-tubulin 1;
DE AltName: Full=Testis-specific alpha-tubulin;
DE AltName: Full=Tubulin H2-alpha;
DE AltName: Full=Tubulin alpha-1 chain;
GN Name=TUBA4A; Synonyms=TUBA1;
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 [GENOMIC DNA].
RX PubMed=3029670; DOI=10.1093/nar/15.1.199;
RA Dobner P.R., Kislauskis E., Wentworth B.M., Villa-Komaroff L.;
RT "Alternative 5' exons either provide or deny an initiator methionine codon
RT to the same alpha-tubulin coding region.";
RL Nucleic Acids Res. 15:199-218(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum;
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 [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP PROTEIN SEQUENCE OF 41-60; 65-79; 85-121; 157-164; 216-280; 327-336;
RP 340-370; 391-401 AND 403-430, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP ACETYLATION AT LYS-40.
RX PubMed=24906155; DOI=10.1016/j.cell.2014.03.061;
RA Szyk A., Deaconescu A.M., Spector J., Goodman B., Valenstein M.L.,
RA Ziolkowska N.E., Kormendi V., Grigorieff N., Roll-Mecak A.;
RT "Molecular basis for age-dependent microtubule acetylation by tubulin
RT acetyltransferase.";
RL Cell 157:1405-1415(2014).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP INVOLVEMENT IN ALS22, VARIANTS ALS22 PRO-145; CYS-215; CYS-320; HIS-320 AND
RP THR-383, AND CHARACTERIZATION OF VARIANTS ALS22 CYS-215; CYS-320; HIS-320
RP AND THR-383.
RX PubMed=25374358; DOI=10.1016/j.neuron.2014.09.027;
RG SLAGEN Consortium;
RA Smith B.N., Ticozzi N., Fallini C., Gkazi A.S., Topp S., Kenna K.P.,
RA Scotter E.L., Kost J., Keagle P., Miller J.W., Calini D., Vance C.,
RA Danielson E.W., Troakes C., Tiloca C., Al-Sarraj S., Lewis E.A., King A.,
RA Colombrita C., Pensato V., Castellotti B., de Belleroche J., Baas F.,
RA ten Asbroek A.L., Sapp P.C., McKenna-Yasek D., McLaughlin R.L., Polak M.,
RA Asress S., Esteban-Perez J., Munoz-Blanco J.L., Simpson M., van Rheenen W.,
RA Diekstra F.P., Lauria G., Duga S., Corti S., Cereda C., Corrado L.,
RA Soraru G., Morrison K.E., Williams K.L., Nicholson G.A., Blair I.P.,
RA Dion P.A., Leblond C.S., Rouleau G.A., Hardiman O., Veldink J.H.,
RA van den Berg L.H., Al-Chalabi A., Pall H., Shaw P.J., Turner M.R.,
RA Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Gellera C.,
RA Ratti A., Brown R.H. Jr., Silani V., Shaw C.E., Landers J.E.;
RT "Exome-wide rare variant analysis identifies TUBA4A mutations associated
RT with familial ALS.";
RL Neuron 84:324-331(2014).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20]
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).
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.
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 CFAP157 (By similarity).
CC {ECO:0000250|UniProtKB:P68368}.
CC -!- INTERACTION:
CC P68366; P05067: APP; NbExp=3; IntAct=EBI-351772, EBI-77613;
CC P68366; P30622: CLIP1; NbExp=3; IntAct=EBI-351772, EBI-2683569;
CC P68366; Q8NA72: POC5; NbExp=5; IntAct=EBI-351772, EBI-2561090;
CC P68366; Q8N4U5: TCP11L2; NbExp=4; IntAct=EBI-351772, EBI-11897462;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P68366-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P68366-2; Sequence=VSP_055194;
CC -!- DOMAIN: The MREC motif may be critical for tubulin autoregulation.
CC {ECO:0000250|UniProtKB:P68363}.
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: Acetylation of alpha chains at Lys-40 is located inside the
CC microtubule lumen. This modification has been correlated with increased
CC microtubule stability, intracellular transport and ciliary assembly.
CC {ECO:0000269|PubMed:24906155}.
CC -!- PTM: Methylation of alpha chains at Lys-40 is found in mitotic
CC microtubules and is required for normal mitosis and cytokinesis
CC contributing to genomic stability. {ECO:0000250|UniProtKB:P68363}.
CC -!- DISEASE: Amyotrophic lateral sclerosis 22, with or without
CC frontotemporal dementia (ALS22) [MIM:616208]: A neurodegenerative
CC disorder affecting upper motor neurons in the brain and lower motor
CC neurons in the brain stem and spinal cord, resulting in fatal
CC paralysis. Sensory abnormalities are absent. The pathologic hallmarks
CC of the disease include pallor of the corticospinal tract due to loss of
CC motor neurons, presence of ubiquitin-positive inclusions within
CC surviving motor neurons, and deposition of pathologic aggregates. The
CC etiology of amyotrophic lateral sclerosis is likely to be
CC multifactorial, involving both genetic and environmental factors. The
CC disease is inherited in 5-10% of the cases. Patients with ALS22 may
CC develop frontotemporal dementia. {ECO:0000269|PubMed:25374358}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: This tubulin does not have a C-terminal tyrosine.
CC -!- SIMILARITY: Belongs to the tubulin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tuba1/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tubulin entry;
CC URL="https://en.wikipedia.org/wiki/Tubulin";
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; X06956; CAA30026.1; -; Genomic_DNA.
DR EMBL; BT006731; AAP35377.1; -; mRNA.
DR EMBL; AK054731; BAG51418.1; -; mRNA.
DR EMBL; AK299958; BAH13182.1; -; mRNA.
DR EMBL; AY895018; AAW65371.1; -; Genomic_DNA.
DR EMBL; AC068946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW70718.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70719.1; -; Genomic_DNA.
DR EMBL; BC009238; AAH09238.1; -; mRNA.
DR CCDS; CCDS2438.1; -. [P68366-1]
DR CCDS; CCDS63131.1; -. [P68366-2]
DR PIR; A25873; A25873.
DR RefSeq; NP_001265481.1; NM_001278552.1. [P68366-2]
DR RefSeq; NP_005991.1; NM_006000.2. [P68366-1]
DR AlphaFoldDB; P68366; -.
DR SMR; P68366; -.
DR BioGRID; 113128; 454.
DR CORUM; P68366; -.
DR IntAct; P68366; 211.
DR MINT; P68366; -.
DR STRING; 9606.ENSP00000248437; -.
DR ChEMBL; CHEMBL2070; -.
DR DrugBank; DB06772; Cabazitaxel.
DR DrugBank; DB05147; CYT997.
DR DrugBank; DB01873; Epothilone D.
DR DrugBank; DB03010; Patupilone.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR DrugBank; DB01179; Podofilox.
DR DrugBank; DB00541; Vincristine.
DR DrugCentral; P68366; -.
DR GlyGen; P68366; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; P68366; -.
DR MetOSite; P68366; -.
DR PhosphoSitePlus; P68366; -.
DR SwissPalm; P68366; -.
DR BioMuta; TUBA4A; -.
DR DMDM; 55977476; -.
DR DOSAC-COBS-2DPAGE; P68366; -.
DR OGP; P05215; -.
DR CPTAC; CPTAC-597; -.
DR CPTAC; CPTAC-598; -.
DR EPD; P68366; -.
DR jPOST; P68366; -.
DR MassIVE; P68366; -.
DR MaxQB; P68366; -.
DR PaxDb; P68366; -.
DR PeptideAtlas; P68366; -.
DR PRIDE; P68366; -.
DR ProteomicsDB; 2093; -.
DR ProteomicsDB; 57534; -. [P68366-1]
DR Antibodypedia; 3138; 504 antibodies from 38 providers.
DR DNASU; 7277; -.
DR Ensembl; ENST00000248437.9; ENSP00000248437.4; ENSG00000127824.15. [P68366-1]
DR Ensembl; ENST00000392088.6; ENSP00000375938.2; ENSG00000127824.15. [P68366-2]
DR GeneID; 7277; -.
DR KEGG; hsa:7277; -.
DR MANE-Select; ENST00000248437.9; ENSP00000248437.4; NM_006000.3; NP_005991.1.
DR UCSC; uc002vkt.3; human. [P68366-1]
DR CTD; 7277; -.
DR DisGeNET; 7277; -.
DR GeneCards; TUBA4A; -.
DR HGNC; HGNC:12407; TUBA4A.
DR HPA; ENSG00000127824; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; TUBA4A; -.
DR MIM; 191110; gene.
DR MIM; 616208; phenotype.
DR neXtProt; NX_P68366; -.
DR OpenTargets; ENSG00000127824; -.
DR PharmGKB; PA162407391; -.
DR VEuPathDB; HostDB:ENSG00000127824; -.
DR eggNOG; KOG1376; Eukaryota.
DR GeneTree; ENSGT00950000183165; -.
DR HOGENOM; CLU_015718_0_0_1; -.
DR InParanoid; P68366; -.
DR OMA; ICHLHIG; -.
DR OrthoDB; 514396at2759; -.
DR PhylomeDB; P68366; -.
DR TreeFam; TF300314; -.
DR PathwayCommons; P68366; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
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-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
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-5620912; Anchoring of the basal body to the plasma membrane.
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-8854518; AURKA Activation by TPX2.
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; P68366; -.
DR SIGNOR; P68366; -.
DR BioGRID-ORCS; 7277; 28 hits in 1094 CRISPR screens.
DR ChiTaRS; TUBA4A; human.
DR GeneWiki; TUBA4A; -.
DR GenomeRNAi; 7277; -.
DR Pharos; P68366; Tchem.
DR PRO; PR:P68366; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P68366; protein.
DR Bgee; ENSG00000127824; Expressed in gingival epithelium and 203 other tissues.
DR ExpressionAtlas; P68366; baseline and differential.
DR Genevisible; P68366; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
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: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; IPR002452; Alpha_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; PR01162; ALPHATUBULIN.
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.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Amyotrophic lateral sclerosis;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; GTP-binding;
KW Methylation; Microtubule; Neurodegeneration; Nitration; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..448
FT /note="Tubulin alpha-4A chain"
FT /id="PRO_0000048106"
FT MOTIF 1..4
FT /note="MREC motif"
FT /evidence="ECO:0000250|UniProtKB:P68363"
FT BINDING 142..148
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255"
FT MOD_RES 40
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:24906155"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 83
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P68368"
FT MOD_RES 432
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BQE3"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5XIF6"
FT VAR_SEQ 1..15
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055194"
FT VARIANT 145
FT /note="T -> P (in ALS22; dbSNP:rs730880029)"
FT /evidence="ECO:0000269|PubMed:25374358"
FT /id="VAR_072714"
FT VARIANT 215
FT /note="R -> C (in ALS22; displays significantly different
FT distribution in terms of incorporation into microtubules;
FT dbSNP:rs730880028)"
FT /evidence="ECO:0000269|PubMed:25374358"
FT /id="VAR_072715"
FT VARIANT 320
FT /note="R -> C (in ALS22; displays significantly lower
FT levels of dimer assembly; dbSNP:rs730880025)"
FT /evidence="ECO:0000269|PubMed:25374358"
FT /id="VAR_072716"
FT VARIANT 320
FT /note="R -> H (in ALS22; displays significantly lower
FT levels of dimer assembly; dbSNP:rs730880026)"
FT /evidence="ECO:0000269|PubMed:25374358"
FT /id="VAR_072717"
FT VARIANT 383
FT /note="A -> T (in ALS22; displays significantly different
FT distribution in terms of incorporation into microtubules;
FT destabilizes the microtubule network; dbSNP:rs368743618)"
FT /evidence="ECO:0000269|PubMed:25374358"
FT /id="VAR_072718"
SQ SEQUENCE 448 AA; 49924 MW; C00ED90A183FE8F2 CRC64;
MRECISVHVG QAGVQMGNAC WELYCLEHGI QPDGQMPSDK TIGGGDDSFT TFFCETGAGK
HVPRAVFVDL EPTVIDEIRN GPYRQLFHPE QLITGKEDAA NNYARGHYTI GKEIIDPVLD
RIRKLSDQCT GLQGFLVFHS FGGGTGSGFT SLLMERLSVD YGKKSKLEFS IYPAPQVSTA
VVEPYNSILT THTTLEHSDC AFMVDNEAIY DICRRNLDIE RPTYTNLNRL ISQIVSSITA
SLRFDGALNV DLTEFQTNLV PYPRIHFPLA TYAPVISAEK AYHEQLSVAE ITNACFEPAN
QMVKCDPRHG KYMACCLLYR GDVVPKDVNA AIAAIKTKRS IQFVDWCPTG FKVGINYQPP
TVVPGGDLAK VQRAVCMLSN TTAIAEAWAR LDHKFDLMYA KRAFVHWYVG EGMEEGEFSE
AREDMAALEK DYEEVGIDSY EDEDEGEE
