TBA3D_HUMAN
ID TBA3D_HUMAN Reviewed; 450 AA.
AC P0DPH8; A6NJQ0; Q13748; Q5W099; Q6PEY3; Q96F18;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Tubulin alpha-3D chain;
DE AltName: Full=Alpha-tubulin 3D;
DE Contains:
DE RecName: Full=Detyrosinated tubulin alpha-3D chain;
GN Name=TUBA3D;
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 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 [4]
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 [5]
RP DETYROSINATION.
RX PubMed=25908662; DOI=10.1126/science.aaa5175;
RA Barisic M., Silva e Sousa R., Tripathy S.K., Magiera M.M., Zaytsev A.V.,
RA Pereira A.L., Janke C., Grishchuk E.L., Maiato H.;
RT "Mitosis. Microtubule detyrosination guides chromosomes during mitosis.";
RL Science 348:799-803(2015).
RN [6]
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 [7]
RP TYROSINATION.
RX PubMed=26972003; DOI=10.1016/j.celrep.2016.02.046;
RA Nirschl J.J., Magiera M.M., Lazarus J.E., Janke C., Holzbaur E.L.;
RT "Alpha-tubulin tyrosination and CLIP-170 phosphorylation regulate the
RT initiation of dynein-driven transport in neurons.";
RL Cell Rep. 14:2637-2652(2016).
RN [8]
RP TISSUE SPECIFICITY, INVOLVEMENT IN KTCN9, AND VARIANT KTCN9 11-GLN--TYR-450
RP DEL.
RX PubMed=29051577; DOI=10.1038/s41598-017-13162-0;
RA Hao X.D., Chen P., Zhang Y.Y., Li S.X., Shi W.Y., Gao H.;
RT "De novo mutations of TUBA3D are associated with keratoconus.";
RL Sci. Rep. 7:13570-13570(2017).
RN [9]
RP DETYROSINATION.
RX PubMed=29146869; DOI=10.1126/science.aao5676;
RA Nieuwenhuis J., Adamopoulos A., Bleijerveld O.B., Mazouzi A., Stickel E.,
RA Celie P., Altelaar M., Knipscheer P., Perrakis A., Blomen V.A.,
RA Brummelkamp T.R.;
RT "Vasohibins encode tubulin detyrosinating activity.";
RL Science 358:1453-1456(2017).
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.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton.
CC -!- TISSUE SPECIFICITY: Expressed in the cornea, sclera, and peripheral
CC blood (PubMed:29051577). {ECO:0000269|PubMed:29051577}.
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 -!- PTM: Nitration of Tyr-450 is irreversible and interferes with normal
CC dynein intracellular distribution. {ECO:0000250|UniProtKB:Q71U36}.
CC -!- PTM: Undergoes a tyrosination/detyrosination cycle, the cyclic removal
CC and re-addition of a C-terminal tyrosine residue by the enzymes tubulin
CC tyrosine carboxypeptidase (VASH1 or VASH2) and tubulin tyrosine ligase
CC (TTL), respectively. {ECO:0000269|PubMed:25908662,
CC ECO:0000269|PubMed:26972003, ECO:0000269|PubMed:29146869}.
CC -!- PTM: [Tubulin alpha-3D chain]: Tyrosination promotes microtubule
CC interaction with CAP-Gly domain-containing proteins such as CLIP1,
CC CLIP2 and DCTN1 (By similarity). Tyrosination regulates the initiation
CC of dynein-dynactin motility via interaction with DCTN1, which brings
CC the dynein-dynactin complex into contact with microtubules
CC (PubMed:26972003). In neurons, tyrosinated tubulins mediate the
CC initiation of retrograde vesicle transport (By similarity).
CC {ECO:0000250|UniProtKB:P68369, ECO:0000250|UniProtKB:Q71U36,
CC ECO:0000269|PubMed:26972003}.
CC -!- PTM: [Detyrosinated tubulin alpha-3D chain]: Detyrosination is involved
CC in metaphase plate congression by guiding chromosomes during mitosis:
CC detyrosination promotes interaction with CENPE, promoting pole-proximal
CC transport of chromosomes toward the equator (PubMed:25908662).
CC Detyrosination increases microtubules-dependent mechanotransduction in
CC dystrophic cardiac and skeletal muscle. In cardiomyocytes,
CC detyrosinated microtubules are required to resist to contractile
CC compression during contraction: detyrosination promotes association
CC with desmin (DES) at force-generating sarcomeres, leading to buckled
CC microtubules and mechanical resistance to contraction (By similarity).
CC {ECO:0000250|UniProtKB:P05214, ECO:0000269|PubMed:25908662}.
CC -!- DISEASE: Keratoconus 9 (KTCN9) [MIM:617928]: An autosomal dominant form
CC of keratoconus, a common degenerative corneal disease characterized by
CC progressive, non-inflammatory thinning of the corneal stroma, corneal
CC ectasia, and cone-shaped corneal protrusion that results in reduced
CC vision. {ECO:0000269|PubMed:29051577}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tubulin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tubulin entry;
CC URL="https://en.wikipedia.org/wiki/Tubulin";
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DR EMBL; AC073869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057810; AAH57810.1; -; mRNA.
DR CCDS; CCDS33290.1; -.
DR RefSeq; NP_525125.2; NM_080386.3.
DR AlphaFoldDB; P0DPH8; -.
DR SMR; P0DPH8; -.
DR BindingDB; P0DPH8; -.
DR GlyGen; P0DPH8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P0DPH8; -.
DR PhosphoSitePlus; P0DPH8; -.
DR jPOST; P0DPH8; -.
DR MassIVE; P0DPH8; -.
DR PRIDE; P0DPH8; -.
DR Antibodypedia; 60456; 49 antibodies from 11 providers.
DR DNASU; 7278; -.
DR Ensembl; ENST00000321253.7; ENSP00000326042.6; ENSG00000075886.11.
DR GeneID; 113457; -.
DR KEGG; hsa:113457; -.
DR MANE-Select; ENST00000321253.7; ENSP00000326042.6; NM_080386.4; NP_525125.2.
DR MANE-Select; ENST00000400113.8; ENSP00000382982.3; NM_006001.3; NP_005992.1.
DR CTD; 113457; -.
DR DisGeNET; 113457; -.
DR DisGeNET; 7278; -.
DR GeneCards; TUBA3D; -.
DR HGNC; HGNC:24071; TUBA3D.
DR HPA; ENSG00000075886; Tissue enriched (testis).
DR MalaCards; TUBA3D; -.
DR MIM; 617878; gene.
DR MIM; 617928; phenotype.
DR neXtProt; NX_P0DPH8; -.
DR OpenTargets; ENSG00000075886; -.
DR OpenTargets; ENSG00000198033; -.
DR VEuPathDB; HostDB:ENSG00000075886; -.
DR GeneTree; ENSGT00950000182825; -.
DR OMA; KVGICYQ; -.
DR PathwayCommons; P0DPH8; -.
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 ChiTaRS; TUBA3D; human.
DR Pharos; P0DPH8; Tdark.
DR PRO; PR:P0DPH8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR Bgee; ENSG00000075886; Expressed in right testis and 93 other tissues.
DR ExpressionAtlas; P0DPH8; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0015630; C:microtubule cytoskeleton; 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: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; Cytoplasm; Cytoskeleton; Disease variant; GTP-binding;
KW Isopeptide bond; Methylation; Microtubule; Nitration; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..450
FT /note="Tubulin alpha-3D chain"
FT /id="PRO_0000444671"
FT CHAIN 1..449
FT /note="Detyrosinated tubulin alpha-3D chain"
FT /evidence="ECO:0000305|PubMed:25908662,
FT ECO:0000305|PubMed:29146869"
FT /id="PRO_0000444672"
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 SITE 450
FT /note="Involved in polymerization"
FT MOD_RES 40
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:24906155"
FT MOD_RES 282
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P68373"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P68373"
FT MOD_RES 450
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q71U36"
FT VARIANT 11..450
FT /note="Missing (in KTCN9; loss of protein)"
FT /evidence="ECO:0000269|PubMed:29051577"
FT /id="VAR_080471"
FT CONFLICT 305
FT /note="C -> Y (in Ref. 2; AAH57810)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 450 AA; 49960 MW; 2A78714CBA782D55 CRC64;
MRECISIHVG QAGVQIGNAC WELYCLEHGI QPDGQMPSDK TIGGGDDSFN TFFSETGAGK
HVPRAVFVDL EPTVVDEVRT GTYRQLFHPE QLITGKEDAA NNYARGHYTI GKEIVDLVLD
RIRKLADLCT GLQGFLIFHS FGGGTGSGFA SLLMERLSVD YGKKSKLEFA IYPAPQVSTA
VVEPYNSILT THTTLEHSDC AFMVDNEAIY DICRRNLDIE RPTYTNLNRL IGQIVSSITA
SLRFDGALNV DLTEFQTNLV PYPRIHFPLA TYAPVISAEK AYHEQLSVAE ITNACFEPAN
QMVKCDPRHG KYMACCMLYR GDVVPKDVNA AIATIKTKRT IQFVDWCPTG FKVGINYQPP
TVVPGGDLAK VQRAVCMLSN TTAIAEAWAR LDHKFDLMYA KRAFVHWYVG EGMEEGEFSE
AREDLAALEK DYEEVGVDSV EAEAEEGEEY
