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P04350

- TBB4A_HUMAN

UniProt

P04350 - TBB4A_HUMAN

Protein

Tubulin beta-4A chain

Gene

TUBB4A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 157 (01 Oct 2014)
      Sequence version 2 (18 Apr 2006)
      Previous versions | rss
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    Functioni

    Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi140 – 1467GTPSequence Analysis

    GO - Molecular functioni

    1. GTPase activity Source: InterPro
    2. GTP binding Source: UniProtKB-KW
    3. protein binding Source: IntAct
    4. structural constituent of cytoskeleton Source: InterPro

    GO - Biological processi

    1. 'de novo' posttranslational protein folding Source: Reactome
    2. cellular protein metabolic process Source: Reactome
    3. G2/M transition of mitotic cell cycle Source: Reactome
    4. microtubule-based process Source: InterPro
    5. mitotic cell cycle Source: Reactome
    6. protein folding Source: Reactome
    7. protein polymerization Source: InterPro

    Keywords - Ligandi

    GTP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_11039. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
    REACT_121399. MHC class II antigen presentation.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    REACT_150425. Resolution of Sister Chromatid Cohesion.
    REACT_150471. Separation of Sister Chromatids.
    REACT_15296. Recruitment of mitotic centrosome proteins and complexes.
    REACT_15364. Loss of Nlp from mitotic centrosomes.
    REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
    REACT_15510. Recruitment of NuMA to mitotic centrosomes.
    REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
    REACT_16936. Prefoldin mediated transfer of substrate to CCT/TriC.
    REACT_16956. Formation of tubulin folding intermediates by CCT/TriC.
    REACT_16967. Post-chaperonin tubulin folding pathway.
    REACT_22365. Recycling pathway of L1.
    REACT_25201. Kinesins.
    REACT_682. Mitotic Prometaphase.
    REACT_9509. Gap junction assembly.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tubulin beta-4A chain
    Alternative name(s):
    Tubulin 5 beta
    Tubulin beta-4 chain
    Gene namesi
    Name:TUBB4A
    Synonyms:TUBB4, TUBB5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:20774. TUBB4A.

    Subcellular locationi

    GO - Cellular componenti

    1. cilium Source: Ensembl
    2. cytosol Source: Reactome
    3. internode region of axon Source: Ensembl
    4. microtubule Source: UniProtKB
    5. myelin sheath Source: Ensembl
    6. neuronal cell body Source: Ensembl
    7. nucleus Source: UniProt

    Keywords - Cellular componenti

    Cytoplasm, Cytoskeleton, Microtubule

    Pathology & Biotechi

    Involvement in diseasei

    Dystonia 4, torsion, autosomal dominant (DYT4) [MIM:128101]: A form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT4 is characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21R → G in DYT4. 1 Publication
    VAR_069798
    Leukodystrophy, hypomyelinating, 6 (HLD) [MIM:612438]: A neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti249 – 2491D → N in HLD. 1 Publication
    VAR_069799

    Keywords - Diseasei

    Disease mutation, Dystonia, Leukodystrophy

    Organism-specific databases

    MIMi128101. phenotype.
    612438. phenotype.
    Orphaneti139441. Hypomyelination with atrophy of basal ganglia and cerebellum.
    98805. Primary dystonia, DYT4 type.
    PharmGKBiPA134949465.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 444444Tubulin beta-4A chainPRO_0000048252Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei172 – 1721Phosphoserine; by CDK1By similarity

    Post-translational modificationi

    Some glutamate residues at the C-terminus are polyglutamylated. This modification occurs exclusively on glutamate residues and results in polyglutamate chains on the gamma-carboxyl group. Also monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. The precise function of such modifications is still unclear but they regulate the assembly and dynamics of axonemal microtubules Probable.Curated

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP04350.
    PeptideAtlasiP04350.
    PRIDEiP04350.

    2D gel databases

    OGPiP04350.
    REPRODUCTION-2DPAGEIPI00023598.

    PTM databases

    PhosphoSiteiP04350.

    Expressioni

    Tissue specificityi

    Major isotype in brain, where it represents 46% of all beta-tubulins. In the brain, highest expression levels in the cerebellum, followed by putamen and white matter. Moderate levels in testis. Very low levels, if any, in other tissues.2 Publications

    Gene expression databases

    ArrayExpressiP04350.
    BgeeiP04350.
    CleanExiHS_TUBB4.
    GenevestigatoriP04350.

    Organism-specific databases

    HPAiCAB010768.
    HPA043640.
    HPA046280.

    Interactioni

    Subunit structurei

    Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    LRRK2Q5S0074EBI-355007,EBI-5323863
    NR4A1P227362EBI-355007,EBI-721550

    Protein-protein interaction databases

    BioGridi115655. 35 interactions.
    IntActiP04350. 35 interactions.
    MINTiMINT-1146958.
    STRINGi9606.ENSP00000264071.

    Structurei

    3D structure databases

    DisProtiDP00114.
    ProteinModelPortaliP04350.
    SMRiP04350. Positions 2-427.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domaini

    The highly acidic C-terminal region may bind cations such as calcium.

    Sequence similaritiesi

    Belongs to the tubulin family.Curated

    Phylogenomic databases

    HOGENOMiHOG000165710.
    KOiK07375.
    OMAiMQLERIN.
    OrthoDBiEOG71ZP1H.
    PhylomeDBiP04350.
    TreeFamiTF300298.

    Family and domain databases

    Gene3Di1.10.287.600. 1 hit.
    3.30.1330.20. 1 hit.
    3.40.50.1440. 1 hit.
    InterProiIPR013838. Beta-tubulin_BS.
    IPR002453. Beta_tubulin.
    IPR008280. Tub_FtsZ_C.
    IPR000217. Tubulin.
    IPR018316. Tubulin/FtsZ_2-layer-sand-dom.
    IPR023123. Tubulin_C.
    IPR017975. Tubulin_CS.
    IPR003008. Tubulin_FtsZ_GTPase.
    [Graphical view]
    PANTHERiPTHR11588. PTHR11588. 1 hit.
    PfamiPF00091. Tubulin. 1 hit.
    PF03953. Tubulin_C. 1 hit.
    [Graphical view]
    PRINTSiPR01163. BETATUBULIN.
    PR01161. TUBULIN.
    SMARTiSM00864. Tubulin. 1 hit.
    SM00865. Tubulin_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF52490. SSF52490. 1 hit.
    SSF55307. SSF55307. 1 hit.
    PROSITEiPS00227. TUBULIN. 1 hit.
    PS00228. TUBULIN_B_AUTOREG. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P04350-1 [UniParc]FASTAAdd to Basket

    « Hide

    MREIVHLQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLERINVY    50
    YNEATGGNYV PRAVLVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN 100
    WAKGHYTEGA ELVDAVLDVV RKEAESCDCL QGFQLTHSLG GGTGSGMGTL 150
    LISKIREEFP DRIMNTFSVV PSPKVSDTVV EPYNATLSVH QLVENTDETY 200
    CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL RFPGQLNADL 250
    RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQMFDAKNMM 300
    AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LSVQSKNSSY FVEWIPNNVK 350
    TAVCDIPPRG LKMAATFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG 400
    EGMDEMEFTE AESNMNDLVS EYQQYQDATA EEGEFEEEAE EEVA 444
    Length:444
    Mass (Da):49,586
    Last modified:April 18, 2006 - v2
    Checksum:iF7429D057C11A3F5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti269 – 2691G → A in CAA25318. (PubMed:6462917)Curated
    Sequence conflicti283 – 2831A → G in CAA25318. (PubMed:6462917)Curated
    Sequence conflicti432 – 4321E → Q in CAA25318. (PubMed:6462917)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti2 – 21R → G in DYT4. 1 Publication
    VAR_069798
    Natural varianti155 – 1551I → M.1 Publication
    Corresponds to variant rs1053262 [ dbSNP | Ensembl ].
    VAR_052673
    Natural varianti249 – 2491D → N in HLD. 1 Publication
    VAR_069799
    Natural varianti365 – 3651A → V.1 Publication
    Corresponds to variant rs1053267 [ dbSNP | Ensembl ].
    VAR_026044

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X00734 Genomic DNA. Translation: CAA25318.1.
    AK075307 mRNA. Translation: BAG52106.1.
    CH471139 Genomic DNA. Translation: EAW69078.1.
    BC006570 mRNA. Translation: AAH06570.1.
    BC013683 mRNA. Translation: AAH13683.1.
    CCDSiCCDS12168.1.
    PIRiA02972. UBHU5B.
    RefSeqiNP_001276052.1. NM_001289123.1.
    NP_001276056.1. NM_001289127.1.
    NP_001276058.1. NM_001289129.1.
    NP_001276059.1. NM_001289130.1.
    NP_001276060.1. NM_001289131.1.
    NP_006078.2. NM_006087.3.
    UniGeneiHs.110837.

    Genome annotation databases

    EnsembliENST00000264071; ENSP00000264071; ENSG00000104833.
    ENST00000540257; ENSP00000443590; ENSG00000104833.
    GeneIDi10382.
    KEGGihsa:10382.
    UCSCiuc002mfg.1. human.

    Polymorphism databases

    DMDMi93141323.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X00734 Genomic DNA. Translation: CAA25318.1 .
    AK075307 mRNA. Translation: BAG52106.1 .
    CH471139 Genomic DNA. Translation: EAW69078.1 .
    BC006570 mRNA. Translation: AAH06570.1 .
    BC013683 mRNA. Translation: AAH13683.1 .
    CCDSi CCDS12168.1.
    PIRi A02972. UBHU5B.
    RefSeqi NP_001276052.1. NM_001289123.1.
    NP_001276056.1. NM_001289127.1.
    NP_001276058.1. NM_001289129.1.
    NP_001276059.1. NM_001289130.1.
    NP_001276060.1. NM_001289131.1.
    NP_006078.2. NM_006087.3.
    UniGenei Hs.110837.

    3D structure databases

    DisProti DP00114.
    ProteinModelPortali P04350.
    SMRi P04350. Positions 2-427.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115655. 35 interactions.
    IntActi P04350. 35 interactions.
    MINTi MINT-1146958.
    STRINGi 9606.ENSP00000264071.

    Chemistry

    BindingDBi P04350.
    ChEMBLi CHEMBL2095182.

    PTM databases

    PhosphoSitei P04350.

    Polymorphism databases

    DMDMi 93141323.

    2D gel databases

    OGPi P04350.
    REPRODUCTION-2DPAGE IPI00023598.

    Proteomic databases

    MaxQBi P04350.
    PeptideAtlasi P04350.
    PRIDEi P04350.

    Protocols and materials databases

    DNASUi 10382.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264071 ; ENSP00000264071 ; ENSG00000104833 .
    ENST00000540257 ; ENSP00000443590 ; ENSG00000104833 .
    GeneIDi 10382.
    KEGGi hsa:10382.
    UCSCi uc002mfg.1. human.

    Organism-specific databases

    CTDi 10382.
    GeneCardsi GC19M006496.
    HGNCi HGNC:20774. TUBB4A.
    HPAi CAB010768.
    HPA043640.
    HPA046280.
    MIMi 128101. phenotype.
    602662. gene.
    612438. phenotype.
    neXtProti NX_P04350.
    Orphaneti 139441. Hypomyelination with atrophy of basal ganglia and cerebellum.
    98805. Primary dystonia, DYT4 type.
    PharmGKBi PA134949465.
    GenAtlasi Search...

    Phylogenomic databases

    HOGENOMi HOG000165710.
    KOi K07375.
    OMAi MQLERIN.
    OrthoDBi EOG71ZP1H.
    PhylomeDBi P04350.
    TreeFami TF300298.

    Enzyme and pathway databases

    Reactomei REACT_11039. Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane.
    REACT_121399. MHC class II antigen presentation.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    REACT_150425. Resolution of Sister Chromatid Cohesion.
    REACT_150471. Separation of Sister Chromatids.
    REACT_15296. Recruitment of mitotic centrosome proteins and complexes.
    REACT_15364. Loss of Nlp from mitotic centrosomes.
    REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
    REACT_15510. Recruitment of NuMA to mitotic centrosomes.
    REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
    REACT_16936. Prefoldin mediated transfer of substrate to CCT/TriC.
    REACT_16956. Formation of tubulin folding intermediates by CCT/TriC.
    REACT_16967. Post-chaperonin tubulin folding pathway.
    REACT_22365. Recycling pathway of L1.
    REACT_25201. Kinesins.
    REACT_682. Mitotic Prometaphase.
    REACT_9509. Gap junction assembly.

    Miscellaneous databases

    ChiTaRSi TUBB4A. human.
    GeneWikii TUBB4.
    GenomeRNAii 10382.
    NextBioi 39331.
    PROi P04350.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P04350.
    Bgeei P04350.
    CleanExi HS_TUBB4.
    Genevestigatori P04350.

    Family and domain databases

    Gene3Di 1.10.287.600. 1 hit.
    3.30.1330.20. 1 hit.
    3.40.50.1440. 1 hit.
    InterProi IPR013838. Beta-tubulin_BS.
    IPR002453. Beta_tubulin.
    IPR008280. Tub_FtsZ_C.
    IPR000217. Tubulin.
    IPR018316. Tubulin/FtsZ_2-layer-sand-dom.
    IPR023123. Tubulin_C.
    IPR017975. Tubulin_CS.
    IPR003008. Tubulin_FtsZ_GTPase.
    [Graphical view ]
    PANTHERi PTHR11588. PTHR11588. 1 hit.
    Pfami PF00091. Tubulin. 1 hit.
    PF03953. Tubulin_C. 1 hit.
    [Graphical view ]
    PRINTSi PR01163. BETATUBULIN.
    PR01161. TUBULIN.
    SMARTi SM00864. Tubulin. 1 hit.
    SM00865. Tubulin_C. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52490. SSF52490. 1 hit.
    SSF55307. SSF55307. 1 hit.
    PROSITEi PS00227. TUBULIN. 1 hit.
    PS00228. TUBULIN_B_AUTOREG. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Sequence of an expressed human beta-tubulin gene containing ten Alu family members."
      Lee M.G.-S., Loomis C., Cowan N.J.
      Nucleic Acids Res. 12:5823-5836(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MET-155 AND VAL-365.
    2. "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries."
      Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.
      , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T.
      DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain and Uterus.
    5. "C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in vitro and associate with amyloid deposits of familial cerebral amyloid angiopathy, British type."
      Baumann M.H., Wisniewski T., Levy E., Plant G.T., Ghiso J.
      Biochem. Biophys. Res. Commun. 219:238-242(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 283-289 AND 310-318.
      Tissue: Brain.
    6. "Evolutionary divergence of enzymatic mechanisms for posttranslational polyglycylation."
      Rogowski K., Juge F., van Dijk J., Wloga D., Strub J.-M., Levilliers N., Thomas D., Bre M.-H., Van Dorsselaer A., Gaertig J., Janke C.
      Cell 137:1076-1087(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCYLATION.
    7. Cited for: TISSUE SPECIFICITY.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "A de novo mutation in the beta-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum."
      Simons C., Wolf N.I., McNeil N., Caldovic L., Devaney J.M., Takanohashi A., Crawford J., Ru K., Grimmond S.M., Miller D., Tonduti D., Schmidt J.L., Chudnow R.S., van Coster R., Lagae L., Kisler J., Sperner J., van der Knaap M.S.
      , Schiffmann R., Taft R.J., Vanderver A.
      Am. J. Hum. Genet. 92:767-773(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HLD ASN-249.
    10. Cited for: VARIANT DYT4 GLY-2, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiTBB4A_HUMAN
    AccessioniPrimary (citable) accession number: P04350
    Secondary accession number(s): B3KQP4, Q969E5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 20, 1987
    Last sequence update: April 18, 2006
    Last modified: October 1, 2014
    This is version 157 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3