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P04350 (TBB4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tubulin beta-4A chain
Alternative name(s):
Tubulin 5 beta
Tubulin beta-4 chain
Gene names
Name:TUBB4A
Synonyms:TUBB4, TUBB5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Cytoplasmcytoskeleton.

Tissue specificity

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. Ref.7 Ref.10

Domain

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

Post-translational modification

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.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Sequence similarities

Belongs to the tubulin family.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
Microtubule
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dystonia
Leukodystrophy
   LigandGTP-binding
Nucleotide-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_process'de novo' posttranslational protein folding

Traceable author statement. Source: Reactome

G2/M transition of mitotic cell cycle

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

microtubule-based process

Inferred from electronic annotation. Source: InterPro

mitotic cell cycle

Traceable author statement. Source: Reactome

protein folding

Traceable author statement. Source: Reactome

protein polymerization

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcilium

Inferred from electronic annotation. Source: Ensembl

cytosol

Traceable author statement. Source: Reactome

internode region of axon

Inferred from electronic annotation. Source: Ensembl

microtubule

Inferred from direct assay PubMed 21525035. Source: UniProtKB

myelin sheath

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 21630459. Source: UniProt

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 20195357PubMed 24275654. Source: IntAct

structural constituent of cytoskeleton

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LRRK2Q5S0074EBI-355007,EBI-5323863
NR4A1P227362EBI-355007,EBI-721550

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 444444Tubulin beta-4A chain
PRO_0000048252

Regions

Nucleotide binding140 – 1467GTP Potential

Amino acid modifications

Modified residue1721Phosphoserine; by CDK1 By similarity

Natural variations

Natural variant21R → G in DYT4. Ref.10
VAR_069798
Natural variant1551I → M. Ref.1
Corresponds to variant rs1053262 [ dbSNP | Ensembl ].
VAR_052673
Natural variant2491D → N in HLD. Ref.9
VAR_069799
Natural variant3651A → V. Ref.1
Corresponds to variant rs1053267 [ dbSNP | Ensembl ].
VAR_026044

Experimental info

Sequence conflict2691G → A in CAA25318. Ref.1
Sequence conflict2831A → G in CAA25318. Ref.1
Sequence conflict4321E → Q in CAA25318. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P04350 [UniParc].

Last modified April 18, 2006. Version 2.
Checksum: F7429D057C11A3F5

FASTA44449,586
        10         20         30         40         50         60 
MREIVHLQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLERINVY YNEATGGNYV 

        70         80         90        100        110        120 
PRAVLVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN WAKGHYTEGA ELVDAVLDVV 

       130        140        150        160        170        180 
RKEAESCDCL QGFQLTHSLG GGTGSGMGTL LISKIREEFP DRIMNTFSVV PSPKVSDTVV 

       190        200        210        220        230        240 
EPYNATLSVH QLVENTDETY CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL 

       250        260        270        280        290        300 
RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQMFDAKNMM 

       310        320        330        340        350        360 
AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LSVQSKNSSY FVEWIPNNVK TAVCDIPPRG 

       370        380        390        400        410        420 
LKMAATFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS 

       430        440 
EYQQYQDATA EEGEFEEEAE EEVA 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Tumoral and tissue-specific expression of the major human beta-tubulin isotypes."
Leandro-Garcia L.J., Leskela S., Landa I., Montero-Conde C., Lopez-Jimenez E., Leton R., Cascon A., Robledo M., Rodriguez-Antona C.
Cytoskeleton 67:214-223(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Mutations in the autoregulatory domain of beta-tubulin 4a cause hereditary dystonia."
Hersheson J., Mencacci N.E., Davis M., Macdonald N., Trabzuni D., Ryten M., Pittman A., Paudel R., Kara E., Fawcett K., Plagnol V., Bhatia K.P., Medlar A.J., Stanescu H.C., Hardy J., Kleta R., Wood N.W., Houlden H.
Ann. Neurol. 73:546-553(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DYT4 GLY-2, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12168.1.
PIRUBHU5B. A02972.
RefSeqNP_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.
UniGeneHs.110837.

3D structure databases

DisProtDP00114.
ProteinModelPortalP04350.
SMRP04350. Positions 2-427.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115655. 38 interactions.
IntActP04350. 29 interactions.
MINTMINT-1146958.
STRING9606.ENSP00000264071.

Chemistry

BindingDBP04350.
ChEMBLCHEMBL2095182.

PTM databases

PhosphoSiteP04350.

Polymorphism databases

DMDM93141323.

2D gel databases

OGPP04350.
REPRODUCTION-2DPAGEIPI00023598.

Proteomic databases

MaxQBP04350.
PeptideAtlasP04350.
PRIDEP04350.

Protocols and materials databases

DNASU10382.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264071; ENSP00000264071; ENSG00000104833.
ENST00000540257; ENSP00000443590; ENSG00000104833.
GeneID10382.
KEGGhsa:10382.
UCSCuc002mfg.1. human.

Organism-specific databases

CTD10382.
GeneCardsGC19M006496.
HGNCHGNC:20774. TUBB4A.
HPACAB010768.
HPA043640.
HPA046280.
MIM128101. phenotype.
602662. gene.
612438. phenotype.
neXtProtNX_P04350.
Orphanet139441. Hypomyelination with atrophy of basal ganglia and cerebellum.
98805. Primary dystonia, DYT4 type.
PharmGKBPA134949465.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000165710.
KOK07375.
OMAMQLERIN.
OrthoDBEOG71ZP1H.
PhylomeDBP04350.
TreeFamTF300298.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_11123. Membrane Trafficking.
REACT_115566. Cell Cycle.
REACT_17015. Metabolism of proteins.
REACT_21300. Mitotic M-M/G1 phases.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressP04350.
BgeeP04350.
CleanExHS_TUBB4.
GenevestigatorP04350.

Family and domain databases

Gene3D1.10.287.600. 1 hit.
3.30.1330.20. 1 hit.
3.40.50.1440. 1 hit.
InterProIPR013838. 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]
PANTHERPTHR11588. PTHR11588. 1 hit.
PfamPF00091. Tubulin. 1 hit.
PF03953. Tubulin_C. 1 hit.
[Graphical view]
PRINTSPR01163. BETATUBULIN.
PR01161. TUBULIN.
SMARTSM00864. Tubulin. 1 hit.
SM00865. Tubulin_C. 1 hit.
[Graphical view]
SUPFAMSSF52490. SSF52490. 1 hit.
SSF55307. SSF55307. 1 hit.
PROSITEPS00227. TUBULIN. 1 hit.
PS00228. TUBULIN_B_AUTOREG. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTUBB4A. human.
GeneWikiTUBB4.
GenomeRNAi10382.
NextBio39331.
PROP04350.
SOURCESearch...

Entry information

Entry nameTBB4A_HUMAN
AccessionPrimary (citable) accession number: P04350
Secondary accession number(s): B3KQP4, Q969E5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: April 18, 2006
Last modified: July 9, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM