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P04350

- TBB4A_HUMAN

UniProt

P04350 - TBB4A_HUMAN

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Protein

Tubulin beta-4A chain

Gene

TUBB4A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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. 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
Complete GO annotation...

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. extracellular vesicular exosome Source: UniProtKB
  4. internode region of axon Source: Ensembl
  5. microtubule Source: UniProtKB
  6. myelin sheath Source: Ensembl
  7. neuronal cell body Source: Ensembl
  8. nucleus Source: UniProt
Complete GO annotation...

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).1 Publication

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

BgeeiP04350.
CleanExiHS_TUBB4.
ExpressionAtlasiP04350. baseline and differential.
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. 45 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

GeneTreeiENSGT00760000119061.
HOGENOMiHOG000165710.
InParanoidiP04350.
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

        10         20         30         40         50
MREIVHLQAG QCGNQIGAKF WEVISDEHGI DPTGTYHGDS DLQLERINVY
60 70 80 90 100
YNEATGGNYV PRAVLVDLEP GTMDSVRSGP FGQIFRPDNF VFGQSGAGNN
110 120 130 140 150
WAKGHYTEGA ELVDAVLDVV RKEAESCDCL QGFQLTHSLG GGTGSGMGTL
160 170 180 190 200
LISKIREEFP DRIMNTFSVV PSPKVSDTVV EPYNATLSVH QLVENTDETY
210 220 230 240 250
CIDNEALYDI CFRTLKLTTP TYGDLNHLVS ATMSGVTTCL RFPGQLNADL
260 270 280 290 300
RKLAVNMVPF PRLHFFMPGF APLTSRGSQQ YRALTVPELT QQMFDAKNMM
310 320 330 340 350
AACDPRHGRY LTVAAVFRGR MSMKEVDEQM LSVQSKNSSY FVEWIPNNVK
360 370 380 390 400
TAVCDIPPRG LKMAATFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG
410 420 430 440
EGMDEMEFTE AESNMNDLVS EYQQYQDATA EEGEFEEEAE EEVA
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. 45 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

GeneTreei ENSGT00760000119061.
HOGENOMi HOG000165710.
InParanoidi P04350.
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

Bgeei P04350.
CleanExi HS_TUBB4.
ExpressionAtlasi P04350. baseline and differential.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 158 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