Q13509 (TBB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tubulin beta-3 chain

Alternative name(s):
Tubulin beta-4 chain
Tubulin beta-III

Gene names

Name:	TUBB3
Synonyms:	TUBB4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	450 AA.
Sequence status	Complete.
Protein existence	Evidence 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. TUBB3 plays a critical role in proper axon guidance and mantainance. Ref.10
Subunit structure	Dimer of alpha and beta chains.
Subcellular location	Cytoplasm › cytoskeleton.
Tissue specificity	Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues. Ref.5 Ref.11
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. Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules. Ref.7
Involvement in disease	Defects in TUBB3 are the cause of congenital fibrosis of extraocular muscles type 3A (CFEOM3A) [MIM:600638]. A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy. Ref.10 Defects in TUBB3 are the cause of cortical dysplasia complex with other brain malformations (CDCBM) [MIM:614039]. CDCBM is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved. Ref.13
Sequence similarities	Belongs to the tubulin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Microtubule
Disease	Disease mutation
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	'de novo' posttranslational protein folding Traceable author statement. Source: Reactome axon guidance Inferred from mutant phenotype Ref.10. Source: UniProtKB microtubule-based movement Inferred from electronic annotation. Source: InterPro protein polymerization Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW microtubule Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from electronic annotation. Source: InterPro structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 450	450	Tubulin beta-3 chain		PRO_0000048250
Regions
	Nucleotide binding	140 – 146	7	GTP Potential
Amino acid modifications
	Modified residue	58	1	N6-acetyllysine Ref.9
	Modified residue	172	1	Phosphoserine; by CDK1 Ref.7
Natural variations
	Natural variant	62	1	R → Q in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. Ref.10		VAR_062758
	Natural variant	178	1	T → M in CDCBM; can form tubulin heterodimers that are properly incorporated into microtubules; the microtubules are less stable than wild-type. Ref.13		VAR_066206
	Natural variant	205	1	E → K in CDCBM; does not form tubulin heterodimers; patient fibroblasts show no major alterations in the microtubule network, but the microtubules are less stable than wild-type. Ref.13		VAR_066207
	Natural variant	262	1	R → C in CFEOM3A; affects heterodimers formation; affects microtubules polymerization and depolymerization rates. Ref.10		VAR_062759
	Natural variant	262	1	R → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures; affects microtubules polymerization and depolymerization rates. Ref.10		VAR_062760
	Natural variant	302	1	A → T in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. Ref.10		VAR_062761
	Natural variant	302	1	A → V in CDCBM; does not form tubulin heterodimers. Ref.13		VAR_066208
	Natural variant	323	1	M → V in CDCBM; reduced heterodimers formation. Ref.13		VAR_066209
	Natural variant	380	1	R → C in CFEOM3A; affects heterodimers formation; results in increased stability and reduced dynamics of microtubules. Ref.10		VAR_062762
	Natural variant	410	1	E → K in CFEOM3A; severe phenotype with congenital facial weakness; lower extremity weakness and sensory loss in the second to third decade of life in one patient; affects microtubules polymerization and depolymerization rates. Ref.10		VAR_062763
	Natural variant	417	1	D → H in CFEOM3A; severe phenotype with congenital facial weakness, congenital wrist and finger contractures. Ref.10		VAR_062764
	Natural variant	417	1	D → N in CFEOM3A; some patients with lower extremity weakness and sensory loss in the second to third decade of life; also found in patients without CFEOM3A who developed polyneuropathy. Ref.10		VAR_062765
Experimental info
	Mutagenesis	172	1	S → A: Loss of CDK1-mediated phosphorylation. Ref.7
	Mutagenesis	172	1	S → D or E: Mimics phosphorylation, unable to incorporate into microtubules. Ref.7
	Sequence conflict	275	1	A → R in AAC52035. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q13509 [UniParc]. Last modified May 2, 2002. Version 2. Checksum: 4B9CDE7DBA102949	FASTA	450	50,433
	10 20 30 40 50 60 MREIVHIQAG QCGNQIGAKF WEVISDEHGI DPSGNYVGDS DLQLERISVY YNEASSHKYV 70 80 90 100 110 120 PRAILVDLEP GTMDSVRSGA FGHLFRPDNF IFGQSGAGNN WAKGHYTEGA ELVDSVLDVV 130 140 150 160 170 180 RKECENCDCL QGFQLTHSLG GGTGSGMGTL LISKVREEYP DRIMNTFSVV PSPKVSDTVV 190 200 210 220 230 240 EPYNATLSIH QLVENTDETY CIDNEALYDI CFRTLKLATP TYGDLNHLVS ATMSGVTTSL 250 260 270 280 290 300 RFPGQLNADL RKLAVNMVPF PRLHFFMPGF APLTARGSQQ YRALTVPELT QQMFDAKNMM 310 320 330 340 350 360 AACDPRHGRY LTVATVFRGR MSMKEVDEQM LAIQSKNSSY FVEWIPNNVK VAVCDIPPRG 370 380 390 400 410 420 LKMSSTFIGN STAIQELFKR ISEQFTAMFR RKAFLHWYTG EGMDEMEFTE AESNMNDLVS 430 440 450 EYQQYQDATA EEEGEMYEDD EEESEAQGPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of human betaIII-tubulin cDNA: induction of betaIII isotype in human prostate carcinoma cells by acute exposure to antimicrotubule agents." Ranganathan S., Dexter D.W., Benetatos C.A., Hudes G.R. Biochim. Biophys. Acta 1395:237-245(1998) [PubMed: 9473684] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Banerjee A. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary cancer.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[4]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 63-77; 104-121; 242-251; 163-174 AND 381-390, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[5]	"Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology." Katsetos C.D., Legido A., Perentes E., Mork S.J. J. Child Neurol. 18:851-866(2003) [PubMed: 14736079] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	Erratum Katsetos C.D., Legido A., Perentes E., Mork S.J. J. Child Neurol. 19:531-531(2004)
[7]	"Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-dependent kinase Cdk1." Fourest-Lieuvin A., Peris L., Gache V., Garcia-Saez I., Juillan-Binard C., Lantez V., Job D. Mol. Biol. Cell 17:1041-1050(2006) [PubMed: 16371510] [Abstract] Cited for: PHOSPHORYLATION AT SER-172 BY CDK1, MUTAGENESIS OF SER-172.
[8]	"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: 19524510] [Abstract] Cited for: GLYCYLATION.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-58, MASS SPECTROMETRY.
[10]	"Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance." Tischfield M.A., Baris H.N., Wu C., Rudolph G., Van Maldergem L., He W., Chan W.M., Andrews C., Demer J.L., Robertson R.L., Mackey D.A., Ruddle J.B., Bird T.D., Gottlob I., Pieh C., Traboulsi E.I., Pomeroy S.L., Hunter D.G. , Soul J.S., Newlin A., Sabol L.J., Doherty E.J., de Uzcategui C.E., de Uzcategui N., Collins M.L., Sener E.C., Wabbels B., Hellebrand H., Meitinger T., de Berardinis T., Magli A., Schiavi C., Pastore-Trossello M., Koc F., Wong A.M., Levin A.V., Geraghty M.T., Descartes M., Flaherty M., Jamieson R.V., Moller H.U., Meuthen I., Callen D.F., Kerwin J., Lindsay S., Meindl A., Gupta M.L. Jr., Pellman D., Engle E.C. Cell 140:74-87(2010) [PubMed: 20074521] [Abstract] Cited for: FUNCTION, VARIANTS CFEOM3A GLN-62; CYS-262; HIS-262; THR-302; CYS-380; LYS-410; HIS-417 AND ASN-417, CHARACTERIZATION OF VARIANTS CFEOM3A GLN-62; CYS-262; HIS-262; THR-302; CYS-380 AND LYS-410.
[11]	"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: 20191564] [Abstract] Cited for: TISSUE SPECIFICITY.
[12]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"Mutations in the neuronal ss-tubulin subunit TUBB3 result in malformation of cortical development and neuronal migration defects." Poirier K., Saillour Y., Bahi-Buisson N., Jaglin X.H., Fallet-Bianco C., Nabbout R., Castelnau-Ptakhine L., Roubertie A., Attie-Bitach T., Desguerre I., Genevieve D., Barnerias C., Keren B., Lebrun N., Boddaert N., Encha-Razavi F., Chelly J. Hum. Mol. Genet. 19:4462-4473(2010) [PubMed: 20829227] [Abstract] Cited for: VARIANTS CDCBM MET-178; LYS-205; VAL-302 AND VAL-323, CHARACTERIZATION OF VARIANTS CDCBM MET-178; LYS-205; VAL-302 AND VAL-323.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U47634 mRNA. Translation: AAC52035.1. AF427491 mRNA. Translation: AAL28094.1. BC000748 mRNA. Translation: AAH00748.1. BC003021 mRNA. Translation: AAH03021.2.
IPI	IPI00013683.
RefSeq	NP_001184110.1. NM_001197181.1. NP_006077.2. NM_006086.3.
UniGene	Hs.511743.
3D structure databases
ProteinModelPortal	Q13509.
SMR	Q13509. Positions 2-427.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13509. 6 interactions.
MINT	MINT-1163245.
STRING	Q13509.
PTM databases
PhosphoSite	Q13509.
Polymorphism databases
DMDM	20455526.
2D gel databases
OGP	Q13509.
Proteomic databases
PRIDE	Q13509.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000315491; ENSP00000320295; ENSG00000198211.
GeneID	10381.
KEGG	hsa:10381.
UCSC	uc002fph.1. human.
Organism-specific databases
CTD	10381.
GeneCards	GC16P089987.
H-InvDB	HIX0013373.
HGNC	HGNC:20772. TUBB3.
HPA	CAB011512.
MIM	600638. phenotype. 602661. gene. 614039. phenotype.
neXtProt	NX_Q13509.
Orphanet	45358. Congenital fibrosis of extraocular muscles.
PharmGKB	PA134953867.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG000089.
PhylomeDB	Q13509.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_11123. Membrane Trafficking. REACT_152. Cell Cycle, Mitotic. REACT_17015. Metabolism of proteins. REACT_383. DNA Replication. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q13509.
Bgee	Q13509.
CleanEx	HS_TUBB3. HS_TUBB4.
Genevestigator	Q13509.
GermOnline	ENSG00000198211. Homo sapiens.
Family and domain databases
InterPro	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]
Gene3D	G3DSA:3.30.1330.20. Tubulin/FtsZ_2-layer-sand-dom. 1 hit. G3DSA:1.10.287.600. Tubulin_C. 1 hit. G3DSA:3.40.50.1440. Tubulin_FtsZ. 1 hit.
KO	K07375.
Pfam	PF00091. Tubulin. 1 hit. PF03953. Tubulin_C. 1 hit. [Graphical view]
PRINTS	PR01163. BETATUBULIN. PR01161. TUBULIN.
SMART	SM00864. Tubulin. 1 hit. SM00865. Tubulin_C. 1 hit. [Graphical view]
SUPFAM	SSF55307. Tub_FtsZ_C. 1 hit. SSF52490. Tubulin_FtsZ. 1 hit.
PROSITE	PS00227. TUBULIN. 1 hit. PS00228. TUBULIN_B_AUTOREG. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	39327.
SOURCE	Search...

Entry information

Entry name

TBB3_HUMAN

Accession

Primary (citable) accession number: Q13509
Secondary accession number(s): Q9BTZ0, Q9BW10

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	May 2, 2002
Last modified:	December 14, 2011
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.