P04350 (TBB4A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tubulin beta-4A chain

Alternative name(s):
Tubulin 5 beta
Tubulin beta-4 chain

Gene names

Name:	TUBB4A
Synonyms:	TUBB4, TUBB5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	444 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.
Subunit structure	Dimer of alpha and beta chains.
Subcellular location	Cytoplasm › cytoskeleton.
Tissue specificity	Major isotype in brain, where it represents 46% of all beta-tubulins. Ref.7
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.
Sequence similarities	Belongs to the tubulin family.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton Microtubule
Coding sequence diversity	Polymorphism
Ligand	GTP-binding Nucleotide-binding
PTM	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 G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome microtubule-based process Inferred from electronic annotation. Source: InterPro protein polymerization Inferred from electronic annotation. Source: InterPro
Cellular_component	cilium Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome internode region of axon Inferred from electronic annotation. Source: Compara microtubule Inferred from direct assay PubMed 21525035. Source: UniProtKB myelin sheath Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Inferred from electronic annotation. Source: InterPro structural constituent of cytoskeleton Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NR4A1	P22736	2	EBI-355007,EBI-721550

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 444	444	Tubulin beta-4A chain		PRO_0000048252
Regions
	Nucleotide binding	140 – 146	7	GTP Potential
Amino acid modifications
	Modified residue	36	1	Phosphotyrosine By similarity
	Modified residue	172	1	Phosphoserine; by CDK1 By similarity
	Modified residue	366	1	Phosphothreonine By similarity
Natural variations
	Natural variant	155	1	I → M. Ref.1 Corresponds to variant rs1053262 [ dbSNP | Ensembl ].		VAR_052673
	Natural variant	365	1	A → V. Ref.1 Corresponds to variant rs1053267 [ dbSNP | Ensembl ].		VAR_026044
Experimental info
	Sequence conflict	269	1	G → A in CAA25318. Ref.1
	Sequence conflict	283	1	A → G in CAA25318. Ref.1
	Sequence conflict	432	1	E → Q in CAA25318. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P04350 [UniParc]. Last modified April 18, 2006. Version 2. Checksum: F7429D057C11A3F5	FASTA	444	49,586
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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].
+	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.
IPI	IPI00023598.
PIR	UBHU5B. A02972.
RefSeq	NP_006078.2. NM_006087.2.
UniGene	Hs.110837.
3D structure databases
DisProt	DP00114.
ProteinModelPortal	P04350.
ModBase	Search...
Protein-protein interaction databases
IntAct	P04350. 28 interactions.
MINT	MINT-1146958.
STRING	9606.ENSP00000264071.
PTM databases
PhosphoSite	P04350.
Polymorphism databases
DMDM	93141323.
2D gel databases
OGP	P04350.
REPRODUCTION-2DPAGE	IPI00023598.
Proteomic databases
PeptideAtlas	P04350.
PRIDE	P04350.
Protocols and materials databases
DNASU	10382.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264071; ENSP00000264071; ENSG00000104833. ENST00000540257; ENSP00000443590; ENSG00000104833.
GeneID	10382.
KEGG	hsa:10382.
UCSC	uc002mff.1. human.
Organism-specific databases
CTD	10382.
GeneCards	GC19M006496.
HGNC	HGNC:20774. TUBB4A.
HPA	CAB010768. HPA043640. HPA046280.
neXtProt	NX_P04350.
PharmGKB	PA134949465.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000165710.
KO	K07375.
OMA	EAENSDC.
OrthoDB	EOG4DFPNJ.
PhylomeDB	P04350.
Enzyme and pathway databases
Reactome	REACT_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
Bgee	P04350.
CleanEx	HS_TUBB4.
Genevestigator	P04350.
GermOnline	ENSG00000104833. Homo sapiens.
Family and domain databases
Gene3D	1.10.287.600. 1 hit. 3.30.1330.20. 1 hit. 3.40.50.1440. 1 hit.
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]
PANTHER	PTHR11588. PTHR11588. 1 hit.
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
BindingDB	P04350.
ChEMBL	CHEMBL3838.
ChiTaRS	TUBB4A. human.
GenomeRNAi	10382.
NextBio	39331.

Entry information

Entry name

TBB4A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 142 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.