Tubulin

Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and β-tubulin. These subunits are slightly acidic with an isoelectric point between 5.2 and 5.8.^[1]

Tubulin was long thought to be specific to eukaryotes. Recently, however, the prokaryotic cell division protein FtsZ was shown to be related to tubulin.^[2]

To form microtubules, the dimers of α- and β-tubulin bind to GTP and assemble onto the (+) ends of microtubules while in the GTP-bound state.^[3] The β-tubulin subunit is exposed on the plus end of the microtubule while the α-tubulin subunit is exposed on the minus end. After the dimer is incorporated into the microtubule, the molecule of GTP bound to the β-tubulin subunit eventually hydrolyzes into GDP through inter-dimer contacts along the microtubule protofilament.^[4] Whether the β-tubulin member of the tubulin dimer is bound to GTP or GDP influences the stability of the dimer in the microtubule. Dimers bound to GTP tend to assemble into microtubules, while dimers bound to GDP tend to fall apart; thus, this GTP cycle is essential for the dynamic instability of the microtubule.

1 α-Tubulin
2 β-Tubulin
3 γ-Tubulin
4 δ And ε tubulin
5 Pharmacology
6 Tubulin domains
- 6.1 Tubulin/FtsZ family, GTPase domain
7 See also
8 References
9 External links

α-Tubulin [edit]

Human α-tubulin subtypes include:^[5]

α-Tubulin
- TUBA1A
- TUBA1B
- TUBA1C
- TUBA3C
- TUBA3D
- TUBA3E
- TUBA4A
- TUBA8

β-Tubulin [edit]

β-tubulin in Tetrahymena sp.

Class III β-tubulin is a microtubule element expressed exclusively in neurons^{[citation needed]}, and is a popular identifier specific for neurons in nervous tissue.

Katanin is a protein complex that severs microtubules at β-tubulin subunits, and is necessary for rapid microtubule transport in neurons and in higher plants.^[6]

β-Tubulin
- TUBB
- TUBB1
- TUBB2A
- TUBB2B
- TUBB2C
- TUBB3
- TUBB4
- TUBB4Q
- TUBB6

γ-Tubulin [edit]

γ-Tubulin, another member of the tubulin family, is important in the nucleation and polar orientation of microtubules. It is found primarily in centrosomes and spindle pole bodies, since these are the areas of most abundant microtubule nucleation. In these organelles, several γ-tubulin and other protein molecules are found in complexes known as γ-tubulin ring complexes (γ-TuRCs), which chemically mimic the (+) end of a microtubule and thus allow microtubules to bind. γ-tubulin also has been isolated as a dimer and as a part of a γ-tubulin small complex (γTuSC), intermediate in size between the dimer and the γTuRC. γ-tubulin is the best understood mechanism of microtubule nucleation, but certain studies have indicated that certain cells may be able to adapt to its absence, as indicated by mutation and RNAi studies that have inhibited its correct expression.

Human γ-tubulin subtypes include:^[5]

TUBG1
TUBG2

Members of the γ-tubulin ring complex:

δ And ε tubulin [edit]

Delta (δ) and epsilon (ε) tubulin have been found to localize at centrioles and may play a role in forming the mitotic spindle during mitosis, though neither is as well-studied as the α- and β- forms.

Human δ- and ε-tubulin subtypes include:^[5]

δ-tubulin
- TUBD1
ε-tubulin
- TUBE1

Pharmacology [edit]

Tubulins are targets for anticancer drugs like Taxol, Tesetaxel and the "Vinca alkaloid" drugs such as vinblastine and vincristine. The anti-gout agent colchicine binds to tubulin and inhibits microtubule formation, arresting neutrophil motility and decreasing inflammation. The anti-fungal drug Griseofulvin targets microtubule formation and has applications in cancer treatment.

Tubulin domains [edit]

Tubulin/FtsZ family, GTPase domain [edit]

Tubulin

kif1a head-microtubule complex structure in atp-form

Identifiers

Symbol

Tubulin

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

In molecular biology, Tubulin/FtsZ family, GTPase domain is an evolutionary conserved protein domain.

This protein domain is found in all tubulin chains,^[7] as well as the bacterial FtsZ family of proteins.^[8] These proteins are involved in polymer formation. Tubulin is the major component of microtubules, while FtsZ is the polymer-forming protein of bacterial cell division, it is part of a ring in the middle of the dividing cell that is required for constriction of cell membrane and cell envelope to yield two daughter cells. FtsZ and tubulin are GTPases,^[2] this entry is the GTPase domain. FtsZ can polymerise into tubes, sheets, and rings in vitro and is ubiquitous in bacteria and archaea.

References [edit]

^ Williams RC Jr, Shah C, Sackett D (November 1999). "Separation of tubulin isoforms by isoelectric focusing in immobilized pH gradient gels". Anal Biochem 275 (2): 265–7. doi:10.1006/abio.1999.4326. PMID 10552916.
^ ^a ^b Nogales E, Downing KH, Amos LA, Löwe J (June 1998). "Tubulin and FtsZ form a distinct family of GTPases". Nat Struct Biol 5 (6): 451–8. doi:10.1038/nsb0698-451. PMID 9628483.
^ Heald R, Nogales E (January 2002). "Microtubule dynamics". J Cell Sci 115 (Pt 1): 3–4. PMID 11801717.
^ Howard J, Hyman AA (April 2003). "Dynamics and mechanics of the microtubule plus end". Nature 422 (6933): 753–8. doi:10.1038/nature01600. PMID 12700769.
^ ^a ^b ^c Dutcher SK (February 2001). "The tubulin fraternity: alpha to eta". Curr Opin Cell Biol 13 (1): 49–54. doi:10.1016/S0955-0674(00)00173-3. PMID 11163133.
^ McNally FJ, Vale RD (November 1993). "Identification of katanin, an ATPase that severs and disassembles stable microtubules". Cell 75 (3): 419–29. doi:10.1016/0092-8674(93)90377-3. PMID 8221885.
^ Nogales E, Wolf SG, Downing KH (January 1998). "Structure of the alpha beta tubulin dimer by electron crystallography". Nature 391 (6663): 199–203. doi:10.1038/34465. PMID 9428769.
^ Löwe J, Amos LA (January 1998). "Crystal structure of the bacterial cell-division protein FtsZ". Nature 391 (6663): 203–6. doi:10.1038/34472. PMID 9428770.

External links [edit]

Tubulin at the US National Library of Medicine Medical Subject Headings (MeSH)
EC 3.6.5.6
protocol for purification of tubulin from bovine brain

Proteins of the cytoskeleton

Human

Microfilaments
(ABPs)

Myofilament

Actins	A1 A2 B C1 G1 G2

Myosins	I MYO1A MYO1B MYO1C MYO1D MYO1E MYO1F MYO1G MYO1H) II MYH1 MYH2 MYH3 MYH4 MYH6 MYH7 MYH7B MYH8 MYH9 MYH10 MYH11 MYH13 MYH14 MYH15 MYH16 III MYO3A MYO3B V MYO5A MYO5B MYO5C VI MYO6 VII MYO7A MYO7B IX MYO9A MYO9B X MYO10 XV MYO15A XVIII MYO18A MYO18B LC MYL1 MYL2 MYL3 MYL4 MYL5 MYL6 MYL6B MYL7 MYL9 MYLIP MYLK MYLK2 MYLL1

Other	Tropomodulin 1 2 3 4 Troponin T 1 2 3 C 1 2 I 1 2 3 Tropomyosin 1 2 3 4 Actinin 1 2 3 4 Arp2/3 complex actin depolymerizing factors Cofilin 1 2 Destrin Gelsolin Profilin 1 2 Titin

Other

IFs

Type 1/2
(Keratin,
Cytokeratin)

Epithelial keratins (soft alpha-keratins)	type I/chromosome 17 10 12 13 14 15 16 17 19 20 chromosome 12 18 none 21 type II/chromosome 12 1 2A 3 4 5 6A 6B 7 8 9

Hair keratins (hard alpha-keratins)	type I/chromosome 17 31 32 33A 33B 34 35 36 37 38 type II/chromosome 12 81 82 83 84 85 86

Ungrouped alpha	chromosome 17 23 24 25 26 27 28 39 40 chromosome 12 71 72 73 74 75 76 77 78 79 80

Not alpha	Beta-keratin

Type 3

Type 4

Type 5

Lamin A
B

Microtubules/
MAPs

Kinesins	KIF1A KIF1B KIF2A KIF2C KIF3B KIF3C KIF4A KIF4B KIF5A KIF5B KIF5C KIF6 KIF7 KIF9 KIF11 KIF12 KIF13A KIF13B KIF14 KIF15 KIF16B KIF17 KIF18A KIF18B KIF19 KIF20A KIF20B KIF21A KIF21B KIF22 KIF23 KIF24 KIF25 KIF26A KIF26B KIF27 KIFC1 KIFC2 KIFC3

Dyneins	axonemal: DNAH1 DNAH2 DNAH3 DNAH5 DNAH6 DNAH7 DNAH8 DNAH9 DNAH10 DNAH11 DNAH12 DNAH13 DNAH14 DNAH17 DNAI1 DNAI2 DNALI1 DNAL1 DNAL4 cytoplasmic: DYNC1H1 DYNC2H1 DYNC1I1 DYNC1I2 DYNC1LI1 DYNC1LI2 DYNC2LI1 DYNLL1 DYNLL2 DYNLRB1 DYNLRB2 DYNLT1 DYNLT3

Other	Tau protein Dynactin DCTN1 Tubulins TUBA1A TUBA1B TUBA1C TUBA3C TUBA3D TUBA3E TUBA4A TUBA8 Stathmin Tektin TEKT1 TEKT2 TEKT3 TEKT4 TEKT5 Dynamin DNM1 DNM2 DNM3

Catenins

Membrane

Dystrophin
- Dystroglycan
Utrophin
Ankyrin
- ANK1
- ANK2
- ANK3
Spectrin
- SPTA1
- SPTAN1
- SPTB
- SPTBN1
- SPTBN2
- SPTBN4
- SPTBN5

Other

Nonhuman

See also: cytoskeletal defects B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)

Hydrolases: acid anhydride hydrolases (EC 3.6)

3.6.1

3.6.2

3.6.3-4: ATPase

3.6.3

Cu++ (3.6.3.4)	Menkes/ATP7A Wilson/ATP7B

Ca+ (3.6.3.8)	SERCA ATP2A1 ATP2A2 ATP2A3 Plasma membrane ATP2B1 ATP2B2 ATP2B3 ATP2B4 SPCA ATP2C1 ATP2C2

Na+/K+ (3.6.3.9)	ATP1A1 ATP1A2 ATP1A3 ATP1A4 ATP1B1 ATP1B2 ATP1B3 ATP1B4

H+/K+ (3.6.3.10)	ATP4A

Other P-type ATPase	ATP8B1 ATP10A ATP11B ATP12A ATP13A2 ATP13A3

3.6.4

3.6.5: GTPase

3.6.5.1: Heterotrimeric G protein	G_αs G_αi GNAI1 GNAI2 GNAI3 G_αq/11 GNAQ GNA11 G_α12/13 GNA12 GNA13 Transducin GNAT1 GNAT2

3.6.5.2: Small GTPase > Ras superfamily	Rho family of GTPases: Cdc42 CDC42 TC10 TCL RhoUV RhoU RhoV Rac Rac1 2 3 RhoG RhoBTB 1 2 RhoH Rho A B C Rnd 1 2 3 RhoDF RhoF RhoD other: Ras HRAS KRAS NRAS Rab RAB23 RAB27 Arf ARF6 SAR1B ARL13B ARL6 Ran Rheb Rap

3.6.5.3: Protein-synthesizing GTPase	Prokaryotic IF-2 EF-Tu EF-G Eukaryotic

3.6.5.5-6: Polymerization motors	Dynamin Tubulin