- Small GTPase
Small GTPases are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a form of G-proteins found in the cytosol which are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The most well-known members are the Ras GTPases and hence they are sometimes called Ras superfamily GTPases.
A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The GDP can be then replaced by free GTP. Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated by GTPase activating proteins (GAPs), while GTP exchange is catalyzed by Guanine nucleotide exchange factors (GEFs). Activation of a GEF typically activates its cognate G-protein, while activation of a GAP results in inactivation of the cognate G-protein. Guanosine nucleotide dissociation inhibitors (GDI) maintain small GTP-ases in the inactive state.
Small GTPases regulate a wide variety of processes in the cell, including growth, cellular differentiation, cell movement and lipid vesicle transport.
The Ras superfamilyMain article: Ras superfamily
There are more than a hundred proteins in the Ras superfamily. Based on structure, sequence and function, the Ras superfamily is divided into eight main families, each of which is further divided into subfamilies: Ras, Rho, Rab, Rap, Arf, Ran, Rheb, Rad and Rit. Miro is a recent contributor to the superfamily.
Each subfamily shares the common core G domain, which provides essential GTPase and nucleotide exchange activity.
The surrounding sequence helps determine the functional specificity of the small GTPase, for example the 'Insert Loop', common to the Rho subfamily, specifically contributes to binding to effector proteins such as IQGAP and WASP.
The Ras family is generally responsible for cell proliferation, Rho for cell morphology, Ran for nuclear transport and Rab and Arf for vesicle transport.
- ^ Wennerberg K, Rossman KL, Der CJ (March 2005). "The Ras superfamily at a glance". J. Cell. Sci. 118 (Pt 5): 843–6. doi:10.1242/jcs.01660. PMID 15731001.
- ^ Munemitsu S, Innis M, Clark R, McCormick F, Ullrich A, Polakis P. (1990). "Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42". Mol Cell Biol 10 (11): 5977–82. ISSN 0270-7306. PMC 361395. PMID 2122236. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=361395.
Hydrolases: acid anhydride hydrolases (EC 3.6) 3.6.1 3.6.2 3.6.3-4: ATPase3.6.3Cu++ (220.127.116.11)Ca+ (18.104.22.168)Na+/K+ (22.214.171.124)H+/K+ (126.96.36.199)ATP4AOther P-type ATPase3.6.4 3.6.5: GTPase188.8.131.52: Heterotrimeric G protein184.108.40.206: Small GTPase > Ras superfamily220.127.116.11: Protein-synthesizing GTPaseProkaryotic (IF-2, EF-Tu, EF-G) · Eukaryotic18.104.22.168-6: Polymerization motors Synaptic vesicleSynaptobrevin/VAMP: VAMP1 · VAMP2 · VAMP3OtherRAB3A COPI COPII RME/ClathrinCLTA · CLTB · CLTC Caveolae Other/ungroupedVesicle formation
Adaptor protein complex 1: AP1AR · AP1B1 · AP1G1 · AP1G2 · AP1M1 · AP1M2 · AP1S1 · AP1S2 · AP1S3
Adaptor protein complex 2: AP2A1 · AP2A2 · AP2B1 · AP2M1 · AP2S1
Adaptor protein complex 3: AP3B1 · AP3B2 · AP3D1 · AP3M1 · AP3M2 · AP3S1 · AP3S2
Adaptor protein complex 4: AP4B1 · AP4E1 · AP4M1 · AP4S1Retromer · TIP47Small GTPaseOther
MAPsee MAP kinase pathway CalciumIntracellular calcium-sensing proteins • Calcineurin • Calcium-calmodulin-dependent protein kinase G protein
cAMP: Heterotrimeric G protein (Gs/Gi) • Adenylate cyclase • cAMP • 3',5'-cyclic-AMP phosphodiesterase • Protein kinase A
cGMP: Guanylate cyclase • cGMP • 3',5'-cyclic-GMP phosphodiesterase • Protein kinase G
Beta-gamma complex Gβ (GNB1, GNB2, GNB3, GNB4, GNB5) • Gγ (GNGT1, GNGT2, GNG2, GNG3, GNG4, GNG5, GNG7, GNG8, GNG10, GNG11, GNG12, GNG13, BSCL2)G protein-coupled receptor kinase • AMP-activated protein kinaseMonomeric
Cyclin LipidPhosphoinositide phospholipase C • Phospholipase c gamma Other protein kinase
Serine/threonine: Casein kinase (1, 2) • eIF-2 kinase (EIF2AK3) • Glycogen synthase kinase (GSK1, GSK2, GSK-3, GSK3A, GSK3B) • IκB kinase (CHUK, IKK2, IKBKG) • Interleukin-1 receptor-associated kinase (IRAK1, IRAK2, IRAK3, IRAK4) • Lim kinase (LIMK1, LIMK2) • p21 activated kinases (PAK1, PAK2, PAK3, PAK4) • Rho-associated protein kinase (ROCK1, ROCK2) • Ribosomal s6 kinase (RPS6KA1)
Tyrosine: ZAP70 • Focal adhesion protein-tyrosine kinase (PTK2, PTK2B) • BTKboth: Dual-specificity kinase
Other phosphoprotein phosphatase
Serine/threonine: Protein phosphatase 2
Tyrosine: protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase • Sh2 domain-containing protein tyrosine phosphataseboth: Dual-specificity phosphatase
Apoptosissee apoptosis signaling pathway GTP-binding protein regulators OtherActivating transcription factor 6 • Signal transducing adaptor protein • I-kappa B protein • Mucin-4 • Olfactory marker protein • Phosphatidylethanolamine binding protein • EDARADD • PRKCSHCategories:
- EC 3.6.5
- Peripheral membrane proteins
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