Small monomeric GTPase |
Identifiers |
EC number |
3.6.5.2 |
Databases |
IntEnz |
IntEnz view |
BRENDA |
BRENDA entry |
ExPASy |
NiceZyme view |
KEGG |
KEGG entry |
MetaCyc |
metabolic pathway |
PRIAM |
profile |
PDB structures |
RCSB PDB PDBe PDBsum |
Search |
PMC |
articles |
PubMed |
articles |
NCBI |
proteins |
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Small GTPases (EC 3.6.5.2) are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that 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 best-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.
Contents
- 1 The Ras superfamily
- 2 See also
- 3 References
- 4 External links
The Ras superfamily
Main article: Ras superfamily
There are more than a hundred proteins in the Ras superfamily.[1] Based on structure, sequence and function, the Ras superfamily is divided into five main families, (Ras, Rho, Ran, Rab and Arf GTPases).[2] The Ras family itself is further divided into 6 subfamilies: Ras, Ral, Rit, Rap, Rheb, and Rad. 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.[3]
See also
- GTP-binding protein regulators
References
- ^ 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.
- ^ Goitre, L; Trapani, E; Trabalzini, L; Retta, SF (26 December 2013). "The Ras superfamily of small GTPases: the unlocked secrets". 1120: 1–18. doi:10.1007/978-1-62703-791-4_1. PMID 24470015. Retrieved 2 January 2015.
- ^ 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.
External links
- Small GTPases at the US National Library of Medicine Medical Subject Headings (MeSH)
Membrane protein: vesicular transport proteins (TC 1F)
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Synaptic vesicle |
SNARE |
Q-SNARE |
- Syntaxin
- STX1A
- STX1B
- STX2
- STX3
- STX4
- STX5
- STX6
- STX7
- STX8
- STX10
- STX11
- STX12
- STX16
- STX17
- STX18
- STX19
- Munc-18: STXBP1
- STXBP2
- STXBP3
- STXBP4
- STXBP5
- STXBP6
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R-SNARE |
- Synaptobrevin/VAMP: VAMP1
- VAMP2
- VAMP3
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Synaptotagmin |
- SYT1
- SYT2
- SYT3
- SYT4
- SYT5
- SYT6
- SYT7
- SYT8
- SYT9
- SYT10
- SYT11
- SYT12
- SYT13
- SYT14
- SYT15
- SYT16
- SYT17
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Other |
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COPI |
- Coatomer
- COPA
- COPB1
- COPB2
- COPD/Archain
- COPE
- COPG
- COPG2
- COPZ1
- COPZ2
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COPII |
- Coatomer
- SEC23A/SEC24A
- SEC13/SEC31
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RME/Clathrin |
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Caveolae |
- Caveolin (CAV1
- CAV2
- CAV3)
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Other/ungrouped |
Vesicle formation |
Adaptor protein complex 1: |
- AP1AR
- AP1B1
- AP1G1
- AP1G2
- AP1M1
- AP1M2
- AP1S1
- AP1S2
- AP1S3
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Adaptor protein complex 2: |
- AP2A1
- AP2A2
- AP2B1
- AP2M1
- AP2S1
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Adaptor protein complex 3: |
- AP3B1
- AP3B2
- AP3D1
- AP3M1
- AP3M2
- AP3S1
- AP3S2
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Adaptor protein complex 4: |
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BLOC-1: |
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BLOC-2: |
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BLOC-3: |
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Coats: |
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Small GTPase |
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Other |
- EHD protein family: EHD1
- EHD2
- EHD3
- EHD4
- Vacuolar protein sorting: VPS13B
- VPS33B
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See also vesicular transport protein disorders
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Intracellular signaling peptides and proteins
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MAP |
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Calcium |
- Intracellular calcium-sensing proteins
- Calcineurin
- Ca2+/calmodulin-dependent protein kinase
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G protein |
Heterotrimeric |
cAMP: |
- Heterotrimeric G protein
- Adenylate cyclase
- cAMP
- 3',5'-cyclic-AMP phosphodiesterase
- Protein kinase A
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cGMP: |
- Transducin
- Gustducin
- Guanylate cyclase
- cGMP
- 3',5'-cyclic-GMP phosphodiesterase
- Protein kinase G
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- G alpha subunit Gα
- GNAO1
- GNAI1
- GNAI2
- GNAI3
- GNAT1
- GNAT2
- GNAT3
- GNAZ
- GNAS
- GNAL
- GNAQ
- GNA11
- GNA12
- GNA13
- GNA14
- GNA15/GNA16
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- G beta-gamma complex Gβ
- Gγ
- GNGT1
- GNGT2
- GNG2
- GNG3
- GNG4
- GNG5
- GNG7
- GNG8
- GNG10
- GNG11
- GNG12
- GNG13
- BSCL2
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- G protein-coupled receptor kinase
- AMP-activated protein kinase
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Monomeric |
- ARFs
- Rabs
- Ras
- Rhos
- Arfs
- Ran
- Rhebs
- Raps
- RGKs
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Cyclin |
- Cyclin-dependent kinase inhibitor protein
- Cyclin-dependent kinase
- Cyclin
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Lipid |
- Phosphoinositide phospholipase C
- Phospholipase C
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Other protein kinase |
Serine/threonine: |
- Casein kinase
- eIF-2 kinase
- Glycogen synthase kinase
- GSK1
- GSK2
- GSK-3
- GSK3A
- GSK3B
- IκB kinase
- Interleukin-1 receptor-associated kinase
- Lim kinase
- p21-activated kinases
- Rho-associated protein kinase
- Ribosomal s6 kinase
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Tyrosine: |
- ZAP70
- Focal adhesion protein-tyrosine kinase
- BTK
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both |
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Other protein phosphatase |
Serine/threonine: |
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Tyrosine: |
- protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase
- Sh2 domain-containing protein tyrosine phosphatase
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both: |
- Dual-specificity phosphatase
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Apoptosis |
- see apoptosis signaling pathway
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GTP-binding protein regulators |
- see GTP-binding protein regulators
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Other |
- Activating transcription factor 6
- Signal transducing adaptor protein
- I-kappa B protein
- Mucin-4
- Olfactory marker protein
- Phosphatidylethanolamine binding protein
- EDARADD
- PRKCSH
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see also deficiencies of intracellular signaling peptides and proteins
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Hydrolases: acid anhydride hydrolases (EC 3.6)
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3.6.1 |
- Pyrophosphatase
- Apyrase
- Thiamine-triphosphatase
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3.6.2 |
- Adenylylsulfatase
- Phosphoadenylylsulfatase
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3.6.3-4: ATPase |
3.6.3 |
Cu++ (3.6.3.4) |
- Menkes/ATP7A
- Wilson/ATP7B
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Ca+ (3.6.3.8) |
- SERCA
- Plasma membrane
- ATP2B1
- ATP2B2
- ATP2B3
- ATP2B4
- SPCA
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Na+/K+ (3.6.3.9) |
- ATP1A1
- ATP1A2
- ATP1A3
- ATP1A4
- ATP1B1
- ATP1B2
- ATP1B3
- ATP1B4
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H+/K+ (3.6.3.10) |
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Other P-type ATPase |
- ATP8B1
- ATP10A
- ATP11B
- ATP12A
- ATP13A2
- ATP13A3
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3.6.4 |
- Dynein
- Kinesin
- Myosin
- Katanin
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3.6.5: GTPase |
3.6.5.1: Heterotrimeric G protein |
- Gαs
- Gαi
- Gαq/11
- Gα12/13
- Transducin
- Gustducin
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3.6.5.2: Small GTPase > Ras superfamily |
- Rho family of GTPases: Cdc42
- RhoUV
- Rac
- RhoBTB
- RhoH
- Rho
- Rnd
- RhoDF
- other: Ras
- Rab
- Arf
- Ran
- Rheb
- Rap
- RGK
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3.6.5.3: Protein-synthesizing GTPase |
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3.6.5.5-6: Polymerization motors |
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Enzymes
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Activity |
- Active site
- Binding site
- Catalytic triad
- Oxyanion hole
- Enzyme promiscuity
- Catalytically perfect enzyme
- Coenzyme
- Cofactor
- Enzyme catalysis
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Regulation |
- Allosteric regulation
- Cooperativity
- Enzyme inhibitor
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Classification |
- EC number
- Enzyme superfamily
- Enzyme family
- List of enzymes
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Kinetics |
- Enzyme kinetics
- Eadie–Hofstee diagram
- Hanes–Woolf plot
- Lineweaver–Burk plot
- Michaelis–Menten kinetics
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Types |
- EC1 Oxidoreductases (list)
- EC2 Transferases (list)
- EC3 Hydrolases (list)
- EC4 Lyases (list)
- EC5 Isomerases (list)
- EC6 Ligases (list)
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