| General information | | DisProt: | DP00408 | | Name: | Ras-related C3 botulinum toxin substrate 1 [Isoform A (Rac1A)] | | Synonym(s): | RAC1_HUMAN
p21-Rac1
Ras-like protein TC25
Cell migration-inducing gene 5 protein
| | First appeared in release: | Release 3.0 (02/17/2006) | | UniProt: | P63000-1 | | UniGene: | Hs.413812 | | SwissProt: | RAC1_HUMAN | | TrEMBL: | | | NCBI (GI): | 51702787 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 192 | | Percent disordered: | 23% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MQAIKCVVVG DGAVGKTCLL ISYTTNAFPG EYIPTVFDNY SANVMVDGKP VNLGLWDTAG - 60
QEDYDRLRPL SYPQTDVFLI CFSLVSPASF ENVRAKWYPE VRHHCPNTPI ILVGTKLDLR - 120
DDKDTIEKLK EKKLTPITYP QGLAMAKEIG AVKYLECSAL TQRGLKTVFD EAIRAVLCPP - 180
PVKKRKRKCL LL
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| Functional narrative |
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | Switch I | | Location: | 30 - 38 | | Length: | 9 | | Region sequence: |
GEYIPTVFD | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- X-ray crystallography (100 K; Tris-HCl (pH 7.5) 20 mM; MgCl2 2 mM; dithioerythritol 2 mM; Hepes (pH 7.5) 100 mM; PEG 3350 (18-30%); isopropanol (2-6%))
| References:
- Fiegen D, Haeusler LC, Blumenstein L, Herbrand U, Dvorsky R, Vetter IR, Ahmadian MR. "Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase." J Biol Chem. 2004; 279(6): 4743-9. PubMed: 14625275
| Comments:
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| Region 2 | | Type: | Disordered | | Name: | Switch II | | Location: | 59 - 75 | | Length: | 17 | | Region sequence: |
AGQEDYDRLRPLSYPQT | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Function arises via a disorder to order transition
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- X-ray crystallography (100 K; dithioerythritol 2 mM; Hepes (pH 7.5) 100 mM; isopropanol (2-6%); MgCl2 2 mM; PEG 3350 (18-30%); Tris-HCl (pH 7.5) 20 mM)
| References:
- Fiegen D, Haeusler LC, Blumenstein L, Herbrand U, Dvorsky R, Vetter IR, Ahmadian MR. "Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase." J Biol Chem. 2004; 279(6): 4743-9. PubMed: 14625275
| Comments:
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| Region 3 | | Type: | Disordered | | Name: | Insertion | | Location: | 76 - 94 | | Length: | 19 | | Region sequence: |
DVFLICFSLVSPASFENVR | | Modification type: | Complex
Fragment
| | PDB: | | | Structural/functional type: | Relationship to function unknown
| | Functional classes: | Unknown
| | Functional subclasses: | Unknown
| Detection methods:
- X-ray crystallography (100 K; dithioerythritol 2 mM; Hepes (pH 7.5) 100 mM; isopropanol (2-6%); MgCl2 2 mM; PEG 3350 (18-30%); Tris-HCl (pH 7.5) 20 mM)
| References:
- Fiegen D, Haeusler LC, Blumenstein L, Herbrand U, Dvorsky R, Vetter IR, Ahmadian MR. "Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase." J Biol Chem. 2004; 279(6): 4743-9. PubMed: 14625275
| Comments:This 19 amino acid insert appears to have a negative affect on the binding abilities of this protein. Proper binding requires stabilization of the two switch regions, and this disordered insert disrupts that stability.
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| References |
- Lapouge K, Smith SJ, Walker PA, Gamblin SJ, Smerdon SJ, Rittinger K. "Structure of the TPR domain of p67phox in complex with Rac.GTP." Mol Cell. 2000; 6(4): 899-907. PubMed: 11090627
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