RHO GTPases activate KTN1 (Homo sapiens)

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3, 41-5, 74, 6cytosolendoplasmic reticulum lumenKLC4 RHOA RAC1 Kinesin-1KLC3 CDC42 KIF5B GTP KLC2 CDC42 KIF5A RHOG KIF5B RAC1 GTP KIF5A RHOA KLC1 RHOA,RHOG,RAC1,CDC42:GTP:KTN1:Kinesin-1RHOG RHOG RHOA,RHOG,RAC1,CDC42:GTPKTN1KLC2 KLC1 GTP KTN1 KTN1 CDC42 RHOA KLC3 RAC1 RHOA,RHOG,RAC1,CDC42:GTP:KTN1KLC4 KTN1 4, 61, 2, 5, 7


Description

GTP-bound active forms of RHO GTPases RHOA, RHOG, RAC1 and CDC42 bind kinectin (KTN1), a protein inserted in endoplasmic reticulum membranes that interacts with the cargo-binding site of kinesin and activates its microtubule-stimulated ATPase activity required for vesicle motility (Vignal et al. 2001, Hotta et al. 1996). The effect of RHOG activity on cellular morphology, exhibited in the formation of microtubule-dependent cellular protrusions, depends both on RHOG interaction with KTN1, as well as on the kinesin activity (Vignal et al. 2001). RHOG and KTN1 also cooperate in microtubule-dependent lysosomal transport (Vignal et al. 2001). The precise mechanism of kinectin-mediated Rho GTPase signaling cascade needs further elucidation, and only the first two steps, KTN1-activated RHO GTPase binding, and KTN1-kinesin-1 binding are annotated here. View original pathway at:Reactome.

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Bibliography

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  1. Kumar J, Erickson HP, Sheetz MP.; ''Ultrastructural and biochemical properties of the 120-kDa form of chick kinectin.''; PubMed Europe PMC Scholia
  2. Ong LL, Lim AP, Er CP, Kuznetsov SA, Yu H.; ''Kinectin-kinesin binding domains and their effects on organelle motility.''; PubMed Europe PMC Scholia
  3. Hotta K, Tanaka K, Mino A, Kohno H, Takai Y.; ''Interaction of the Rho family small G proteins with kinectin, an anchoring protein of kinesin motor.''; PubMed Europe PMC Scholia
  4. Leung E, Print CG, Parry DA, Closey DN, Lockhart PJ, Skinner SJ, Batchelor DC, Krissansen GW.; ''Cloning of novel kinectin splice variants with alternative C-termini: structure, distribution and evolution of mouse kinectin.''; PubMed Europe PMC Scholia
  5. Xu J, Bird PH, Bradley MP, Janssens PA, Hardy CM.; ''Molecular cloning and characterization of fox testis kinectin.''; PubMed Europe PMC Scholia
  6. Yu H, Nicchitta CV, Kumar J, Becker M, Toyoshima I, Sheetz MP.; ''Characterization of kinectin, a kinesin-binding protein: primary sequence and N-terminal topogenic signal analysis.''; PubMed Europe PMC Scholia
  7. Vignal E, Blangy A, Martin M, Gauthier-Rouvière C, Fort P.; ''Kinectin is a key effector of RhoG microtubule-dependent cellular activity.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114984view16:51, 25 January 2021ReactomeTeamReactome version 75
113428view11:50, 2 November 2020ReactomeTeamReactome version 74
112630view16:01, 9 October 2020ReactomeTeamReactome version 73
101545view11:41, 1 November 2018ReactomeTeamreactome version 66
101080view21:23, 31 October 2018ReactomeTeamreactome version 65
100610view19:58, 31 October 2018ReactomeTeamreactome version 64
100161view16:43, 31 October 2018ReactomeTeamreactome version 63
99711view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99291view12:46, 31 October 2018ReactomeTeamreactome version 62
93889view13:43, 16 August 2017ReactomeTeamreactome version 61
93459view11:24, 9 August 2017ReactomeTeamreactome version 61
89084view08:02, 22 August 2016EgonwOntology Term : 'signaling pathway' added !
86554view09:20, 11 July 2016ReactomeTeamreactome version 56
83112view09:59, 18 November 2015ReactomeTeamVersion54
81445view12:58, 21 August 2015ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CDC42 ProteinP60953 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
KIF5A ProteinQ12840 (Uniprot-TrEMBL)
KIF5B ProteinP33176 (Uniprot-TrEMBL)
KLC1 ProteinQ07866 (Uniprot-TrEMBL)
KLC2 ProteinQ9H0B6 (Uniprot-TrEMBL)
KLC3 ProteinQ6P597 (Uniprot-TrEMBL)
KLC4 ProteinQ9NSK0 (Uniprot-TrEMBL)
KTN1 ProteinQ86UP2 (Uniprot-TrEMBL)
KTN1ComplexR-HSA-5672103 (Reactome)
Kinesin-1ComplexR-HSA-983227 (Reactome)
RAC1 ProteinP63000 (Uniprot-TrEMBL)
RHOA ProteinP61586 (Uniprot-TrEMBL)
RHOA,RHOG,RAC1,CDC42:GTP:KTN1:Kinesin-1ComplexR-HSA-5672087 (Reactome)
RHOA,RHOG,RAC1,CDC42:GTP:KTN1ComplexR-HSA-5625955 (Reactome)
RHOA,RHOG,RAC1,CDC42:GTPComplexR-HSA-5625964 (Reactome)
RHOG ProteinP84095 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
KTN1R-HSA-5625959 (Reactome)
Kinesin-1R-HSA-5672083 (Reactome)
R-HSA-5625959 (Reactome) Kinectin, a kinesin anchor involved in kinesin-mediated vesicle motility, interacts with GTP bound (active) forms of Rho GTPases RHOG (Vignal et al. 2001), RHOA, RAC1 and CDC42 (Hotta et al. 1996). Separate domains of kinectin are responsible for its interaction with RHOG and RHOA (Vignal et al. 2001). Based on several studies in different organisms, kinectin likely exists as a coiled-coil dimer (Yu et al. 1995, Leung et al. 1996, Kumar et al. 1998, Xu et al. 2002).
R-HSA-5672083 (Reactome) The C-terminal region of KTN1 (kinectin) binds the cargo-binding tail of the kinesin heavy chain KIF5A and enhances microtubule-stimulated ATPase activity of KIF5A. KIF5A is a part of the conventional kinesin complex, kinesin-1. RHO GTPases, KTN1 and kinesin-1 colocalize on endoplasmic reticulum (ER) membranes and ER-derived vesicles and are thought to be involved in organelle/vesicle motility (Ong et al. 2000, Vignal et al. 2001)
RHOA,RHOG,RAC1,CDC42:GTP:KTN1:Kinesin-1ArrowR-HSA-5672083 (Reactome)
RHOA,RHOG,RAC1,CDC42:GTP:KTN1ArrowR-HSA-5625959 (Reactome)
RHOA,RHOG,RAC1,CDC42:GTP:KTN1R-HSA-5672083 (Reactome)
RHOA,RHOG,RAC1,CDC42:GTPR-HSA-5625959 (Reactome)
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