Translocation of SLC2A4 (GLUT4) to the plasma membrane (Homo sapiens)

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Bibliography

1. Bogan JS, Kandror KV.; ''Biogenesis and regulation of insulin-responsive vesicles containing GLUT4.''; PubMed Europe PMC Scholia
2. Ramm G, Larance M, Guilhaus M, James DE.; ''A role for 14-3-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160.''; PubMed Europe PMC Scholia
3. Mîinea CP, Sano H, Kane S, Sano E, Fukuda M, Peränen J, Lane WS, Lienhard GE.; ''AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain.''; PubMed Europe PMC Scholia
4. Murga-Zamalloa CA, Atkins SJ, Peranen J, Swaroop A, Khanna H.; ''Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration.''; PubMed Europe PMC Scholia
5. Koumanov F, Richardson JD, Murrow BA, Holman GD.; ''AS160 phosphotyrosine-binding domain constructs inhibit insulin-stimulated GLUT4 vesicle fusion with the plasma membrane.''; PubMed Europe PMC Scholia
6. Karlsson HK, Zierath JR, Kane S, Krook A, Lienhard GE, Wallberg-Henriksson H.; ''Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects.''; PubMed Europe PMC Scholia
7. Leney SE, Tavaré JM.; ''The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets.''; PubMed Europe PMC Scholia
8. Polakis PG, Weber RF, Nevins B, Didsbury JR, Evans T, Snyderman R.; ''Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets.''; PubMed Europe PMC Scholia
9. Kinsella BT, Erdman RA, Maltese WA.; ''Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA.''; PubMed Europe PMC Scholia
10. Vichaiwong K, Purohit S, An D, Toyoda T, Jessen N, Hirshman MF, Goodyear LJ.; ''Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle.''; PubMed Europe PMC Scholia
11. Xie X, Gong Z, Mansuy-Aubert V, Zhou QL, Tatulian SA, Sehrt D, Gnad F, Brill LM, Motamedchaboki K, Chen Y, Czech MP, Mann M, Krüger M, Jiang ZY.; ''C2 domain-containing phosphoprotein CDP138 regulates GLUT4 insertion into the plasma membrane.''; PubMed Europe PMC Scholia
12. Ngo S, Barry JB, Nisbet JC, Prins JB, Whitehead JP.; ''Reduced phosphorylation of AS160 contributes to glucocorticoid-mediated inhibition of glucose uptake in human and murine adipocytes.''; PubMed Europe PMC Scholia
13. Chen S, Murphy J, Toth R, Campbell DG, Morrice NA, Mackintosh C.; ''Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators.''; PubMed Europe PMC Scholia
14. Frøsig C, Pehmøller C, Birk JB, Richter EA, Wojtaszewski JF.; ''Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle.''; PubMed Europe PMC Scholia
15. Foley K, Boguslavsky S, Klip A.; ''Endocytosis, recycling, and regulated exocytosis of glucose transporter 4.''; PubMed Europe PMC Scholia
16. Kandror KV, Pilch PF.; ''The sugar is sIRVed: sorting Glut4 and its fellow travelers.''; PubMed Europe PMC Scholia
17. Jaldin-Fincati JR, Pavarotti M, Frendo-Cumbo S, Bilan PJ, Klip A.; ''Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action.''; PubMed Europe PMC Scholia
18. Syed NA, Horner KN, Misra V, Khandelwal RL.; ''Different cellular localization, translocation, and insulin-induced phosphorylation of PKBalpha in HepG2 cells and hepatocytes.''; PubMed Europe PMC Scholia
19. Zaid H, Antonescu CN, Randhawa VK, Klip A.; ''Insulin action on glucose transporters through molecular switches, tracks and tethers.''; PubMed Europe PMC Scholia
20. Hoffman NJ, Elmendorf JS.; ''Signaling, cytoskeletal and membrane mechanisms regulating GLUT4 exocytosis.''; PubMed Europe PMC Scholia
21. Howlett KF, Sakamoto K, Garnham A, Cameron-Smith D, Hargreaves M.; ''Resistance exercise and insulin regulate AS160 and interaction with 14-3-3 in human skeletal muscle.''; PubMed Europe PMC Scholia
22. Pessin JE, Bell GI.; ''Mammalian facilitative glucose transporter family: structure and molecular regulation.''; PubMed Europe PMC Scholia
23. Yoshimura S, Gerondopoulos A, Linford A, Rigden DJ, Barr FA.; ''Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors.''; PubMed Europe PMC Scholia
24. Meier R, Alessi DR, Cron P, Andjelković M, Hemmings BA.; ''Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta.''; PubMed Europe PMC Scholia
25. Albright CF, Giddings BW, Liu J, Vito M, Weinberg RA.; ''Characterization of a guanine nucleotide dissociation stimulator for a ras-related GTPase.''; PubMed Europe PMC Scholia
26. Andjelković M, Alessi DR, Meier R, Fernandez A, Lamb NJ, Frech M, Cron P, Cohen P, Lucocq JM, Hemmings BA.; ''Role of translocation in the activation and function of protein kinase B.''; PubMed Europe PMC Scholia
27. Treebak JT, Frøsig C, Pehmøller C, Chen S, Maarbjerg SJ, Brandt N, MacKintosh C, Zierath JR, Hardie DG, Kiens B, Richter EA, Pilegaard H, Wojtaszewski JF.; ''Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle.''; PubMed Europe PMC Scholia
28. Bhullar RP, Seneviratne HD.; ''Characterization of human platelet GTPase activating protein for the Ral GTP-binding protein.''; PubMed Europe PMC Scholia
29. Navarro-Lérida I, Sánchez-Perales S, Calvo M, Rentero C, Zheng Y, Enrich C, Del Pozo MA.; ''A palmitoylation switch mechanism regulates Rac1 function and membrane organization.''; PubMed Europe PMC Scholia
30. Park SY, Jin W, Woo JR, Shoelson SE.; ''Crystal structures of human TBC1D1 and TBC1D4 (AS160) RabGTPase-activating protein (RabGAP) domains reveal critical elements for GLUT4 translocation.''; PubMed Europe PMC Scholia
31. Andjelković M, Maira SM, Cron P, Parker PJ, Hemmings BA.; ''Domain swapping used to investigate the mechanism of protein kinase B regulation by 3-phosphoinositide-dependent protein kinase 1 and Ser473 kinase.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
14-3-3 dimer		R-HSA-1445138 (Reactome)
ADP	Metabolite	CHEBI:16761 (ChEBI)
AMP	Metabolite	CHEBI:16027 (ChEBI)
AMPK-alpha2:AMPK-beta:AMPK-gamma:AMP	Complex	R-HSA-1454683 (Reactome)
AS160:IRAP	Complex	R-HSA-1445125 (Reactome)
ASPSCR1	Protein	Q9BZE9 (Uniprot-TrEMBL)
ASPSCR1	Protein	Q9BZE9 (Uniprot-TrEMBL)
ATP	Metabolite	CHEBI:15422 (ChEBI)
C2CD5	Protein	Q86YS7 (Uniprot-TrEMBL)
C2CD5:2xCa2+	Complex	R-HSA-5260209 (Reactome)
CALM1	Protein	P62158 (Uniprot-TrEMBL)
Ca2+	Metabolite	CHEBI:29108 (ChEBI)
EXOC1	Protein	Q9NV70 (Uniprot-TrEMBL)
EXOC2	Protein	Q96KP1 (Uniprot-TrEMBL)
EXOC3	Protein	O60645 (Uniprot-TrEMBL)
EXOC4	Protein	Q96A65 (Uniprot-TrEMBL)
EXOC5	Protein	O00471 (Uniprot-TrEMBL)
EXOC6	Protein	Q8TAG9 (Uniprot-TrEMBL)
EXOC7	Protein	Q9UPT5 (Uniprot-TrEMBL)
EXOC8	Protein	Q8IYI6 (Uniprot-TrEMBL)
Exocyst Complex	Complex	R-HSA-264974 (Reactome)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GGC-PalmC-RAC1	Protein	P63000 (Uniprot-TrEMBL)
GLUT4:TUG	Complex	R-HSA-1449566 (Reactome)
GTP	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
KIF3A	Protein	Q9Y496 (Uniprot-TrEMBL)
KIF3B	Protein	O15066 (Uniprot-TrEMBL)
KIF3	Complex	R-HSA-2316334 (Reactome)
KIFAP3	Protein	Q92845 (Uniprot-TrEMBL)
LNPEP	Protein	Q9UIQ6 (Uniprot-TrEMBL)
MYH2-like proteins		R-HSA-4127437 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
MYH4-like proteins		R-HSA-4127445 (Reactome)	This CandidateSet contains sequences identified by William Pearson's analysis of Reactome catalyst entities. Catalyst entity sequences were used to identify analagous sequences that shared overall homology and active site homology. Sequences in this Candidate set were identified in an April 24, 2012 analysis.
MYO1C	Protein	O00159 (Uniprot-TrEMBL)
MYO1C:CALM1	Complex	R-HSA-2316345 (Reactome)
MYO5A	Protein	Q9Y4I1 (Uniprot-TrEMBL)
PRKAB1	Protein	Q9Y478 (Uniprot-TrEMBL)
PRKAB2	Protein	O43741 (Uniprot-TrEMBL)
PRKAG1	Protein	P54619 (Uniprot-TrEMBL)
PRKAG2	Protein	Q9UGJ0 (Uniprot-TrEMBL)
PRKAG3	Protein	Q9UGI9 (Uniprot-TrEMBL)
Pi	Metabolite	CHEBI:18367 (ChEBI)
RAB10	Protein	P61026 (Uniprot-TrEMBL)
RAB11A	Protein	P62491 (Uniprot-TrEMBL)
RAB11A:GTP	Complex	R-HSA-1458542 (Reactome)
RAB13	Protein	P51153 (Uniprot-TrEMBL)
RAB14	Protein	P61106 (Uniprot-TrEMBL)
RAB4A	Protein	P20338 (Uniprot-TrEMBL)
RAB4A:GTP:KIF3:microtubule	Complex	R-HSA-1458522 (Reactome)
RAB4A:GTP	Complex	R-HSA-1458538 (Reactome)
RAB8A	Protein	P61006 (Uniprot-TrEMBL)
RAB8A,10,13,14:GDP	Complex	R-HSA-1445130 (Reactome)
RAB8A,10,13,14:GTP	Complex	R-HSA-1445137 (Reactome)
RAC1:GTP	Complex	R-HSA-2316448 (Reactome)
RALA	Protein	P11233 (Uniprot-TrEMBL)
RALA:GDP	Complex	R-HSA-1458466 (Reactome)
RALA:GTP:MYO1C:Calmodulin:F-actin	Complex	R-HSA-2316344 (Reactome)
RALA:GTP:MYO1C:Exocyst	Complex	R-HSA-2316343 (Reactome)
RALA:GTP	Complex	R-HSA-1458506 (Reactome)
RALGAPA2	Protein	Q2PPJ7 (Uniprot-TrEMBL)
RALGAPB	Protein	Q86X10 (Uniprot-TrEMBL)
RGC1:RGC2	Complex	R-HSA-1458509 (Reactome)
RGC1:p-486,696-T715-RGC2	Complex	R-HSA-1458472 (Reactome)
RHOQ	Protein	P17081 (Uniprot-TrEMBL)
RHOQ:GTP	Complex	R-HSA-2316453 (Reactome)
SFN	Protein	P31947 (Uniprot-TrEMBL)
SLC2A4	Protein	P14672 (Uniprot-TrEMBL)
SLC2A4	Protein	P14672 (Uniprot-TrEMBL)
SNAP23	Protein	O00161 (Uniprot-TrEMBL)
SNAP23	Protein	O00161 (Uniprot-TrEMBL)
STX4	Protein	Q12846 (Uniprot-TrEMBL)
STX4:STXBP3 (MUNC18C)	Complex	R-HSA-2263479 (Reactome)
STXBP3	Protein	O00186 (Uniprot-TrEMBL)
TBC1D1	Protein	Q86TI0 (Uniprot-TrEMBL)	As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.
TBC1D4	Protein	O60343 (Uniprot-TrEMBL)
TBC1D4	Protein	O60343 (Uniprot-TrEMBL)
VAMP2	Protein	P63027 (Uniprot-TrEMBL)
VAMP2:STX4:SNAP23	Complex	R-HSA-1449628 (Reactome)
VAMP2	Protein	P63027 (Uniprot-TrEMBL)
YWHAB	Protein	P31946 (Uniprot-TrEMBL)
YWHAE	Protein	P62258 (Uniprot-TrEMBL)
YWHAG	Protein	P61981 (Uniprot-TrEMBL)
YWHAH	Protein	Q04917 (Uniprot-TrEMBL)
YWHAQ	Protein	P27348 (Uniprot-TrEMBL)
YWHAZ	Protein	P63104 (Uniprot-TrEMBL)
f-actin (ADP)		R-HSA-202998 (Reactome)
microtubule		R-HSA-190599 (Reactome)
p-5S,T642-AS160:14-3-3:IRAP	Complex	R-HSA-1445124 (Reactome)
p-5S,T642-AS160:IRAP	Complex	R-HSA-1445133 (Reactome)	AS160 (TBC1D4) phosphorylated on serines 318, 341, 570, 588, and 751 and threonine 642 binds to all 14-3-3 proteins, although binding to 14-3-3 delta (YWHAZ) is comparatively low (Ramm et al. 2006, Howlett et al. 2007, Ngo et al. 2009, Treebak et al. 2009, Koumanov et al. 2011). As inferred from mouse, binding to 14-3-3 does not interfere with the interaction between AS160 and IRAP (LNPEP).
p-5S,T642-TBC1D4	Protein	O60343 (Uniprot-TrEMBL)
p-S1652-MYO5A	Protein	Q9Y4I1 (Uniprot-TrEMBL)
p-S1652-MYO5A:F-actin	Complex	R-HSA-2316339 (Reactome)
p-S197-C2CD5	Protein	Q86YS7 (Uniprot-TrEMBL)
p-S197-C2CD5:2xCa2+	Complex	R-HSA-5260210 (Reactome)
p-S237-TBC1D1	Protein	Q86TI0 (Uniprot-TrEMBL)	As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.
p-S237-TBC1D1:14-3-3	Complex	R-HSA-1454696 (Reactome)
p-S237-TBC1D1	Protein	Q86TI0 (Uniprot-TrEMBL)	As inferred from rat L6 muscle cells, TBC1D1 is located in the perinuclear cytosol (Chen et al. 2008). TBC1D1 is observed throughout the cytosol and, based on its homology to TBC1D4 and its interaction with membrane-bound RAB proteins, TBC1D1 is expected to be concentrated near vesicle membranes.
p-S486,S696,T715-RALGAPA2	Protein	Q2PPJ7 (Uniprot-TrEMBL)
p-T172-PRKAA2	Protein	P54646 (Uniprot-TrEMBL)
p-T308,S473-AKT1	Protein	P31749 (Uniprot-TrEMBL)
p-T309,S474-AKT2	Protein	P31751 (Uniprot-TrEMBL)
p-Y521-STXBP3	Protein	O00186 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
14-3-3 dimer			R-HSA-1445149 (Reactome)
14-3-3 dimer			R-HSA-1454689 (Reactome)
	ADP	Arrow	R-HSA-1445144 (Reactome)
	ADP	Arrow	R-HSA-1449574 (Reactome)
	ADP	Arrow	R-HSA-1449597 (Reactome)
	ADP	Arrow	R-HSA-1454699 (Reactome)
	ADP	Arrow	R-HSA-1458463 (Reactome)
	ADP	Arrow	R-HSA-5260201 (Reactome)
AMPK-alpha2:AMPK-beta:AMPK-gamma:AMP		mim-catalysis	R-HSA-1454699 (Reactome)
AS160:IRAP			R-HSA-1445144 (Reactome)
	ASPSCR1	Arrow	R-HSA-1449574 (Reactome)
ATP			R-HSA-1445144 (Reactome)
ATP			R-HSA-1449574 (Reactome)
ATP			R-HSA-1449597 (Reactome)
ATP			R-HSA-1454699 (Reactome)
ATP			R-HSA-1458463 (Reactome)
ATP			R-HSA-5260201 (Reactome)
		Arrow	R-HSA-2316352 (Reactome)
C2CD5:2xCa2+			R-HSA-5260201 (Reactome)
Exocyst Complex			R-HSA-2316352 (Reactome)
	GDP	Arrow	R-HSA-2255342 (Reactome)
	GDP	Arrow	R-HSA-2255343 (Reactome)
GLUT4:TUG			R-HSA-1449574 (Reactome)
GTP			R-HSA-2255342 (Reactome)
GTP			R-HSA-2255343 (Reactome)
KIF3			R-HSA-2316347 (Reactome)
MYH2-like proteins		mim-catalysis	R-HSA-2316352 (Reactome)
MYH4-like proteins		mim-catalysis	R-HSA-2316352 (Reactome)
MYO1C:CALM1			R-HSA-2316349 (Reactome)
MYO5A			R-HSA-1449597 (Reactome)
	Pi	Arrow	R-HSA-1458485 (Reactome)
			R-HSA-1445143 (Reactome)	RAB proteins have intrinsic weak GTPase activity that is enhanced by RAB-GTPase activating proteins (RAB-GAPs, Sano et al. 2007). The GTPase activity of RAB13 is inferred from other RAB proteins. AS160 (TBC1D4) and TBC1D1 are GAPs that activate the GTPase activity of RAB8A/10/13. Insulin signaling activates AKT, which phosphorylates and inactivates AS160 and TBC1D1, allowing GTP-bound (active) RABs to accumulate.
			R-HSA-1445144 (Reactome)	As inferred from mouse, AKT2 and, to a lesser extent, AKT1 phosphorylate AS160 (TBC1D4) in response to insulin signaling (Howlett et al. 2007, Karlsson et al 2005). AS160, a RAB GTPase activating protein, interacts with IRAP (LNPEP) and is associated with cytoplasmic vesicles containing GLUT4 (SLC2A4).
			R-HSA-1445149 (Reactome)	AS160 (TBC1D4) phosphorylated on serines 318, 341, 570, 588, and 751 and threonine 642 binds to all 14-3-3 proteins, although binding to 14-3-3 delta (YWHAZ) is comparatively low (Ramm et al. 2006, Howlett et al. 2007, Ngo et al. 2009, Treebak et al. 2009, Koumanov et al. 2011). As inferred from mouse, binding to 14-3-3 does not interfere with the interaction between AS160 and IRAP (LNPEP).
			R-HSA-1449574 (Reactome)	After docking at the membrane VAMP2 on the vesicle interacts with SYNTAXIN-4 and SNAP23 on the plasma membrane to catalyze fusion of the vesicle with the plasma membrane. STXBP3 (MUNC18C) bound to STX4 prevents fusion until STXBP3 is phosphorylated.
			R-HSA-1449597 (Reactome)	As inferred from mouse, AKT2 phosphorylates Myosin 5A on serine-1652. The phosphorylation promotes association of Myosin 5A with actin and ATPase activity of Myosin 5A.
			R-HSA-1454689 (Reactome)	TBC1D1 phosphorylated on serine-237 binds 14-3-3 proteins in assays with yeast 14-3-3 proteins BMH1 and BMH2 (Chen et al. 2008, Frosig et al. 2010). Binding with human 14-3-3 proteins is inferred.
			R-HSA-1454699 (Reactome)	In response to muscle contraction and insulin signaling, AMPK-alpha2 phosphorylates TBC1D1 on serine 237 and probably other residues (Frosig et al. 2010, Vichaiwong et al. 2010). As inferred from rat L6 muscle cells TBC1D1 colocalizes with perinuclear vesicles bearing GLUT4 (SLC2A4) and may be involved in an early step that mobilizes them (Chen et al. 2008). Human TBC1D1 appears cytosolic and is believed to be concentrated near vesicle membranes (Park et al. 2011).
			R-HSA-1458463 (Reactome)	As inferred from mouse, AKT2 (PKB-beta) phosphorylates RBC2 (RALGAPA2) on serine-486, serine-696, and threonine-715 in response to insulin. The phosphorylation prevents RBC1:RBC2 from activating RALA GTPase and allows RALA:GTP to accumulate.
			R-HSA-1458485 (Reactome)	RALA is a guanine nucleotide binding protein that hydrolyzes bound GTP to yield GDP and phosphate. RGC1 and RGC2 are GAPs (GTPase-activating proteins) that activate the GTPase activity of RALA. Insulin activates AKT, which phosphorylates RGC2, inactivating the GAP activity of RGC1:RGC2 and allowing RALA:GTP to accumulate.
			R-HSA-2255342 (Reactome)	RALA releases GDP and binds GTP, producing the active form of RALA. The reaction is accelerated by guanine nucleotide exchange factors (GEFs) and opposed by GTPase-activating proteins (GAPs) which enhance the conversion of RALA:GTP back to RALA:GDP by activating the GTPase activity of RALA.
			R-HSA-2255343 (Reactome)	RAB8A/10/13/14 release GDP and bind GTP to yield the active complex. Guanine nucleotide exchange factors (GEFs) stimulate the reaction. GTPase-activating proteins (GAPs) oppose the reaction by stimulating the intrinsic GTPase activity of the RAB proteins.
			R-HSA-2316347 (Reactome)	As inferred from mouse adipocytes, insulin signals via PKC-lambda to cause Rab4 to load GTP and associate with Kif3, which then has higher affinity for microtubules. Motor activity of Kif3 along microtubules is believed to transport vesicles containing Glut4 (Slc2a4) across the cytosol to the cortical actin network.
			R-HSA-2316349 (Reactome)	As inferred from mouse, insulin causes phosphorylation and inactivation of the Ral GTPase activating complex RGC, causing RALA:GTP to accumulate and associate with the unconventional myosin MYO1C. MYO1C, with calmodulin as a light chain, motors across cortical actin and interacts with the exocyst complex to tether vesicles at the plasma membrane (Chen et al. 2007).
			R-HSA-2316352 (Reactome)	As inferred from mouse, GLUT4 (SLC2A4) initially translocates from endosomes to insulin-responsive vesicles (IRVs, GSVs). RAB11 appears to play a role in this process. IRVs bearing GLUT4 are then translocated across the cortical actin network to the plasma membrane. Myosins 2A, 2B, 5A, and 5B contribute to translocation and are presumed to be involved in this step. Myosin 1C appears to act close to the plasma membrane and may facilitate fusion of the vesicle with the plasma membrane. RAB:GTP complexes coupled to the vesicles may interact with myosins to regulate their activity.
			R-HSA-5260201 (Reactome)	The protein kinase B beta (AKT) pathway mediates insulin-stimulated glucose transport by increasing glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. C2 domain-containing protein 5 (C2CD5 aka C2 domain-containing phosphoprotein 138kDa) has been shown to be required for optimal insulin-stimulated GLUT4 translocation and fusion of GLUT4 vesicles with the plasma membrane in adipocytes. It is also able to bind Ca2+ and lipid membranes in its C2 domain. C2CD5 is a substrate for RAC-beta serine/threonine-protein kinase (AKT2), which phosphorylates C2CD5 at serine 197. Phosphorylated C2CD5 optimises GLUT4 translocation to the plasma membrane. The role of human C2CD5 is inferred from the role of the orthologous mouse protein (Xie et al. 2011).
RAB11A:GTP		Arrow	R-HSA-2316352 (Reactome)
	RAB4A:GTP:KIF3:microtubule	Arrow	R-HSA-2316347 (Reactome)
RAB4A:GTP			R-HSA-2316347 (Reactome)
	RAB8A,10,13,14:GDP	Arrow	R-HSA-1445143 (Reactome)
RAB8A,10,13,14:GDP			R-HSA-2255343 (Reactome)
	RAB8A,10,13,14:GTP	Arrow	R-HSA-2255343 (Reactome)
RAB8A,10,13,14:GTP		Arrow	R-HSA-2316352 (Reactome)
RAB8A,10,13,14:GTP			R-HSA-1445143 (Reactome)
RAB8A,10,13,14:GTP		mim-catalysis	R-HSA-1445143 (Reactome)
	RALA:GDP	Arrow	R-HSA-1458485 (Reactome)
RALA:GDP			R-HSA-2255342 (Reactome)
	RALA:GTP:MYO1C:Calmodulin:F-actin	Arrow	R-HSA-2316349 (Reactome)
RALA:GTP:MYO1C:Calmodulin:F-actin			R-HSA-2316352 (Reactome)
RALA:GTP:MYO1C:Calmodulin:F-actin		mim-catalysis	R-HSA-2316352 (Reactome)
	RALA:GTP:MYO1C:Exocyst	Arrow	R-HSA-2316352 (Reactome)
	RALA:GTP	Arrow	R-HSA-2255342 (Reactome)
RALA:GTP			R-HSA-1458485 (Reactome)
RALA:GTP			R-HSA-2316349 (Reactome)
RALA:GTP		mim-catalysis	R-HSA-1458485 (Reactome)
RGC1:RGC2		Arrow	R-HSA-1458485 (Reactome)
RGC1:RGC2			R-HSA-1458463 (Reactome)
	RGC1:p-486,696-T715-RGC2	Arrow	R-HSA-1458463 (Reactome)
	SLC2A4	Arrow	R-HSA-1449574 (Reactome)
SNAP23			R-HSA-1449574 (Reactome)
STX4:STXBP3 (MUNC18C)			R-HSA-1449574 (Reactome)
TBC1D1		Arrow	R-HSA-1445143 (Reactome)
TBC1D1			R-HSA-1454699 (Reactome)
TBC1D4		Arrow	R-HSA-1445143 (Reactome)
	VAMP2:STX4:SNAP23	Arrow	R-HSA-1449574 (Reactome)
VAMP2			R-HSA-1449574 (Reactome)
f-actin (ADP)			R-HSA-1449597 (Reactome)
f-actin (ADP)			R-HSA-2316349 (Reactome)
microtubule			R-HSA-2316347 (Reactome)
		mim-catalysis	R-HSA-1445144 (Reactome)
	p-5S,T642-AS160:14-3-3:IRAP	Arrow	R-HSA-1445149 (Reactome)
	p-5S,T642-AS160:IRAP	Arrow	R-HSA-1445144 (Reactome)
p-5S,T642-AS160:IRAP			R-HSA-1445149 (Reactome)
	p-S1652-MYO5A:F-actin	Arrow	R-HSA-1449597 (Reactome)
p-S1652-MYO5A:F-actin		mim-catalysis	R-HSA-2316352 (Reactome)
p-S197-C2CD5:2xCa2+		Arrow	R-HSA-2316352 (Reactome)
	p-S197-C2CD5:2xCa2+	Arrow	R-HSA-5260201 (Reactome)
	p-S237-TBC1D1:14-3-3	Arrow	R-HSA-1454689 (Reactome)
	p-S237-TBC1D1	Arrow	R-HSA-1454699 (Reactome)
p-S237-TBC1D1			R-HSA-1454689 (Reactome)
p-T308,S473-AKT1		mim-catalysis	R-HSA-1445144 (Reactome)
p-T309,S474-AKT2		mim-catalysis	R-HSA-1449597 (Reactome)
p-T309,S474-AKT2		mim-catalysis	R-HSA-1458463 (Reactome)
p-T309,S474-AKT2		mim-catalysis	R-HSA-5260201 (Reactome)
	p-Y521-STXBP3	Arrow	R-HSA-1449574 (Reactome)