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

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11, 14, 15, 17, 21...13, 1929254, 71, 39, 13, 19, 232, 122, 5, 6, 18, 24RALAGDP RALAGTP p-S1652-MYO5AF-actin MYO1CCALM1 14-3-3 theta dimer 14-3-3 theta dimer YWHAE dimer cytoplasmic membrane-bounded vesicle lumenPhospho AS160IRAP RGC1RGC2 VAMP2STX4SNAP23 AMPK gamma Phospho AS16014-3-3 Phospho AS16014-3-3IRAP KIF3 AMPK-alpha2AMPK-betaAMPK-gammaAMP 14-3-3 dimer RALAGTPMYO1CExocyst STX4STXBP3 RAB8A/10/13/14GTP Exocyst Complex AS160IRAP 14-3-3 sigma dimer YWHAB dimer p-S237-TBC1D114-3-3 RAB8A,10,13,14 RAB11AGTP RGC1p-486,696-T715-RGC2 AMPK gammaAMP 14-3-3 sigma dimer TC10GTP RALAGTP GLUT4TUG RAC1GTP YWHAB dimer 14-3-3 eta dimer RAB4AGTPKIF3microtubule AMPK beta Exocyst Complex KIF3 RAB8A,10,13,14 cytosol14-3-3 dimer 14-3-3zeta dimer 14-3-3 gamma dimer MYO1CCALM1 14-3-3zeta dimer 14-3-3 gamma dimer RALAGTPMYO1CCalmodulinF-actin RAB8A/10/13/14GDP RALAGTP RAB4AGTP RAB4AGTP MYO1CCALM1 RALAGTPMYO1CCalmodulinF-actin 14-3-3 eta dimer YWHAE dimer RALA EXOC1 RALAGTPMYO1CCalmodulinF-actinGDP RAB14 p-5S,T642-TBC1D4 YWHAZ GTP RALGAPB KIF3A ADPPRKAG3 GTPp-5S,T642-TBC1D4 EXOC4 STX4 14-3-3 dimerp-T308,S473-AKT1KIF3B GDPATPPRKAB2 KIF3A YWHAZ YWHABp-Y521-STXBP3MYO1C GTPRAB11A RAB4APRKAG1 PRKAB1MYO5ASTX4 EXOC6 p-S1652-MYO5A AMPK-alpha2AMPK-betaAMPK-gammaAMPATPRAB4AGTPKIF3microtubulep-S237-TBC1D1RGC1p-486,696-T715-RGC2GDP p-S1652-MYO5AF-actinAS160IRAPSTX4STXBP3 YWHABCALM1 ATPEXOC6 VAMP2LNPEPRALAGDPEXOC4 ADPMYH4SFN MYH2f-actin PRKAG2 CALM1 EXOC2 p-S237-TBC1D1 YWHAH 14-3-3 dimerRALA CALM1 GTP RALGAPA2 GGC-PalmC-RAC1 RALAGTPMYO1CExocystYWHAGGLUT4TUGTC10GTPTBC1D4ATPp-S486,S696,T715-RALGAPA2 KIF3B RAB4AEXOC1 p-T172-PRKAA2 GTP GTP LNPEPGTP TBC1D1PiAMP Exocyst ComplexGDPTBC1D4 RALAGTPp-S237-TBC1D114-3-3RAB11AGTPRAB10 Phospho AS160IRAPVAMP2STX4SNAP23YWHAH RHOQ RAB10 EXOC7 KIFAP3 EXOC8 RAB8A RAB8A RALA Phospho AS16014-3-3IRAPATPSFN LNPEPRAB13 RAB13 MYO1C ADPKIFAP3 RAB4AGTPEXOC5 VAMP2 SNAP23RAB8A/10/13/14GDPADPSLC2A4 GTP KIF3GTP EXOC3 GTP YWHAQ SNAP23 ASPSCR1EXOC3 p-T309,S474-AKT2YWHAQ ASPSCR1microtubuleADPMYO1C RAB8A/10/13/14GTPSLC2A4EXOC5 GTP MYO1CCALM1EXOC8 RGC1RGC2YWHAGEXOC7 RAC1GTPYWHAE STXBP3 RALA RALGAPB YWHAE RAB14 EXOC2 8, 16, 269, 1310, 221813, 232813, 232220


Description

In adipocytes and myocytes insulin signaling causes intracellular vesicles carrying the GLUT4 glucose transporter to translocate to the plasma membrane, allowing the cells to take up glucose from the bloodstream (reviewed in Zaid et al. 2008, Leney and Tavare 2009, Bogan and Kandror 2010, Foley et al. 2011, Hoffman and Elmendorf 2011, Kandror and Pilch 2011). In myocytes muscle contraction alone can also cause translocation of GLUT4.
Though the entire pathway leading to GLUT4 translocation has not been elucidated, several steps are known. Insulin activates the kinases AKT1 and AKT2. Muscle contraction activates the kinase AMPK-alpha2 and possibly also AKT. AKT2 and, to a lesser extent, AKT1 phosphorylate the RAB GTPase activators TBC1D1 and TBC1D4, causing them to bind 14-3-3 proteins and lose GTPase activation activity. As a result RAB proteins (probably RAB8A, RAB10, RAB14 and possibly RAB13) accumulate GTP. The connection between RAB:GTP and vesicle translocation is unknown but may involve recruitment and activation of myosins.
Myosins 1C, 2A, 2B, 5A, 5B have all been shown to play a role in translocating GLUT4 vesicles near the periphery of the cell. Following docking at the plasma membrane the vesicles fuse with the plasma membrane in a process that depends on interaction between VAMP2 on the vesicle and SNAP23 and SYNTAXIN-4 at the plasma membrane. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=1445148

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Bibliography

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History

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CompareRevisionActionTimeUserComment
115083view17:03, 25 January 2021ReactomeTeamReactome version 75
113525view12:00, 2 November 2020ReactomeTeamReactome version 74
112724view16:12, 9 October 2020ReactomeTeamReactome version 73
101640view11:50, 1 November 2018ReactomeTeamreactome version 66
101176view21:37, 31 October 2018ReactomeTeamreactome version 65
100702view20:10, 31 October 2018ReactomeTeamreactome version 64
100252view16:55, 31 October 2018ReactomeTeamreactome version 63
99804view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99352view12:48, 31 October 2018ReactomeTeamreactome version 62
94027view13:52, 16 August 2017ReactomeTeamreactome version 61
93648view11:29, 9 August 2017ReactomeTeamreactome version 61
88359view16:37, 1 August 2016FehrhartOntology Term : 'pathway pertinent to protein folding, sorting, modification, translocation and degradation' added !
86764view09:25, 11 July 2016ReactomeTeamreactome version 56
83070view09:51, 18 November 2015ReactomeTeamVersion54
81775view10:34, 26 August 2015ReactomeTeamVersion53
77058view08:35, 17 July 2014ReactomeTeamFixed remaining interactions
76763view12:12, 16 July 2014ReactomeTeamFixed remaining interactions
76087view10:15, 11 June 2014ReactomeTeamRe-fixing comment source
75798view11:33, 10 June 2014ReactomeTeamReactome 48 Update
75149view14:09, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74796view08:53, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
14-3-3 dimerProteinREACT_147925 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AMP MetaboliteCHEBI:16027 (ChEBI)
AMPK-alpha2

AMPK-beta AMPK-gamma

AMP		ComplexREACT_148254 (Reactome)
AS160 IRAPComplexREACT_148263 (Reactome)
ASPSCR1ProteinQ9BZE9 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
EXOC1 ProteinQ9NV70 (Uniprot-TrEMBL)
EXOC2 ProteinQ96KP1 (Uniprot-TrEMBL)
EXOC3 ProteinO60645 (Uniprot-TrEMBL)
EXOC4 ProteinQ96A65 (Uniprot-TrEMBL)
EXOC5 ProteinO00471 (Uniprot-TrEMBL)
EXOC6 ProteinQ8TAG9 (Uniprot-TrEMBL)
EXOC7 ProteinQ9UPT5 (Uniprot-TrEMBL)
EXOC8 ProteinQ8IYI6 (Uniprot-TrEMBL)
Exocyst ComplexComplexREACT_15928 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GGC-PalmC-RAC1 ProteinP63000 (Uniprot-TrEMBL)
GLUT4 TUGComplexREACT_148426 (Reactome)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
KIF3A ProteinQ9Y496 (Uniprot-TrEMBL)
KIF3B ProteinO15066 (Uniprot-TrEMBL)
KIF3ComplexREACT_148146 (Reactome)
KIFAP3 ProteinQ92845 (Uniprot-TrEMBL)
LNPEPProteinQ9UIQ6 (Uniprot-TrEMBL)
MYH2ProteinQ9UKX2 (Uniprot-TrEMBL)
MYH4ProteinQ9Y623 (Uniprot-TrEMBL)
MYO1C CALM1ComplexREACT_148117 (Reactome)
MYO1C ProteinO00159 (Uniprot-TrEMBL)
MYO5AProteinQ9Y4I1 (Uniprot-TrEMBL)
PRKAB1ProteinQ9Y478 (Uniprot-TrEMBL)
PRKAB2 ProteinO43741 (Uniprot-TrEMBL)
PRKAG1 ProteinP54619 (Uniprot-TrEMBL)
PRKAG2 ProteinQ9UGJ0 (Uniprot-TrEMBL)
PRKAG3 ProteinQ9UGI9 (Uniprot-TrEMBL)
Phospho AS160

14-3-3

IRAP		ComplexREACT_148392 (Reactome)
Phospho AS160 IRAPComplexREACT_147981 (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 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).
PiMetaboliteCHEBI:18367 (ChEBI)
RAB10 ProteinP61026 (Uniprot-TrEMBL)
RAB11A GTPComplexREACT_120028 (Reactome)
RAB11A ProteinP62491 (Uniprot-TrEMBL)
RAB13 ProteinP51153 (Uniprot-TrEMBL)
RAB14 ProteinP61106 (Uniprot-TrEMBL)
RAB4A

GTP KIF3

microtubule		ComplexREACT_148401 (Reactome)
RAB4A GTPComplexREACT_148449 (Reactome)
RAB4AProteinP20338 (Uniprot-TrEMBL)
RAB8A ProteinP61006 (Uniprot-TrEMBL)
RAB8A/10/13/14 GDPComplexREACT_148262 (Reactome)
RAB8A/10/13/14 GTPComplexREACT_148450 (Reactome)
RAC1 GTPComplexREACT_148456 (Reactome)
RALA GDPComplexREACT_147970 (Reactome)
RALA

GTP MYO1C Calmodulin

F-actin		ComplexREACT_148239 (Reactome)
RALA

GTP MYO1C

Exocyst		ComplexREACT_148060 (Reactome)
RALA GTPComplexREACT_148153 (Reactome)
RALA ProteinP11233 (Uniprot-TrEMBL)
RALGAPA2 ProteinQ2PPJ7 (Uniprot-TrEMBL)
RALGAPB ProteinQ86X10 (Uniprot-TrEMBL)
RGC1 RGC2ComplexREACT_148495 (Reactome)
RGC1 p-486,696-T715-RGC2ComplexREACT_148586 (Reactome)
RHOQ ProteinP17081 (Uniprot-TrEMBL)
SFN ProteinP31947 (Uniprot-TrEMBL)
SLC2A4 ProteinP14672 (Uniprot-TrEMBL)
SLC2A4ProteinP14672 (Uniprot-TrEMBL)
SNAP23 ProteinO00161 (Uniprot-TrEMBL)
SNAP23ProteinO00161 (Uniprot-TrEMBL)
STX4 STXBP3 ComplexREACT_147908 (Reactome)
STX4 ProteinQ12846 (Uniprot-TrEMBL)
STXBP3 ProteinO00186 (Uniprot-TrEMBL)
TBC1D1ProteinQ86TI0 (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 ProteinO60343 (Uniprot-TrEMBL)
TBC1D4ProteinO60343 (Uniprot-TrEMBL)
TC10 GTPComplexREACT_148007 (Reactome)
VAMP2

STX4

SNAP23		ComplexREACT_147982 (Reactome)
VAMP2 ProteinP63027 (Uniprot-TrEMBL)
VAMP2ProteinP63027 (Uniprot-TrEMBL)
YWHABProteinP31946 (Uniprot-TrEMBL)
YWHAE ProteinP62258 (Uniprot-TrEMBL)
YWHAGProteinP61981 (Uniprot-TrEMBL)
YWHAH ProteinQ04917 (Uniprot-TrEMBL)
YWHAQ ProteinP27348 (Uniprot-TrEMBL)
YWHAZ ProteinP63104 (Uniprot-TrEMBL)
f-actin REACT_148010 (Reactome)
microtubuleREACT_10446 (Reactome)
p-5S,T642-TBC1D4 ProteinO60343 (Uniprot-TrEMBL)
p-S1652-MYO5A F-actinComplexREACT_148237 (Reactome)
p-S1652-MYO5A ProteinQ9Y4I1 (Uniprot-TrEMBL)
p-S237-TBC1D1 14-3-3ComplexREACT_148394 (Reactome)
p-S237-TBC1D1 ProteinQ86TI0 (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-TBC1D1ProteinQ86TI0 (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 ProteinQ2PPJ7 (Uniprot-TrEMBL)
p-T172-PRKAA2 ProteinP54646 (Uniprot-TrEMBL)
p-T308,S473-AKT1ProteinP31749 (Uniprot-TrEMBL)
p-T309,S474-AKT2ProteinP31751 (Uniprot-TrEMBL)
p-Y521-STXBP3ProteinO00186 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
14-3-3 dimerREACT_147698 (Reactome)
14-3-3 dimerREACT_147700 (Reactome)
ADPArrowREACT_147770 (Reactome)
ADPArrowREACT_147780 (Reactome)
ADPArrowREACT_147852 (Reactome)
ADPArrowREACT_147871 (Reactome)
ADPArrowREACT_147884 (Reactome)
AMPK-alpha2

AMPK-beta AMPK-gamma

AMP		REACT_147871 (Reactome)
AS160 IRAPREACT_147770 (Reactome)
ASPSCR1ArrowREACT_147780 (Reactome)
ATPREACT_147770 (Reactome)
ATPREACT_147780 (Reactome)
ATPREACT_147852 (Reactome)
ATPREACT_147871 (Reactome)
ATPREACT_147884 (Reactome)
Exocyst ComplexREACT_147776 (Reactome)
GDPArrowREACT_147712 (Reactome)
GDPArrowREACT_147746 (Reactome)
GLUT4 TUGREACT_147780 (Reactome)
GTPREACT_147712 (Reactome)
GTPREACT_147746 (Reactome)
KIF3REACT_147824 (Reactome)
MYH2REACT_147776 (Reactome)
MYH4REACT_147776 (Reactome)
MYO1C CALM1REACT_147829 (Reactome)
MYO5AREACT_147884 (Reactome)
Phospho AS160 IRAPArrowREACT_147770 (Reactome)
Phospho AS160 IRAPREACT_147698 (Reactome)
PiArrowREACT_147722 (Reactome)
RAB11A GTPArrowREACT_147776 (Reactome)
RAB4A GTPREACT_147824 (Reactome)
RAB8A/10/13/14 GDPREACT_147746 (Reactome)
RAB8A/10/13/14 GTPArrowREACT_147746 (Reactome)
RAB8A/10/13/14 GTPArrowREACT_147776 (Reactome)
RAB8A/10/13/14 GTPREACT_147836 (Reactome)
RAC1 GTPArrowREACT_147776 (Reactome)
RALA GDPArrowREACT_147722 (Reactome)
RALA GDPREACT_147712 (Reactome)
RALA

GTP MYO1C Calmodulin

F-actin		REACT_147776 (Reactome)
RALA GTPArrowREACT_147712 (Reactome)
RALA GTPREACT_147722 (Reactome)
RALA GTPREACT_147829 (Reactome)
REACT_147698 (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 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).
REACT_147700 (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.
REACT_147712 (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.
REACT_147722 (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.
REACT_147746 (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.
REACT_147770 (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.
REACT_147776 (Reactome) As inferred from mouse, GLUT4 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.
REACT_147780 (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.
REACT_147824 (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 across the cytosol to the cortical actin network.
REACT_147829 (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).
REACT_147836 (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.
REACT_147852 (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.
REACT_147871 (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 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).
REACT_147884 (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.
RGC1 RGC2ArrowREACT_147722 (Reactome)
RGC1 RGC2REACT_147852 (Reactome)
RGC1 p-486,696-T715-RGC2ArrowREACT_147852 (Reactome)
SLC2A4ArrowREACT_147780 (Reactome)
SNAP23REACT_147780 (Reactome)
STX4 STXBP3 REACT_147780 (Reactome)
TBC1D1ArrowREACT_147836 (Reactome)
TBC1D1REACT_147871 (Reactome)
TBC1D4ArrowREACT_147836 (Reactome)
TC10 GTPArrowREACT_147776 (Reactome)
VAMP2

STX4

SNAP23		ArrowREACT_147780 (Reactome)
VAMP2REACT_147780 (Reactome)
f-actin REACT_147829 (Reactome)
f-actin REACT_147884 (Reactome)
microtubuleREACT_147824 (Reactome)
p-S1652-MYO5A F-actinArrowREACT_147884 (Reactome)
p-S1652-MYO5A F-actinREACT_147776 (Reactome)
p-S237-TBC1D1ArrowREACT_147871 (Reactome)
p-S237-TBC1D1REACT_147700 (Reactome)
p-T308,S473-AKT1REACT_147770 (Reactome)
p-T309,S474-AKT2REACT_147770 (Reactome)
p-T309,S474-AKT2REACT_147852 (Reactome)
p-T309,S474-AKT2REACT_147884 (Reactome)
p-Y521-STXBP3ArrowREACT_147780 (Reactome)
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