Membrane trafficking (Bos taurus)

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161, 382717, 23, 351, 32, 3815, 2512, 1323, 27, 301, 32, 382319, 2311623, 27, 3031, 36332, 7101, 381, 3861, 384, 8, 14, 23, 272219, 234, 8, 14, 23, 271027, 282017, 23, 3537, 4021, 33Sar1b:GTP Complex[endoplasmicreticulum membrane]Cargo:AP-1:Beta-arrestin:ClathrinTriskelion:VampComplex [cytoplasmicvesicle membrane]Sar1b:GDP Complex[cytosol]cytosolCoatomer [cytosol]AP-1 sigma [Golgimembrane]HSC70:AuxillinComplex [cytosol]Cargo:AP-1:beta-Arrestin-1:VampComplex [Golgimembrane]CHMP4 [cytosol]lysosomal lumenAP-1 sigma[cytoplasmic vesiclemembrane]Clathrin Triskelion[cytosol]Lysosome DestinedCargo:AP-1:beta-Arrestin-1:VampComplex [Golgimembrane]Sec24 [endoplasmicreticulum membrane]Clathrin Triskelion[cytosol]Sar1b:Sec23p:Sec24p:Sec13p:Sec31pComplex [ER to Golgitransport vesiclemembrane]ER to Golgi transport vesicleUbiquinated and PIP3Endosmal MembraneBound Cargo[endosome membrane]Vamp8:SNAP23:Syn4Secretory granuledocking and fusioncomplex [plasmamembrane, secretorygranule membrane]Arf1-GDP [cytosol]ubiquitin [endocyticvesicle membrane]Coatomer [cytosol]ubiquitin [endosomemembrane]Sec24 [cytosol]secretory granule membraneAP-1 sigma [Golgimembrane]Arf1-GTP [Golgimembrane]Arf1-GDP [cytosol]AP-1 Complex[cytoplasmic vesiclemembrane]Arf1-GTP [Golgimembrane]ubiquitin [endosomemembrane]AP-1 Complex [Golgimembrane]AP-1 mu [cytosol]ubiquitin [endosomemembrane]AP-1 sigma [cytosol]Sec13p:Sec31pComplex [ER to Golgitransport vesiclemembrane]Ubiquinated and PIP3Endosmal MembraneBound Cargo[endocytic vesiclemembrane]FTH1:FTL [cytosol]STAM [cytosol]Sec23p:Sec24pComplex [ER to Golgitransport vesiclemembrane]AP-1 sigma[lysosomal membrane]Golgi lumenendosome membranecytoplasmic vesicle membraneSec24 [endoplasmicreticulum membrane]Sar1b:GTP Complex[endoplasmicreticulum membrane]ESCRT-0 [cytosol]Sar1b:GTP:Sec23p:Sec24p:Sec13p:Sec31pComplex [endoplasmicreticulum membrane]Clathrin Triskelion[cytosol]AP-1 Complex[cytosol]LysosomeCargo:AP-1:Beta-arrestin:ClathrinTriskelion:VampComplex [lysosomalmembrane]Clathrin Triskelion[cytosol]Cargo:AP-1:Beta-arrestin:Vamp:ClathrinTriskelion:Dynamin:EndophilinComplex [Golgimembrane]ESCRT-0 [cytosol]AP-1 mu [Golgimembrane]AP-1 mu [cytosol]AP-1 sigma [cytosol]Clathrin Triskelion[cytosol]ESCRT-III [cytosol]Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:VampComplex [Golgimembrane]Arf1-GTP [Golgimembrane]Lysosome DestinedCargo:AP-1:Arf1-GTP:beta-Arrestin-1:VampComplex [Golgimembrane]AP-1 mu [Golgimembrane]Arf1-GDP [cytosol]AP-1 mu [lysosomalmembrane]Arf1-GDP [Golgimembrane]Ubiquinated and PIP3Endosmal MembraneBound Cargo[endosome membrane]AP-1 Complex[cytosol]Vps/Vta1 [cytosol]Sec23p:Sec24pComplex [cytosol]Ubiquinated and PIP3Endosmal MembraneBound Cargo[endosome membrane]Ferritin Complex[cytosol]Arf1-GTP [Golgimembrane]ESCRT-0/CargoComplex [endosomemembrane]Sec13p:Sec31pComplex [endoplasmicreticulum membrane]Arf1-GTP [Golgimembrane]Sec23p:Sec24pComplex [endoplasmicreticulum membrane]Sar1b:GTP Complex[endoplasmicreticulum membrane]HSC70:AuxillinComplex [cytosol]Sec24 [ER to Golgitransport vesiclemembrane]CHMP4 [cytosol]Clathrin Triskelion[cytosol]CHMP2 [cytosol]Ubiquinated and PIP3Endosmal MembraneBound Cargo[endosome membrane]AP-1 mu [cytosol]Coatomer:Arf1-GTPComplex [Golgimembrane]Clathrin Triskelion[cytosol]AP-1 Complex [Golgimembrane]Arf1-GTP [Golgimembrane]Sar1b:GTP:Sec23p:Sec24p[endoplasmicreticulum membrane]AP-1 Complex[lysosomal membrane]CHMP2 [cytosol]AP-1 Complex [Golgimembrane]AP-1 mu [Golgimembrane]AP-1 sigma [cytosol]Vamp2:SNAP23:Syn4Secretory granuledocking and fusioncomplex [plasmamembrane, secretorygranule membrane]AP-1 Complex[cytosol]ESCRT-I/CargoComplex [endosomemembrane]Coatomer [cytosol]BLOC-1 Complex[lysosomal membrane]ESCRT-II [cytosol]AP-1 sigma [Golgimembrane]AP-1 mu [Golgimembrane]AP-1 mu [cytoplasmicvesicle membrane]ESCRT-II/CargoComplex [endosomemembrane]STAM [cytosol]Arf1-GDP [cytosol]ESCRT-III/CargoComplex [endosomemembrane]ESCRT-III [cytosol]ESCRT-II [cytosol]Lysosome DestinedCargo:AP-1:Beta-arrestin:Vamp:ClathrinTriskelion:Dynamin:EndophilinComplex [Golgimembrane]cytoplasmic vesicle membraneESCRT-I [endosomemembrane]Sec23p:Sec24pComplex [endoplasmicreticulum membrane]AP-1 sigma [Golgimembrane]ubiquitin [endosomemembrane]Coatomer:Arf1-GTP:GAPComplex [Golgimembrane]Sar1b:GTP:Sec23p:Sec24p[endoplasmicreticulum membrane]ESCRT-I [endosomemembrane]endoplasmic reticulum lumenAP-1 Complex [Golgimembrane]Vamp7:SNAP23:Syn4Plasma membranevesicle docking andfusion complex[plasma membrane,lysosomal membrane]AP1S1RPS27AGTP [cytosol]UBBARCN1PI(3,4,5)P3[endosome membrane]PUM1COPEVAMP7VPS37CUBC(609-684)[endosome membrane]ATPSEC24ACOPASTX4Arf1-GDPHGSSEC31ADTNBP1GTP [cytosol]AP1G1VAMP7 [lysosomalmembrane]VAMP2UBC(609-684)[endosome membrane]VAMP7AP1S2UBC(77-152)[endocytic vesiclemembrane]GTP [cytosol]SEC24CUBBCLTC-1 [cytosol]Sar1b:GTP:Sec23p:Sec24p:Sec13p:Sec31pComplexTXNDC5SEC13DNM2PI(3,4,5)P3[endocytic vesiclemembrane]SEC31ACNOVPS25UBC(153-228)[endocytic vesiclemembrane]AP1S1VPS37DSec24CHMP2AVAMP8RPS27AVPS37AHSC70:AuxillinComplexSEC24BAP1M1VampDNM2DTNBP1AP1G1VAMP2AP1S1AP1G1UBBCOPEArf1-GDPUBC(381-456)[endosome membrane]SEC24BClathrin light chain[cytosol]PI(3,4,5)P3[endosome membrane]VPS36GBF1ARRB1AP1S3ARRB1COPB2AP1S3BLOC1S1(1-125)UBC(457-532)[endocytic vesiclemembrane]Arf1-GTPAP1B1Lysosome DestinedCargoUBA52COPG1SEC23ASEC24ACHMP4CBLOC-1 ComplexAP1S2ARF1ESCRT-IESCRT-0/CargoComplexUBC(1-76) [endosomemembrane]UBC(457-532)[endosome membrane]COPG1GTPARF1AP1M1UBA52AP1M1ESCRT-I/CargoComplexCHMP2ASEC23ALysosome DestinedCargo:AP-1:Beta-arrestin:Vamp:ClathrinTriskelion:Dynamin:EndophilinComplexSTAM2COPZ1CHMP6CLTC-1 [cytosol]COPZ1UBC(533-608)[endocytic vesiclemembrane]UBC(229-304)[endosome membrane]GBF1BLOC1S1(1-125)[lysosomal membrane]ARF1UBA52Sar1b:GTP ComplexVPS37B [endosomemembrane]RPS27ASEC13ARFGAP3HSPA8Arf1-GDPGDP [cytosol]UBC(229-304)[endosome membrane]TSG101CLTC-1 [cytosol]UBBAP1G1UBBCargo:AP-1:Beta-arrestin:ClathrinTriskelion:VampComplexSEC24CATPSTAMGolgi-associatedVesicle CargoSEC24AClathrin light chain[cytosol]SEC23AAP1M2Coatomer:Arf1-GTPComplexPI(3,4,5)P3[endosome membrane]SH3D19ADPSAR1BSAR1BPiSEC24AARF1CHMP6AP1S1COPB1UBBAP1S2ARCN1AP1M1SEC24DSEC13AP1M2SH3GL2Ubiquinated and PIP3Endosmal MembraneBound CargoADPUBC(153-228)[endosome membrane]Golgi-associatedVesicle CargoUBC(305-380)[endosome membrane]SNAP23CHMP4BBLOC1S6DNAJC6PiTranslocation ofGLUT4 to the PlasmaMembraneUBC(77-152)[endosome membrane]ESCRT-III/CargoComplexCoatomer:ARFGAP1latticeUBC(77-152)[endosome membrane]SNF8BLOC1S3DNAJC6SAR1BLysosome CargoGTP [cytosol]ARCN1UBC(153-228)[endosome membrane]AP1B1COPEAP1M2CHMP4CAP1S3COPB1AP1S1VPS28AP1M2LysosomeCargo:AP-1:Beta-arrestin:ClathrinTriskelion:VampComplexAP1M2CHMP4BAP1M2Vamp7:SNAP23:Syn4Plasma membranevesicle docking andfusion complexLysosome DestinedCargo:AP-1:Arf1-GTP:beta-Arrestin-1:VampComplexESCRT-IIFTH1(2-183)[cytosol]ARFGAP3GDP [cytosol]AP1S3AP1G1UBC(381-456)[endocytic vesiclemembrane]SEC24BUBA52AP1B1VPS36SAR1BSEC24DSTAMAP1B1GDP [cytosol]Clathrin TriskelionClathrin light chain[cytosol]ARRB1AP1M1UBBCOPB1SNAP23Arf1-GDPGDPGDP [cytosol]Sar1b:Sec23p:Sec24p:Sec13p:Sec31pComplexGTPUBC(533-608)[endosome membrane]PiSar1b:GDP ComplexCoatomer:GAP LatticeSEC23AAP1B1VAMP8VPS37DSEC23AFTL [cytosol]SH3GL2Vps/Vta1Coatomer:Arf1-GDP:GAPLatticeUBC(457-532)[endosome membrane]SNAP23AP1S2TXNDC5AP1M1Coatomer:Arf1-GTP:GAPLatticeCHMP4Arf1-GDPCHMP7GDPARRB1UBC(609-684)[endosome membrane]RPS27AGTPUBC(305-380)[endosome membrane]UBC(229-304)[endosome membrane]Clathrin TriskelionCOPG1AP1G1Cargo:AP-1:Beta-arrestin:Vamp:ClathrinTriskelion:Dynamin:EndophilinComplexCHMP6PiARRB1STX4AP-1 ComplexARF1UBBAP1M1SNAP23SAR1BCHMP5SH3GL2DNM2SEC24DAP1M2Clathrin light chain[cytosol]NAPAUBBAP1B1SEC24BAP1S3UBC(229-304)[endocytic vesiclemembrane]GDPGDPPiUBC(457-532)[endosome membrane]GDP [cytosol]SH3GL2UBC(229-304)[endosome membrane]UBA52CHMP3TSG101ARRB1ARRB1AP1S1HSC70:AuxillinComplexVPS28PiSTX4UBC(305-380)[endosome membrane]CHMP2BVampAP1S2ARF1CHMP2BVPS37AUBC(77-152)[endosome membrane]Sec23p:Sec24pComplexVPS37CCOPALysosome DestinedCargoCoatomerGolgi-associatedVesicle DestinedCargoPI(3,4,5)P3[endosome membrane]ADPAP1S3AP-1 ComplexBLOC1S3UBC(153-228)[endosome membrane]CHMP4AGap junctiontrafficking andregulationAP1S2GTP [cytosol]UBC(381-456)[endosome membrane]CHMP3ARF1AP1M2COPZ1AP1B1CHMP3PiUBBSNAP23VPS4AHGSGTPAP1M2DNM2GDPARRB1AP1B1ESCRT-II/CargoComplexUBC(609-684)[endosome membrane]Sar1b:GTP:Sec23p:Sec24pESCRT-IIIRPS27AUBC(1-76) [endosomemembrane]Clathrin light chain[cytosol]Vamp8:SNAP23:Syn4Secretory granuledocking and fusioncomplexUBC(1-76) [endosomemembrane]Coatomer:Arf1-GTP:GAPComplexAP1M1ESCRT-0UBC(533-608)[endosome membrane]CHMP7Lysosome CargoGTPUBC(457-532)[endosome membrane]SNF8STX4ARF1UBC(77-152)[endosome membrane]AP1S2VAMP8UBC(1-76) [endocyticvesicle membrane]AP1G1STAM2AP1S3UBC(153-228)[endosome membrane]CLTC-1 [cytosol]ARF1AP1S3PREBCNOFerritin ComplexSTX4UBC(1-76) [endosomemembrane]Golgi-associatedvesicle interactingproteinsARRB1COPB2HSPA8AP1G1CLINT1PiGTP [cytosol]NAPASEC31AGTP [cytosol]VTA1ARF1SEC24CUBBSAR1BPiAP-1 ComplexAP1B1VPS4BVPS25ARF1COPB2CLTC-1 [cytosol]Vamp2:SNAP23:Syn4Secretory granuledocking and fusioncomplexAP1S1CLTC-1 [cytosol]CHMP2UBC(305-380)[endosome membrane]VampUBBGolgi-associatedVesicle DestinedCargoVAMP2Arf1-GTPCOPAAP1S2Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:VampComplexUBBSNAP23AP1S2UBC(533-608)[endosome membrane]SEC24CAP1S3UBC(381-456)[endosome membrane]AP1S1UBBCLTC-1 [cytosol]UBC(609-684)[endocytic vesiclemembrane]Clathrin TriskelionSEC24DUBC(381-456)[endosome membrane]GDP [cytosol]UBC(533-608)[endosome membrane]AP1S1AP1G1CHMP4AUBBClathrin light chain[cytosol]UBC(305-380)[endocytic vesiclemembrane]VPS37B [endosomemembrane]BLOC1S6GTP [cytosol]AP1M1GTP [cytosol]CHMP7ATPClathrin light chain[cytosol]3, 9, 26, 395, 18, 24, 29, 34...


Description

The secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is made up of distinct organelles, including the endoplasmic reticulum (ER), Golgi complex, plasma membrane, and tubulovesicular transport intermediates. These organelles mediate intracellular membrane transport between themselves and the cell surface. Membrane traffic within this system flows along highly organized directional routes. Secretory cargo is synthesized and assembled in the ER and then transported to the Golgi complex for further processing and maturation. Upon arrival at the trans Golgi network (TGN), the cargo is sorted and packaged into post-Golgi carriers that move through the cytoplasm to fuse with the cell surface. This directional membrane flow is balanced by retrieval pathways that bring membrane and selected proteins back to the compartment of origin.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=199991

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP1846(76873) with a 75.0% conversion rate.

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Ontology Terms

 

Bibliography

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History

CompareRevisionActionTimeUserComment
117559view11:19, 21 May 2021EweitzModified title
87772view11:00, 25 July 2016ElisaOntology Term : 'regulatory pathway' added !
80810view15:26, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AP-1 ComplexComplexREACT_11249 (Reactome)
AP1B1ProteinENSBTAG00000001189 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q10567
AP1G1ProteinENSBTAG00000002769 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O43747
AP1M1ProteinENSBTAG00000013329 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9BXS5
AP1M2ProteinENSBTAG00000021160 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9Y6Q5
AP1S1ProteinENSBTAG00000014468 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P61966
AP1S2ProteinENSBTAG00000020420 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P56377
AP1S3ProteinENSBTAG00000011133 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96PC3
ARCN1ProteinENSBTAG00000006690 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P48444
ARF1ProteinENSBTAG00000007725 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P84077
ARFGAP3ProteinENSBTAG00000004916 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q8N6T3
ARRB1ProteinENSBTAG00000020485 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P49407
ATPMetaboliteCHEBI:15422 (ChEBI)
Arf1-GDPComplexREACT_11263 (Reactome)
Arf1-GDPComplexREACT_11922 (Reactome)
Arf1-GTPComplexREACT_11673 (Reactome)
BLOC-1 ComplexComplexREACT_19646 (Reactome)
BLOC1S1(1-125)Protein
BLOC1S1(1-125) [lysosomal membrane]Protein
BLOC1S3ProteinENSBTAG00000007070 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q6QNY0
BLOC1S6ProteinENSBTAG00000012250 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9UL45
CHMP2Protein
CHMP2AProteinENSBTAG00000013882 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O43633
CHMP2BProteinENSBTAG00000007939 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9UQN3
CHMP3ProteinENSBTAG00000013589 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9Y3E7
CHMP4Protein
CHMP4AProteinENSBTAG00000039415 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9BY43
CHMP4BProteinENSBTAG00000013387 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9H444
CHMP4CProteinENSBTAG00000004792 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96CF2
CHMP5ProteinENSBTAG00000012383 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9NZZ3
CHMP6ProteinENSBTAG00000038745 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96FZ7
CHMP7ProteinENSBTAG00000013528 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q8WUX9
CLINT1ProteinENSBTAG00000016199 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q14677
CLTC-1 [cytosol]Protein
CNOProteinENSBTAG00000003766 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9NUP1
COPAProteinENSBTAG00000004333 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P53621
COPB1ProteinENSBTAG00000006556 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P53618
COPB2ProteinENSBTAG00000014843 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P35606
COPEProteinENSBTAG00000000810 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O14579
COPG1ProteinENSBTAG00000013212 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9Y678
COPZ1ProteinENSBTAG00000005384 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P61923
Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp ComplexComplexREACT_20036 (Reactome)
Cargo:AP-1:Beta-arrestin:Clathrin

Triskelion:Vamp

Complex
ComplexREACT_15080 (Reactome)
Cargo:AP-1:Beta-arrestin:Vamp:Clathrin

Triskelion:Dynamin:Endophilin

Complex
ComplexREACT_14893 (Reactome)
Clathrin TriskelionComplexREACT_15049 (Reactome)
Clathrin light chain [cytosol]Protein
Coatomer:ARFGAP1 latticeREACT_11929 (Reactome)
Coatomer:Arf1-GDP:GAP LatticeREACT_11944 (Reactome)
Coatomer:Arf1-GTP ComplexComplexREACT_11791 (Reactome)
Coatomer:Arf1-GTP:GAP ComplexComplexREACT_11350 (Reactome)
Coatomer:Arf1-GTP:GAP LatticeREACT_11353 (Reactome)
Coatomer:GAP LatticeREACT_11478 (Reactome)
CoatomerComplexREACT_11329 (Reactome)
DNAJC6ProteinENSBTAG00000030749 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O75061
DNM2ProteinENSBTAG00000013362 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P50570
DTNBP1ProteinENSBTAG00000012939 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96EV8
ESCRT-0/Cargo ComplexComplexREACT_27808 (Reactome)
ESCRT-0ComplexREACT_27831 (Reactome)
ESCRT-I/Cargo ComplexComplexREACT_27922 (Reactome)
ESCRT-II/Cargo ComplexComplexREACT_27742 (Reactome)
ESCRT-III/Cargo ComplexComplexREACT_27876 (Reactome)
ESCRT-IIIComplexREACT_27898 (Reactome)
ESCRT-IIComplexREACT_27749 (Reactome)
ESCRT-IComplexREACT_27580 (Reactome)
FTH1(2-183) [cytosol]Protein
FTL [cytosol]ProteinENSBTAG00000019709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P02792
Ferritin ComplexComplexREACT_19855 (Reactome) The ferritin complex is an oligomer of 24 subunits with light and heavy chains. The major chain can be light or heavy, depending on the tissue type. The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited. Iron metabolism provides a useful example of gene expression translational control. Increased iron levels stimulate the synthesis of the iron-binding protein, ferritin, without any corresponding increase in the amount of ferritin mRNA. The 5?-UTR of both ferritin heavy chain mRNA and light chain mRNA contain a single iron-response element (IRE), a specific cis-acting regulatory sequence which forms a hairpin structure.
GBF1ProteinENSBTAG00000006014 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q92538
GDP [cytosol]MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GTP [cytosol]MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
Gap junction

trafficking and

regulation
PathwayWP1820 (WikiPathways) Gap junctions are clusters of intercellular channels connecting adjacent cells and permitting the direct exchange of ions and small molecules between cells. These channels are composed of two hemichannels, or connexons, one located on each of the two neighboring cells. Each connexon is composed of 6 trans-membrane protein subunits of the connexin (Cx) family. A gap of approximately 3 nm remains between the adjacent cell membranes, but two connexons interact and dock head-to-head in the extra-cellular space forming a tightly sealed, double-membrane intercellular channel (see Segretain and Falk, 2004). The activity of these intercellular channels is regulated, particularly by intramolecular modifications such as phosphorylation which appears to regulate connexin turnover, gap junction assembly and the opening and closure (gating) of gap junction channels.
Golgi-associated Vesicle CargoProtein
Golgi-associated

Vesicle Destined

Cargo
Protein
Golgi-associated

vesicle interacting

proteins
Protein
HGSProteinENSBTAG00000000411 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O14964
HSC70:Auxillin ComplexComplexREACT_15197 (Reactome)
HSPA8ProteinENSBTAG00000013162 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P11142
Lysosome

Cargo:AP-1:Beta-arrestin:Clathrin Triskelion:Vamp

Complex
ComplexREACT_19609 (Reactome)
Lysosome CargoProtein
Lysosome Destined CargoProtein
Lysosome Destined

Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp

Complex
ComplexREACT_19668 (Reactome)
Lysosome Destined

Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin

Complex
ComplexREACT_20224 (Reactome)
NAPAProteinENSBTAG00000013084 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P54920
PI(3,4,5)P3

[endocytic vesicle

membrane]
MetaboliteCHEBI:16618 (ChEBI)
PI(3,4,5)P3 [endosome membrane]MetaboliteCHEBI:16618 (ChEBI)
PREBProteinENSBTAG00000007080 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9HCU5
PUM1ProteinENSBTAG00000018979 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q14671
PiMetaboliteCHEBI:18367 (ChEBI)
RPS27AProteinENSBTAG00000015473 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P62979
SAR1BProteinENSBTAG00000021226 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9Y6B6
SEC13ProteinENSBTAG00000017825 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P55735
SEC23AProteinENSBTAG00000003708 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q15436
SEC24AProteinENSBTAG00000018322 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O95486
SEC24BProteinENSBTAG00000010945 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O95487
SEC24CProteinENSBTAG00000002791 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P53992
SEC24DProteinENSBTAG00000003619 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O94855
SEC31AProteinENSBTAG00000020525 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O94979
SH3D19ProteinENSBTAG00000016813 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q5HYK7
SH3GL2ProteinENSBTAG00000014103 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q99962
SNAP23ProteinENSBTAG00000005661 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O00161
SNF8ProteinENSBTAG00000018803 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q96H20
STAM2ProteinENSBTAG00000001887 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O75886
STAMProteinENSBTAG00000002658 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q92783
STX4ProteinENSBTAG00000007523 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q12846
Sar1b:GDP ComplexComplexREACT_12715 (Reactome)
Sar1b:GTP ComplexComplexREACT_12713 (Reactome)
Sar1b:GTP:Sec23p:Sec24p:Sec13p:Sec31p ComplexComplexREACT_13165 (Reactome)
Sar1b:GTP:Sec23p:Sec24pComplexREACT_13151 (Reactome)
Sar1b:Sec23p:Sec24p:Sec13p:Sec31p ComplexComplexREACT_12742 (Reactome)
Sec23p:Sec24p ComplexComplexREACT_13290 (Reactome)
Sec24Protein
TSG101ProteinENSBTAG00000013563 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q99816
TXNDC5ProteinENSBTAG00000019237 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q8NBS9
Translocation of

GLUT4 to the Plasma

Membrane
PathwayWP2777 (WikiPathways) 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.
UBA52ProteinENSBTAG00000007737 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P62987
UBBProteinENSBTAG00000017246 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P0CG47
UBC(1-76) [endocytic vesicle membrane]Protein
UBC(1-76) [endosome membrane]Protein
UBC(153-228)

[endocytic vesicle

membrane]
Protein
UBC(153-228) [endosome membrane]Protein
UBC(229-304)

[endocytic vesicle

membrane]
Protein
UBC(229-304) [endosome membrane]Protein
UBC(305-380)

[endocytic vesicle

membrane]
Protein
UBC(305-380) [endosome membrane]Protein
UBC(381-456)

[endocytic vesicle

membrane]
Protein
UBC(381-456) [endosome membrane]Protein
UBC(457-532)

[endocytic vesicle

membrane]
Protein
UBC(457-532) [endosome membrane]Protein
UBC(533-608)

[endocytic vesicle

membrane]
Protein
UBC(533-608) [endosome membrane]Protein
UBC(609-684)

[endocytic vesicle

membrane]
Protein
UBC(609-684) [endosome membrane]Protein
UBC(77-152)

[endocytic vesicle

membrane]
Protein
UBC(77-152) [endosome membrane]Protein
Ubiquinated and PIP3

Endosmal Membrane

Bound Cargo
ComplexREACT_27362 (Reactome)
VAMP2ProteinENSBTAG00000003891 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:P63027
VAMP7Protein
VAMP7 [lysosomal membrane]Protein
VAMP8ProteinENSBTAG00000023997 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9BV40
VPS25ProteinENSBTAG00000019906 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9BRG1
VPS28ProteinENSBTAG00000026320 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9UK41
VPS36ProteinENSBTAG00000004307 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q86VN1
VPS37AProteinENSBTAG00000010355 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q8NEZ2
VPS37B [endosome membrane]Protein
VPS37CProteinENSBTAG00000008064 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:A5D8V6
VPS37DProteinENSBTAG00000008487 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q86XT2
VPS4AProteinENSBTAG00000001659 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9UN37
VPS4BProteinENSBTAG00000010492 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:O75351
VTA1ProteinENSBTAG00000005851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = S:Q9NP79
VampProtein
Vamp2:SNAP23:Syn4

Secretory granule docking and fusion

complex
ComplexREACT_15108 (Reactome)
Vamp7:SNAP23:Syn4

Plasma membrane vesicle docking and

fusion complex
ComplexREACT_14917 (Reactome)
Vamp8:SNAP23:Syn4

Secretory granule docking and fusion

complex
ComplexREACT_15240 (Reactome)
Vps/Vta1ComplexREACT_27371 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_19124 (Reactome)
ADPArrowREACT_19206 (Reactome)
ADPArrowREACT_27184 (Reactome)
AP-1 ComplexArrowREACT_19124 (Reactome)
AP-1 ComplexArrowREACT_19206 (Reactome)
AP-1 ComplexREACT_19371 (Reactome)
AP-1 ComplexREACT_19391 (Reactome)
ARFGAP3ArrowREACT_11078 (Reactome)
ARFGAP3REACT_11111 (Reactome)
ARFGAP3mim-catalysisREACT_11107 (Reactome)
ARRB1ArrowREACT_19124 (Reactome)
ARRB1ArrowREACT_19206 (Reactome)
ARRB1REACT_19371 (Reactome)
ARRB1REACT_19391 (Reactome)
ATPREACT_19124 (Reactome)
ATPREACT_19206 (Reactome)
ATPREACT_27184 (Reactome)
Arf1-GDPArrowREACT_11073 (Reactome)
Arf1-GDPArrowREACT_19167 (Reactome)
Arf1-GDPArrowREACT_19334 (Reactome)
Arf1-GDPREACT_11099 (Reactome)
Arf1-GDPREACT_14808 (Reactome)
Arf1-GTPArrowREACT_11099 (Reactome)
Arf1-GTPArrowREACT_14808 (Reactome)
Arf1-GTPREACT_11243 (Reactome)
Arf1-GTPREACT_19371 (Reactome)
Arf1-GTPREACT_19391 (Reactome)
BLOC-1 ComplexArrowREACT_19390 (Reactome)
BLOC1S1(1-125)REACT_19390 (Reactome)
BLOC1S3REACT_19390 (Reactome)
BLOC1S6REACT_19390 (Reactome)
CHMP2ArrowREACT_27184 (Reactome)
CHMP3ArrowREACT_27184 (Reactome)
CHMP4ArrowREACT_27184 (Reactome)
CHMP6ArrowREACT_27184 (Reactome)
CHMP7ArrowREACT_27184 (Reactome)
CLINT1REACT_19237 (Reactome)
CNOREACT_19390 (Reactome)
Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp ComplexArrowREACT_19391 (Reactome)
Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp ComplexREACT_19334 (Reactome)
Cargo:AP-1:Beta-arrestin:Clathrin

Triskelion:Vamp

Complex
ArrowREACT_19255 (Reactome)
Cargo:AP-1:Beta-arrestin:Clathrin

Triskelion:Vamp

Complex
REACT_19124 (Reactome)
Cargo:AP-1:Beta-arrestin:Vamp:Clathrin

Triskelion:Dynamin:Endophilin

Complex
ArrowREACT_19334 (Reactome)
Cargo:AP-1:Beta-arrestin:Vamp:Clathrin

Triskelion:Dynamin:Endophilin

Complex
REACT_19255 (Reactome)
Cargo:AP-1:Beta-arrestin:Vamp:Clathrin

Triskelion:Dynamin:Endophilin

Complex
mim-catalysisREACT_19255 (Reactome)
Clathrin TriskelionArrowREACT_19124 (Reactome)
Clathrin TriskelionArrowREACT_19206 (Reactome)
Clathrin TriskelionREACT_19167 (Reactome)
Clathrin TriskelionREACT_19334 (Reactome)
Coatomer:ARFGAP1 latticeArrowREACT_11138 (Reactome)
Coatomer:ARFGAP1 latticeREACT_11078 (Reactome)
Coatomer:Arf1-GDP:GAP LatticeArrowREACT_11107 (Reactome)
Coatomer:Arf1-GDP:GAP LatticeREACT_11073 (Reactome)
Coatomer:Arf1-GTP ComplexArrowREACT_11243 (Reactome)
Coatomer:Arf1-GTP ComplexREACT_11111 (Reactome)
Coatomer:Arf1-GTP:GAP ComplexArrowREACT_11111 (Reactome)
Coatomer:Arf1-GTP:GAP ComplexREACT_11107 (Reactome)
Coatomer:Arf1-GTP:GAP ComplexREACT_11126 (Reactome)
Coatomer:Arf1-GTP:GAP LatticeArrowREACT_11126 (Reactome)
Coatomer:GAP LatticeArrowREACT_11073 (Reactome)
Coatomer:GAP LatticeREACT_11138 (Reactome)
CoatomerArrowREACT_11078 (Reactome)
CoatomerREACT_11243 (Reactome)
DNM2ArrowREACT_19194 (Reactome)
DNM2ArrowREACT_19255 (Reactome)
DNM2REACT_19167 (Reactome)
DNM2REACT_19334 (Reactome)
DTNBP1REACT_19390 (Reactome)
ESCRT-0/Cargo ComplexREACT_27272 (Reactome)
ESCRT-0ArrowREACT_27272 (Reactome)
ESCRT-I/Cargo ComplexArrowREACT_27272 (Reactome)
ESCRT-I/Cargo ComplexREACT_27319 (Reactome)
ESCRT-IArrowREACT_27319 (Reactome)
ESCRT-II/Cargo ComplexArrowREACT_27319 (Reactome)
ESCRT-II/Cargo ComplexREACT_27290 (Reactome)
ESCRT-IIArrowREACT_27290 (Reactome)
ESCRT-III/Cargo ComplexArrowREACT_27290 (Reactome)
ESCRT-III/Cargo ComplexREACT_27184 (Reactome)
ESCRT-IIIREACT_27290 (Reactome)
ESCRT-IIREACT_27319 (Reactome)
ESCRT-IREACT_27272 (Reactome)
Ferritin ComplexREACT_19237 (Reactome)
GBF1mim-catalysisREACT_11099 (Reactome)
GBF1mim-catalysisREACT_14808 (Reactome)
GDPArrowREACT_11099 (Reactome)
GDPArrowREACT_12554 (Reactome)
GDPArrowREACT_14808 (Reactome)
GDPArrowREACT_19194 (Reactome)
GDPArrowREACT_19255 (Reactome)
GTPREACT_11099 (Reactome)
GTPREACT_12554 (Reactome)
GTPREACT_14808 (Reactome)
GTPREACT_19194 (Reactome)
GTPREACT_19255 (Reactome)
Golgi-associated Vesicle CargoArrowREACT_19124 (Reactome)
Golgi-associated

Vesicle Destined

Cargo
REACT_19391 (Reactome)
Golgi-associated

vesicle interacting

proteins
ArrowREACT_19237 (Reactome)
HSC70:Auxillin ComplexArrowREACT_19124 (Reactome)
HSC70:Auxillin ComplexArrowREACT_19206 (Reactome)
HSC70:Auxillin ComplexREACT_19124 (Reactome)
HSC70:Auxillin ComplexREACT_19206 (Reactome)
Lysosome

Cargo:AP-1:Beta-arrestin:Clathrin Triskelion:Vamp

Complex
ArrowREACT_19194 (Reactome)
Lysosome

Cargo:AP-1:Beta-arrestin:Clathrin Triskelion:Vamp

Complex
REACT_19206 (Reactome)
Lysosome CargoArrowREACT_19206 (Reactome)
Lysosome Destined

Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp

Complex
ArrowREACT_19371 (Reactome)
Lysosome Destined

Cargo:AP-1:Arf1-GTP:beta-Arrestin-1:Vamp

Complex
REACT_19167 (Reactome)
Lysosome Destined

Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin

Complex
ArrowREACT_19167 (Reactome)
Lysosome Destined

Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin

Complex
REACT_19194 (Reactome)
Lysosome Destined

Cargo:AP-1:Beta-arrestin:Vamp:Clathrin Triskelion:Dynamin:Endophilin

Complex
mim-catalysisREACT_19194 (Reactome)
Lysosome Destined CargoREACT_19371 (Reactome)
NAPAREACT_19390 (Reactome)
PREBmim-catalysisREACT_12554 (Reactome)
PUM1REACT_19237 (Reactome)
PiArrowREACT_11107 (Reactome)
PiArrowREACT_12396 (Reactome)
PiArrowREACT_12456 (Reactome)
PiArrowREACT_19124 (Reactome)
PiArrowREACT_19167 (Reactome)
PiArrowREACT_19194 (Reactome)
PiArrowREACT_19206 (Reactome)
PiArrowREACT_19255 (Reactome)
PiArrowREACT_19334 (Reactome)
PiArrowREACT_27184 (Reactome)
REACT_11073 (Reactome) Inactive Arf1-GDP then diffuses away from the membrane, initiating the disassembly of the lattice.
REACT_11078 (Reactome) Ultimately the hydrolysis of Arf1-bound GTP, induced by the recruited ArfGAP, allows the inactive Arf1-GDP to diffuse away from the membrane, initiating disassembly of the lattice from the vesicle (Lippincott-Schwartz and Liu 2006).
REACT_11099 (Reactome) The formation of the COPI coat requires membrane recruitment and activation of Arf1. Arf1 activation is normally mediated by guanine nucleotide exchange factors (GEFs) that convert Arf1 to its active GTP-bound state on the membrane. In this reaction that GEF is represented by GBF1.
REACT_11107 (Reactome) The hydrolysis of Arf1-bound GTP is induced by the recruited ArfGAP.
REACT_11111 (Reactome) Once both coatomer and the active form of Arf1 have been recruited to the Golgi membrane surface, ArfGAP joins the complex.
REACT_11126 (Reactome) Together, the complex of coatomer, Arf1, and ArfGAP assembles into a lattice that concentrates cargo proteins and deforms the membrane. Eventually this membrane pocket forms into a bud that pinches off the membrane, and is released into the cytoplasm (Lippincott-Schwartz and Liu 2006).
REACT_11138 (Reactome) All of the key components and regulators of the COPI coat (GBF1, Arf1, ArfGAP1 and coatomer) cycle on and off the Golgi membrane. This cycle is required for vesicle formation, but is uncoupled from the actual vesicle release. Continuous membrane binding and release of these molecules enables the COPI lattice to be dynamically modulated. Once the vesicle is released from the Golgi apparatus, this lattice is completely disassociated from the vesicle.
REACT_11243 (Reactome) In models of COPI coat assembly and disassembly, after GBF1 activates Arf1 on membranes, the active form of Arf1 recruits coatomer complexes from the cytoplasm.
REACT_12393 (Reactome) Sar1p-GTP recruits the cytoplasmic Sec23p-Sec24p complex. Though not represented in the subsequent steps, Sec23p-Sec24p would bind to members of the p24 protein family of possible cargo receptors, and together with Sar1p bind the appropiate v-SNARE, and Rab-GTP.
REACT_12396 (Reactome) Sar1p-GTP hydrolysis is increased 15-30-fold by Sec23p. Sar1p-GDP is released as a result of this hydrolysis and used in further vesicle sculpting cycles. Sar1p-GTP hydrolysis occurs at two critical points during the cycle, first (as represented here) as a proofreading step, insuring that the cargo is loaded. Later in the cycle Sar1p-GTP hydrolysis triggers the uncoating of the budded vesicle.
REACT_12422 (Reactome) Cytosolic Sec13p-Sec31p complexes bind to pre-bound Sec23p-Sec24p complexes.
REACT_12456 (Reactome) Vesicle uncoating is triggered by Sar1p-GTP hydrolysis leaving only the vesicle cargo and the v-SNARE to target the vesicle to the Golgi membrane.
REACT_12554 (Reactome) Sar1p-GDP is recruited to the ER membrane by the transmembrane GEF (Guanine nucleotide exchange factor) Sec12, where it is converted to Sar1p-GTP.
REACT_12610 (Reactome) Once loaded the vesicles become fully sculpted, pinch off from the ER and bud into the cytosol.
REACT_14778 (Reactome) The lysosomal vesicle is targeted to and fused with the plasma membrane, releasing its contents into the extracellular space.
REACT_14808 (Reactome) ARF1 helps to recruit AP-1 to Golgi membrane. AP-1 is not alone in this process of establishing a docking complex at the trans-Golgi Network. This section of the Golgi membrane will be where the new vesicle will be built and loaded.
REACT_14821 (Reactome) The vamp8 associated vesicle docks and fuses with the plasma membrane.
REACT_14822 (Reactome) The vamp2 associated vesicle docks and fuses with the plasma membrane.
REACT_19124 (Reactome) The heat shock protein Hsc70 and auxilin, a J-domain containing protein, are responsible for clathrin disassembly through an ATP-dependent reaction. This uncoating step may be a point in the pathway subject to regulation. This final step releases the vesicle from the clathrin cage. The vesicle still contatins a specific Vamp molecule, part of the targeting and fusion mechanism that delivers the vesicle to its ultimate destination. This vesicle also contains its cargo, membrane proteins embeded in the Golgi-associated vesicle membrane.
REACT_19167 (Reactome) Once the basic components of the docking complex are assembled with one end of AP-1 bound to cargo molecules, the other end binds to clathrin. Clathrin triskelions polymerize into hexagons and pentagons, forming a cage, which leads to membrane deformation. This polymerization step drives the sculpting of the lysosome vesicle. Here only 5 clathrin triskelions are represented, though in reality many more would be involved in sculpting an entire vesicle.
REACT_19194 (Reactome) Dynamin is recruited to the growing lysosome destined vesicle and, under conditions that interfere with its GTPase activity, dynamin forms a collar or ring around the neck of the budding vesicle. It is unclear whether dynamin acts as a mechanochemical transducer to generate fission or as a recruiter to attach other proteins that are directly responsible for the fission step. Lipid-modifying enzymes such as endophilin are also involved in vesicle formation. Endophilin is an acyltransferase that interacts with dynamin and that generates lysophosphatidic acid. The current view is that this reaction produces a negative curvature at the neck of the vesicle.
REACT_19206 (Reactome) The heat shock protein Hsc70 and auxilin, a J-domain containing protein, are responsible for clathrin disassembly through an ATP-dependent reaction. This uncoating step may be a point in the pathway subject to regulation. This final step releases the vesicle from the clathrin cage. The vesicle still contatins a specific Vamp molecule, part of the targeting and fusion mechanism that delivers the vesicle to its ultimate destination. This vesicle also contains its cargo, membrane proteins embeded in the lysosome membrane.
REACT_19237 (Reactome) Cytosolic proteins are also recruited to the cyctoplasmic face of newly formed vesicles.
REACT_19255 (Reactome) Dynamin is recruited to the growing vesicle and, under conditions that interfere with its GTPase activity, dynamin forms a collar or ring around the neck of the budding vesicle. It is unclear whether dynamin acts as a mechanochemical transducer to generate fission or as a recruiter to attach other proteins that are directly responsible for the fission step. Lipid-modifying enzymes such as endophilin are also involved in vesicle formation. Endophilin is an acyltransferase that interacts with dynamin and that generates lysophosphatidic acid. The current view is that this reaction produces a negative curvature at the neck of the vesicle.
REACT_19334 (Reactome) Once the basic components of the docking complex are assembled with one end of AP-1 bound to cargo molecules, the other end binds to clathrin. Clathrin triskelions polymerize into hexagons and pentagons, forming a cage, which leads to membrane deformation. This polymerization step drives the sculpting of the vesicle. The number of clathrin triskelions required to sculpt a vesicle appears to be variable, but has been estimated to require 36 - 60 triskelions assocaited with 30 - 66 AP-1 complexes. Here a ~380 angstroms vesicle is represented with 48 clathrin triskelions and 52 AP-1 complexes.
REACT_19371 (Reactome) Once AP-1 is recruited to the trans-Golgi Network membrane the complex of functional vesicle building proteins is joined by the cargo that will be within that vesicle. As with other types of vesicles the cargo itself is part of the vesicle development. Here the cargo is destined for the lysosome membrane. It is at this stage that a specific Synaptobrevin (Vamp) molecule also joins the complex. It should be noted that only certain Vamp molecules will be found with specific cargo molecules on the newly forming vesicles. However here we represent this reaction in bulk, without specific Vamp and cargo molecule pairings.
REACT_19390 (Reactome) The ubiquitously expressed protein complexes, named biogenesis of lysosome-related organelles complex or BLOC are required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules.
REACT_19391 (Reactome) Once AP-1 is recruited to the trans-Golgi Network membrane the complex of functional vesicle building proteins is joined by the cargo that will be within that vesicle. As with other types of vesicles the cargo itself is part of the vesicle development. Here the cargo is destined for the Golgi-associated vesicle membrane. It is at this stage that a specific Synaptobrevin (Vamp) molecule also joins the complex. It should be noted that only certain Vamp molecules will be found with specific cargo molecules on the newly forming vesicles. However here we represent this reaction in bulk, without specific Vamp and cargo molecule pairings.
REACT_27184 (Reactome) Disassembly Phase
The AAA-ATPase, Vps4 disassembles ESCRT-III and catalyzes the final step of the MVB pathway. The microtubule interacting and trafficking (MIT) domain of Vps4 interacts directly with the C-terminal region of Vps2 (MIM1) and Vps20 (MIM2). The association of Vta1, which contains two MIT domains, greatly enhances the activity of Vps4. Please note that the recomended names of the Vacuolar protein sorting-associated proteins (Vps) are Charged multivesicular body proteins or CHMPs.
REACT_27272 (Reactome) Initiation/Cargo Recognition is mediated by ESCRT-0, a heterodimer consisting of Vps27 and Hse1. ESCRT-0 binds Phosphatidyl inositol 3- phosphate (PI3P) on endosomes via a FVYE domain and ubiquitinated cargo via two UIM domains.
REACT_27290 (Reactome) ESCRT-III assembles into a highly ordered filament-like hetero-oligomer. Vps20 nucleates the homo-oligomerization of Snf7 that is capped by Vps24. Vps24 recruits Vps2 and initiates Vps4-dependent ESCRT-III disassembly. ESCRT-III is required for the last steps of MVB sorting, cargo sequestration, and MVB vesicle formation.
REACT_27319 (Reactome) ESCRT-0 recruits ESCRT-I and thereby initiates the MVB pathway. Cargo Sorting ESCRT-I is a heterotetramer consisting of Vps23, Vps28, Vps37, and Mvb12. The UEV domain of Vps23 binds ubiquitinated membrane proteins. Vps28 interacts with the GLUE domain of Vps36 in ESCRT-II. Cargo Sorting ESCRT-II is a heterotetramer formed of Vps36, Vps22, and two Vps25 molecules. The GLUE domain of Vps36 binds PI3P, Vps28, and ubiquitinated membrane proteins. Vps25 interacts with Vps20 of ESCRT-III.
SAR1BArrowREACT_12456 (Reactome)
SEC13ArrowREACT_12456 (Reactome)
SEC13REACT_12422 (Reactome)
SEC23AArrowREACT_12456 (Reactome)
SEC31AArrowREACT_12456 (Reactome)
SEC31AREACT_12422 (Reactome)
SH3D19REACT_19237 (Reactome)
SH3GL2ArrowREACT_19194 (Reactome)
SH3GL2ArrowREACT_19255 (Reactome)
SH3GL2REACT_19167 (Reactome)
SH3GL2REACT_19334 (Reactome)
SNAP23ArrowREACT_14778 (Reactome)
SNAP23ArrowREACT_14821 (Reactome)
SNAP23ArrowREACT_14822 (Reactome)
SNAP23REACT_14778 (Reactome)
SNAP23REACT_14821 (Reactome)
SNAP23REACT_14822 (Reactome)
STX4ArrowREACT_14778 (Reactome)
STX4ArrowREACT_14821 (Reactome)
STX4ArrowREACT_14822 (Reactome)
STX4REACT_14778 (Reactome)
STX4REACT_14821 (Reactome)
STX4REACT_14822 (Reactome)
Sar1b:GDP ComplexArrowREACT_12396 (Reactome)
Sar1b:GDP ComplexREACT_12554 (Reactome)
Sar1b:GTP ComplexArrowREACT_12554 (Reactome)
Sar1b:GTP ComplexREACT_12393 (Reactome)
Sar1b:GTP:Sec23p:Sec24p:Sec13p:Sec31p ComplexArrowREACT_12422 (Reactome)
Sar1b:GTP:Sec23p:Sec24p:Sec13p:Sec31p ComplexREACT_12610 (Reactome)
Sar1b:GTP:Sec23p:Sec24pArrowREACT_12393 (Reactome)
Sar1b:GTP:Sec23p:Sec24pREACT_12396 (Reactome)
Sar1b:GTP:Sec23p:Sec24pREACT_12422 (Reactome)
Sar1b:GTP:Sec23p:Sec24pmim-catalysisREACT_12396 (Reactome)
Sar1b:Sec23p:Sec24p:Sec13p:Sec31p ComplexArrowREACT_12610 (Reactome)
Sar1b:Sec23p:Sec24p:Sec13p:Sec31p ComplexREACT_12456 (Reactome)
Sar1b:Sec23p:Sec24p:Sec13p:Sec31p Complexmim-catalysisREACT_12456 (Reactome)
Sec23p:Sec24p ComplexArrowREACT_12396 (Reactome)
Sec23p:Sec24p ComplexREACT_12393 (Reactome)
Sec24ArrowREACT_12456 (Reactome)
TXNDC5REACT_19390 (Reactome)
Ubiquinated and PIP3

Endosmal Membrane

Bound Cargo
ArrowREACT_27184 (Reactome)
VAMP2ArrowREACT_14822 (Reactome)
VAMP2REACT_14822 (Reactome)
VAMP7ArrowREACT_14778 (Reactome)
VAMP7REACT_14778 (Reactome)
VAMP8ArrowREACT_14821 (Reactome)
VAMP8REACT_14821 (Reactome)
Vamp2:SNAP23:Syn4

Secretory granule docking and fusion

complex
mim-catalysisREACT_14822 (Reactome)
Vamp7:SNAP23:Syn4

Plasma membrane vesicle docking and

fusion complex
mim-catalysisREACT_14778 (Reactome)
Vamp8:SNAP23:Syn4

Secretory granule docking and fusion

complex
mim-catalysisREACT_14821 (Reactome)
VampArrowREACT_19124 (Reactome)
VampArrowREACT_19206 (Reactome)
VampArrowREACT_19237 (Reactome)
VampREACT_19237 (Reactome)
VampREACT_19371 (Reactome)
VampREACT_19391 (Reactome)
Vps/Vta1mim-catalysisREACT_27184 (Reactome)
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