KEGG   PATHWAY: xco04144
Entry
xco04144                    Pathway                                
Name
Endocytosis - Xiphophorus couchianus (Monterrey platyfish)
Description
Endocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins entering through clathrin-dependent endocytosis (CDE) have sequences in their cytoplasmic domains that bind to the APs (adaptor-related protein complexes) and enable their rapid removal from the PM. In addition to APs and clathrin, there are numerous accessory proteins including dynamin. Depending on the various proteins that enter the endosome membrane, these cargoes are sorted to distinct destinations. Some cargoes, such as nutrient receptors, are recycled back to the PM. Ubiquitylated membrane proteins, such as activated growth-factor receptors, are sorted into intraluminal vesicles and eventually end up in the lysosome lumen via multivesicular endosomes (MVEs). There are distinct mechanisms of clathrin-independent endocytosis (CIE) depending upon the cargo and the cell type.
Class
Cellular Processes; Transport and catabolism
Pathway map
xco04144  Endocytosis
xco04144

Other DBs
GO: 0006897
Organism
Xiphophorus couchianus (Monterrey platyfish) [GN:xco]
Gene
114133212  git1; ARF GTPase-activating protein GIT1 isoform X1 [KO:K05737]
114133311  [KO:K12469]
114133345  [KO:K19366]
114133505  ehd2; EH domain-containing protein 2 isoform X1 [KO:K12469]
114133576  [KO:K00909] [EC:2.7.11.14]
114133667  cbl; E3 ubiquitin-protein ligase CBL [KO:K04707] [EC:2.3.2.27]
114133714  [KO:K07939]
114133738  rab11fip3; rab11 family-interacting protein 3 isoform X1 [KO:K12485]
114133814  asap2; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K12488]
114133896  pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
114133904  [KO:K21269]
114133957  chmp3; charged multivesicular body protein 3 [KO:K12193]
114134047  fgfr3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
114134201  ldlrap1; low density lipoprotein receptor adapter protein 1 isoform X1 [KO:K12474]
114134212  vps29; vacuolar protein sorting-associated protein 29 isoform X1 [KO:K18467]
114134220  [KO:K12488]
114134402  [KO:K07941]
114134640  itch; E3 ubiquitin-protein ligase Itchy homolog [KO:K05632] [EC:2.3.2.26]
114134779  [KO:K12495]
114134780  [KO:K12484]
114134936  [KO:K23612]
114134946  [KO:K12489]
114135093  [KO:K07897]
114135099  [KO:K07897]
114135180  [KO:K17920]
114135208  [KO:K04513]
114135246  [KO:K04393]
114135255  [KO:K12194]
114135298  [KO:K05704] [EC:2.7.10.2]
114135331  [KO:K12488]
114135418  [KO:K17848]
114135467  [KO:K07939]
114135506  [KO:K05632] [EC:2.3.2.26]
114135570  arfgap1; ADP-ribosylation factor GTPase-activating protein 1 isoform X1 [KO:K12492]
114135592  capzb; F-actin-capping protein subunit beta isoform X1 [KO:K10365]
114135615  [KO:K07938]
114135632  [KO:K07891]
114135673  tsg101; tumor susceptibility gene 101 protein [KO:K12183]
114135737  hras; GTPase HRas [KO:K02833]
114135778  [KO:K12495]
114135819  [KO:K12958]
114135945  arpc4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
114135963  [KO:K10396] [EC:5.6.1.3]
114136035  cav3; caveolin-3 [KO:K12959]
114136165  [KO:K07897]
114136166  [KO:K05755]
114136168  [KO:K12958]
114136421  [KO:K04361] [EC:2.7.10.1]
114136423  [KO:K01115] [EC:3.1.4.4]
114136716  asap1; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 isoform X1 [KO:K12488]
114136721  sh3kbp1; SH3 domain-containing kinase-binding protein 1 isoform X1 [KO:K12470]
114136748  [KO:K12198]
114136767  [KO:K18584]
114136810  arfgef1; brefeldin A-inhibited guanine nucleotide-exchange protein 1 isoform X1 [KO:K18442]
114136816  [KO:K04237]
114136832  kif5b; kinesin-1 heavy chain isoform X1 [KO:K10396] [EC:5.6.1.3]
114136944  [KO:K24782]
114136982  wwp1; NEDD4-like E3 ubiquitin-protein ligase WWP1 [KO:K05633] [EC:2.3.2.26]
114136987  [KO:K06503]
114136997  [KO:K11248]
114137384  [KO:K12486]
114137491  chmp1a; charged multivesicular body protein 1a [KO:K12197]
114137719  snx5; sorting nexin-5 [KO:K17920]
114137832  rab11fip2; rab11 family-interacting protein 2 isoform X1 [KO:K12484]
114137855  gbf1; Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 isoform X1 [KO:K18443]
114138010  [KO:K12494]
114138158  actr2; actin-related protein 2 [KO:K17260]
114138187  [KO:K18462]
114138286  wipf1; WAS/WASL-interacting protein family member 1 [KO:K19475]
114138295  [KO:K05093] [EC:2.7.10.1]
114139077  [KO:K12482]
114139117  [KO:K12494]
114139160  [KO:K04180]
114139230  [KO:K12197]
114139294  cltb; clathrin light chain B isoform X1 [KO:K04645]
114139442  rab11fip5; rab11 family-interacting protein 5 isoform X1 [KO:K12484]
114139452  [KO:K12483]
114139599  arap3; arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 isoform X1 [KO:K12490]
114139967  cblc; E3 ubiquitin-protein ligase CBL-C isoform X1 [KO:K22518] [EC:2.3.2.27]
114140241  [KO:K05050]
114140270  agap2; arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K17848]
114140289  [KO:K12495]
114140324  acap3; arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3 isoform X1 [KO:K12489]
114140524  [KO:K12491]
114140616  [KO:K12562]
114140643  [KO:K12471]
114140813  arpc2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
114140849  [KO:K18584]
114140865  [KO:K05704] [EC:2.7.10.2]
114140909  [KO:K10396] [EC:5.6.1.3]
114140965  [KO:K07904]
114141005  pard6b; partitioning defective 6 homolog beta [KO:K06093]
114141053  rnf41; E3 ubiquitin-protein ligase NRDP1 [KO:K11981] [EC:2.3.2.27]
114141472  [KO:K12495]
114141653  [KO:K07887]
114141819  [KO:K00889] [EC:2.7.1.68]
114141827  washc5; WASH complex subunit 5 [KO:K18464]
114141833  [KO:K03283]
114141962  cyth2; cytohesin-2 [KO:K18441]
114141996  prkcz; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
114142284  [KO:K04393]
114142351  [KO:K04180]
114142528  [KO:K11824]
114142532  [KO:K04513]
114142614  grk1; rhodopsin kinase [KO:K00909] [EC:2.7.11.14]
114142654  arf3; ADP-ribosylation factor 3 isoform X1 [KO:K07938]
114142666  [KO:K10364]
114142670  nedd4; E3 ubiquitin-protein ligase NEDD4 isoform X1 [KO:K10591] [EC:2.3.2.26]
114142760  traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
114142765  spg21; maspardin [KO:K19367]
114142844  cav1; caveolin-1 [KO:K06278]
114142876  ist1; IST1 homolog isoform X1 [KO:K19476]
114142908  vps26a; vacuolar protein sorting-associated protein 26A isoform X1 [KO:K18466]
114142937  capza2; F-actin-capping protein subunit alpha-2 [KO:K10364]
114142973  [KO:K23612]
114142987  arfgap2; ADP-ribosylation factor GTPase-activating protein 2 isoform X1 [KO:K12493]
114142996  [KO:K23605]
114143064  [KO:K05087] [EC:2.7.10.1]
114143065  usp8; ubiquitin carboxyl-terminal hydrolase 8 isoform X1 [KO:K11839] [EC:3.4.19.12]
114143258  vps35; vacuolar protein sorting-associated protein 35 isoform X1 [KO:K18468]
114143439  cav2; caveolin-2 isoform X1 [KO:K12958]
114143450  rufy2; RUN and FYVE domain-containing protein 2 isoform X1 [KO:K12482]
114143509  rab4a; ras-related protein Rab-4A [KO:K07879]
114143580  [KO:K17917]
114143638  rbsn; rabenosyn-5 [KO:K12481]
114143685  rab11a; ras-related protein Rab-11A [KO:K07904]
114143715  iqsec2; IQ motif and SEC7 domain-containing protein 2 isoform X1 [KO:K12495]
114143925  [KO:K05069]
114143985  arfgef2; brefeldin A-inhibited guanine nucleotide-exchange protein 2 [KO:K18442]
114143993  [KO:K12473]
114144101  [KO:K04513]
114144411  grk4; G protein-coupled receptor kinase 4 isoform X1 [KO:K08291] [EC:2.7.11.16]
114144413  [KO:K18441]
114144573  [KO:K19475]
114144608  [KO:K23484]
114144616  [KO:K12471]
114144619  [KO:K04393]
114144638  zfyve27; protrudin isoform X1 [KO:K19368]
114144699  clta; clathrin light chain A isoform X1 [KO:K04644]
114144713  [KO:K04678] [EC:2.3.2.26]
114144773  vps37a; vacuolar protein sorting-associated protein 37A [KO:K12185]
114144822  rab11fip4; rab11 family-interacting protein 4 isoform X1 [KO:K12485]
114144829  [KO:K05069]
114144845  [KO:K10396] [EC:5.6.1.3]
114144872  sh3gl2; endophilin-A1 isoform X1 [KO:K11247]
114144905  [KO:K05757]
114145015  [KO:K04388] [EC:2.7.11.30]
114145037  [KO:K05757]
114145075  [KO:K12486]
114145340  mvb12a; multivesicular body subunit 12A [KO:K12186]
114145415  [KO:K12185]
114145896  [KO:K01528] [EC:3.6.5.5]
114145938  grk7; rhodopsin kinase [KO:K00909] [EC:2.7.11.14]
114146011  [KO:K12472]
114146044  [KO:K03283]
114146071  [KO:K04237]
114146089  [KO:K07905]
114146109  [KO:K12472]
114146154  [KO:K07901]
114146157  vps4b; vacuolar protein sorting-associated protein 4B isoform X1 [KO:K12196]
114146452  [KO:K07891]
114146482  arf1; ADP-ribosylation factor 1 [KO:K07937]
114146503  amph; amphiphysin isoform X1 [KO:K12562]
114146588  [KO:K10396] [EC:5.6.1.3]
114146596  egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114146637  ap2m1; AP-2 complex subunit mu isoform X1 [KO:K11826]
114146641  [KO:K04189]
114146829  [KO:K11247]
114146844  [KO:K05754]
114146875  stam; signal transducing adapter molecule 1 [KO:K04705]
114146941  prkci; protein kinase C iota type [KO:K06069] [EC:2.7.11.13]
114146962  zfyve9; zinc finger FYVE domain-containing protein 9 isoform X1 [KO:K04679]
114147080  [KO:K00889] [EC:2.7.1.68]
114147191  tfrc; transferrin receptor protein 1 [KO:K06503]
114147206  [KO:K12198]
114147241  [KO:K12491]
114147889  [KO:K11824]
114147918  [KO:K04705]
114147998  [KO:K07888]
114148020  [KO:K05050]
114148030  [KO:K05757]
114148108  [KO:K18584]
114148133  bin1; myc box-dependent-interacting protein 1 isoform X1 [KO:K12562]
114148140  chmp2b; charged multivesicular body protein 2b [KO:K12192]
114148328  snx4; sorting nexin-4 [KO:K17919]
114148419  [KO:K12958]
114148517  [KO:K00909] [EC:2.7.11.14]
114148634  [KO:K10396] [EC:5.6.1.3]
114148669  [KO:K05050]
114148729  cxcr4; C-X-C chemokine receptor type 4 [KO:K04189]
114148734  [KO:K12485]
114148995  [KO:K08291] [EC:2.7.11.16]
114149124  mvb12b; multivesicular body subunit 12B isoform X1 [KO:K12186]
114149258  [KO:K12495]
114149332  [KO:K12487]
114149372  chmp4b; charged multivesicular body protein 4b [KO:K12194]
114149459  dnm1; dynamin-1 isoform X1 [KO:K01528] [EC:3.6.5.5]
114149461  [KO:K04679]
114149509  dab2; disabled homolog 2 isoform X1 [KO:K12475]
114149514  nedd4l; E3 ubiquitin-protein ligase NEDD4-like isoform X1 [KO:K13305] [EC:2.3.2.26]
114149548  smad2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500]
114149683  [KO:K12494]
114149699  [KO:K13712] [EC:2.7.1.68]
114149700  [KO:K13712] [EC:2.7.1.68]
114149748  [KO:K21269]
114149780  [KO:K00889] [EC:2.7.1.68]
114149782  [KO:K04674] [EC:2.7.11.30]
114150001  [KO:K12484]
114150183  arpc3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
114150251  grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
114150377  [KO:K12472]
114150573  eps15; epidermal growth factor receptor substrate 15 isoform X1 [KO:K12472]
114150756  [KO:K04679]
114150776  dnajc6; putative tyrosine-protein phosphatase auxilin isoform X1 [KO:K09526]
114150812  arpc5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
114150814  sh3gl1; endophilin-A2 [KO:K11247]
114150828  [KO:K12196]
114150850  pip5k1c; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
114150855  [KO:K07905]
114150856  [KO:K07905]
114150927  [KO:K11247]
114150976  dnm3; dynamin-3 isoform X1 [KO:K01528] [EC:3.6.5.5]
114151056  vps4a; vacuolar protein sorting-associated protein 4A [KO:K12196]
114151105  pdgfra; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
114151242  [KO:K07901]
114151346  [KO:K17917]
114151388  [KO:K18441]
114151557  acap2; arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K12489]
114151824  [KO:K12494]
114151978  snf8; vacuolar-sorting protein SNF8 [KO:K12188]
114152004  chmp2a; charged multivesicular body protein 2a [KO:K12191]
114152046  [KO:K07937]
114152177  [KO:K07889]
114152267  chmp6; charged multivesicular body protein 6 [KO:K12195]
114152308  vps25; vacuolar protein-sorting-associated protein 25 [KO:K12189]
114152392  [KO:K18441]
114152738  [KO:K04646]
114152754  [KO:K05070]
114152755  snx12; sorting nexin-12 isoform X1 [KO:K17918]
114152860  vps36; vacuolar protein-sorting-associated protein 36 [KO:K12190]
114152969  chmp1b; charged multivesicular body protein 1b [KO:K12197]
114152980  [KO:K03283]
114153038  [KO:K04707] [EC:2.3.2.27]
114153113  [KO:K18439]
114153153  eea1; early endosome antigen 1 isoform X1 [KO:K12478]
114153166  [KO:K04513]
114153168  [KO:K01115] [EC:3.1.4.4]
114153203  [KO:K12185]
114153282  rabep1; rab GTPase-binding effector protein 1 isoform X1 [KO:K12480]
114153290  [KO:K18466]
114153297  grk6; G protein-coupled receptor kinase 6 [KO:K08291] [EC:2.7.11.16]
114153476  spart; spartin isoform X1 [KO:K19366]
114153549  [KO:K04513]
114153593  arrb2; beta-arrestin-2 isoform X1 [KO:K04439]
114153742  [KO:K11825]
114153804  [KO:K00909] [EC:2.7.11.14]
114153957  [KO:K12186]
114154072  cltcl1; clathrin heavy chain 2 isoform X1 [KO:K04646]
114154140  [KO:K11866] [EC:3.4.19.12]
114154214  [KO:K00889] [EC:2.7.1.68]
114154319  vps37b; vacuolar protein sorting-associated protein 37B [KO:K12185]
114154408  [KO:K21269]
114154485  git2; ARF GTPase-activating protein GIT2 isoform X1 [KO:K12487]
114154609  [KO:K12484]
114154788  snx2; sorting nexin-2 isoform X1 [KO:K17917]
114154830  rab35; ras-related protein Rab-35 isoform X1 [KO:K07876]
114154831  chmp7; charged multivesicular body protein 7 isoform X1 [KO:K15053]
114154950  [KO:K08291] [EC:2.7.11.16]
114155259  [KO:K04500]
114155461  snx6; sorting nexin-6 isoform X1 [KO:K17920]
114155507  [KO:K12486]
114155694  vps45; vacuolar protein sorting-associated protein 45 isoform X1 [KO:K12479]
114155705  [KO:K12477]
114155900  [KO:K19475]
114155909  pdcd6ip; programmed cell death 6-interacting protein isoform X1 [KO:K12200]
114156095  [KO:K12474]
114156104  [KO:K04393]
114156140  [KO:K04388] [EC:2.7.11.30]
114156257  vps28; vacuolar protein sorting-associated protein 28 homolog [KO:K12184]
114156258  [KO:K07887]
114156351  [KO:K06751]
114156401  smad3; mothers against decapentaplegic homolog 3 [KO:K23605]
114156457  pard6g; partitioning defective 6 homolog gamma [KO:K06093]
114156478  [KO:K06751]
114156479  [KO:K06751]
114156480  [KO:K06751]
114156481  [KO:K06751]
114156619  [KO:K00889] [EC:2.7.1.68]
114156953  [KO:K11247]
114157257  [KO:K05087] [EC:2.7.10.1]
114157412  [KO:K17260]
114157453  washc1; WASH complex subunit 1 [KO:K18461]
114157457  acap1; arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 1 [KO:K12489]
114157769  arap2; arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K18440]
114157935  [KO:K12474]
114158394  rab10; ras-related protein Rab-10 [KO:K07903]
114158471  washc4; WASH complex subunit 4 isoform X1 [KO:K18465]
114158495  igf2r; cation-independent mannose-6-phosphate receptor [KO:K06564]
114158528  [KO:K07941]
114158582  vta1; vacuolar protein sorting-associated protein VTA1 homolog [KO:K12199]
114158656  [KO:K12476]
114158690  [KO:K06093]
114158720  [KO:K12488]
114158750  snx3; sorting nexin-3 [KO:K17918]
114159087  [KO:K12474]
114159394  [KO:K12471]
114159417  [KO:K03283]
114159562  [KO:K03283]
114159614  epn2; epsin-2 isoform X1 [KO:K12471]
114159676  [KO:K19475]
114159681  [KO:K18441]
114159736  rab5c; ras-related protein Rab-5C [KO:K07889]
114159764  smurf1; E3 ubiquitin-protein ligase SMURF1 isoform X1 [KO:K04678] [EC:2.3.2.26]
114159770  hgs; hepatocyte growth factor-regulated tyrosine kinase substrate isoform X1 [KO:K12182]
114159826  [KO:K04678] [EC:2.3.2.26]
114159835  [KO:K18441]
114159853  [KO:K18441]
114159915  ldlr; low-density lipoprotein receptor [KO:K12473]
114159989  [KO:K07876]
114160004  [KO:K24782]
114160085  [KO:K23484]
114160097  [KO:K12195]
114160287  [KO:K07937]
114160471  [KO:K05069]
114160676  wasl; neural Wiskott-Aldrich syndrome protein isoform X1 [KO:K23612]
114160805  [KO:K17919]
114160947  mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
114160990  washc3; WASH complex subunit 3 [KO:K18463]
114161164  arf5; ADP-ribosylation factor 5 [KO:K07939]
114161182  arfgap3; ADP-ribosylation factor GTPase-activating protein 3 [KO:K12493]
114161379  ap2s1; AP-2 complex subunit sigma [KO:K11827]
114161417  vps26b; vacuolar protein sorting-associated protein 26B [KO:K18466]
114161475  [KO:K03283]
114161568  [KO:K04646]
114161657  arap1; arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 isoform X1 [KO:K18439]
114161713  [KO:K12489]
114161734  [KO:K04439]
114162012  folr2; folate receptor beta [KO:K13649]
Compound
C00035  GDP
C00044  GTP
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C11556  1-Phosphatidyl-1D-myo-inositol 3,5-bisphosphate
Reference
PMID:19007773
  Authors
Acconcia F, Sigismund S, Polo S
  Title
Ubiquitin in trafficking: the network at work.
  Journal
Exp Cell Res 315:1610-8 (2009)
DOI:10.1016/j.yexcr.2008.10.014
Reference
PMID:18647649
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Donaldson JG, Porat-Shliom N, Cohen LA
  Title
Clathrin-independent endocytosis: a unique platform for cell signaling and PM remodeling.
  Journal
Cell Signal 21:1-6 (2009)
DOI:10.1016/j.cellsig.2008.06.020
Reference
PMID:15261671
  Authors
Sorkin A
  Title
Cargo recognition during clathrin-mediated endocytosis: a team effort.
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Curr Opin Cell Biol 16:392-9 (2004)
DOI:10.1016/j.ceb.2004.06.001
Reference
PMID:19325624
  Authors
Raiborg C, Stenmark H
  Title
The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.
  Journal
Nature 458:445-52 (2009)
DOI:10.1038/nature07961
Reference
PMID:20110990
  Authors
Scita G, Di Fiore PP
  Title
The endocytic matrix.
  Journal
Nature 463:464-73 (2010)
DOI:10.1038/nature08910
Reference
PMID:15687999
  Authors
Le Roy C, Wrana JL
  Title
Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling.
  Journal
Nat Rev Mol Cell Biol 6:112-26 (2005)
DOI:10.1038/nrm1571
Reference
PMID:19924646
  Authors
Jovic M, Sharma M, Rahajeng J, Caplan S
  Title
The early endosome: a busy sorting station for proteins at the crossroads.
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Histol Histopathol 25:99-112 (2010)
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Reference
PMID:16203612
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Pietiainen VM, Marjomaki V, Heino J, Hyypia T
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Viral entry, lipid rafts and caveosomes.
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Ann Med 37:394-403 (2005)
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Reference
PMID:19696797
  Authors
Grant BD, Donaldson JG
  Title
Pathways and mechanisms of endocytic recycling.
  Journal
Nat Rev Mol Cell Biol 10:597-608 (2009)
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PMID:22193161
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Cullen PJ, Korswagen HC
  Title
Sorting nexins provide diversity for retromer-dependent trafficking events.
  Journal
Nat Cell Biol 14:29-37 (2012)
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Related
pathway
xco04060  Cytokine-cytokine receptor interaction
xco04070  Phosphatidylinositol signaling system
xco04130  SNARE interactions in vesicular transport
xco04142  Lysosome
xco04350  TGF-beta signaling pathway
KO pathway
ko04144   

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