KEGG   PATHWAY: ko04144
Entry
ko04144                     Pathway                                
Name
Endocytosis
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
ko04144  Endocytosis
ko04144

Other DBs
GO: 0006897
Orthology
K00889  PIP5K; 1-phosphatidylinositol-4-phosphate 5-kinase [EC:2.7.1.68]
K00909  GRK1_7; rhodopsin kinase [EC:2.7.11.14]
K00910  ADRBK, GRK; beta-adrenergic-receptor kinase [EC:2.7.11.15]
K01115  PLD1_2; phospholipase D1/2 [EC:3.1.4.4]
K01528  DNM1_3; dynamin 1/3 [EC:3.6.5.5]
K02833  HRAS; GTPase HRas
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03283  HSPA1_6_8; heat shock 70kDa protein 1/6/8
K04175  CXCR1, IL8RA, CD181; C-X-C chemokine receptor type 1
K04180  CCR5, CD195; C-C chemokine receptor type 5
K04189  CXCR4, CD184; C-X-C chemokine receptor type 4
K04237  PARD3; partitioning defective protein 3
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04363  PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K04388  TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]
K04393  CDC42; cell division control protein 42
K04439  ARRB; beta-arrestin
K04500  SMAD2; mothers against decapentaplegic homolog 2
K04513  RHOA; Ras homolog gene family, member A
K04644  CLTA, LCA; clathrin light chain A
K04645  CLTB, LCB; clathrin light chain B
K04646  CLTC; clathrin heavy chain
K04674  TGFBR1, ALK5; TGF-beta receptor type-1 [EC:2.7.11.30]
K04678  SMURF; E3 ubiquitin ligase SMURF1/2 [EC:2.3.2.26]
K04679  MADHIP, SARA; MAD, mothers against decapentaplegic interacting protein
K04705  STAM; signal transducing adaptor molecule
K04707  CBL; E3 ubiquitin-protein ligase CBL [EC:2.3.2.27]
K05050  CXCR2, IL8RB, CD182; C-X-C chemokine receptor type 2
K05068  IL2RA, CD25; interleukin 2 receptor alpha
K05069  IL2RB, CD122; interleukin 2 receptor beta
K05070  IL2RG, CD132; interleukin 2 receptor gamma
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05093  FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  FGFR3, CD333; fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  FGFR4, CD334; fibroblast growth factor receptor 4 [EC:2.7.10.1]
K05632  ITCH, AIP4; E3 ubiquitin-protein ligase Itchy [EC:2.3.2.26]
K05633  WWP1, AIP5; NEDD4-like E3 ubiquitin-protein ligase WWP1 [EC:2.3.2.26]
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05737  GIT1; G protein-coupled receptor kinase interactor 1
K05754  ARPC5; actin related protein 2/3 complex, subunit 5
K05755  ARPC4; actin related protein 2/3 complex, subunit 4
K05756  ARPC3; actin related protein 2/3 complex, subunit 3
K05757  ARPC1A_B; actin related protein 2/3 complex, subunit 1A/1B
K05758  ARPC2; actin related protein 2/3 complex, subunit 2
K06069  PRKCI; atypical protein kinase C iota type [EC:2.7.11.13]
K06093  PARD6; partitioning defective protein 6
K06278  CAV1; caveolin 1
K06503  TFRC, CD71; transferrin receptor
K06564  IGF2R, CD222; insulin-like growth factor 2 receptor
K06643  MDM2; E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K06751  MHC1; MHC class I antigen
K07876  RAB35, RAB1C; Ras-related protein Rab-35
K07879  RAB4A, RAB4; Ras-related protein Rab-4A
K07887  RAB5A; Ras-related protein Rab-5A
K07888  RAB5B; Ras-related protein Rab-5B
K07889  RAB5C; Ras-related protein Rab-5C
K07891  RAB22; Ras-related protein Rab-22
K07897  RAB7A; Ras-related protein Rab-7A
K07901  RAB8A, MEL; Ras-related protein Rab-8A
K07903  RAB10; Ras-related protein Rab-10
K07904  RAB11A; Ras-related protein Rab-11A
K07905  RAB11B; Ras-related protein Rab-11B
K07937  ARF1_2; ADP-ribosylation factor 1/2
K07938  ARF3; ADP-ribosylation factor 3
K07939  ARF4; ADP-ribosylation factor 4
K07940  ARF5; ADP-ribosylation factor 5
K07941  ARF6; ADP-ribosylation factor 6
K08291  GRK4_5_6; G protein-coupled receptor kinase [EC:2.7.11.16]
K09526  DNAJC6; DnaJ homolog subfamily C member 6
K10054  PML, TRIM19; E3 SUMO-protein ligase PML [EC:2.3.2.-]
K10364  CAPZA; F-actin-capping protein subunit alpha
K10365  CAPZB; F-actin-capping protein subunit beta
K10396  KIF5; kinesin family member 5 (plus-end-directed kinesin ATPase) [EC:5.6.1.3]
K10591  NEDD4, RSP5; E3 ubiquitin-protein ligase NEDD4 [EC:2.3.2.26]
K11247  SH3GL; endophilin-A
K11248  SH3GLB1; endophilin-B1
K11824  AP2A; AP-2 complex subunit alpha
K11825  AP2B1; AP-2 complex subunit beta-1
K11826  AP2M1; AP-2 complex subunit mu-1
K11827  AP2S1; AP-2 complex subunit sigma-1
K11839  USP8, UBP5; ubiquitin carboxyl-terminal hydrolase 8 [EC:3.4.19.12]
K11866  STAMBP, AMSH; STAM-binding protein [EC:3.4.19.12]
K11981  RNF41, NRDP1; E3 ubiquitin-protein ligase NRDP1 [EC:2.3.2.27]
K12182  HGS, HRS, VPS27; hepatocyte growth factor-regulated tyrosine kinase substrate
K12183  TSG101, STP22, VPS23; ESCRT-I complex subunit TSG101
K12184  VPS28; ESCRT-I complex subunit VPS28
K12185  VPS37; ESCRT-I complex subunit VPS37
K12186  FAM125; ESCRT-I complex subunit MVB12
K12187  MVB12; ESCRT-I complex subunit MVB12
K12188  SNF8, EAP30; ESCRT-II complex subunit VPS22
K12189  VPS25, EAP20; ESCRT-II complex subunit VPS25
K12190  VPS36, EAP45; ESCRT-II complex subunit VPS36
K12191  CHMP2A; charged multivesicular body protein 2A
K12192  CHMP2B; charged multivesicular body protein 2B
K12193  VPS24, CHMP3; charged multivesicular body protein 3
K12194  CHMP4A_B, SNF7, VPS32A_B; charged multivesicular body protein 4A/B
K12195  CHMP6, VPS20; charged multivesicular body protein 6
K12196  VPS4; vacuolar protein-sorting-associated protein 4
K12197  CHMP1, VPS46, DID2; charged multivesicular body protein 1
K12198  CHMP5, VPS60; charged multivesicular body protein 5
K12199  VTA1, LIP5; vacuolar protein sorting-associated protein VTA1
K12200  PDCD6IP, ALIX, RIM20; programmed cell death 6-interacting protein
K12469  EHD2; EH domain-containing protein 2
K12470  SH3KBP1, CIN85; SH3 domain-containing kinase-binding protein 1
K12471  EPN; epsin
K12472  EPS15; epidermal growth factor receptor substrate 15
K12473  LDLR; low-density lipoprotein receptor
K12474  LDLRAP1, ARH; low density lipoprotein receptor adapter protein 1
K12475  DAB2; disabled homolog 2
K12476  EHD3; EH domain-containing protein 3
K12477  EHD4; EH domain-containing protein 4
K12478  EEA1; early endosome antigen 1
K12479  VPS45; vacuolar protein sorting-associated protein 45
K12480  RABEP1; Rab GTPase-binding effector protein 1
K12481  RBSN, ZFYVE20; rabenosyn-5
K12482  RUFY1_2, RABIP4; RUN and FYVE domain-containing protein 1/2
K12483  EHD1; EH domain-containing protein 1
K12484  RAB11FIP1_2_5; Rab11 family-interacting protein 1/2/5
K12485  RAB11FIP3_4; Rab11 family-interacting protein 3/4
K12486  SMAP; stromal membrane-associated protein
K12487  GIT2; G protein-coupled receptor kinase interactor 2
K12488  ASAP; Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein
K12489  ACAP; Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein
K12490  ARAP3; Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
K12491  AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1/3/4/5/6/9/11
K12492  ARFGAP1; ADP-ribosylation factor GTPase-activating protein 1
K12493  ARFGAP2_3; ADP-ribosylation factor GTPase-activating protein 2/3
K12494  PSD; PH and SEC7 domain-containing protein
K12495  IQSEC; IQ motif and SEC7 domain-containing protein
K12562  AMPH; amphiphysin
K12958  CAV2; caveolin 2
K12959  CAV3; caveolin 3
K13305  NEDD4L; E3 ubiquitin-protein ligase NEDD4-like [EC:2.3.2.26]
K13649  FOLR; folate receptor
K13712  PIP5KL1; phosphatidylinositol-4-phosphate 5-kinase-like protein 1 [EC:2.7.1.68]
K15053  CHMP7; charged multivesicular body protein 7
K17260  ACTR2, ARP2; actin-related protein 2
K17848  AGAP2; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
K17917  SNX1_2; sorting nexin-1/2
K17918  SNX3_12; sorting nexin-3/12
K17919  SNX4; sorting nexin-4
K17920  SNX5_6_32; sorting nexin-5/6/32
K18439  ARAP1; Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1
K18440  ARAP2; Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 2
K18441  CYTH; cytohesin
K18442  ARFGEF, BIG; brefeldin A-inhibited guanine nucleotide-exchange protein
K18443  GBF1; golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1
K18461  WASH1; WAS protein family homolog 1
K18462  FAM21; WASH complex subunit FAM21
K18463  CCDC53; WASH complex subunit CCDC53
K18464  RTSC, SPG8; WASH complex subunit strumpellin
K18465  MRT43, SWIP; WASH complex subunit 7
K18466  VPS26A_B; vacuolar protein sorting-associated protein 26A/B
K18467  VPS29; vacuolar protein sorting-associated protein 29
K18468  VPS35; vacuolar protein sorting-associated protein 35
K18584  ACTR3, ARP3; actin-related protein 3
K18952  PRKCZ; atypical protein kinase C zeta type [EC:2.7.11.13]
K19366  SPG20; spartin
K19367  SPG21; maspardin
K19368  ZFYVE27; protrudin
K19475  WIPF; WAS/WASL-interacting protein
K19476  IST1; vacuolar protein sorting-associated protein IST1
K21269  SH3GLB2; endophilin-B2
K22517  CBLB; E3 ubiquitin-protein ligase CBL-B [EC:2.3.2.27]
K22518  CBLC; E3 ubiquitin-protein ligase CBL-C [EC:2.3.2.27]
K23484  DNM2; dynamin 2
K23605  SMAD3; mothers against decapentaplegic homolog 3
K23612  WASL; neural Wiskott-Aldrich syndrome protein
K24782  CHMP4C, SNF7, VPS32C; charged multivesicular body protein 4C
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
  Authors
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.
  Journal
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.
  Journal
Histol Histopathol 25:99-112 (2010)
DOI:10.14670/HH-25.99
Reference
PMID:16203612
  Authors
Pietiainen VM, Marjomaki V, Heino J, Hyypia T
  Title
Viral entry, lipid rafts and caveosomes.
  Journal
Ann Med 37:394-403 (2005)
DOI:10.1080/07853890510011976
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)
DOI:10.1038/nrm2755
Reference
PMID:22193161
  Authors
Cullen PJ, Korswagen HC
  Title
Sorting nexins provide diversity for retromer-dependent trafficking events.
  Journal
Nat Cell Biol 14:29-37 (2012)
DOI:10.1038/ncb2374
Related
pathway
ko04060  Cytokine-cytokine receptor interaction
ko04070  Phosphatidylinositol signaling system
ko04130  SNARE interactions in vesicular transport
ko04142  Lysosome
ko04350  TGF-beta signaling pathway

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