BioPAX pathway converted from "Reinsertion of L1 into the plasma membrane" in the Reactome database.Reinsertion of L1 into the plasma membraneReinsertion of L1 into the plasma membraneL1 transported to the P-domain of growth cones is reinserted into the plasma membrane at the leading edge.Authored: Garapati, P V, 2008-07-30 10:22:58Reviewed: Maness, PF, 2010-02-16Edited: Garapati, P V, 2008-07-30 10:22:58Reactome DB_ID: 4450221cytosolGO0005829AP2 clathrin:L1:KIF4:microtubule [cytosol]AP2 clathrin:L1:KIF4:microtubuleReactome DB_ID: 4450131KIF4 dimer [cytosol]KIF4 dimerConverted from EntitySet in ReactomeReactome DB_ID: 4450002KIF4 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityKIF4B [cytosol]KIF4A [cytosol]Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtQ2VIQ3UniProtO95239Reactome Database ID Release 75445013Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=445013ReactomeR-HSA-4450131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-445013.1Reactome DB_ID: 3927461endosomeGO0005768L1:AP-2 Clathrin complex [endosome]L1:AP-2 Clathrin complexReactome DB_ID: 1774951plasma membraneGO0005886UniProt:Q99962 SH3GL2SH3GL2SH3D2ACNSA2SH3GL2FUNCTION Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes.SUBUNIT Monomer; in cytoplasm. Homodimer; when associated with membranes (By similarity). Interacts with OPHN1 (By similarity). Interacts with SYNJ1 (PubMed:10542231). Interacts with DNM1 (By similarity). Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation (By similarity). Interacts with PDCD6IP (PubMed:17350572). Interacts with ATX2 (PubMed:18602463). Interacts with ADAM9 and ADAM15 cytoplasmic tails (PubMed:10531379). Interacts with BIN2 (PubMed:23285027). Interacts with TMEM108 (By similarity). Interacts with ADGRB2 (PubMed:28891236).TISSUE SPECIFICITY Brain, mostly in frontal cortex. Expressed at high level in fetal cerebellum.DOMAIN An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface.MISCELLANEOUS HeLa cells expressing the N-BAR domain of SH3GL2 show tubulation of the plasma membrane. The N-BAR domain binds liposomes and induces formation of tubules from liposomes. The N-terminal amphipathic helix is required for liposome binding. The second amphipathic helix enhances liposome tubulation.SIMILARITY Belongs to the endophilin family.UniProtQ99962Chain Coordinates1EQUAL352EQUALReactome DB_ID: 1914651UniProt:P32004 L1CAML1CAMCAML1MIC5L1CAMFUNCTION Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity.SUBUNIT Interacts with SHTN1; the interaction occurs in axonal growth cones (By similarity). Interacts with isoform 2 of BSG (By similarity).DISEASE Defects in L1CAM may contribute to Hirschsprung disease by modifying the effects of Hirschsprung disease-associated genes to cause intestinal aganglionosis.DISEASE Defects in L1CAM are associated with a wide phenotypic spectrum which varies from severe hydrocephalus and prenatal death (HSAS) to a milder phenotype (MASA). These variations may even occur within the same family. Due to the overlap of phenotypes between HSAS and MASA, many authors use the general concept of L1 syndrome which covers both ends of the spectrum.SIMILARITY Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.UniProtP3200420EQUAL1257EQUALReactome DB_ID: 1775051Clathrin:AP-2 complex [plasma membrane]Clathrin:AP-2 complexClathrin-coated vesicleReactome DB_ID: 1774801AP-2 complex [plasma membrane]AP-2 complexAdaptor protein 2 complexConverted from EntitySet in ReactomeReactome DB_ID: 4449991Adaptor protein complex 2 (AP-2) large adaptins [plasma membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityAP2A2(1-939) [plasma membrane]AP2A1 [plasma membrane]UniProtO94973UniProtO95782Reactome DB_ID: 3893821UniProt:P53680 AP2S1AP2S1CLAPS2AP2S1AP17FUNCTION Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein Transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity). May also play a role in extracellular calcium homeostasis.SUBUNIT Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1).SIMILARITY Belongs to the adaptor complexes small subunit family.UniProtP536801EQUAL142EQUALReactome DB_ID: 1675851UniProt:Q96CW1 AP2M1AP2M1KIAA0109AP2M1CLAPM1FUNCTION Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at 'Tyr-156' in membrane-associated AP-2. The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).SUBUNIT Adapter protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (By similarity). Interacts with ATP6V1H and MEGF10 (PubMed:12032142, PubMed:17643423). Interacts with EGFR and TTGN1 (By similarity). Interacts with F2R (PubMed:16581796). Interacts with PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction (By similarity). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319 (PubMed:19419997). Interacts with DVL2 (via DEP domain) (By similarity). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with P2RX4 (via internalization motif) (By similarity). Together with AP2A1 or AP2A2 and AP2B1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497).TISSUE SPECIFICITY Expressed in the brain (at protein level).PTM Phosphorylation at Thr-156 increases the affinity of the AP-2 complex for cargo membrane proteins during the initial stages of endocytosis.SIMILARITY Belongs to the adaptor complexes medium subunit family.UniProtQ96CW11EQUAL435EQUALReactome DB_ID: 1676901UniProt:P63010 AP2B1AP2B1ADTB2CLAPB1AP2B1FUNCTION Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly.SUBUNIT Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (PubMed:12086608, PubMed:19140243). Interacts with EPN1 (PubMed:10944104, PubMed:16516836). Interacts with EPS15; clathrin competes with EPS15 (PubMed:10944104, PubMed:16903783). Interacts with SNAP91; clathrin competes with SNAP91 (PubMed:10944104, PubMed:16516836, PubMed:16903783). Interacts with CLTC; clathrin competes with EPS15, SNAP91 and PIP5K1C (PubMed:10944104). Interacts with LDLRAP1 (PubMed:15728179, PubMed:16516836, PubMed:16903783). Interacts with AMPH and BIN1 (PubMed:16516836, PubMed:16903783). Interacts with ARF6 (GDP-bound) (PubMed:17719203). Interacts (dephosphorylated at Tyr-737) with ARRB1; phosphorylation of AP2B1 at Tyr-737 disrupts the interaction (PubMed:11777907, PubMed:17456551, PubMed:16516836, PubMed:16903783). Interacts with SLC2A8 (PubMed:16723738). Interacts with SCYL1 and SCYL2 (PubMed:16903783). Interacts with TGFBR1 and TGFBR2 (PubMed:12429842). Interacts with PIP5K1C; clathrin competes with PIP5K1C (By similarity). Interacts with DENND1B, but not with DENND1A, nor DENND1C (PubMed:20154091). Interacts with FCHO1 (PubMed:22484487). Interacts with RFTN1 (PubMed:27022195). Interacts with KIAA1107 (PubMed:29262337). Together with AP2A1 or AP2A2 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497).TISSUE SPECIFICITY Expressed in the brain (at protein level).PTM Phosphorylation at Tyr-737 by SRC occurs at the plasma membrane in clathrin-coated vesicles (CCVs).SIMILARITY Belongs to the adaptor complexes large subunit family.UniProtP630101EQUAL937EQUALReactome Database ID Release 75177480Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177480ReactomeR-HSA-1774801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177480.1Reactome DB_ID: 1774821Clathrin [plasma membrane]Clathrin3xCLTA:3xCLTCReactome DB_ID: 29806683UniProt:Q00610 CLTCCLTCCLTCL2CLH17CLTCKIAA0034FUNCTION Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:16968737, PubMed:21297582). The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Plays a role in early autophagosome formation (PubMed:20639872).SUBUNIT Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat (PubMed:16968737). In the presence of light chains, hub assembly is influenced by both the pH and the concentration of calcium. Interacts with HIP1 (PubMed:11532990). Interacts with DENND1A, DENND1B and DENND1C (By similarity). May interact with OCRL (By similarity). Interacts with ERBB2 (PubMed:16314522). Interacts with FKBP6 (PubMed:18529014). Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions; TACC3 and CLTC are proposed to form a composite microtubule interaction surface (PubMed:21297582). Interacts with ATG16L1 (via N-terminus) (PubMed:20639872). Interacts with RFTN1; the interaction occurs in response to pathogens (PubMed:27022195, PubMed:21266579). Interacts with USP2 isoform 4 (PubMed:26756164).DOMAIN The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node.SIMILARITY Belongs to the clathrin heavy chain family.UniProtQ006102EQUAL1675EQUALReactome DB_ID: 29806113UniProt:P09496 CLTACLTACLTAFUNCTION Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:21297582).SUBUNIT Clathrin coats are formed from molecules containing 3 heavy chains and 3 light chains. Interacts with CALY; the interaction stimulates clathrin self-assembly and clathrin-mediated endocytosis. Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions.SIMILARITY Belongs to the clathrin light chain family.UniProtP094961EQUAL248EQUALReactome Database ID Release 75177482Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177482ReactomeR-HSA-1774822Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177482.2Reactome Database ID Release 75177505Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=177505ReactomeR-HSA-1775052Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-177505.2Reactome Database ID Release 75392746Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=392746ReactomeR-HSA-3927461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-392746.1Reactome DB_ID: 1905991Microtubule [cytosol]MicrotubuleReactome DB_ID: 898242413Microtubule protofilament [cytosol]Microtubule protofilamentReactome Database ID Release 75190599Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=190599ReactomeR-HSA-1905992Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-190599.2Reactome Database ID Release 75445022Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=445022ReactomeR-HSA-4450221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-445022.1Reactome DB_ID: 17749511EQUAL352EQUALReactome DB_ID: 4450131Reactome DB_ID: 191465120EQUAL1257EQUALReactome DB_ID: 1775051Reactome DB_ID: 1905991Reactome Database ID Release 75445071Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=445071ReactomeR-HSA-4450712Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-445071.210804209Pubmed2000Recycling of the cell adhesion molecule L1 in axonal growth conesKamiguchi, HLemmon, VJ Neurosci 20:3676-8610747093Pubmed2000Evidence for the involvement of KIF4 in the anterograde transport of L1-containing vesiclesPeretti, DPeris, LRosso, SQuiroga, SCaceres, AlfredoJ Cell Biol 149:141-52