BioPAX pathway converted from "Interaction of NUMB with L1" in the Reactome database.Interaction of NUMB with L1Interaction of NUMB with L1Numb is thought to be a phosphotyrosine binding (PTB) domain containing cargo specific adaptor protein, which links specific cargo to the endocytic machinery. It associates with collapsin response mediator protein-2 (CRMP 2) with its PTB domain and alpha adaptin (a subunit of the AP 2 adaptor complex) through its tripeptide Asp-Pro-Phe (DPF) motif, and is involved in clathrin dependent endocytosis at the plasma membrane. Numb is associated with L1 under physiological conditions and functions in endocytosis of L1 in the C domain membrane of axonal growth cones.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: 1914651plasma membraneGO0005886UniProt: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.Reactomehttp://www.reactome.orgHomo sapiensNCBI Taxonomy9606UniProtP32004Chain Coordinates20EQUAL1257EQUALReactome DB_ID: 4436691CRMP-2:NUMB:alpha adaptin [plasma membrane]CRMP-2:NUMB:alpha adaptinConverted 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: 4435951UniProt:P49757 NUMBNUMBC14orf41NUMBFUNCTION Regulates clathrin-mediated receptor endocytosis (PubMed:18657069). Plays a role in the process of neurogenesis (By similarity). Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate (By similarity). Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity (By similarity). May also mediate local repair of brain ventricular wall damage (By similarity).SUBUNIT Interacts with SIAH1 (PubMed:11752454). Interacts with LNX (By similarity). Interacts with CDH1 (By similarity). Interacts with TFAP2A and TFAP2B (By similarity). Interacts with RALBP1 in a complex also containing EPN1 and TFAP2A during interphase and mitosis (PubMed:12775724). Interacts with AAK1 (PubMed:18657069). May interact with DUOXA1 (PubMed:14670962).PTM Phosphorylated on Ser-276 and Ser-295 by CaMK1.PTM Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their subsequent proteasomal degradation (By similarity). Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation.UniProtP497571EQUAL651EQUALReactome DB_ID: 3969431cytosolGO0005829UniProt:Q16555 DPYSL2DPYSL2ULIP2DPYSL2CRMP2FUNCTION Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis.SUBUNIT Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1. Interacts with HTR4. Interacts with CLN6. Interacts with MICALL1.TISSUE SPECIFICITY Ubiquitous.PTM 3F4, a monoclonal antibody which strongly stains neurofibrillary tangles in Alzheimer disease brains, specifically labels DPYSL2 when phosphorylated on Ser-518, Ser-522 and Thr-509.PTM Phosphorylation at Thr-514 by GSK3B abolishes tubulin-binding leading to destabilization of microtubule assembly in axons and neurodegeneration (By similarity). Phosphorylation by DYRK2 at Ser-522 is required for subsequent phosphorylation by GSK3B.SIMILARITY Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.CAUTION Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.UniProtQ165551EQUAL572EQUALReactome Database ID Release 75443669Database 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=443669ReactomeR-HSA-4436691Reactome 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-443669.1Reactome DB_ID: 4436571clathrin-coated endocytic vesicleGO0045334L1:NUMB:CRMP-2:alpha-adaptin [clathrin-coated endocytic vesicle]L1:NUMB:CRMP-2:alpha-adaptinReactome DB_ID: 191465120EQUAL1257EQUALReactome DB_ID: 4436691Reactome Database ID Release 75443657Database 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=443657ReactomeR-HSA-4436571Reactome 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-443657.1Reactome Database ID Release 75443783Database 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=443783ReactomeR-HSA-4437831Reactome 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-443783.112942088Pubmed2003CRMP-2 regulates polarized Numb-mediated endocytosis for axon growthNishimura, TFukata, YKato, KYamaguchi, TatsuyaMatsuura, YKamiguchi, HKaibuchi, KNat Cell Biol 5:819-26