BioPAX pathway converted from "TSPAN7 binds PICK1" in the Reactome database.LEFT-TO-RIGHTTSPAN7 binds PICK1Tetraspanin 7 (TSPAN7) a member of the tetraspanin superfamily associates dynamically with numerous partner proteins in tetraspanin-enriched microdomains (TEMs) of the plasma membrane (Boucheix and Rubinstein, 2001). TSPAN7 promotes filopodia and dendritic spine formation in cultured hippocampal neurons, and is required for spine stability and normal synaptic transmission. Via its C-terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking (Bassani et al. 2012). PICK1 is involved in the internalization and recycling of AMPA receptors (AMPARs) (Perez et al. 2001). In hippocampal neurons, TSPAN7 may regulate AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability (Bassani et al. 2012).Authored: Garapati, Phani Vijay, 2016-02-19Reviewed: Meldal, Birgit, 2016-09-14Edited: Garapati, Phani Vijay, 2016-02-19CD231TSPAN7Tetraspanin-7TSN7_HUMANReactome DB_ID: 400337plasma membraneGENE ONTOLOGYGO:0005886UniProt:P41732 TSPAN7TSPAN7A15DXS1692EMXS1TM4SF2FUNCTION May be involved in cell proliferation and cell motility.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1 (HHV-1) UL35.TISSUE SPECIFICITY Not solely expressed in T-cells. Expressed in acute myelocytic leukemia cells of some patients.SIMILARITY Belongs to the tetraspanin (TM4SF) family.Homo sapiensNCBI Taxonomy9606UniProtP417321EQUAL249EQUALReactome Database ID Release 70400337Database 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=400337ReactomeR-HSA-4003371Reactome 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-400337.1Reactomehttp://www.reactome.orgPICK1PRKCA-binding proteinPICK1_HUMANReactome DB_ID: 416989UniProt:Q9NRD5 PICK1PICK1PRKCABPFUNCTION Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competetive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.SUBUNIT Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR. Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition.TISSUE SPECIFICITY Ubiquitous.DOMAIN The AH domain mediates binding to F-actin.DOMAIN The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization (By similarity).PTM Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.PTM Palmitoylation on Cys-413 is essential for long-term synaptic depression (LTD).UniProtQ9NRD51EQUAL415EQUALReactome Database ID Release 70416989Database 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=416989ReactomeR-HSA-4169891Reactome 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-416989.1TSPAN7:PICK1Reactome DB_ID: 885843311Reactome Database ID Release 708858433Database 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=8858433ReactomeR-HSA-88584331Reactome 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-8858433.1Reactome Database ID Release 708858435Database 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=8858435ReactomeR-HSA-88584351Reactome 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-8858435.122445342Pubmed2012The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR traffickingBassani, SilviaCingolani, Lorenzo AValnegri, PamelaFolci, AlessandraZapata, JonathanGianfelice, AntonellaSala, CarloGoda, YukikoPassafaro, MariaNeuron 73:1143-5811577978Pubmed2001TetraspaninsBoucheix, CRubinstein, ECell. Mol. Life Sci. 58:1189-20511466413Pubmed2001PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2Perez, J LKhatri, LChang, CSrivastava, SOsten, PZiff, E BJ. Neurosci. 21:5417-28