Protein: F-box/SPRY domain-containing protein 1 (P0C2W1)
Organism: Homo sapiens (Human)
Function: Component of E3 ubiquitin ligase complex consisting of FBXO45, MYCBP2 and SKP1. Functions in substrate recognition but also plays an important role in assembly of the complex. Required for normal neuromuscular synaptogenesis, axon pathfinding and neuronal migration (By similarity). Regulates neuron migration during brain development through interaction with N- cadherin/CDH2 after secretion via a non-classical mechanism (By similarity). Plays a role in the regulation of neurotransmission at mature neurons (By similarity). May control synaptic activity by controlling UNC13A via ubiquitin dependent pathway (By similarity). Specifically recognizes TP73, promoting its ubiquitination and degradation. Polyubiquitinates NMNAT2, an adenylyltransferase that acts as an axon maintenance factor, and regulates its stability and degradation by the proteasome. Also acts by ubiquitinating FBXW7 during prolonged mitotic arrest and promotes FBXW7 proteasomal degradation. Induces subsequently an increase in mitotic slippage and prevents mitotic cell death. In response to influenza infection, mediates interferon-lambda receptor IFNLR1 polyubiquitination and degradation through the ubiquitin-proteasome system by docking with its intracellular receptor domain
Subcellular location: Secreted. Postsynaptic cell membrane. Presynaptic cell membrane. Nucleus. Note=Secreted by a non-classical mechanism
Sequence: MAAPAPGAGAASGGAGCSGGGAGAGAGSGSGAAGAGGRLPSRVLELVFSYLELSELRSCALVCKHWYRCLHGDENSEVWRSLCARSLAEEALRTDILCNLPSYKAKIRAFQHAFSTNDCSRNVYIKKNGFTLHRNPIAQSTDGARTKIGFSEGRHAWEVWWEGPLGTVAVIGIATKRAPMQCQGYVALLGSDDQSWGWNLVDNNLLHNGEVNGSFPQCNNAPKYQIGERIRVILDMEDKTLAFERGYEFLGVAFRGLPKVCLYPAVSAVYGNTEVTLVYLGKPLDG
InterPro domains: - IPR013320: Concanavalin A-like lectin/glucanase domain superfamily (homologous_superfamily) [79-283]
- IPR001870: B30.2/SPRY domain (domain) [92-284]
- IPR003877: SPRY domain (domain) [152-284]
- IPR001810: F-box domain (domain) [33-84]
- IPR043136: B30.2/SPRY domain superfamily (homologous_superfamily) [110-284]
- IPR050672: F-box/SPRY and SOCS box protein families (family) [44-278]
- IPR036047: F-box-like domain superfamily (homologous_superfamily) [38-87]
- IPR035784: Fbxo45, SPRY domain (domain) [112-286]
Interaction partners: - E3 ubiquitin-protein ligase MYCBP2
- S-phase kinase-associated protein 1
- S-phase kinase-associated protein 1
- Cullin-1
- Protein unc-13 homolog A
- SPRY domain-containing protein 3
- E3 ubiquitin-protein ligase SIAH1
- F-box/WD repeat-containing protein 7
- WD repeat-containing protein 53
- MAGUK p55 subfamily member 3
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048869 (cellular developmental process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0048870 (cell motility), GO:0009653 (anatomical structure morphogenesis), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0051050 (positive regulation of transport), GO:0050794 (regulation of cellular process), GO:0023051 (regulation of signaling), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0032989 (cellular component morphogenesis), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0019538 (protein metabolic process), GO:0048513 (animal organ development), GO:0051649 (establishment of localization in cell), GO:0060627 (regulation of vesicle-mediated transport), GO:0051130 (positive regulation of cellular component organization), GO:0043170 (macromolecule metabolic process), GO:0000902 (cell morphogenesis), GO:0009887 (animal organ morphogenesis), GO:0060322 (head development), GO:0010646 (regulation of cell communication), GO:0006810 (transport), GO:0016043 (cellular component organization), GO:0045807 (positive regulation of endocytosis), GO:1901575 (organic substance catabolic process), GO:0051128 (regulation of cellular component organization), GO:0044260 (cellular macromolecule metabolic process), GO:0016477 (cell migration), GO:0030100 (regulation of endocytosis), GO:0030030 (cell projection organization), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0030163 (protein catabolic process), GO:0032990 (cell part morphogenesis), GO:0030163 (protein catabolic process), GO:0048522 (positive regulation of cellular process), GO:0048666 (neuron development), GO:0022607 (cellular component assembly), GO:0036211 (protein modification process), GO:0007420 (brain development), GO:0009057 (macromolecule catabolic process), GO:0022008 (neurogenesis), GO:0000904 (cell morphogenesis involved in differentiation), GO:0043412 (macromolecule modification), GO:0007399 (nervous system development), GO:0001764 (neuron migration), GO:0044265 (cellular macromolecule catabolic process), GO:0007417 (central nervous system development), GO:0048858 (cell projection morphogenesis), GO:0034330 (cell junction organization), GO:0030182 (neuron differentiation), GO:0007416 (synapse assembly), GO:0048667 (cell morphogenesis involved in neuron differentiation), GO:0048259 (regulation of receptor-mediated endocytosis), GO:0021953 (central nervous system neuron differentiation), GO:0120039 (plasma membrane bounded cell projection morphogenesis), GO:0070647 (protein modification by small protein conjugation or removal), GO:0120036 (plasma membrane bounded cell projection organization), GO:0043632 (modification-dependent macromolecule catabolic process), GO:0051603 (proteolysis involved in protein catabolic process), GO:0034329 (cell junction assembly), GO:0031175 (neuron projection development), GO:0048699 (generation of neurons), GO:0050808 (synapse organization), GO:0010498 (proteasomal protein catabolic process), GO:0021954 (central nervous system neuron development), GO:0048812 (neuron projection morphogenesis), GO:0061564 (axon development), GO:0002090 (regulation of receptor internalization), GO:0106027 (neuron projection organization), GO:0007409 (axonogenesis), GO:0019941 (modification-dependent protein catabolic process), GO:0007409 (axonogenesis), GO:0021952 (central nervous system projection neuron axonogenesis), GO:0006511 (ubiquitin-dependent protein catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)