FBXL2
entrez
25827
canonical
uniprot
Q9UKC9
canonical
ensembl
ENSG00000153558
resolver
ensp
ENSP00000417601
resolver
ensp
ENSP00000568704
resolver
ensp
ENSP00000568706
resolver
genesymbol
FBXL2
resolver
genesymbol_syn
FBL2
resolver
genesymbol_syn
FBL3
resolver
hgnc
HGNC:13598
resolver
uniprot
B4DQV0
resolver
uniprot
B4E1B8
resolver
uniprot
E9PD06
resolver
uniprot
Q6IAN3
resolver
uniprot
Q9NVQ8
resolver
uniprot
Q9UK27
resolver
uniprot
Q9UKA5
resolver
uniprot
Q9Y3Y9
resolver
uniprot_entry
B4E1B8_HUMAN
resolver
uniprot_entry
FBXL2_HUMAN
resolver
uniprot_sec
B4DQV0
resolver
uniprot_sec
E9PD06
resolver
uniprot_sec
Q6IAN3
resolver
uniprot_sec
Q9NVQ8
resolver
uniprot_sec
Q9UK27
resolver
uniprot_sec
Q9UKA5
resolver
uniprot_sec
Q9Y3Y9
resolver
amino_acid_sequence
MVFSNNDEGLINKKLPKELLLRIFSFLDIVTLCRCAQISKAWNILALDGSNWQRIDLFNFQTDVEGRVVENISKRCGGFLRKLSLRGCIGVGDSSLKTFAQNCRNIEHLNLNGCTKITDSTCYSLSRFCSKLKHLDLTSCVSITNSSLKGISEGCRNLEYLNLSWCDQITKDGIEALVRGCRGLKALLLRGCTQLEDEALKHIQNYCHELVSLNLQSCSRITDEGVVQICRGCHRLQALCLSGCSNLTDASLTALGLNCPRLQILEAARCSHLTDAGFTLLARNCHELEKMDLEECILITDSTLIQLSIHCPKLQALSLSHCELITDDGILHLSNSTCGHERLRVLELDNCLLITDVALEHLENCRGLERLELYDCQQVTRAGIKRMRAQLPHVKVHAYFAPVTPPTAVAGSGQRLCRCCVIL
uniprot
proteins
function
FUNCTION: Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:22020328, PubMed:22323446, PubMed:31209342). Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin (PubMed:22020328, PubMed:22323446). This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin (PubMed:22020328, PubMed:22323446). Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity). The SCF(FBXL2) complex acts as a regulator of inflammation by mediating ubiquitination and degradation of TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (By similarity). The SCF(FBXL2) complex acts as a negative regulator of the NLRP3 inflammasome by mediating ubiquitination and degradation of NLRP3 (PubMed:26037928). The GGTase-3 complex, composed of PTAR1 and RABGGTB, geranylgeranylates and targets FBXL2 to the cellular membranes, where FBXL2 forms part of the SCF(FBXL2) complex that mediates the degradation of membrane-anchored proteins (PubMed:31209342, PubMed:32128853). {ECO:0000250|UniProtKB:Q8BH16, ECO:0000269|PubMed:22020328, ECO:0000269|PubMed:22323446, ECO:0000269|PubMed:23604317, ECO:0000269|PubMed:26037928, ECO:0000269|PubMed:31209342}.
uniprot
proteins
mass_dalton
47062
uniprot
proteins
mutagenesis
MUTAGEN 43..44; /note="Missing: Abolishes interaction with PTAR1."; /evidence="ECO:0000269|PubMed:31209342"; MUTAGEN 43; /note="N->G: Impairs interaction with PTAR1."; /evidence="ECO:0000269|PubMed:31209342"; MUTAGEN 398..400; /note="AYF->DAA: Abolishes interaction with PTAR1."; /evidence="ECO:0000269|PubMed:31209342"; MUTAGEN 420; /note="C->S: Loss of geranylgeranylation and association to membranes. Loss of interaction with NS5A, PIK3R1 and PIK3R2. No effect on interaction with PTPN13."; /evidence="ECO:0000269|PubMed:15893726, ECO:0000269|PubMed:23604317, ECO:0000269|PubMed:31209342
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:26037928}.
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by GSK-beta (GSK3B), promoting recognition by FBXO3, leading to its ubiquitination by the SCF(FBXO3) complex. {ECO:0000250|UniProtKB:Q8BH16}.; PTM: Ubiquitinated at Lys-201 by the SCF(FBXO3) complex in response to lipopolysaccharide (LPS), leading to its degradation by the proteasome. {ECO:0000305|PubMed:26037928}.; PTM: Geranylgeranylation at Cys-420 is mediated by the GGTase-3 complex and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex. {ECO:0000269|PubMed:31209342}.
uniprot
proteins
pubmed
10531035
uniprot
proteins
pubmed
10531037
uniprot
proteins
pubmed
10945468
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15893726
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
22020328
uniprot
proteins
pubmed
22323446
uniprot
proteins
pubmed
23604317
uniprot
proteins
pubmed
26037928
uniprot
proteins
pubmed
31209342
uniprot
proteins
pubmed
32128853
uniprot
proteins
sequence_length
423
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15893726, ECO:0000269|PubMed:31209342}; Lipid-anchor {ECO:0000269|PubMed:15893726}.
uniprot
proteins