ID FBXL2_BOVIN Reviewed; 423 AA. AC A6H779; DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 1. DT 27-MAR-2024, entry version 96. DE RecName: Full=F-box/LRR-repeat protein 2 {ECO:0000305}; DE AltName: Full=F-box and leucine-rich repeat protein 2 {ECO:0000305}; GN Name=FBXL2 {ECO:0000305}; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Hereford; TISSUE=Fetal pons; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Calcium-activated substrate recognition component of the SCF CC (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, CC SCF(FBXL2), which mediates the ubiquitination and subsequent CC proteasomal degradation of target proteins (By similarity). Unlike many CC F-box proteins, FBXL2 does not seem to target phosphodegron within its CC substrates but rather calmodulin-binding motifs and is thereby CC antagonized by calmodulin. This is the case for the cyclins CCND2 and CC CCND3 which polyubiquitination and subsequent degradation are inhibited CC by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle CC arrest in G(0). SCF(FBXL2) also mediates PIK3R2 ubiquitination and CC proteasomal degradation thereby regulating phosphatidylinositol 3- CC kinase signaling and autophagy (By similarity). PCYT1A CC monoubiquitination by SCF(FBXL2) and subsequent degradation regulates CC synthesis of phosphatidylcholine, which is utilized for formation of CC membranes and of pulmonary surfactant. The SCF(FBXL2) complex acts as a CC regulator of inflammation by mediating ubiquitination and degradation CC of TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (By CC similarity). The SCF(FBXL2) complex acts as a negative regulator of the CC NLRP3 inflammasome by mediating ubiquitination and degradation of NLRP3 CC (By similarity). {ECO:0000250|UniProtKB:Q8BH16, CC ECO:0000250|UniProtKB:Q9UKC9}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000250|UniProtKB:Q9UKC9}. CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase CC complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2. Interacts CC with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2). CC May interact with PIK3R1. Interacts with PTPN13. CC {ECO:0000250|UniProtKB:Q9UKC9}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9UKC9}; Lipid- CC anchor {ECO:0000250|UniProtKB:Q9UKC9}. CC -!- DOMAIN: The CAAX motif is a signal for the geranylgeranylation of FBXL2 CC and is required for its association with cell membranes and the CC recruitment of substrates to the active SCF(FBXL2) complex. CC {ECO:0000250|UniProtKB:Q9UKC9}. CC -!- PTM: Phosphorylated by GSK-beta (GSK3B), promoting recognition by CC FBXO3, leading to its ubiquitination by the SCF(FBXO3) complex. CC {ECO:0000250|UniProtKB:Q8BH16}. CC -!- PTM: Ubiquitinated at Lys-201 by the SCF(FBXO3) complex in response to CC lipopolysaccharide (LPS), leading to its degradation by the proteasome. CC {ECO:0000250|UniProtKB:Q8BH16}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC146145; AAI46146.1; -; mRNA. DR RefSeq; NP_001092623.1; NM_001099153.2. DR AlphaFoldDB; A6H779; -. DR SMR; A6H779; -. DR STRING; 9913.ENSBTAP00000060031; -. DR PaxDb; 9913-ENSBTAP00000005160; -. DR Ensembl; ENSBTAT00000005160.6; ENSBTAP00000005160.5; ENSBTAG00000003952.6. DR GeneID; 616212; -. DR KEGG; bta:616212; -. DR CTD; 25827; -. DR VEuPathDB; HostDB:ENSBTAG00000003952; -. DR VGNC; VGNC:52775; FBXL2. DR eggNOG; KOG4341; Eukaryota. DR GeneTree; ENSGT00940000153845; -. DR HOGENOM; CLU_016072_7_1_1; -. DR InParanoid; A6H779; -. DR OMA; VTRDSCE; -. DR OrthoDB; 1078060at2759; -. DR TreeFam; TF313434; -. DR UniPathway; UPA00143; -. DR Proteomes; UP000009136; Chromosome 22. DR Bgee; ENSBTAG00000003952; Expressed in semen and 110 other cell types or tissues. DR ExpressionAtlas; A6H779; baseline. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; IEA:Ensembl. DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl. DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB. DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; IEA:Ensembl. DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB. DR GO; GO:0006513; P:protein monoubiquitination; IEA:Ensembl. DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB. DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB. DR CDD; cd22115; F-box_FBXL2-like; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR PANTHER; PTHR13382; MITOCHONDRIAL ATP SYNTHASE COUPLING FACTOR B; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF13516; LRR_6; 5. DR SMART; SM00256; FBOX; 1. DR SMART; SM00367; LRR_CC; 11. DR SUPFAM; SSF52047; RNI-like; 1. DR PROSITE; PS50181; FBOX; 1. PE 2: Evidence at transcript level; KW Calcium; Calmodulin-binding; Isopeptide bond; Leucine-rich repeat; KW Lipoprotein; Membrane; Phosphoprotein; Prenylation; Reference proteome; KW Repeat; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..423 FT /note="F-box/LRR-repeat protein 2" FT /id="PRO_0000354084" FT DOMAIN 9..55 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 61..87 FT /note="LRR 1" FT REPEAT 88..113 FT /note="LRR 2" FT REPEAT 114..139 FT /note="LRR 3" FT REPEAT 140..165 FT /note="LRR 4" FT REPEAT 166..191 FT /note="LRR 5" FT REPEAT 192..217 FT /note="LRR 6" FT REPEAT 218..243 FT /note="LRR 7" FT REPEAT 244..269 FT /note="LRR 8" FT REPEAT 270..295 FT /note="LRR 9" FT REPEAT 296..321 FT /note="LRR 10" FT REPEAT 322..350 FT /note="LRR 11" FT REPEAT 351..375 FT /note="LRR 12" FT REPEAT 376..401 FT /note="LRR 13" FT REGION 80..90 FT /note="Interaction with Calmodulin" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" FT MOTIF 420..423 FT /note="CAAX motif" FT MOD_RES 404 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" FT LIPID 420 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q9UKC9" FT CROSSLNK 201 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q8BH16" SQ SEQUENCE 423 AA; 46975 MW; 6850504C474C7CE7 CRC64; MVFSNNDEGL INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS NWQRIDLFNF QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA QNCRNIEHLN LNGCTKITDS TCYSLSRFCS KLKHLDLTSC VSITNSSLKG ISEGCRHLEY LNLSWCDQIT KDGVEALVRG CRGLRALLLR GCTQLEDEAL KHIQNYCHEL VSLNLQSCSR VTDDGVVQLC RGCPRLQALC LSGCGSLTDA SLTALALNCP RLQILEAARC SHLTDAGFTL LARNCHDLEK MDLEECILIT DRTLTQLSIH CPKLQALSLS HCELITDDGI LHLSNSPCGH ERLRVLELDN CLLITDVALE HLEHCRGLER LELYDCQQVT RAGIKRMRAQ LPHVRVHAYF APVTPPTAAG GGGPRLCRCC VIL //