FBXL2_PONAB
ID FBXL2_PONAB Reviewed; 423 AA.
AC Q5R3Z8; Q5R4A1;
DT 25-NOV-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 86.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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. Unlike many F-box proteins,
CC FBXL2 does not seem to target phosphodegron within its substrates but
CC rather calmodulin-binding motifs and is thereby antagonized by
CC calmodulin. This is the case for the cyclins CCND2 and CCND3 which
CC polyubiquitination and subsequent degradation are inhibited by
CC 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. PCYT1A monoubiquitination by SCF(FBXL2)
CC and subsequent degradation regulates synthesis of phosphatidylcholine,
CC which is utilized for formation of membranes and of pulmonary
CC surfactant. {ECO:0000250|UniProtKB:Q8BH16,
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 PCYT1A. Interacts with calmodulin; may antagonize substrate
CC ubiquitination by SCF(FBXL2). Interacts with CCND2 and CCND3. Interacts
CC with PIK3R2; PIK3R2 is a substrate ubiquitinated by the SCF(FBXL2)
CC complex. May interact with PIK3R1. Interacts with PTPN13.
CC {ECO:0000250|UniProtKB:Q8BH16, ECO:0000250|UniProtKB:Q9UKC9}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9UKC9}; Lipid-
CC anchor {ECO:0000250|UniProtKB:Q9UKC9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5R3Z8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5R3Z8-2; Sequence=VSP_035780, VSP_035781;
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}.
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DR EMBL; CR861354; CAH93415.1; -; mRNA.
DR EMBL; CR861462; CAH93518.1; -; mRNA.
DR RefSeq; NP_001127056.1; NM_001133584.1. [Q5R3Z8-1]
DR RefSeq; NP_001128909.1; NM_001135437.1.
DR AlphaFoldDB; Q5R3Z8; -.
DR SMR; Q5R3Z8; -.
DR STRING; 9601.ENSPPYP00000015699; -.
DR GeneID; 100174084; -.
DR GeneID; 100189854; -.
DR KEGG; pon:100174084; -.
DR CTD; 25827; -.
DR eggNOG; KOG4341; Eukaryota.
DR InParanoid; Q5R3Z8; -.
DR OrthoDB; 1046098at2759; -.
DR Proteomes; UP000001595; Unplaced.
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:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 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 Pfam; PF12937; F-box-like; 1.
DR Pfam; PF13516; LRR_6; 5.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00367; LRR_CC; 11.
DR PROSITE; PS50181; FBOX; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Calmodulin-binding; Leucine-rich repeat;
KW Lipoprotein; Membrane; Prenylation; Reference proteome; Repeat;
KW Ubl conjugation pathway.
FT CHAIN 1..423
FT /note="F-box/LRR-repeat protein 2"
FT /id="PRO_0000354085"
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 LIPID 420
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKC9"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_035780"
FT VAR_SEQ 106..119
FT /note="IEHLNLNGCTKITD -> MDAQKSLTVRLLFF (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_035781"
FT CONFLICT 147
FT /note="S -> P (in Ref. 1; CAH93415)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="S -> G (in Ref. 1; CAH93415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 423 AA; 47135 MW; AEEFF6DA1FFAB61E CRC64;
MVFSNNDEGR INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS NWQRIDLFNF
QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA QNCRNIEHLN LNGCTKITDS
TCYSLSRFCS KLKHLDLTSC VSITNSSLKG ISEGCRNLEY LNLSWCDQIT KDGIEALVRG
CRGLKALLLR GCTQLEDEAL KHIQNYCHEL VSLNLQSCSR ITDEGVVQIC RGCHRLQALC
LSGCSNLTDA SLTALGLNCP RLQILEAARC SHLTDAGFTL LARNCHELEK MDLEECILIT
DSTLIQLSIH CPKLQALSLS HCELITDDGI LHLSNSTCGH ERLRVLELDN CLLITDVALE
HLENCRGLER LELYDCQQVT RAGIKRMRAQ LPHVKVHAYF APVTPPTAVT GSGQRLCRCC
VIL
