FBXL2_MOUSE
ID FBXL2_MOUSE Reviewed; 423 AA.
AC Q8BH16; Q8BXM4;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=F-box/LRR-repeat protein 2 {ECO:0000305};
DE AltName: Full=F-box and leucine-rich repeat protein 2 {ECO:0000312|MGI:MGI:1919429};
GN Name=Fbxl2 {ECO:0000312|MGI:MGI:1919429};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, Hypothalamus, and Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP FUNCTION, INTERACTION WITH PCYT1A AND CALMODULIN, AND MISCELLANEOUS.
RX PubMed=21343341; DOI=10.1128/mcb.00723-10;
RA Chen B.B., Coon T.A., Glasser J.R., Mallampalli R.K.;
RT "Calmodulin antagonizes a calcium-activated SCF ubiquitin E3 ligase
RT subunit, FBXL2, to regulate surfactant homeostasis.";
RL Mol. Cell. Biol. 31:1905-1920(2011).
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 (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 (PubMed:21343341).
CC {ECO:0000250|UniProtKB:Q9UKC9, ECO:0000269|PubMed:21343341}.
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 (By
CC similarity). Interacts with PCYT1A (PubMed:21343341). Interacts with
CC calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2)
CC (PubMed:21343341). Interacts with CCND2 and CCND3. Interacts with
CC PIK3R2; PIK3R2 is a substrate ubiquitinated by the SCF(FBXL2) complex.
CC May interact with PIK3R1. Interacts with PTPN13 (By similarity).
CC {ECO:0000250|UniProtKB:Q9UKC9, ECO:0000269|PubMed:21343341}.
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 -!- MISCELLANEOUS: May play a role in P. Aeruginosa-induced surfactant
CC deficiency by inhibiting PCYT1A in a calcium-dependent manner.
CC {ECO:0000269|PubMed:21343341}.
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DR EMBL; AK039010; BAC30203.1; -; mRNA.
DR EMBL; AK044693; BAC32036.1; -; mRNA.
DR EMBL; AK045742; BAC32477.1; -; mRNA.
DR EMBL; AK089994; BAC41033.1; -; mRNA.
DR CCDS; CCDS40790.1; -.
DR RefSeq; NP_848739.1; NM_178624.6.
DR AlphaFoldDB; Q8BH16; -.
DR SMR; Q8BH16; -.
DR BioGRID; 215202; 3.
DR STRING; 10090.ENSMUSP00000035090; -.
DR PhosphoSitePlus; Q8BH16; -.
DR MaxQB; Q8BH16; -.
DR PaxDb; Q8BH16; -.
DR PRIDE; Q8BH16; -.
DR ProteomicsDB; 270972; -.
DR Antibodypedia; 27896; 179 antibodies from 27 providers.
DR DNASU; 72179; -.
DR Ensembl; ENSMUST00000035090; ENSMUSP00000035090; ENSMUSG00000032507.
DR Ensembl; ENSMUST00000117537; ENSMUSP00000114075; ENSMUSG00000032507.
DR GeneID; 72179; -.
DR KEGG; mmu:72179; -.
DR UCSC; uc009rxa.1; mouse.
DR CTD; 25827; -.
DR MGI; MGI:1919429; Fbxl2.
DR VEuPathDB; HostDB:ENSMUSG00000032507; -.
DR eggNOG; KOG4341; Eukaryota.
DR GeneTree; ENSGT00940000153845; -.
DR HOGENOM; CLU_016072_7_1_1; -.
DR InParanoid; Q8BH16; -.
DR OMA; AENCTEL; -.
DR OrthoDB; 1046098at2759; -.
DR PhylomeDB; Q8BH16; -.
DR TreeFam; TF313434; -.
DR BioGRID-ORCS; 72179; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Fbxl2; mouse.
DR PRO; PR:Q8BH16; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8BH16; protein.
DR Bgee; ENSMUSG00000032507; Expressed in lumbar dorsal root ganglion and 126 other tissues.
DR ExpressionAtlas; Q8BH16; baseline and differential.
DR Genevisible; Q8BH16; MM.
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; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0044830; P:modulation by host of viral RNA genome replication; ISO:MGI.
DR GO; GO:0006513; P:protein monoubiquitination; IMP:MGI.
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 GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:MGI.
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 1: Evidence at protein level;
KW Calcium; Calmodulin-binding; Leucine-rich repeat; Lipoprotein; Membrane;
KW Prenylation; Reference proteome; Repeat; Ubl conjugation pathway.
FT CHAIN 1..423
FT /note="F-box/LRR-repeat protein 2"
FT /id="PRO_0000119841"
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:0000269|PubMed:21343341"
FT MOTIF 420..423
FT /note="CAAX motif"
FT LIPID 420
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKC9"
FT CONFLICT 277
FT /note="G -> S (in Ref. 1; BAC32036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 423 AA; 46890 MW; 597713D0407195CC CRC64;
MVFSNSDDGL INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS NWQRVDLFNF
QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA QNCRNIEHLN LNGCTKITDS
TCYSLSRFCS KLKHLDLTSC VSVTNSSLKG ISEGCRNLEY LNLSWCDQIT KEGIEALVRG
CRGLKALLLR GCTQLEDEAL KHIQNHCHEL VSLNLQSCSR ITDDGVVQIC RGCHRLQALC
LSGCSNLTDA SLTALGLNCP RLQVLEAARC SHLTDAGFTL LARNCHELEK MDLEECVLIT
DSTLVQLSIH CPKLQALSLS HCELITDEGI LHLSSSTCGH ERLRVLELDN CLLVTDASLE
HLENCRGLER LELYDCQQVT RAGIKRMRAQ LPHVKVHAYF APVTPPPAVA GSGHRLCRCC
VIL
