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Protein

F-box/LRR-repeat protein 2

Gene

Fbxl2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation induces cell-cycle arrest in G0. SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (By similarity). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (PubMed:21343341).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Calcium, Calmodulin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/LRR-repeat protein 2Curated
Alternative name(s):
F-box and leucine-rich repeat protein 2Imported
Gene namesi
Name:Fbxl2Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1919429. Fbxl2.

Subcellular locationi

  • Membrane By similarity; Lipid-anchor By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198411 – 423F-box/LRR-repeat protein 2Add BLAST423

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi420S-geranylgeranyl cysteineBy similarity1

Keywords - PTMi

Lipoprotein, Prenylation

Proteomic databases

MaxQBiQ8BH16.
PaxDbiQ8BH16.
PRIDEiQ8BH16.

PTM databases

PhosphoSitePlusiQ8BH16.

Expressioni

Gene expression databases

BgeeiENSMUSG00000032507.
CleanExiMM_FBXL2.
ExpressionAtlasiQ8BH16. baseline and differential.
GenevisibleiQ8BH16. MM.

Interactioni

Subunit structurei

Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2 (By similarity). Interacts with PCYT1A (PubMed:21343341). Interacts with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2) (PubMed:21343341). Interacts with CCND2 and CCND3. Interacts with PIK3R2; PIK3R2 is a substrate ubiquitinated by the SCF(FBXL2) complex. May interact with PIK3R1. Interacts with PTPN13 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi215202. 3 interactors.
STRINGi10090.ENSMUSP00000035090.

Structurei

3D structure databases

ProteinModelPortaliQ8BH16.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 55F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati61 – 87LRR 1Add BLAST27
Repeati88 – 113LRR 2Add BLAST26
Repeati114 – 139LRR 3Add BLAST26
Repeati140 – 165LRR 4Add BLAST26
Repeati166 – 191LRR 5Add BLAST26
Repeati192 – 217LRR 6Add BLAST26
Repeati218 – 243LRR 7Add BLAST26
Repeati244 – 269LRR 8Add BLAST26
Repeati270 – 295LRR 9Add BLAST26
Repeati296 – 321LRR 10Add BLAST26
Repeati322 – 350LRR 11Add BLAST29
Repeati351 – 375LRR 12Add BLAST25
Repeati376 – 401LRR 13Add BLAST26

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni80 – 90Interaction with Calmodulin1 PublicationAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi420 – 423CAAX motif4

Domaini

The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.By similarity

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 13 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG4341. Eukaryota.
ENOG410XQ54. LUCA.
GeneTreeiENSGT00760000119059.
HOGENOMiHOG000230659.
HOVERGENiHBG051586.
InParanoidiQ8BH16.
KOiK10268.
OMAiITDSTCI.
OrthoDBiEOG091G060Y.
PhylomeDBiQ8BH16.
TreeFamiTF313434.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF13516. LRR_6. 4 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 11 hits.
[Graphical view]
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BH16-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVFSNSDDGL INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS
60 70 80 90 100
NWQRVDLFNF QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA
110 120 130 140 150
QNCRNIEHLN LNGCTKITDS TCYSLSRFCS KLKHLDLTSC VSVTNSSLKG
160 170 180 190 200
ISEGCRNLEY LNLSWCDQIT KEGIEALVRG CRGLKALLLR GCTQLEDEAL
210 220 230 240 250
KHIQNHCHEL VSLNLQSCSR ITDDGVVQIC RGCHRLQALC LSGCSNLTDA
260 270 280 290 300
SLTALGLNCP RLQVLEAARC SHLTDAGFTL LARNCHELEK MDLEECVLIT
310 320 330 340 350
DSTLVQLSIH CPKLQALSLS HCELITDEGI LHLSSSTCGH ERLRVLELDN
360 370 380 390 400
CLLVTDASLE HLENCRGLER LELYDCQQVT RAGIKRMRAQ LPHVKVHAYF
410 420
APVTPPPAVA GSGHRLCRCC VIL
Length:423
Mass (Da):46,890
Last modified:March 1, 2003 - v1
Checksum:i597713D0407195CC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti277G → S in BAC32036 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK039010 mRNA. Translation: BAC30203.1.
AK044693 mRNA. Translation: BAC32036.1.
AK045742 mRNA. Translation: BAC32477.1.
AK089994 mRNA. Translation: BAC41033.1.
CCDSiCCDS40790.1.
RefSeqiNP_848739.1. NM_178624.6.
UniGeneiMm.386808.

Genome annotation databases

EnsembliENSMUST00000035090; ENSMUSP00000035090; ENSMUSG00000032507.
ENSMUST00000117537; ENSMUSP00000114075; ENSMUSG00000032507.
GeneIDi72179.
KEGGimmu:72179.
UCSCiuc009rxa.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK039010 mRNA. Translation: BAC30203.1.
AK044693 mRNA. Translation: BAC32036.1.
AK045742 mRNA. Translation: BAC32477.1.
AK089994 mRNA. Translation: BAC41033.1.
CCDSiCCDS40790.1.
RefSeqiNP_848739.1. NM_178624.6.
UniGeneiMm.386808.

3D structure databases

ProteinModelPortaliQ8BH16.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi215202. 3 interactors.
STRINGi10090.ENSMUSP00000035090.

PTM databases

PhosphoSitePlusiQ8BH16.

Proteomic databases

MaxQBiQ8BH16.
PaxDbiQ8BH16.
PRIDEiQ8BH16.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035090; ENSMUSP00000035090; ENSMUSG00000032507.
ENSMUST00000117537; ENSMUSP00000114075; ENSMUSG00000032507.
GeneIDi72179.
KEGGimmu:72179.
UCSCiuc009rxa.1. mouse.

Organism-specific databases

CTDi25827.
MGIiMGI:1919429. Fbxl2.

Phylogenomic databases

eggNOGiKOG4341. Eukaryota.
ENOG410XQ54. LUCA.
GeneTreeiENSGT00760000119059.
HOGENOMiHOG000230659.
HOVERGENiHBG051586.
InParanoidiQ8BH16.
KOiK10268.
OMAiITDSTCI.
OrthoDBiEOG091G060Y.
PhylomeDBiQ8BH16.
TreeFamiTF313434.

Miscellaneous databases

ChiTaRSiFbxl2. mouse.
PROiQ8BH16.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032507.
CleanExiMM_FBXL2.
ExpressionAtlasiQ8BH16. baseline and differential.
GenevisibleiQ8BH16. MM.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF13516. LRR_6. 4 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 11 hits.
[Graphical view]
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBXL2_MOUSE
AccessioniPrimary (citable) accession number: Q8BH16
Secondary accession number(s): Q8BXM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 21, 2003
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

May play a role in P. Aeruginosa-induced surfactant deficiency by inhibiting PCYT1A in a calcium-dependent manner.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.