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Protein

F-box/LRR-repeat protein 21

Gene

Fbxl21

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

Functioni

Substrate-recognition component of the SCF(FBXL21) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL21) complex mainly acts in the cytosol and mediates ubiquitination of CRY proteins (CRY1 and CRY2), leading to CRY proteins stabilization. The SCF(FBXL21) complex counteracts the activity of the SCF(FBXL3) complex and protects CRY proteins from degradation. Involved in the hypothalamic suprachiasmatic nucleus (SCN) clock regulating temporal organization of the daily activities.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Biological processi

  • entrainment of circadian clock by photoperiod Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Biological rhythms, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/LRR-repeat protein 21
Alternative name(s):
F-box and leucine-rich repeat protein 21
F-box and leucine-rich repeat protein 3B
F-box/LRR-repeat protein 3B
Gene namesi
Name:Fbxl21
Synonyms:Fbl21, Fbxl3b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:2442921. Fbxl21.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • nucleus Source: UniProtKB
  • SCF ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice show normal periodicity of wheel-running rhythms with compromised organization of daily activities: mice do not display significant difference from their wild-type littermates in both the free-running period in constant darkness (DD) and activity onset in 12 hours of light/12 hours of darkness (LD). However, an alteration in the daily activities is observed: while wild-type mice show 2 peaks of activity during the active period, the late night activity is eliminated in Fbxl21-deficient mice. Mice lacking both Fbxl3 and Fbxl21 show an attenuated phenotype in behavioral rhythm compared to Fbxl3-deficient mice; however, they exhibit unstable behavioral rhythms, sometimes eliciting arrhythmicity.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi149 – 1491G → E in Past-time (Psttm) mutant; causes period shortening due to Cry1 and Cry2 destabilization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 434434F-box/LRR-repeat protein 21PRO_0000119874Add
BLAST

Proteomic databases

PaxDbiQ8BFZ4.
PRIDEiQ8BFZ4.

PTM databases

iPTMnetiQ8BFZ4.
PhosphoSiteiQ8BFZ4.

Expressioni

Tissue specificityi

Expressed in the hypothalamus, especially in the suprachiasmatic nucleus (SCN). Expression is driven by the core-clock. There is a pronounced diurnal and circadian expression rhythms rising rapidly at the start of the day and declining at the onset of the night.1 Publication

Gene expression databases

BgeeiENSMUSG00000035509.
CleanExiMM_FBXL21.
ExpressionAtlasiQ8BFZ4. baseline and differential.
GenevisibleiQ8BFZ4. MM.

Interactioni

Subunit structurei

Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL21) composed of CUL1, SKP1, RBX1 and FBXL21. Interacts with CRY1 and CRY2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cry1P9778410EBI-6898235,EBI-1266607
Cry2Q9R1944EBI-6898235,EBI-1266619
CUL1Q136163EBI-6898235,EBI-359390From a different organism.
SKP1P632083EBI-6898235,EBI-307486From a different organism.

Protein-protein interaction databases

IntActiQ8BFZ4. 7 interactions.
STRINGi10090.ENSMUSP00000035248.

Structurei

3D structure databases

ProteinModelPortaliQ8BFZ4.
SMRiQ8BFZ4. Positions 41-434.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini39 – 8547F-boxPROSITE-ProRule annotationAdd
BLAST
Repeati187 – 21327LRR 1Add
BLAST
Repeati214 – 23926LRR 2Add
BLAST
Repeati242 – 26524LRR 3Add
BLAST
Repeati322 – 34726LRR 4Add
BLAST
Repeati349 – 37426LRR 5Add
BLAST
Repeati375 – 40026LRR 6Add
BLAST

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 6 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG1947. Eukaryota.
ENOG410XQ54. LUCA.
GeneTreeiENSGT00390000007432.
HOGENOMiHOG000060185.
HOVERGENiHBG051587.
InParanoidiQ8BFZ4.
KOiK10287.
PhylomeDBiQ8BFZ4.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8BFZ4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKRNNFSAVN KVVQSSPVVK QPKRGLCSSL RQTHALSVLL DWGTLPHHVI
60 70 80 90 100
LQIFQYLPLI DRARASSVCR RWNEVFHIPD LWRKFEFELN QSATSYFKST
110 120 130 140 150
HPDLIQQIIK KHAAHLQYVS FKVDSSTESA EAACDILSQL VNCSIQTLGL
160 170 180 190 200
ISTAKPSFMN VPKSHFVSAL TVVFVNSKSL SSIKIEDTPV DDPSLKILVA
210 220 230 240 250
NNSDTLRLLK MSSCPHVSSD GILCVADHCQ GLRELALNYY ILSDEILLAL
260 270 280 290 300
SSETHVNLEH LRIDVVSENP GQIKFHSIKK RSWDALIKHS PRVNVVMYFF
310 320 330 340 350
LYEEEFEAFF KEETPVTHLY FGRSVSRAIL GRIGLNCPRL IELVVCANGL
360 370 380 390 400
LPLDSELIRI AKHCKNLTSL GLSECEVSCS AFVEFVRLCG RRLTQLSIME
410 420 430
EVLVPDDRYT PDEVHTEVSK HLGRVWFPDV MPIW
Length:434
Mass (Da):49,154
Last modified:March 1, 2003 - v1
Checksum:iDAE94BEC79D1D4A2
GO
Isoform 2 (identifier: Q8BFZ4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     124-128: DSSTE → QSSFR
     129-434: Missing.

Show »
Length:128
Mass (Da):14,971
Checksum:i830BA9DC3850727D
GO

Sequence cautioni

The sequence BAC37751 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei124 – 1285DSSTE → QSSFR in isoform 2. 1 PublicationVSP_008415
Alternative sequencei129 – 434306Missing in isoform 2. 1 PublicationVSP_008416Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK035290 mRNA. Translation: BAC29018.1.
AK079800 mRNA. Translation: BAC37751.1. Different initiation.
AK085598 mRNA. Translation: BAC39482.1.
CH466546 Genomic DNA. Translation: EDL41240.1.
BC138940 mRNA. Translation: AAI38941.1.
BC138941 mRNA. Translation: AAI38942.1.
CCDSiCCDS26563.1. [Q8BFZ4-1]
RefSeqiNP_848789.2. NM_178674.4. [Q8BFZ4-1]
UniGeneiMm.233904.

Genome annotation databases

EnsembliENSMUST00000045428; ENSMUSP00000035248; ENSMUSG00000035509. [Q8BFZ4-1]
GeneIDi213311.
KEGGimmu:213311.
UCSCiuc007qsp.1. mouse. [Q8BFZ4-2]
uc007qsr.1. mouse. [Q8BFZ4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK035290 mRNA. Translation: BAC29018.1.
AK079800 mRNA. Translation: BAC37751.1. Different initiation.
AK085598 mRNA. Translation: BAC39482.1.
CH466546 Genomic DNA. Translation: EDL41240.1.
BC138940 mRNA. Translation: AAI38941.1.
BC138941 mRNA. Translation: AAI38942.1.
CCDSiCCDS26563.1. [Q8BFZ4-1]
RefSeqiNP_848789.2. NM_178674.4. [Q8BFZ4-1]
UniGeneiMm.233904.

3D structure databases

ProteinModelPortaliQ8BFZ4.
SMRiQ8BFZ4. Positions 41-434.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8BFZ4. 7 interactions.
STRINGi10090.ENSMUSP00000035248.

PTM databases

iPTMnetiQ8BFZ4.
PhosphoSiteiQ8BFZ4.

Proteomic databases

PaxDbiQ8BFZ4.
PRIDEiQ8BFZ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000045428; ENSMUSP00000035248; ENSMUSG00000035509. [Q8BFZ4-1]
GeneIDi213311.
KEGGimmu:213311.
UCSCiuc007qsp.1. mouse. [Q8BFZ4-2]
uc007qsr.1. mouse. [Q8BFZ4-1]

Organism-specific databases

CTDi26223.
MGIiMGI:2442921. Fbxl21.

Phylogenomic databases

eggNOGiKOG1947. Eukaryota.
ENOG410XQ54. LUCA.
GeneTreeiENSGT00390000007432.
HOGENOMiHOG000060185.
HOVERGENiHBG051587.
InParanoidiQ8BFZ4.
KOiK10287.
PhylomeDBiQ8BFZ4.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ8BFZ4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035509.
CleanExiMM_FBXL21.
ExpressionAtlasiQ8BFZ4. baseline and differential.
GenevisibleiQ8BFZ4. MM.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR001810. F-box_dom.
IPR032675. L_dom-like.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFXL21_MOUSE
AccessioniPrimary (citable) accession number: Q8BFZ4
Secondary accession number(s): B2RSN8, Q8BIJ8, Q8BIW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: March 1, 2003
Last modified: September 7, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The mechanism by which the SCF(FBXL21) complex stabilizes CRY proteins (CRY1 and CRY2) is still unclear: according to a report, the SCF(FBXL21) complex does not catalyze 'Lys-48'-linked polyubiquitin chains, but catalyzes a different type of ubiquitin chains that do not lead to degradation (PubMed:23452856). According to a second report, FBXL21 has a higher affinity for CRY proteins compared to FBXL3, while the SCF(FBXL21) complex has weaker ubiquitin-ligase activity compared to the SCF(FBXL3) complex: as a consequence, the SCF(FBXL21) complex protects CRY proteins from SCF(FBXL3) activity and degradation in the nucleus, while it promotes slow degradation of CRY proteins in the cytosol (PubMed:23452855).2 Publications

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.