FBXL2 F-box and leucine rich repeat protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FBXL2provided by HGNC
Official Full Name: F-box and leucine rich repeat protein 2provided by HGNC
Primary source: HGNC:HGNC:13598
See related: Ensembl:ENSG00000153558 MIM:605652; AllianceGenome:HGNC:13598
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FBL2; FBL3
Summary: This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
Expression: Broad expression in brain (RPKM 5.0), testis (RPKM 4.2) and 22 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 3p22.3

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (33277025..33422698)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (33278817..33424454)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (33318517..33464190)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance.
Title: FBXL2 promotes E47 protein instability to inhibit breast cancer stemness and paclitaxel resistance.
FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
Title: FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction with cis-Acting Regulatory Elements within the Fbxl2 Gene Promoter.
Title: Tumor Necrosis Factor Alpha Regulates Skeletal Myogenesis by Inhibiting SP1 Interaction with cis-Acting Regulatory Elements within the Fbxl2 Gene Promoter.
The interaction with FBXL2 and ubiquitination of FOXM1 were reduced by elevated O-GlcNAcylation. Elevated O-GlcNAcylation contributes to cancer progression by suppressing FBXL2-mediated degradation of FOXM1.
Title: O-GlcNAcylation-mediated degradation of FBXL2 stabilizes FOXM1 to induce cancer progression.
miR-346-5p promoted colorectal cancer cell growth in vitro and in vivo by targeting FBXL2 and activating the beta-catenin signaling.
Title: MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the β-catenin signaling pathway.
PTEN counteracts FBXL2 to promote IP3R3- and Ca(2+)-mediated apoptosis limiting tumour growth
Title: PTEN counteracts FBXL2 to promote IP3R3- and Ca(2+)-mediated apoptosis limiting tumour growth.
these results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.
Title: F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.
FBXL2 recognizes Trp-73 within NALP3 for interaction and targets Lys-689 within NALP3 for ubiquitin ligation and degradation.
Title: Lipopolysaccharide Primes the NALP3 Inflammasome by Inhibiting Its Ubiquitination and Degradation Mediated by the SCFFBXL2 E3 Ligase.
FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes.
Title: FBXL2- and PTPL1-mediated degradation of p110-free p85β regulatory subunit controls the PI(3)K signalling cascade.
These results suggested that the involvement of the reduction of FBL2 level is related to AD progression.
Title: Neuronal expression of F-box and leucine-rich-repeat protein 2 decreases over Braak stages in the brains of Alzheimer's disease patients.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

G63277 (e-PCR)
- UniSTS:140390

G63013 (e-PCR)
- UniSTS:140138

D3S3815 (e-PCR)
- UniSTS:27835

HSC28B082 (e-PCR)
- UniSTS:4827

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol 3-kinase regulatory subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in modulation by host of viral RNA genome replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of NLRP3 inflammasome complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in protein modification process	TAS Traceable Author Statement more info	PubMed
involved_in protein monoubiquitination	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of SCF ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: F-box/LRR-repeat protein 2

Names: F-box protein FBL2/FBL3; F-box protein containing leucine-rich repeats

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001349316.2 → NP_001336245.1 F-box/LRR-repeat protein 2 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (3).

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B3KM70

Conserved Domains (3) summary

sd00034
Location:106 → 131

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:15 → 56

F-box-like; F-box-like

cl28166
Location:168 → 398

AMN1; Antagonist of mitotic exit network protein 1
NM_001349319.2 → NP_001336248.1 F-box/LRR-repeat protein 2 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4), as well as variants 5 and 6, encodes isoform 4.

Source sequence(s)

AC122176, AC123900

Conserved Domains (2) summary

cd09293
Location:63 → 293

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349320.2 → NP_001336249.1 F-box/LRR-repeat protein 2 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (5), as well as variants 4 and 6, encodes isoform 4.

Source sequence(s)

AC122176, AC123900

Conserved Domains (2) summary

cd09293
Location:63 → 293

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349321.2 → NP_001336250.1 F-box/LRR-repeat protein 2 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (6), as well as variants 4 and 5, encodes isoform 4.

Source sequence(s)

AC122176, AC123900

Conserved Domains (2) summary

cd09293
Location:63 → 293

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349322.2 → NP_001336251.1 F-box/LRR-repeat protein 2 isoform 5 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (7) encodes isoform 5.

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B4E1B8

Conserved Domains (2) summary

cd09293
Location:84 → 283

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:22 → 47

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349323.2 → NP_001336252.1 F-box/LRR-repeat protein 2 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (8), as well as variants 9, 10, and 11, encodes isoform 6.

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B4DMM3

Conserved Domains (2) summary

cd09293
Location:63 → 262

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349324.2 → NP_001336253.1 F-box/LRR-repeat protein 2 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (9), as well as variants 8, 10, and 11, encodes isoform 6.

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B4DMM3

Conserved Domains (2) summary

cd09293
Location:63 → 262

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349325.2 → NP_001336254.1 F-box/LRR-repeat protein 2 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (10), as well as variants 8, 9, and 11, encodes isoform 6.

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B4DMM3

Conserved Domains (2) summary

cd09293
Location:63 → 262

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_001349326.2 → NP_001336255.1 F-box/LRR-repeat protein 2 isoform 6

Status: REVIEWED

Description

Transcript Variant: This variant (11), as well as variants 8, 9, and 10, encodes isoform 6.

Source sequence(s)

AC122176, AC123900

UniProtKB/TrEMBL

B4DMM3

Conserved Domains (2) summary

cd09293
Location:63 → 262

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:27 → 52

LRR_AMN1; leucine-rich repeat [structural motif]
NM_012157.5 → NP_036289.3 F-box/LRR-repeat protein 2 isoform 1

See identical proteins and their annotated locations for NP_036289.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AC122176, AK001271

Consensus CDS

CCDS2658.1

UniProtKB/Swiss-Prot

B4DQV0, E9PD06, Q6IAN3, Q9NVQ8, Q9UK27, Q9UKA5, Q9UKC9, Q9Y3Y9

UniProtKB/TrEMBL

B3KM70

Related

ENSP00000417601.1, ENST00000484457.6

Conserved Domains (3) summary

cd09293
Location:168 → 367

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:106 → 131

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:15 → 56

F-box-like

RNA

NR_146121.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146122.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146123.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146124.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146125.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146126.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146127.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146128.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900

Related

ENST00000463736.5
NR_146129.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146130.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146131.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146132.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146133.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146134.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900
NR_146135.2 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC122176, AC123900

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

33277025..33422698

Download

GenBank, FASTA, Sequence Viewer (Graphics)

RNA

XR_007095659.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

33278817..33424454

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346016.1 → XP_054201991.1 F-box/LRR-repeat protein 2 isoform X1
XM_054346017.1 → XP_054201992.1 F-box/LRR-repeat protein 2 isoform X2

RNA

XR_008486695.1 RNA Sequence
XR_008486694.1 RNA Sequence
XR_008486696.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001171713.2: Suppressed sequence

Description

NM_001171713.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.