FBXL5 F-box and leucine rich repeat protein 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FBXL5provided by HGNC
Official Full Name: F-box and leucine rich repeat protein 5provided by HGNC
Primary source: HGNC:HGNC:13602
See related: Ensembl:ENSG00000118564 MIM:605655; AllianceGenome:HGNC:13602
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: FBL4; FBL5; FLR1
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 several tandem leucine-rich repeats. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]
Expression: Ubiquitous expression in kidney (RPKM 49.5), fat (RPKM 39.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p15.32

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (15604381..15681569, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (15586272..15663882, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (15606004..15656980, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
Title: FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB.
Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.
Title: Loss of F-Box and Leucine Rich Repeat Protein 5 (FBXL5) Expression Is Associated With Poor Survival in Patients With Hepatocellular Carcinoma After Curative Resection: A Two-institute Study.
Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma.
Title: Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma.
This study has identified an iron-sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.
Title: FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster.
Dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human hepatocellular carcinoma, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.
Title: Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis.
We demonstrate that the CIA-targeting complex promotes the ability of FBXL5 to degrade iron regulatory proteins. In addition, the FBXL5-CIA-targeting complex interaction is regulated by oxygen (O2) tension displaying a robust association in 21% O2 that is severely diminished in 1% O2 and contributes to O2-dependent regulation of IRP degradation
Title: An Oxygen-Dependent Interaction between FBXL5 and the CIA-Targeting Complex Regulates Iron Homeostasis.
MiR-1306-3p directly targets FBXL5 and modulates FBXL5-meadiated snail protein stability in hepatocellular carcinoma.
Title: miR-1306-3p targets FBXL5 to promote metastasis of hepatocellular carcinoma through suppressing snail degradation.
this study demonstrated that FBXL5 functioned as an oncogene in the progression of colon cancer through regulating PTEN/PI3K/AKT signaling
Title: F-box and leucine-rich repeat protein 5 promotes colon cancer progression by modulating PTEN/PI3K/AKT signaling pathway.
Transcriptomic analysis shows downregulation of FBXL5 expression in HSCs of patients with myelodysplastic syndrome.
Title: Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells.
regulatory circuit involving FBXL5 and CIA acts through both IRPs to control iron metabolism and promote optimal cell growth
Title: A synergistic role of IRP1 and FBXL5 proteins in coordinating iron metabolism during cell proliferation.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D4S3149 (e-PCR)
- UniSTS:27157

RH36445 (e-PCR)
- UniSTS:15145

D4S2682 (e-PCR)
- UniSTS:62873

FBXL5 (e-PCR)
- UniSTS:503511

SHGC-63591 (e-PCR)
- UniSTS:66536

SHGC-36262 (e-PCR)
- UniSTS:8686

G33822 (e-PCR)
- UniSTS:45299

FBXL5__7649 (e-PCR)
- UniSTS:466170

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables iron ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-protein transferase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular iron ion homeostasis	IEP Inferred from Expression Pattern more info	PubMed
involved_in intracellular iron ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multicellular organismal-level iron ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IEA Inferred from Electronic Annotation more info
involved_in protein ubiquitination	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of SCF ubiquitin ligase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of SCF ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
part_of ubiquitin ligase complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: F-box/LRR-repeat protein 5

Names: F-box protein FBL4/FBL5; p45SKP2-like protein

NCBI Reference Sequences (RefSeq)

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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.

Genomic

NG_047143.2 RefSeqGene

Range

31212..82188

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193534.2 → NP_001180463.1 F-box/LRR-repeat protein 5 isoform 3

See identical proteins and their annotated locations for NP_001180463.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.

Source sequence(s)

AC116651, AF142481, AF199420, AI858616, BC030656, BF432189

UniProtKB/TrEMBL

H0Y9Y0

Conserved Domains (4) summary

cd09293
Location:353 → 407

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:7 → 160

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:331 → 356

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:204 → 248

F-box-like; F-box-like
NM_001193535.2 → NP_001180464.1 F-box/LRR-repeat protein 5 isoform 4

See identical proteins and their annotated locations for NP_001180464.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.

Source sequence(s)

AC116651, AI858616, BF432189, BX537957

Consensus CDS

CCDS54745.1

UniProtKB/TrEMBL

H0Y9Y0

Related

ENSP00000408679.2, ENST00000412094.6

Conserved Domains (4) summary

cd09293
Location:337 → 391

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:7 → 143

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:315 → 340

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:188 → 232

F-box-like; F-box-like
NM_012161.4 → NP_036293.1 F-box/LRR-repeat protein 5 isoform 1

See identical proteins and their annotated locations for NP_036293.1

Status: REVIEWED

Description

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

Source sequence(s)

AC116651, AF142481, AI858616, BC030656, BF432189

Consensus CDS

CCDS3415.1

UniProtKB/Swiss-Prot

A8MSK4, B4DIB5, Q4W5A8, Q8NHP3, Q9NXN2, Q9P0I0, Q9P0X5, Q9UJT7, Q9UKA1, Q9UKC8

UniProtKB/TrEMBL

H0Y9Y0

Related

ENSP00000344866.3, ENST00000341285.8

Conserved Domains (4) summary

cd09293
Location:354 → 408

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:7 → 160

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:332 → 357

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:205 → 249

F-box-like; F-box-like

RNA

NR_036464.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC116651, AI858616, BC012320, BC030656, BF432189

Related

ENST00000511441.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

15604381..15681569 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047450056.1 → XP_047306012.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450055.1 → XP_047306011.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450059.1 → XP_047306015.1 F-box/LRR-repeat protein 5 isoform X2
XM_047450050.1 → XP_047306006.1 F-box/LRR-repeat protein 5 isoform X1
XM_011513831.3 → XP_011512133.1 F-box/LRR-repeat protein 5 isoform X2

UniProtKB/TrEMBL

H0Y9Y0

Conserved Domains (4) summary

cd09293
Location:318 → 372

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:9 → 124

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:296 → 321

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:169 → 213

F-box-like; F-box-like
XM_047450054.1 → XP_047306010.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450053.1 → XP_047306009.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450058.1 → XP_047306014.1 F-box/LRR-repeat protein 5 isoform X2
XM_047450049.1 → XP_047306005.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450057.1 → XP_047306013.1 F-box/LRR-repeat protein 5 isoform X2
XM_006713959.4 → XP_006714022.1 F-box/LRR-repeat protein 5 isoform X1

UniProtKB/TrEMBL

H0Y9Y0

Conserved Domains (4) summary

cd09293
Location:335 → 389

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:10 → 141

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:313 → 338

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:186 → 230

F-box-like; F-box-like
XM_047450060.1 → XP_047306016.1 F-box/LRR-repeat protein 5 isoform X2
XM_017008019.3 → XP_016863508.1 F-box/LRR-repeat protein 5 isoform X3

UniProtKB/TrEMBL

H0Y9Y0

Conserved Domains (4) summary

cd09293
Location:299 → 353

AMN1; Antagonist of mitotic exit network protein 1

cd12109
Location:1 → 105

Hr_FBXL5; Hemerythrin-like domain of FBXL5-like proteins

sd00034
Location:277 → 302

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:150 → 194

F-box-like; F-box-like
XM_047450061.1 → XP_047306017.1 F-box/LRR-repeat protein 5 isoform X3
XM_047450051.1 → XP_047306007.1 F-box/LRR-repeat protein 5 isoform X1
XM_047450052.1 → XP_047306008.1 F-box/LRR-repeat protein 5 isoform X1
XM_011513833.3 → XP_011512135.1 F-box/LRR-repeat protein 5 isoform X4

UniProtKB/TrEMBL

H0Y9Y0

Conserved Domains (4) summary

cd09293
Location:282 → 336

AMN1; Antagonist of mitotic exit network protein 1

sd00034
Location:260 → 285

LRR_AMN1; leucine-rich repeat [structural motif]

pfam12937
Location:133 → 177

F-box-like; F-box-like

cl15774
Location:20 → 88

Hemerythrin-like; Hemerythrin family