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Protein

F-box/LRR-repeat protein 5

Gene

FBXL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. Upon high iron and oxygen level, it specifically recognizes and binds IREB2/IRP2, promoting its ubiquitination and degradation by the proteasome. Promotes ubiquitination and subsequent degradation of DCTN1/p150-glued.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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi15Iron 11
Metal bindingi57Iron 11
Metal bindingi58Iron 11
Metal bindingi61Iron 11
Metal bindingi61Iron 21
Metal bindingi80Iron 21
Metal bindingi126Iron 21
Metal bindingi130Iron 11
Metal bindingi130Iron 21

GO - Molecular functioni

  • iron ion binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • iron ion homeostasis Source: UniProtKB
  • positive regulation of cellular protein catabolic process Source: Ensembl
  • protein ubiquitination Source: UniProtKB
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/LRR-repeat protein 5
Alternative name(s):
F-box and leucine-rich repeat protein 5
F-box protein FBL4/FBL5
p45SKP2-like protein
Gene namesi
Name:FBXL5
Synonyms:FBL4, FBL5, FLR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:13602. FBXL5.

Subcellular locationi

GO - Cellular componenti

  • perinuclear region of cytoplasm Source: UniProtKB
  • SCF ubiquitin ligase complex Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi15H → A: Abolishes iron-binding and promotes its degradation. 1 Publication1
Mutagenesisi57H → A: Abolishes iron-binding and promotes its degradation. 2 Publications1
Mutagenesisi61E → A: Abolishes iron-binding and promotes its degradation. 1 Publication1

Organism-specific databases

DisGeNETi26234.
OpenTargetsiENSG00000118564.
PharmGKBiPA28025.

Polymorphism and mutation databases

BioMutaiFBXL5.
DMDMi37537864.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001198451 – 691F-box/LRR-repeat protein 5Add BLAST691

Post-translational modificationi

Polybiquitinated upon iron and oxygen depletion, leading to its degradation by the proteasome. Ubiquitination is regulated by the hemerythrin-like region that acts as an oxygen and iron sensor.2 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ9UKA1.
PRIDEiQ9UKA1.

PTM databases

iPTMnetiQ9UKA1.
PhosphoSitePlusiQ9UKA1.

Expressioni

Gene expression databases

BgeeiENSG00000118564.
CleanExiHS_FBXL5.
ExpressionAtlasiQ9UKA1. baseline and differential.
GenevisibleiQ9UKA1. HS.

Organism-specific databases

HPAiCAB022085.
CAB025148.

Interactioni

Subunit structurei

Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with ACO1/IRP1, IREB2/IRP2; the interaction depends on the 4Fe-4S cluster. Interacts with DCTN1/p150-glued.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SKP1P6320812EBI-2692340,EBI-307486

Protein-protein interaction databases

BioGridi117625. 38 interactors.
IntActiQ9UKA1. 7 interactors.
MINTiMINT-8247431.
STRINGi9606.ENSP00000344866.

Structurei

Secondary structure

1691
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 8Combined sources3
Helixi12 – 31Combined sources20
Helixi37 – 64Combined sources28
Helixi66 – 73Combined sources8
Helixi85 – 98Combined sources14
Helixi102 – 132Combined sources31
Helixi134 – 141Combined sources8
Helixi144 – 158Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U9JX-ray1.60A/B1-160[»]
3U9MX-ray1.95A/C/E/G1-160[»]
3V5XX-ray1.85A/B1-161[»]
3V5YX-ray2.10A/B/C/D1-161[»]
3V5ZX-ray2.18A/B1-161[»]
ProteinModelPortaliQ9UKA1.
SMRiQ9UKA1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini202 – 248F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati340 – 364LRR 1Add BLAST25
Repeati365 – 392LRR 2Add BLAST28
Repeati393 – 418LRR 3Add BLAST26
Repeati479 – 508LRR 4Add BLAST30
Repeati576 – 607LRR 5Add BLAST32
Repeati608 – 635LRR 6Add BLAST28
Repeati636 – 661LRR 7Add BLAST26

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 159Hemerythrin-likeAdd BLAST159

Domaini

The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded.2 Publications

Sequence similaritiesi

Contains 1 F-box domain.PROSITE-ProRule annotation
Contains 7 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IHDI. Eukaryota.
ENOG410ZKEM. LUCA.
GeneTreeiENSGT00390000006172.
HOVERGENiHBG051589.
InParanoidiQ9UKA1.
KOiK10271.
OMAiTKQYACL.
OrthoDBiEOG091G02J5.
PhylomeDBiQ9UKA1.
TreeFamiTF331105.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR001810. F-box_dom.
IPR012312. Haemerythrin-like.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF01814. Hemerythrin. 1 hit.
PF13516. LRR_6. 2 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 4 hits.
[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: Q9UKA1-1) [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
MAPFPEEVDV FTAPHWRMKQ LVGLYCDKLS KTNFSNNNDF RALLQSLYAT
60 70 80 90 100
FKEFKMHEQI ENEYIIGLLQ QRSQTIYNVH SDNKLSEMLS LFEKGLKNVK
110 120 130 140 150
NEYEQLNYAK QLKERLEAFT RDFLPHMKEE EEVFQPMLME YFTYEELKDI
160 170 180 190 200
KKKVIAQHCS QKDTAELLRG LSLWNHAEER QKFFKYSVDE KSDKEAEVSE
210 220 230 240 250
HSTGITHLPP EVMLSIFSYL NPQELCRCSQ VSMKWSQLTK TGSLWKHLYP
260 270 280 290 300
VHWARGDWYS GPATELDTEP DDEWVKNRKD ESRAFHEWDE DADIDESEES
310 320 330 340 350
AEESIAISIA QMEKRLLHGL IHNVLPYVGT SVKTLVLAYS SAVSSKMVRQ
360 370 380 390 400
ILELCPNLEH LDLTQTDISD SAFDSWSWLG CCQSLRHLDL SGCEKITDVA
410 420 430 440 450
LEKISRALGI LTSHQSGFLK TSTSKITSTA WKNKDITMQS TKQYACLHDL
460 470 480 490 500
TNKGIGEEID NEHPWTKPVS SENFTSPYVW MLDAEDLADI EDTVEWRHRN
510 520 530 540 550
VESLCVMETA SNFSCSTSGC FSKDIVGLRT SVCWQQHCAS PAFAYCGHSF
560 570 580 590 600
CCTGTALRTM SSLPESSAMC RKAARTRLPR GKDLIYFGSE KSDQETGRVL
610 620 630 640 650
LFLSLSGCYQ ITDHGLRVLT LGGGLPYLEH LNLSGCLTIT GAGLQDLVSA
660 670 680 690
CPSLNDEYFY YCDNINGPHA DTASGCQNLQ CGFRACCRSG E
Length:691
Mass (Da):78,555
Last modified:October 3, 2003 - v2
Checksum:i923A1B31590E5145
GO
Isoform 2 (identifier: Q9UKA1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     29-45: Missing.

Note: No experimental confirmation available.
Show »
Length:674
Mass (Da):76,590
Checksum:iB114C4C0F0A37AE9
GO

Sequence cautioni

The sequence AAF66616 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAF67489 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH30656 differs from that shown. Reason: Erroneous initiation.Curated
The sequence EAW92737 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti52K → T in AAH30656 (PubMed:15489334).Curated1
Sequence conflicti195Missing in AAF09249 (PubMed:10945468).Curated1
Sequence conflicti242G → R in AAH30656 (PubMed:15489334).Curated1
Sequence conflicti532V → I in BAA90978 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00841729 – 45Missing in isoform 2. 2 PublicationsAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176700 mRNA. Translation: AAF03700.1.
AF199420 mRNA. Translation: AAF09249.1.
AF142481 mRNA. Translation: AAF66616.1. Different initiation.
AK000153 mRNA. Translation: BAA90978.1.
AK295510 mRNA. Translation: BAG58427.1.
BX537957 mRNA. Translation: CAD97924.1.
AC114744 Genomic DNA. Translation: AAY40929.1.
AC116651 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW92737.1. Sequence problems.
CH471069 Genomic DNA. Translation: EAW92739.1.
BC030656 mRNA. Translation: AAH30656.1. Different initiation.
AF157323 mRNA. Translation: AAF67489.1. Different initiation.
AF174591 mRNA. Translation: AAF04512.1.
CCDSiCCDS3415.1. [Q9UKA1-1]
CCDS54745.1. [Q9UKA1-2]
RefSeqiNP_001180463.1. NM_001193534.1.
NP_001180464.1. NM_001193535.1. [Q9UKA1-2]
NP_036293.1. NM_012161.3. [Q9UKA1-1]
UniGeneiHs.643433.
Hs.714386.

Genome annotation databases

EnsembliENST00000341285; ENSP00000344866; ENSG00000118564. [Q9UKA1-1]
ENST00000412094; ENSP00000408679; ENSG00000118564. [Q9UKA1-2]
GeneIDi26234.
KEGGihsa:26234.
UCSCiuc003goc.3. human. [Q9UKA1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF176700 mRNA. Translation: AAF03700.1.
AF199420 mRNA. Translation: AAF09249.1.
AF142481 mRNA. Translation: AAF66616.1. Different initiation.
AK000153 mRNA. Translation: BAA90978.1.
AK295510 mRNA. Translation: BAG58427.1.
BX537957 mRNA. Translation: CAD97924.1.
AC114744 Genomic DNA. Translation: AAY40929.1.
AC116651 Genomic DNA. No translation available.
CH471069 Genomic DNA. Translation: EAW92737.1. Sequence problems.
CH471069 Genomic DNA. Translation: EAW92739.1.
BC030656 mRNA. Translation: AAH30656.1. Different initiation.
AF157323 mRNA. Translation: AAF67489.1. Different initiation.
AF174591 mRNA. Translation: AAF04512.1.
CCDSiCCDS3415.1. [Q9UKA1-1]
CCDS54745.1. [Q9UKA1-2]
RefSeqiNP_001180463.1. NM_001193534.1.
NP_001180464.1. NM_001193535.1. [Q9UKA1-2]
NP_036293.1. NM_012161.3. [Q9UKA1-1]
UniGeneiHs.643433.
Hs.714386.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U9JX-ray1.60A/B1-160[»]
3U9MX-ray1.95A/C/E/G1-160[»]
3V5XX-ray1.85A/B1-161[»]
3V5YX-ray2.10A/B/C/D1-161[»]
3V5ZX-ray2.18A/B1-161[»]
ProteinModelPortaliQ9UKA1.
SMRiQ9UKA1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117625. 38 interactors.
IntActiQ9UKA1. 7 interactors.
MINTiMINT-8247431.
STRINGi9606.ENSP00000344866.

PTM databases

iPTMnetiQ9UKA1.
PhosphoSitePlusiQ9UKA1.

Polymorphism and mutation databases

BioMutaiFBXL5.
DMDMi37537864.

Proteomic databases

PaxDbiQ9UKA1.
PRIDEiQ9UKA1.

Protocols and materials databases

DNASUi26234.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341285; ENSP00000344866; ENSG00000118564. [Q9UKA1-1]
ENST00000412094; ENSP00000408679; ENSG00000118564. [Q9UKA1-2]
GeneIDi26234.
KEGGihsa:26234.
UCSCiuc003goc.3. human. [Q9UKA1-1]

Organism-specific databases

CTDi26234.
DisGeNETi26234.
GeneCardsiFBXL5.
H-InvDBHIX0004110.
HGNCiHGNC:13602. FBXL5.
HPAiCAB022085.
CAB025148.
MIMi605655. gene.
neXtProtiNX_Q9UKA1.
OpenTargetsiENSG00000118564.
PharmGKBiPA28025.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHDI. Eukaryota.
ENOG410ZKEM. LUCA.
GeneTreeiENSGT00390000006172.
HOVERGENiHBG051589.
InParanoidiQ9UKA1.
KOiK10271.
OMAiTKQYACL.
OrthoDBiEOG091G02J5.
PhylomeDBiQ9UKA1.
TreeFamiTF331105.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-390471. Association of TriC/CCT with target proteins during biosynthesis.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiFBXL5. human.
GeneWikiiFBXL5.
GenomeRNAii26234.
PROiQ9UKA1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118564.
CleanExiHS_FBXL5.
ExpressionAtlasiQ9UKA1. baseline and differential.
GenevisibleiQ9UKA1. HS.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR001810. F-box_dom.
IPR012312. Haemerythrin-like.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamiPF12937. F-box-like. 1 hit.
PF01814. Hemerythrin. 1 hit.
PF13516. LRR_6. 2 hits.
[Graphical view]
SMARTiSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 4 hits.
[Graphical view]
SUPFAMiSSF81383. SSF81383. 1 hit.
PROSITEiPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFBXL5_HUMAN
AccessioniPrimary (citable) accession number: Q9UKA1
Secondary accession number(s): A8MSK4
, B4DIB5, Q4W5A8, Q8NHP3, Q9NXN2, Q9P0I0, Q9P0X5, Q9UJT7, Q9UKC8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 30, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.