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Protein

F-box/LRR-repeat protein 5

Gene

FBXL5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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: Reactome

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway
LigandIron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664 Neddylation
R-HSA-917937 Iron uptake and transport
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00143

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

EuPathDBiHostDB:ENSG00000118564.14
HGNCiHGNC:13602 FBXL5
MIMi605655 gene
neXtProtiNX_Q9UKA1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiQ9UKA1
PaxDbiQ9UKA1
PeptideAtlasiQ9UKA1
PRIDEiQ9UKA1
ProteomicsDBi84748
84749 [Q9UKA1-2]

PTM databases

iPTMnetiQ9UKA1
PhosphoSitePlusiQ9UKA1

Expressioni

Gene expression databases

BgeeiENSG00000118564 Expressed in 244 organ(s), highest expression level in blood
CleanExiHS_FBXL5
ExpressionAtlasiQ9UKA1 baseline and differential
GenevisibleiQ9UKA1 HS

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
SKP1P6320810EBI-2692340,EBI-307486

Protein-protein interaction databases

BioGridi117625, 45 interactors
IntActiQ9UKA1, 7 interactors
MINTiQ9UKA1
STRINGi9606.ENSP00000344866

Structurei

Secondary structure

1691
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiENOG410IHDI Eukaryota
ENOG410ZKEM LUCA
GeneTreeiENSGT00390000006172
HOVERGENiHBG051589
InParanoidiQ9UKA1
KOiK10271
OMAiLNDEHFY
OrthoDBiEOG091G02J5
PhylomeDBiQ9UKA1
TreeFamiTF331105

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR012312 Haemerythrin-like
IPR001611 Leu-rich_rpt
IPR006553 Leu-rich_rpt_Cys-con_subtyp
IPR032675 LRR_dom_sf
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF01814 Hemerythrin, 1 hit
PF13516 LRR_6, 2 hits
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00367 LRR_CC, 4 hits
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YAG2H0YAG2_HUMAN
F-box/LRR-repeat protein 5
FBXL5
183Annotation score:
D6RCR7D6RCR7_HUMAN
F-box/LRR-repeat protein 5
FBXL5
129Annotation score:
D6RBW7D6RBW7_HUMAN
F-box/LRR-repeat protein 5
FBXL5
78Annotation score:
D6RHC3D6RHC3_HUMAN
F-box/LRR-repeat protein 5
FBXL5
125Annotation score:
H0Y9Y0H0Y9Y0_HUMAN
F-box/LRR-repeat protein 5
FBXL5
612Annotation score:
D6RED6D6RED6_HUMAN
F-box/LRR-repeat protein 5
FBXL5
110Annotation score:
D6R9Y4D6R9Y4_HUMAN
F-box/LRR-repeat protein 5
FBXL5
95Annotation score:
D6RB50D6RB50_HUMAN
F-box/LRR-repeat protein 5
FBXL5
56Annotation score:

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

Similar proteinsi

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, 45 interactors
IntActiQ9UKA1, 7 interactors
MINTiQ9UKA1
STRINGi9606.ENSP00000344866

PTM databases

iPTMnetiQ9UKA1
PhosphoSitePlusiQ9UKA1

Polymorphism and mutation databases

BioMutaiFBXL5
DMDMi37537864

Proteomic databases

EPDiQ9UKA1
PaxDbiQ9UKA1
PeptideAtlasiQ9UKA1
PRIDEiQ9UKA1
ProteomicsDBi84748
84749 [Q9UKA1-2]

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
EuPathDBiHostDB:ENSG00000118564.14
GeneCardsiFBXL5
H-InvDBiHIX0004110
HGNCiHGNC:13602 FBXL5
MIMi605655 gene
neXtProtiNX_Q9UKA1
OpenTargetsiENSG00000118564
PharmGKBiPA28025
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHDI Eukaryota
ENOG410ZKEM LUCA
GeneTreeiENSGT00390000006172
HOVERGENiHBG051589
InParanoidiQ9UKA1
KOiK10271
OMAiLNDEHFY
OrthoDBiEOG091G02J5
PhylomeDBiQ9UKA1
TreeFamiTF331105

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-8951664 Neddylation
R-HSA-917937 Iron uptake and transport
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiFBXL5 human
GeneWikiiFBXL5
GenomeRNAii26234
PROiPR:Q9UKA1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118564 Expressed in 244 organ(s), highest expression level in blood
CleanExiHS_FBXL5
ExpressionAtlasiQ9UKA1 baseline and differential
GenevisibleiQ9UKA1 HS

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR012312 Haemerythrin-like
IPR001611 Leu-rich_rpt
IPR006553 Leu-rich_rpt_Cys-con_subtyp
IPR032675 LRR_dom_sf
PfamiView protein in Pfam
PF12937 F-box-like, 1 hit
PF01814 Hemerythrin, 1 hit
PF13516 LRR_6, 2 hits
SMARTiView protein in SMART
SM00256 FBOX, 1 hit
SM00367 LRR_CC, 4 hits
SUPFAMiSSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: November 7, 2018
This is version 163 of the entry and version 2 of the sequence. See 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
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