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Q9UKA1 (FBXL5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:FBXL5
Synonyms:FBL4, FBL5, FLR1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length691 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.12 Ref.13

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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. Ref.11 Ref.12 Ref.13

Subcellular location

Cytoplasmperinuclear region Ref.11.

Domain

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. Ref.12 Ref.13

Post-translational modification

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.

Sequence similarities

Contains 1 F-box domain.

Contains 7 LRR (leucine-rich) repeats.

Sequence caution

The sequence AAF66616.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAF67489.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH30656.1 differs from that shown. Reason: Erroneous initiation.

The sequence EAW92737.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKA1-1)

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.
Isoform 2 (identifier: Q9UKA1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     29-45: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 691691F-box/LRR-repeat protein 5
PRO_0000119845

Regions

Domain202 – 24847F-box
Repeat340 – 36425LRR 1
Repeat365 – 39228LRR 2
Repeat393 – 41826LRR 3
Repeat479 – 50830LRR 4
Repeat576 – 60732LRR 5
Repeat608 – 63528LRR 6
Repeat636 – 66126LRR 7
Region1 – 159159Hemerythrin-like

Sites

Metal binding151Iron 1
Metal binding571Iron 1
Metal binding581Iron 1
Metal binding611Iron 1
Metal binding611Iron 2
Metal binding801Iron 2
Metal binding1261Iron 2
Metal binding1301Iron 1
Metal binding1301Iron 2

Natural variations

Alternative sequence29 – 4517Missing in isoform 2.
VSP_008417

Experimental info

Mutagenesis151H → A: Abolishes iron-binding and promotes its degradation. Ref.12
Mutagenesis571H → A: Abolishes iron-binding and promotes its degradation. Ref.12 Ref.13
Mutagenesis611E → A: Abolishes iron-binding and promotes its degradation. Ref.13
Sequence conflict521K → T in AAH30656. Ref.8
Sequence conflict1951Missing in AAF09249. Ref.2
Sequence conflict2421G → R in AAH30656. Ref.8
Sequence conflict5321V → I in BAA90978. Ref.4

Secondary structure

................. 691
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 3, 2003. Version 2.
Checksum: 923A1B31590E5145

FASTA69178,555
        10         20         30         40         50         60 
MAPFPEEVDV FTAPHWRMKQ LVGLYCDKLS KTNFSNNNDF RALLQSLYAT FKEFKMHEQI 

        70         80         90        100        110        120 
ENEYIIGLLQ QRSQTIYNVH SDNKLSEMLS LFEKGLKNVK NEYEQLNYAK QLKERLEAFT 

       130        140        150        160        170        180 
RDFLPHMKEE EEVFQPMLME YFTYEELKDI KKKVIAQHCS QKDTAELLRG LSLWNHAEER 

       190        200        210        220        230        240 
QKFFKYSVDE KSDKEAEVSE HSTGITHLPP EVMLSIFSYL NPQELCRCSQ VSMKWSQLTK 

       250        260        270        280        290        300 
TGSLWKHLYP VHWARGDWYS GPATELDTEP DDEWVKNRKD ESRAFHEWDE DADIDESEES 

       310        320        330        340        350        360 
AEESIAISIA QMEKRLLHGL IHNVLPYVGT SVKTLVLAYS SAVSSKMVRQ ILELCPNLEH 

       370        380        390        400        410        420 
LDLTQTDISD SAFDSWSWLG CCQSLRHLDL SGCEKITDVA LEKISRALGI LTSHQSGFLK 

       430        440        450        460        470        480 
TSTSKITSTA WKNKDITMQS TKQYACLHDL TNKGIGEEID NEHPWTKPVS SENFTSPYVW 

       490        500        510        520        530        540 
MLDAEDLADI EDTVEWRHRN VESLCVMETA SNFSCSTSGC FSKDIVGLRT SVCWQQHCAS 

       550        560        570        580        590        600 
PAFAYCGHSF CCTGTALRTM SSLPESSAMC RKAARTRLPR GKDLIYFGSE KSDQETGRVL 

       610        620        630        640        650        660 
LFLSLSGCYQ ITDHGLRVLT LGGGLPYLEH LNLSGCLTIT GAGLQDLVSA CPSLNDEYFY 

       670        680        690 
YCDNINGPHA DTASGCQNLQ CGFRACCRSG E 

« Hide

Isoform 2 [UniParc].

Checksum: B114C4C0F0A37AE9
Show »

FASTA67476,590

References

« Hide 'large scale' references
[1]"A family of mammalian F-box proteins."
Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.
Curr. Biol. 9:1180-1182(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"cDNA cloning and expression analysis of new members of the mammalian F-box protein family."
Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.
Genomics 67:40-47(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"cDNA cloning of a new human protein, FLR1, containing both motifs of F-box and leucine-rich repeat."
Shimbara N.
Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 56-691 (ISOFORMS 1/2).
Tissue: Colon and Hippocampus.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Cervix.
[6]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[9]"A novel gene expressed in the human adrenal gland."
Huang C., Zhang C., Wu T., Peng Y., Gu Y., Jin Y., Jiang C., Li Y., Han Z., Wang Y., Chen Z., Fu G.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-691 (ISOFORM 1).
Tissue: Adrenal gland.
[10]"Identification of a family of human F-box proteins."
Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., Pagano M.
Curr. Biol. 9:1177-1179(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 157-691 (ISOFORMS 1/2).
[11]"FBXL5 interacts with p150Glued and regulates its ubiquitination."
Zhang N., Liu J., Ding X., Aikhionbare F., Jin C., Yao X.
Biochem. Biophys. Res. Commun. 359:34-39(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DCTN1.
[12]"Control of iron homeostasis by an iron-regulated ubiquitin ligase."
Vashisht A.A., Zumbrennen K.B., Huang X., Powers D.N., Durazo A., Sun D., Bhaskaran N., Persson A., Uhlen M., Sangfelt O., Spruck C., Leibold E.A., Wohlschlegel J.A.
Science 326:718-721(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACO1 AND IREB2, IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, IRON-BINDING, DOMAIN HEMERYTHRIN-LIKE, UBIQUITINATION, MUTAGENESIS OF HIS-15 AND HIS-57.
[13]"An E3 ligase possessing an iron responsive hemerythrin domain is a regulator of iron homeostasis."
Salahudeen A.A., Thompson J.W., Ruiz J.C., Ma H.-W., Kinch L.N., Li Q., Grishin N.V., Bruick R.K.
Science 326:722-726(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACO1 AND IREB2, IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, IRON-BINDING, DOMAIN HEMERYTHRIN-LIKE, UBIQUITINATION, MUTAGENESIS OF HIS-57 AND GLU-61.
[14]"The structural basis of iron sensing by the human F-box protein FBXL5."
Shu C., Sung M.W., Stewart M.D., Igumenova T.I., Tan X., Li P.
ChemBioChem 13:788-791(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 1-160, IRON-BINDING SITES.
[15]"Structural and molecular characterization of iron-sensing hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5)."
Thompson J.W., Salahudeen A.A., Chollangi S., Ruiz J.C., Brautigam C.A., Makris T.M., Lipscomb J.D., Tomchick D.R., Bruick R.K.
J. Biol. Chem. 287:7357-7365(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1-161, IRON-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001180463.1. NM_001193534.1.
NP_001180464.1. NM_001193535.1.
NP_036293.1. NM_012161.3.
UniGeneHs.643433.
Hs.714386.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ9UKA1.
SMRQ9UKA1. Positions 4-160, 206-245, 329-415, 596-657.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117625. 19 interactions.
IntActQ9UKA1. 7 interactions.
MINTMINT-8247431.

PTM databases

PhosphoSiteQ9UKA1.

Polymorphism databases

DMDM37537864.

Proteomic databases

PaxDbQ9UKA1.
PRIDEQ9UKA1.

Protocols and materials databases

DNASU26234.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000341285; ENSP00000344866; ENSG00000118564. [Q9UKA1-1]
ENST00000412094; ENSP00000408679; ENSG00000118564. [Q9UKA1-2]
GeneID26234.
KEGGhsa:26234.
UCSCuc003gob.2. human. [Q9UKA1-1]
uc003god.2. human. [Q9UKA1-2]

Organism-specific databases

CTD26234.
GeneCardsGC04M015548.
H-InvDBHIX0004110.
HGNCHGNC:13602. FBXL5.
MIM605655. gene.
neXtProtNX_Q9UKA1.
PharmGKBPA28025.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG29620.
HOVERGENHBG051589.
InParanoidQ9UKA1.
KOK10271.
OMATKQYACL.
OrthoDBEOG76MK7S.
PhylomeDBQ9UKA1.
TreeFamTF331105.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9UKA1.
BgeeQ9UKA1.
CleanExHS_FBXL5.
GenevestigatorQ9UKA1.

Family and domain databases

InterProIPR001810. F-box_dom.
IPR012312. Haemerythrin/HHE_cat-bd_motif.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamPF01814. Hemerythrin. 1 hit.
[Graphical view]
SMARTSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 1 hit.
[Graphical view]
SUPFAMSSF81383. SSF81383. 1 hit.
PROSITEPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFBXL5.
GenomeRNAi26234.
NextBio48417.
PROQ9UKA1.
SOURCESearch...

Entry information

Entry nameFBXL5_HUMAN
AccessionPrimary (citable) accession number: Q9UKA1
Secondary accession number(s): A8MSK4 expand/collapse secondary AC list , B4DIB5, Q4W5A8, Q8NHP3, Q9NXN2, Q9P0I0, Q9P0X5, Q9UJT7, Q9UKC8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: October 3, 2003
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM