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Q9UKC9 (FBXL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. 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 2
Alternative name(s):
F-box and leucine-rich repeat protein 2
F-box protein FBL2/FBL3
Gene names
Name:FBXL2
Synonyms:FBL2, FBL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-activated substrate recognition component of a SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 doesn't seem to target phosphodegron within its substrates but rather calmodulin-binding motifs. Targets PCYT1A for its monoubiquitination and degradation, this is antagonized by calmodulin By similarity. Targets the cyclins CCND2 and CCND3 for polyubiquitination and degradation, leading to cell-cycle arrest in G0, also antagonized by calmodulin. Binds to hepatitis C virus non-structural protein 5A (NS5A) in a reaction crucial for hepatitis C virus RNA replication. Ref.9 Ref.10 Ref.11

Subunit structure

Interacts with SKP1. Interacts with PCYT1A. Part of a SCF (SKP1-cullin-F-box) protein ligase complex By similarity. Interacts (via CAAX motif) with hepatitis C virus non-structural protein 5A (NS5A). May also interact, but less efficiently, with hepatitis C virus non-structural protein 5B (NS5B). Interacts with CCND2 and CCND3. Ref.2 Ref.9 Ref.10 Ref.11

Subcellular location

Membrane; Lipid-anchor Ref.9.

Tissue specificity

Expressed in brain, heart, kidney, liver, lung, pancreas and placenta. Ref.2

Miscellaneous

Deletion of the F-box domain creates a dominant-negative protein that inhibits replication of hepatitis C virus RNA when overexpressed in a hepatoma cell line; this inhibition could be overcome by NS5A coexpression.

Sequence similarities

Contains 1 F-box domain.

Contains 13 LRR (leucine-rich) repeats.

Sequence caution

The sequence AAF03128.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UKC9-1)

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: Q9UKC9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-199: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 423423F-box/LRR-repeat protein 2
PRO_0000119840

Regions

Domain9 – 5547F-box
Repeat61 – 8727LRR 1
Repeat88 – 11326LRR 2
Repeat114 – 13926LRR 3
Repeat140 – 16526LRR 4
Repeat166 – 19126LRR 5
Repeat192 – 21726LRR 6
Repeat218 – 24326LRR 7
Repeat244 – 26926LRR 8
Repeat270 – 29526LRR 9
Repeat296 – 32126LRR 10
Repeat322 – 35029LRR 11
Repeat351 – 37525LRR 12
Repeat376 – 40126LRR 13
Region80 – 9011Interaction with Calmodulin By similarity
Motif420 – 4234CAAX motif

Amino acid modifications

Lipidation4201S-geranylgeranyl cysteine Probable

Natural variations

Alternative sequence132 – 19968Missing in isoform 2.
VSP_044600
Natural variant2261V → M in a colorectal cancer sample; somatic mutation. Ref.12
VAR_036071

Experimental info

Mutagenesis4201C → S: Loss of geranylgeranylation and association to membranes. Ref.9
Sequence conflict621T → I in AAF04510. Ref.1
Sequence conflict621T → I in AAF03128. Ref.2
Sequence conflict621T → I in CAG33402. Ref.5
Sequence conflict771G → V in AAF04510. Ref.1
Sequence conflict811R → K in BAA91691. Ref.4
Sequence conflict1081H → Q in BAG61062. Ref.4
Sequence conflict1741I → W in CAB43222. Ref.8
Sequence conflict3201S → P in CAB43222. Ref.8
Sequence conflict3421R → G in CAG33402. Ref.5

Sequences

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

Last modified April 17, 2007. Version 3.
Checksum: 61938E434618BA3D

FASTA42347,062
        10         20         30         40         50         60 
MVFSNNDEGL INKKLPKELL LRIFSFLDIV TLCRCAQISK AWNILALDGS NWQRIDLFNF 

        70         80         90        100        110        120 
QTDVEGRVVE NISKRCGGFL RKLSLRGCIG VGDSSLKTFA QNCRNIEHLN LNGCTKITDS 

       130        140        150        160        170        180 
TCYSLSRFCS KLKHLDLTSC VSITNSSLKG ISEGCRNLEY LNLSWCDQIT KDGIEALVRG 

       190        200        210        220        230        240 
CRGLKALLLR GCTQLEDEAL KHIQNYCHEL VSLNLQSCSR ITDEGVVQIC RGCHRLQALC 

       250        260        270        280        290        300 
LSGCSNLTDA SLTALGLNCP RLQILEAARC SHLTDAGFTL LARNCHELEK MDLEECILIT 

       310        320        330        340        350        360 
DSTLIQLSIH CPKLQALSLS HCELITDDGI LHLSNSTCGH ERLRVLELDN CLLITDVALE 

       370        380        390        400        410        420 
HLENCRGLER LELYDCQQVT RAGIKRMRAQ LPHVKVHAYF APVTPPTAVA GSGQRLCRCC 


VIL 

« Hide

Isoform 2 [UniParc].

Checksum: F1C3CDED0C7F0131
Show »

FASTA35539,613

References

« Hide 'large scale' references
[1]"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] (ISOFORM 1).
[2]"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), INTERACTION WITH SKP1, TISSUE SPECIFICITY.
[3]"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).
[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] (ISOFORMS 1 AND 2).
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Brain.
[8]"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] OF 174-423 (ISOFORM 1).
Tissue: Brain.
[9]"Identification of FBL2 as a geranylgeranylated cellular protein required for hepatitis C virus RNA replication."
Wang C., Gale M. Jr., Keller B.C., Huang H., Brown M.S., Goldstein J.L., Ye J.
Mol. Cell 18:425-434(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HEPATITIS C VIRUS NS5A, ISOPRENYLATION AT CYS-420, MUTAGENESIS OF CYS-420, SUBCELLULAR LOCATION.
[10]"F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation."
Chen B.B., Glasser J.R., Coon T.A., Zou C., Miller H.L., Fenton M., McDyer J.F., Boyiadzis M., Mallampalli R.K.
Blood 119:3132-3141(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CCND2.
[11]"F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest."
Chen B.B., Glasser J.R., Coon T.A., Mallampalli R.K.
Oncogene 31:2566-2579(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CCND3.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-226.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF174589 mRNA. Translation: AAF04510.1.
AF176518 mRNA. Translation: AAF03128.1. Different initiation.
AF186273 mRNA. Translation: AAD56248.1.
AK001438 mRNA. Translation: BAA91691.1.
AK298967 mRNA. Translation: BAG61062.1.
CR457121 mRNA. Translation: CAG33402.1.
AC122176 Genomic DNA. No translation available.
AC123900 Genomic DNA. No translation available.
BC031556 mRNA. Translation: AAH31556.1.
AL049953 mRNA. Translation: CAB43222.1.
PIRT08680.
RefSeqNP_001165184.1. NM_001171713.1.
NP_036289.3. NM_012157.3.
UniGeneHs.475872.

3D structure databases

ProteinModelPortalQ9UKC9.
SMRQ9UKC9. Positions 15-394.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117355. 14 interactions.
IntActQ9UKC9. 6 interactions.
MINTMINT-1390736.
STRING9606.ENSP00000417601.

Polymorphism databases

DMDM145559475.

Proteomic databases

PaxDbQ9UKC9.
PRIDEQ9UKC9.

Protocols and materials databases

DNASU25827.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000484457; ENSP00000417601; ENSG00000153558. [Q9UKC9-1]
ENST00000507198; ENSP00000426163; ENSG00000153558. [Q9UKC9-2]
ENST00000538892; ENSP00000441228; ENSG00000153558. [Q9UKC9-2]
GeneID25827.
KEGGhsa:25827.
UCSCuc003cfp.3. human. [Q9UKC9-1]
uc021wuy.1. human.

Organism-specific databases

CTD25827.
GeneCardsGC03P033293.
HGNCHGNC:13598. FBXL2.
HPAHPA003240.
MIM605652. gene.
neXtProtNX_Q9UKC9.
PharmGKBPA28021.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300245.
HOGENOMHOG000230659.
HOVERGENHBG051586.
InParanoidQ9UKC9.
KOK10268.
OMAHSCETIS.
OrthoDBEOG7CVPXM.
PhylomeDBQ9UKC9.
TreeFamTF313434.

Gene expression databases

ArrayExpressQ9UKC9.
BgeeQ9UKC9.
CleanExHS_FBXL2.
GenevestigatorQ9UKC9.

Family and domain databases

InterProIPR001810. F-box_dom.
IPR006553. Leu-rich_rpt_Cys-con_subtyp.
[Graphical view]
PfamPF00646. F-box. 1 hit.
[Graphical view]
SMARTSM00256. FBOX. 1 hit.
SM00367. LRR_CC. 2 hits.
[Graphical view]
PROSITEPS50181. FBOX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFBXL2. human.
GeneWikiFBXL2.
GenomeRNAi25827.
NextBio47109.
PROQ9UKC9.
SOURCESearch...

Entry information

Entry nameFBXL2_HUMAN
AccessionPrimary (citable) accession number: Q9UKC9
Secondary accession number(s): B4DQV0 expand/collapse secondary AC list , E9PD06, Q6IAN3, Q9NVQ8, Q9UK27, Q9UKA5, Q9Y3Y9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 21, 2003
Last sequence update: April 17, 2007
Last modified: April 16, 2014
This is version 114 of the entry and version 3 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM