Q9UKT7 (FBXL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box/LRR-repeat protein 3

Alternative name(s):
F-box and leucine-rich repeat protein 3A
F-box/LRR-repeat protein 3A

Gene names

Name:	FBXL3
Synonyms:	FBL3A, FBXL3A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2. Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex. FBXL3 probably recognizes and binds phosphorylated CRY1 and CRY2. Ref.5 Ref.6
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL3) composed of CUL1, SKP1, RBX1 and FBXL3. Interacts with CRY1 and CRY2. Ref.5
Subcellular location	Nucleus. Cytoplasm. Note: Predominantly nuclear. Ref.1
Tissue specificity	Widely expressed. Ref.1
Sequence similarities	Contains 1 F-box domain. Contains 7 LRR (leucine-rich) repeats.

Ontologies

Keywords
Biological process	Biological rhythms Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Domain	Leucine-rich repeat Repeat
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.5. Source: UniProtKB entrainment of circadian clock by photoperiod Inferred from sequence or structural similarity. Source: UniProtKB rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	SCF ubiquitin ligase complex Inferred from direct assay Ref.5. Source: UniProtKB cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ubiquitin-protein ligase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 428	428	F-box/LRR-repeat protein 3		PRO_0000119842
Regions
	Domain	34 – 81	48	F-box
	Repeat	119 – 146	28	LRR 1
	Repeat	181 – 207	27	LRR 2
	Repeat	208 – 233	26	LRR 3
	Repeat	234 – 259	26	LRR 4
	Repeat	316 – 341	26	LRR 5
	Repeat	343 – 368	26	LRR 6
	Repeat	369 – 394	26	LRR 7
Experimental info
	Mutagenesis	358	1	C → A: Loss of binding with CRY1. Ref.5
	Mutagenesis	358	1	C → S: Decrease in binding efficiency with CRY2 and of CRY2 ubiquitination efficiency, loss of binding with CRY1. Ref.5
	Sequence conflict	10	1	R → H in AAF37383. Ref.2
	Sequence conflict	13	1	S → A in AAF37383. Ref.2
	Sequence conflict	353	1	R → A in AAF37383. Ref.2
	Sequence conflict	364	1	I → V in BAG37051. Ref.3
	Sequence conflict	412	1	V → A in BAG37051. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9UKT7 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: AAEAB31BAF0EA5A5	FASTA	428	48,707
	10 20 30 40 50 60 MKRGGRDSDR NSSEEGTAEK SKKLRTTNEH SQTCDWGNLL QDIILQVFKY LPLLDRAHAS 70 80 90 100 110 120 QVCRNWNQVF HMPDLWRCFE FELNQPATSY LKATHPELIK QIIKRHSNHL QYVSFKVDSS 130 140 150 160 170 180 KESAEAACDI LSQLVNCSLK TLGLISTARP SFMDLPKSHF ISALTVVFVN SKSLSSLKID 190 200 210 220 230 240 DTPVDDPSLK VLVANNSDTL KLLKMSSCPH VSPAGILCVA DQCHGLRELA LNYHLLSDEL 250 260 270 280 290 300 LLALSSEKHV RLEHLRIDVV SENPGQTHFH TIQKSSWDAF IRHSPKVNLV MYFFLYEEEF 310 320 330 340 350 360 DPFFRYEIPA THLYFGRSVS KDVLGRVGMT CPRLVELVVC ANGLRPLDEE LIRIAERCKN 370 380 390 400 410 420 LSAIGLGECE VSCSAFVEFV KMCGGRLSQL SIMEEVLIPD QKYSLEQIHW EVSKHLGRVW FPDMMPTW

References

	« Hide 'large scale' referencesShow '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], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]	"Transcript mapping on the CLN5 region on 13q22." Klockars T., Holmberg V., Savukoski M., Lander E.S., Peltonen L. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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. , 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]. Tissue: Placenta.
[4]	"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]. Tissue: Skin.
[5]	"SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins." Busino L., Bassermann F., Maiolica A., Lee C., Nolan P.M., Godinho S.I., Draetta G.F., Pagano M. Science 316:900-904(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CRY1 AND CRY2, MUTAGENESIS OF CYS-358.
[6]	"Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm." Yoo S.H., Mohawk J.A., Siepka S.M., Shan Y., Huh S.K., Hong H.K., Kornblum I., Kumar V., Koike N., Xu M., Nussbaum J., Liu X., Chen Z., Chen Z.J., Green C.B., Takahashi J.S. Cell 152:1091-1105(2013) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF129532 mRNA. Translation: AAF04466.1.
AF126028 mRNA. Translation: AAF37383.1.
AK314442 mRNA. Translation: BAG37051.1.
BC072448 mRNA. Translation: AAH72448.1.

IPI

IPI00164336.

RefSeq

NP_036290.1. NM_012158.2.

UniGene

Hs.508284.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4I6J	X-ray	2.70	B	1-428	[»]

ProteinModelPortal

Q9UKT7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UKT7. 3 interactions.

MINT

MINT-108681.

STRING

9606.ENSP00000347834.

PTM databases

PhosphoSite

Q9UKT7.

Polymorphism databases

DMDM

37537866.

Proteomic databases

PaxDb

Q9UKT7.

PRIDE

Q9UKT7.

Protocols and materials databases

DNASU

26224.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355619; ENSP00000347834; ENSG00000005812.

GeneID

26224.

KEGG

hsa:26224.

UCSC

uc001vkd.3. human.

Organism-specific databases

CTD

26224.

GeneCards

GC13M077566.

HGNC

HGNC:13599. FBXL3.

MIM

605653. gene.

neXtProt

NX_Q9UKT7.

PharmGKB

PA28022.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG71260.

HOGENOM

HOG000060185.

HOVERGEN

HBG051587.

InParanoid

Q9UKT7.

KO

K10269.

OMA

TTSEHSQ.

OrthoDB

EOG4Q84XH.

PhylomeDB

Q9UKT7.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.
REACT_24941. Circadian Clock.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q9UKT7.

Bgee

Q9UKT7.

CleanEx

HS_FBXL3.

Genevestigator

Q9UKT7.

GermOnline

ENSG00000005812. Homo sapiens.

Family and domain databases

InterPro

IPR001810. F-box_dom_cyclin-like.
[Graphical view]

SMART

SM00256. FBOX. 1 hit.
[Graphical view]

SUPFAM

SSF81383. F-box_dom_Skp2-like. 1 hit.

PROSITE

PS50181. FBOX. False negative.
PS51450. LRR. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

FBXL3. human.

GenomeRNAi

26224.

NextBio

48369.

SOURCE

Search...

Entry information

Entry name

FBXL3_HUMAN

Accession

Primary (citable) accession number: Q9UKT7
Secondary accession number(s): B2RB04, Q9P122

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.