Q9NRD1 (FBX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box only protein 6

Alternative name(s):
F-box protein that recognizes sugar chains 2
F-box/G-domain protein 2

Gene names

Name:	FBXO6
Synonyms:	FBG2, FBS2, FBX6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	293 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranlocated into the cytosol and promoting their ubiquitination and subsequent degradation. Able to recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. Also recognizes sulfated glycans. Also involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. Ubiquitination of CHEK1 is required to insure that activated CHEK1 does not accumulate as cells progress through S phase, or when replication forks encounter transient impediments during normal DNA replication. Ref.7 Ref.8
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with VCP By similarity. Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CHEK1 and CUL1. Ref.7 Ref.8
Subcellular location	Cytoplasm Ref.8.
Sequence similarities	Contains 1 F-box domain. Contains 1 FBA (F-box associated) domain.
Sequence caution	The sequence AAF04470.1 differs from that shown. Reason: Erroneous initiation. The sequence CAI20215.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway Unfolded protein response
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA damage checkpoint Traceable author statement Ref.8. Source: UniProtKB DNA repair Traceable author statement Ref.8. Source: UniProtKB ER-associated protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay Ref.8. Source: UniProtKB response to unfolded protein Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	SCF ubiquitin ligase complex Inferred from direct assay Ref.8. Source: UniProtKB cytoplasm Inferred from direct assay Ref.8. Source: UniProtKB
Molecular function	glycoprotein binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 293	293	F-box only protein 6		PRO_0000119882
Regions
	Domain	10 – 57	48	F-box
	Domain	78 – 259	182	FBA
Natural variations
	Natural variant	60	1	R → Q. Corresponds to variant rs3125818 [ dbSNP | Ensembl ].		VAR_049039
	Natural variant	201	1	P → T. Corresponds to variant rs2294639 [ dbSNP | Ensembl ].		VAR_022158
Experimental info
	Mutagenesis	241 – 242	2	YW → AA: Abolishes interaction with glycosylated concanavalin-A in vitro. Ref.7
	Sequence conflict	18	1	E → D in AAF04470. Ref.1
	Sequence conflict	51	1	M → L in AAF04470. Ref.1
	Sequence conflict	61	1	E → K in AAF04470. Ref.1
	Sequence conflict	96	1	E → N in AAF04470. Ref.1
	Sequence conflict	114	1	E → D in AAF04470. Ref.1
	Sequence conflict	123	1	D → E in AAF04470. Ref.1
	Sequence conflict	132	1	Y → S in AAF04470. Ref.1
	Sequence conflict	139	1	M → L in AAF04470. Ref.1
	Sequence conflict	143 – 144	2	SQ → WE in AAF04470. Ref.1
	Sequence conflict	149 – 152	4	VAEG → LADR in AAF04470. Ref.1
	Sequence conflict	287	1	R → G in AAF04470. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9NRD1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: EA4235CD9CCD80FF	FASTA	293	33,933
	10 20 30 40 50 60 MDAPHSKAAL DSINELPENI LLELFTHVPA RQLLLNCRLV CSLWRDLIDL MTLWKRKCLR 70 80 90 100 110 120 EGFITKDWDQ PVADWKIFYF LRSLHRNLLR NPCAEEDMFA WQIDFNGGDR WKVESLPGAH 130 140 150 160 170 180 GTDFPDPKVK KYFVTSYEMC LKSQLVDLVA EGYWEELLDT FRPDIVVKDW FAARADCGCT 190 200 210 220 230 240 YQLKVQLASA DYFVLASFEP PPVTIQQWNN ATWTEVSYTF SDYPRGVRYI LFQHGGRDTQ 250 260 270 280 290 YWAGWYGPRV TNSSIVVSPK MTRNQASSEA QPGQKHGQEE AAQSPYRAVV QIF

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: 10531035] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 10945468] [Abstract] 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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. , 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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[7]	"Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases." Glenn K.A., Nelson R.F., Wen H.M., Mallinger A.J., Paulson H.L. J. Biol. Chem. 283:12717-12729(2008) [PubMed: 18203720] [Abstract] Cited for: FUNCTION, SUGAR-BINDING, INTERACTION WITH CUL1, MUTAGENESIS OF 241-TYR-TRP-242.
[8]	"The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress." Zhang Y.-W., Brognard J., Coughlin C., You Z., Dolled-Filhart M., Aslanian A., Manning G., Abraham R.T., Hunter T. Mol. Cell 35:442-453(2009) [PubMed: 19716789] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, INTERACTION WITH CHEK1.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - Glycan Binding

hFBG2

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF129536 mRNA. Translation: AAF04470.1. Different initiation. AF233223 mRNA. Translation: AAF67153.1. AK314989 mRNA. Translation: BAG37485.1. AL031731 Genomic DNA. Translation: CAI20214.1. AL031731 Genomic DNA. Translation: CAI20215.1. Sequence problems. CH471130 Genomic DNA. Translation: EAW71696.1. BC020880 mRNA. Translation: AAH20880.1.
IPI	IPI00171291.
RefSeq	NP_060908.1. NM_018438.5.
UniGene	Hs.464419.
3D structure databases
ProteinModelPortal	Q9NRD1.
SMR	Q9NRD1. Positions 9-259.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NRD1. 1 interaction.
STRING	Q9NRD1.
PTM databases
PhosphoSite	Q9NRD1.
Polymorphism databases
DMDM	24636846.
Proteomic databases
PRIDE	Q9NRD1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000376749; ENSP00000365940; ENSG00000116663. ENST00000376753; ENSP00000365944; ENSG00000116663. ENST00000449067; ENSP00000388781; ENSG00000116663.
GeneID	26270.
KEGG	hsa:26270.
UCSC	uc001aso.1. human.
Organism-specific databases
CTD	26270.
GeneCards	GC01P011724.
H-InvDB	HIX0023158.
HGNC	HGNC:13585. FBXO6.
MIM	605647. gene.
neXtProt	NX_Q9NRD1.
PharmGKB	PA28046.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10376.
GeneTree	ENSGT00390000003865.
HOGENOM	HBG716440.
HOVERGEN	HBG003593.
InParanoid	Q9NRD1.
OMA	KYFVTSF.
OrthoDB	EOG4VX267.
PhylomeDB	Q9NRD1.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9NRD1.
Bgee	Q9NRD1.
CleanEx	HS_FBXO6.
Genevestigator	Q9NRD1.
GermOnline	ENSG00000116663. Homo sapiens.
Family and domain databases
InterPro	IPR007397. F-box-assoc_dom. IPR001810. F-box_dom_cyclin-like. IPR022364. F-box_dom_Skp2-like. IPR008979. Galactose-bd-like. [Graphical view]
KO	K10100.
Pfam	PF04300. FBA. 1 hit. [Graphical view]
SMART	SM00256. FBOX. 1 hit. [Graphical view]
SUPFAM	SSF81383. F-box_dom_Skp2-like. 1 hit. SSF49785. Gal_bind_like. 1 hit.
PROSITE	PS51114. FBA. 1 hit. PS50181. FBOX. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	48557.
SOURCE	Search...

Entry information

Entry name

FBX6_HUMAN

Accession

Primary (citable) accession number: Q9NRD1
Secondary accession number(s): B1AK42, B2RC88, Q9UKT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 2002
Last sequence update:	October 1, 2000
Last modified:	January 25, 2012
This is version 94 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.