Q8N3Y1 (FBXW8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box/WD repeat-containing protein 8

Alternative name(s):
F-box and WD-40 domain-containing protein 8
F-box only protein 29

Gene names

Name:	FBXW8
Synonyms:	FBW6, FBW8, FBX29, FBXO29, FBXW6

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	598 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Substrate-recognition component of a SCF-like E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. In complex with CUL7, mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Ref.7
Subunit structure	Part of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN isoform 1. Interacts with CUL7. Interacts with OBSL1, CUL1, CUL2, SKP1, CCT6B, PFDN5, CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1. Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Cytoplasm › perinuclear region. Golgi apparatus. Note: Co-localizes with CUL7 at the Golgi apparatus in neurons By similarity. Ref.7
Sequence similarities	Contains 1 F-box domain. Contains 5 WD repeats.
Sequence caution	The sequence AAF03129.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAF03129.1 differs from that shown. Reason: Frameshift at positions 282 and 295.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara spongiotrophoblast layer development Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell SCF ubiquitin ligase complex Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MYC	P01106	3	EBI-914770,EBI-447544

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8N3Y1-1)

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: Q8N3Y1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     41-106: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 598	598	F-box/WD repeat-containing protein 8		PRO_0000050997
Regions
	Domain	113 – 159	47	F-box
	Repeat	197 – 245	49	WD 1
	Repeat	254 – 294	41	WD 2
	Repeat	297 – 336	40	WD 3
	Repeat	430 – 470	41	WD 4
	Repeat	473 – 510	38	WD 5
Amino acid modifications
	Modified residue	85	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	41 – 106	66	Missing in isoform 2.		VSP_008501
	Natural variant	192	1	R → Q. Ref.1 Ref.3 Corresponds to variant rs4076700 [ dbSNP | Ensembl ].		VAR_060326
	Natural variant	211	1	T → A. Corresponds to variant rs36021180 [ dbSNP | Ensembl ].		VAR_057597
	Natural variant	536	1	T → M. Corresponds to variant rs3741466 [ dbSNP | Ensembl ].		VAR_057598
	Natural variant	563	1	V → M. Corresponds to variant rs56350562 [ dbSNP | Ensembl ].		VAR_062096
Experimental info
	Sequence conflict	46	1	G → S in AAH37296. Ref.3
	Sequence conflict	58	1	R → G in AAH37296. Ref.3
	Sequence conflict	380	1	L → I in AAH37296. Ref.3
	Sequence conflict	510	1	E → K in AAF03129. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 03B3C283BA46DB6B	FASTA	598	67,394
	10 20 30 40 50 60 MDDYSLDEFR RRWQEELAQA QAPKKRRRPE AAERRARRPE VGSGRGEQAS GDPALAQRLL 70 80 90 100 110 120 EGAGRPPAAR ATRAEGQDVA SRSRSPLARE GAGGGEQLVD QLIRDLNEMN DVPFFDIQLP 130 140 150 160 170 180 YELAINIFQY LDRKELGRCA QVSKTWKVIA EDEVLWYRLC QQEGHLPDSS ISDYSCWKLI 190 200 210 220 230 240 FQECRAKEHM LRTNWKNRKG AVSELEHVPD TVLCDVHSHD GVVIAGYTSG DVRVWDTRTW 250 260 270 280 290 300 DYVAPFLESE DEEDEPGMQP NVSFVRINSS LAVAAYEDGF LNIWDLRTGK YPVHRFEHDA 310 320 330 340 350 360 RIQALALSQD DATVATASAF DVVMLSPNEE GYWQIAAEFE VPKLVQYLEI VPETRRYPVA 370 380 390 400 410 420 VAAAGDLMYL LKAEDSARTL LYAHGPPVTC LDVSANQVAF GVQGLGWVYE GSKILVYSLE 430 440 450 460 470 480 AGRRLLKLGN VLRDFTCVNL SDSPPNLMVS GNMDGRVRIH DLRSGNIALS LSAHQLRVSA 490 500 510 520 530 540 VQMDDWKIVS GGEEGLVSVW DYRMNQKLWE VYSGHPVQHI SFSSHSLITA NVPYQTVMRN 550 560 570 580 590 ADLDSFTTHR RHRGLIRAYE FAVDQLAFQS PLPVCRSSCD AMATHYYDLA LAFPYNHV
	Isoform 2 [UniParc]. Checksum: 921550273E26D2F2	FASTA	532	60,705
	10 20 30 40 50 60 MDDYSLDEFR RRWQEELAQA QAPKKRRRPE AAERRARRPE NEMNDVPFFD IQLPYELAIN 70 80 90 100 110 120 IFQYLDRKEL GRCAQVSKTW KVIAEDEVLW YRLCQQEGHL PDSSISDYSC WKLIFQECRA 130 140 150 160 170 180 KEHMLRTNWK NRKGAVSELE HVPDTVLCDV HSHDGVVIAG YTSGDVRVWD TRTWDYVAPF 190 200 210 220 230 240 LESEDEEDEP GMQPNVSFVR INSSLAVAAY EDGFLNIWDL RTGKYPVHRF EHDARIQALA 250 260 270 280 290 300 LSQDDATVAT ASAFDVVMLS PNEEGYWQIA AEFEVPKLVQ YLEIVPETRR YPVAVAAAGD 310 320 330 340 350 360 LMYLLKAEDS ARTLLYAHGP PVTCLDVSAN QVAFGVQGLG WVYEGSKILV YSLEAGRRLL 370 380 390 400 410 420 KLGNVLRDFT CVNLSDSPPN LMVSGNMDGR VRIHDLRSGN IALSLSAHQL RVSAVQMDDW 430 440 450 460 470 480 KIVSGGEEGL VSVWDYRMNQ KLWEVYSGHP VQHISFSSHS LITANVPYQT VMRNADLDSF 490 500 510 520 530 TTHRRHRGLI RAYEFAVDQL AFQSPLPVCR SSCDAMATHY YDLALAFPYN HV

References

	« Hide 'large scale' referencesShow '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 2), VARIANT GLN-192.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., 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., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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), VARIANT GLN-192. Tissue: Brain.
[4]	"CUL7: a DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex." Dias D.C., Dolios G., Wang R., Pan Z.Q. Proc. Natl. Acad. Sci. U.S.A. 99:16601-16606(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN SCF-LIKE COMPLEX.
[5]	"Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis." Arai T., Kasper J.S., Skaar J.R., Ali S.H., Takahashi C., DeCaprio J.A. Proc. Natl. Acad. Sci. U.S.A. 100:9855-9860(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CUL7; SKP1; RBX1 AND GLMN.
[6]	"PARC and CUL7 form atypical cullin RING ligase complexes." Skaar J.R., Florens L., Tsutsumi T., Arai T., Tron A., Swanson S.K., Washburn M.P., DeCaprio J.A. Cancer Res. 67:2006-2014(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL7.
[7]	"An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning." Litterman N., Ikeuchi Y., Gallardo G., O'Connell B.C., Sowa M.E., Gygi S.P., Harper J.W., Bonni A. PLoS Biol. 9:E1001060-E1001060(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH OBSL1; CUL1; CUL2; CUL7; SKP1; CCT6B; PFDN5; CCT2; CCT3; CCT6A; CCT7; VBP1; CCDC8; ARF1; TRIP13; PDCD5 AND GORASP1, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF176707 mRNA. Translation: AAF03129.1. Sequence problems. AC026368 Genomic DNA. No translation available. AC083806 Genomic DNA. No translation available. AC127164 Genomic DNA. No translation available. BC037296 mRNA. Translation: AAH37296.1.
IPI	IPI00166657. IPI00384859.
RefSeq	NP_036306.1. NM_012174.1. NP_699179.2. NM_153348.2.
UniGene	Hs.624537. Hs.696428.
3D structure databases
ProteinModelPortal	Q8N3Y1.
SMR	Q8N3Y1. Positions 119-558.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8N3Y1. 2 interactions.
MINT	MINT-8415331.
STRING	9606.ENSP00000310686.
PTM databases
PhosphoSite	Q8N3Y1.
Polymorphism databases
DMDM	296434513.
Proteomic databases
PaxDb	Q8N3Y1.
PRIDE	Q8N3Y1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309909; ENSP00000310686; ENSG00000174989. ENST00000455858; ENSP00000389144; ENSG00000174989. ENST00000505227; ENSP00000442489; ENSG00000174989.
GeneID	26259.
KEGG	hsa:26259.
UCSC	uc001twf.1. human. uc001twg.1. human.
Organism-specific databases
CTD	26259.
GeneCards	GC12P117348.
H-InvDB	HIX0026457. HIX0037115.
HGNC	HGNC:13597. FBXW8.
HPA	HPA038851.
MIM	609073. gene.
neXtProt	NX_Q8N3Y1.
PharmGKB	PA28039.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG115403.
HOGENOM	HOG000112555.
HOVERGEN	HBG051597.
InParanoid	Q8N3Y1.
KO	K10264.
OMA	NIFQYLD.
OrthoDB	EOG4894M6.
PhylomeDB	Q8N3Y1.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
SignaLink	Q8N3Y1.
Gene expression databases
Bgee	Q8N3Y1.
CleanEx	HS_FBXW8.
Genevestigator	Q8N3Y1.
GermOnline	ENSG00000174989. Homo sapiens.
Family and domain databases
Gene3D	2.130.10.10. 2 hits.
InterPro	IPR001810. F-box_dom_cyclin-like. IPR011047. Quinonprotein_ADH-like_supfam. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Pfam	PF00646. F-box. 1 hit. PF00400. WD40. 1 hit. [Graphical view]
SMART	SM00256. FBOX. 1 hit. SM00320. WD40. 5 hits. [Graphical view]
SUPFAM	SSF81383. F-box_dom_Skp2-like. 1 hit. SSF50998. Quin_alc_DH_like. 1 hit.
PROSITE	PS50181. FBOX. 1 hit. PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. 1 hit. PS50294. WD_REPEATS_REGION. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FBXW8. human.
GenomeRNAi	26259.
NextBio	48503.
SOURCE	Search...

Entry information

Entry name

FBXW8_HUMAN

Accession

Primary (citable) accession number: Q8N3Y1
Secondary accession number(s): Q9UK95

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2003
Last sequence update:	May 18, 2010
Last modified:	May 29, 2013
This is version 109 of the entry and version 2 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.