ID FBXW2_HUMAN Reviewed; 454 AA. AC Q9UKT8; B3KRL8; Q4VXH2; Q7Z4V6; Q8WV51; Q9HA09; Q9UKA3; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2005, sequence version 2. DT 10-JUN-2026, entry version 219. DE RecName: Full=F-box/WD repeat-containing protein 2; DE AltName: Full=F-box and WD-40 domain-containing protein 2; DE AltName: Full=Protein MD6; GN Name=FBXW2; Synonyms=FBW2, FWD2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10531037; DOI=10.1016/s0960-9822(00)80021-4; RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.; RT "A family of mammalian F-box proteins."; RL Curr. Biol. 9:1180-1182(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Zhou Y., Yu L., Zhao S.Y.; RT "Cloning and characterization of human MD6 protein."; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, and Mammary gland; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-422 (ISOFORM 1), AND INTERACTION WITH SKP1 RP AND CUL1. RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2; RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., RA Pagano M.; RT "Identification of a family of human F-box proteins."; RL Curr. Biol. 9:1177-1179(1999). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-298, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). CC -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box CC protein)-type E3 ubiquitin ligase complex. CC -!- SUBUNIT: Directly interacts with SKP1 and CUL1. CC {ECO:0000269|PubMed:10531035}. CC -!- INTERACTION: CC Q9UKT8; Q16543: CDC37; NbExp=2; IntAct=EBI-914727, EBI-295634; CC Q9UKT8; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-914727, EBI-12357161; CC Q9UKT8; Q13616: CUL1; NbExp=5; IntAct=EBI-914727, EBI-359390; CC Q9UKT8; Q9NP62: GCM1; NbExp=4; IntAct=EBI-914727, EBI-21194843; CC Q9UKT8; P08238: HSP90AB1; NbExp=2; IntAct=EBI-914727, EBI-352572; CC Q9UKT8; Q9Y266: NUDC; NbExp=2; IntAct=EBI-914727, EBI-357298; CC Q9UKT8; P63244: RACK1; NbExp=11; IntAct=EBI-914727, EBI-296739; CC Q9UKT8; P63208: SKP1; NbExp=8; IntAct=EBI-914727, EBI-307486; CC Q9UKT8; Q9BYV2: TRIM54; NbExp=2; IntAct=EBI-914727, EBI-2130429; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UKT8-1; Sequence=Displayed; CC Name=2; Synonyms=MD6b; CC IsoId=Q9UKT8-2; Sequence=VSP_012983; CC -!- SEQUENCE CAUTION: CC Sequence=AAF04465.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAF13226.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAP97276.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAP97280.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF176698; AAF13226.1; ALT_FRAME; mRNA. DR EMBL; AF145024; AAP97276.1; ALT_FRAME; mRNA. DR EMBL; AF193594; AAP97280.1; ALT_FRAME; mRNA. DR EMBL; AK022484; BAB14051.1; -; mRNA. DR EMBL; AK091860; BAG52430.1; -; mRNA. DR EMBL; AL161911; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC018738; AAH18738.1; -; mRNA. DR EMBL; BC110334; AAI10335.1; -; mRNA. DR EMBL; AF129531; AAF04465.1; ALT_FRAME; mRNA. DR CCDS; CCDS43872.1; -. [Q9UKT8-1] DR RefSeq; NP_001362817.1; NM_001375888.1. [Q9UKT8-1] DR RefSeq; NP_036296.2; NM_012164.4. [Q9UKT8-1] DR RefSeq; XP_016870104.1; XM_017014615.3. [Q9UKT8-2] DR RefSeq; XP_024303277.1; XM_024447509.2. [Q9UKT8-2] DR RefSeq; XP_054218685.1; XM_054362710.1. [Q9UKT8-2] DR RefSeq; XP_054218686.1; XM_054362711.1. [Q9UKT8-2] DR AlphaFoldDB; Q9UKT8; -. DR SMR; Q9UKT8; -. DR BioGRID; 117603; 42. DR ComplexPortal; CPX-7747; SCF E3 ubiquitin ligase complex, FBXW2 variant. DR CORUM; Q9UKT8; -. DR DIP; DIP-37972N; -. DR FunCoup; Q9UKT8; 1662. DR IntAct; Q9UKT8; 28. DR MINT; Q9UKT8; -. DR NDEx; IQUERY-CP-FBXW2; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000476369; -. DR GlyGen; Q9UKT8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UKT8; -. DR PhosphoSitePlus; Q9UKT8; -. DR BioMuta; FBXW2; -. DR DMDM; 60416443; -. DR jPOST; Q9UKT8; -. DR MassIVE; Q9UKT8; -. DR PaxDb; 9606-ENSP00000476369; -. DR PeptideAtlas; Q9UKT8; -. DR ProteomicsDB; 84853; -. [Q9UKT8-1] DR ProteomicsDB; 84854; -. [Q9UKT8-2] DR Pumba; Q9UKT8; -. DR Antibodypedia; 30094; 148 antibodies from 28 providers. DR DNASU; 26190; -. DR Ensembl; ENST00000608872.6; ENSP00000476369.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000684001.2; ENSP00000507010.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000684047.2; ENSP00000508157.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882759.1; ENSP00000552818.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882760.1; ENSP00000552819.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000882761.1; ENSP00000552820.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882762.1; ENSP00000552821.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000882764.1; ENSP00000552823.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882765.1; ENSP00000552824.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882767.1; ENSP00000552826.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882768.1; ENSP00000552827.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882769.1; ENSP00000552828.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000882771.1; ENSP00000552830.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000882773.1; ENSP00000552832.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000917243.1; ENSP00000587302.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000917245.1; ENSP00000587304.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000917247.1; ENSP00000587305.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000917248.1; ENSP00000587307.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000917249.1; ENSP00000587308.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000955468.1; ENSP00000625527.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000955469.1; ENSP00000625528.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000955470.1; ENSP00000625529.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000955471.1; ENSP00000625530.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000955472.1; ENSP00000625531.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000955473.1; ENSP00000625532.1; ENSG00000119402.19. [Q9UKT8-2] DR Ensembl; ENST00000955474.1; ENSP00000625533.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000955475.1; ENSP00000625534.1; ENSG00000119402.19. [Q9UKT8-1] DR Ensembl; ENST00000955476.1; ENSP00000625535.1; ENSG00000119402.19. [Q9UKT8-2] DR GeneID; 26190; -. DR KEGG; hsa:26190; -. DR MANE-Select; ENST00000608872.6; ENSP00000476369.1; NM_012164.4; NP_036296.2. DR UCSC; uc004bkm.2; human. [Q9UKT8-1] DR AGR; HGNC:13608; -. DR ClinPGx; PA28052; -. DR CTD; 26190; -. DR DisGeNET; 26190; -. DR GeneCards; FBXW2; -. DR HGNC; HGNC:13608; FBXW2. DR HPA; ENSG00000119402; Low tissue specificity. DR MalaCards; FBXW2; -. DR MIM; 609071; gene. DR OpenTargets; ENSG00000119402; -. DR VEuPathDB; HostDB:ENSG00000119402; -. DR eggNOG; KOG0274; Eukaryota. DR GeneTree; ENSGT00930000151016; -. DR HOGENOM; CLU_041488_0_0_1; -. DR InParanoid; Q9UKT8; -. DR OMA; TIACWDW; -. DR OrthoDB; 538223at2759; -. DR PAN-GO; Q9UKT8; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q9UKT8; -. DR PathwayCommons; Q9UKT8; -. DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9UKT8; -. DR SIGNOR; Q9UKT8; -. DR Agora; ENSG00000119402; -. DR BioGRID-ORCS; 26190; 11 hits in 1193 CRISPR screens. DR ChiTaRS; FBXW2; human. DR GeneWiki; FBXW2; -. DR GenomeRNAi; 26190; -. DR Pharos; Q9UKT8; Tbio. DR PRO; PR:Q9UKT8; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9UKT8; protein. DR Bgee; ENSG00000119402; Expressed in buccal mucosa cell and 210 other cell types or tissues. DR ExpressionAtlas; Q9UKT8; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0006508; P:proteolysis; TAS:ProtInc. DR GO; GO:0010564; P:regulation of cell cycle process; NAS:ComplexPortal. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR CDD; cd22131; F-box_FBXW2; 1. DR CDD; cd00200; WD40; 1. DR FunFam; 2.130.10.10:FF:000151; F-box/WD repeat-containing protein 2 isoform X1; 1. DR Gene3D; 1.20.1280.50; -; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR042627; FBXW2. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR020472; WD40_PAC1. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR44436; F-BOX/WD REPEAT-CONTAINING PROTEIN 2; 1. DR PANTHER; PTHR44436:SF1; F-BOX_WD REPEAT-CONTAINING PROTEIN 2; 1. DR Pfam; PF12937; F-box-like; 1. DR Pfam; PF00400; WD40; 3. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00256; FBOX; 1. DR SMART; SM00320; WD40; 5. DR SUPFAM; SSF81383; F-box domain; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50181; FBOX; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 2. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Proteomics identification; KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat. FT CHAIN 1..454 FT /note="F-box/WD repeat-containing protein 2" FT /id="PRO_0000050988" FT DOMAIN 54..101 FT /note="F-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080" FT REPEAT 139..175 FT /note="WD 1" FT REPEAT 179..213 FT /note="WD 2" FT REPEAT 217..255 FT /note="WD 3" FT REPEAT 259..306 FT /note="WD 4" FT REPEAT 313..352 FT /note="WD 5" FT REPEAT 364..403 FT /note="WD 6" FT REPEAT 410..452 FT /note="WD 7" FT MOD_RES 298 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 164..228 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_012983" FT CONFLICT 405 FT /note="E -> G (in Ref. 3; BAB14051)" FT /evidence="ECO:0000305" FT CONFLICT 408 FT /note="K -> E (in Ref. 1; AAF04465)" FT /evidence="ECO:0000305" SQ SEQUENCE 454 AA; 51512 MW; F182998504BF2734 CRC64; MERKDFETWL DNISVTFLSL TDLQKNETLD HLISLSGAVQ LRHLSNNLET LLKRDFLKLL PLELSFYLLK WLDPQTLLTC CLVSKQWNKV ISACTEVWQT ACKNLGWQID DSVQDALHWK KVYLKAILRM KQLEDHEAFE TSSLIGHSAR VYALYYKDGL LCTGSDDLSA KLWDVSTGQC VYGIQTHTCA AVKFDEQKLV TGSFDNTVAC WEWSSGARTQ HFRGHTGAVF SVDYNDELDI LVSGSADFTV KVWALSAGTC LNTLTGHTEW VTKVVLQKCK VKSLLHSPGD YILLSADKYE IKIWPIGREI NCKCLKTLSV SEDRSICLQP RLHFDGKYIV CSSALGLYQW DFASYDILRV IKTPEIANLA LLGFGDIFAL LFDNRYLYIM DLRTESLISR WPLPEYRKSK RGSSFLAGEA SWLNGLDGHN DTGLVFATSM PDHSIHLVLW KEHG //