FBXW2_HUMAN
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 03-AUG-2022, entry version 201.
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=4; 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};
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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_036296.2; NM_012164.3. [Q9UKT8-1]
DR RefSeq; XP_005251967.1; XM_005251910.3.
DR RefSeq; XP_016870104.1; XM_017014615.1. [Q9UKT8-2]
DR AlphaFoldDB; Q9UKT8; -.
DR SMR; Q9UKT8; -.
DR BioGRID; 117603; 39.
DR CORUM; Q9UKT8; -.
DR DIP; DIP-37972N; -.
DR IntAct; Q9UKT8; 24.
DR MINT; Q9UKT8; -.
DR STRING; 9606.ENSP00000476369; -.
DR iPTMnet; Q9UKT8; -.
DR PhosphoSitePlus; Q9UKT8; -.
DR BioMuta; FBXW2; -.
DR DMDM; 60416443; -.
DR EPD; Q9UKT8; -.
DR jPOST; Q9UKT8; -.
DR MassIVE; Q9UKT8; -.
DR MaxQB; Q9UKT8; -.
DR PaxDb; Q9UKT8; -.
DR PeptideAtlas; Q9UKT8; -.
DR PRIDE; Q9UKT8; -.
DR ProteomicsDB; 84853; -. [Q9UKT8-1]
DR ProteomicsDB; 84854; -. [Q9UKT8-2]
DR Antibodypedia; 30094; 153 antibodies from 29 providers.
DR DNASU; 26190; -.
DR Ensembl; ENST00000608872.6; ENSP00000476369.1; ENSG00000119402.18. [Q9UKT8-1]
DR Ensembl; ENST00000684001.1; ENSP00000507010.1; ENSG00000119402.18. [Q9UKT8-1]
DR Ensembl; ENST00000684047.1; ENSP00000508157.1; ENSG00000119402.18. [Q9UKT8-1]
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 CTD; 26190; -.
DR DisGeNET; 26190; -.
DR GeneCards; FBXW2; -.
DR HGNC; HGNC:13608; FBXW2.
DR HPA; ENSG00000119402; Low tissue specificity.
DR MIM; 609071; gene.
DR neXtProt; NX_Q9UKT8; -.
DR OpenTargets; ENSG00000119402; -.
DR PharmGKB; PA28052; -.
DR VEuPathDB; HostDB:ENSG00000119402; -.
DR eggNOG; KOG0274; Eukaryota.
DR GeneTree; ENSGT00930000151016; -.
DR HOGENOM; CLU_041488_0_0_1; -.
DR InParanoid; Q9UKT8; -.
DR OMA; ASHWKGI; -.
DR OrthoDB; 1121375at2759; -.
DR PhylomeDB; Q9UKT8; -.
DR TreeFam; TF333134; -.
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 BioGRID-ORCS; 26190; 10 hits in 1112 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 208 other tissues.
DR ExpressionAtlas; Q9UKT8; baseline and differential.
DR Genevisible; Q9UKT8; HS.
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 Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR042627; FBXW2.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR44436; PTHR44436; 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; SSF50978; SSF50978; 1.
DR SUPFAM; SSF81383; SSF81383; 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; Reference proteome; Repeat;
KW 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