Q9Y297 (FBW1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
F-box/WD repeat-containing protein 1A

Alternative name(s):
E3RSIkappaB
Epididymis tissue protein Li 2a
F-box and WD repeats protein beta-TrCP
pIkappaBalpha-E3 receptor subunit

Gene names

Name:	BTRC
Synonyms:	BTRCP, FBW1A, FBXW1A

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

General annotation (Comments)

Function	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling. SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22'. SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, SMAD3, SMAD4, CDC25A, DLG1, FBXO5 and probably NFKB2. SCF(BTRC) mediates the ubiquitination of phosphorylated SNAI1. May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3. Ref.1 Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.29
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Homodimer. Self-associates. Component of the SCF(BTRC) complex formed of CUL1, SKP1, RBX1 and a BTRC dimer. Direct interaction with SKP1 occurs via the F-box domain. Interacts with phosphorylated ubiquitination substrates SMAD3 and SMAD4. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of the 2 serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. Interacts with HIV-1 Vpu. Interacts with the phosphorylated form of GLI3. Interacts with CLU. Ref.2 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.32
Subcellular location	Cytoplasm. Nucleus By similarity.
Tissue specificity	Expressed in epididymis (at protein level). Ref.4
Domain	The N-terminal D domain mediates homodimerization. Ref.32
Sequence similarities	Contains 1 F-box domain. Contains 7 WD repeats.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat WD repeat
Molecular function	Ligase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process Traceable author statement. Source: Reactome branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara cellular response to organic cyclic compound Inferred from electronic annotation. Source: Compara mammary gland epithelial cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 11001584. Source: BHF-UCL negative regulation of smoothened signaling pathway Traceable author statement PubMed 11001584. Source: BHF-UCL negative regulation of transcription, DNA-dependent Inferred from mutant phenotype PubMed 19966869. Source: UniProtKB positive regulation of circadian rhythm Inferred from electronic annotation. Source: Compara positive regulation of proteolysis Inferred from mutant phenotype PubMed 16885022. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle Traceable author statement. Source: Reactome protein dephosphorylation Inferred from electronic annotation. Source: Compara protein destabilization Inferred from mutant phenotype PubMed 16885022. Source: UniProtKB protein polyubiquitination Inferred from electronic annotation. Source: Compara protein ubiquitination Inferred from direct assay PubMed 16885022. Source: UniProtKB regulation of I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara regulation of cell cycle Inferred from electronic annotation. Source: Compara regulation of proteasomal protein catabolic process Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 9990853. Source: ProtInc viral reproduction Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	SCF ubiquitin ligase complex Inferred from direct assay PubMed 19966869. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	9	EBI-307461,EBI-389668
SKP1	P63208	4	EBI-307461,EBI-307486
WEE1	P30291	2	EBI-307461,EBI-914695

Alternative products

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

Isoform 1 (identifier: Q9Y297-1)

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: Q9Y297-2)

The sequence of this isoform differs from the canonical sequence as follows:
     17-52: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 605

605

F-box/WD repeat-containing protein 1A

PRO_0000050980

Regions

Domain

190 – 228

39

F-box

Repeat

301 – 338

38

WD 1

Repeat

341 – 378

38

WD 2

Repeat

381 – 418

38

WD 3

Repeat

424 – 461

38

WD 4

Repeat

464 – 503

40

WD 5

Repeat

505 – 541

37

WD 6

Repeat

553 – 590

38

WD 7

Region

128 – 177

50

Homodimerization domain D

Region

190 – 228

39

Required for down-regulation of SNAI1

Natural variations

Alternative sequence

17 – 52

36

Missing in isoform 2.

VSP_006764

Natural variant

543

1

A → S.
Corresponds to variant rs4151060 [ dbSNP | Ensembl ].

VAR_022027

Natural variant

592

1

P → H.
Corresponds to variant rs2270439 [ dbSNP | Ensembl ].

VAR_020119

Secondary structure

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605

Helix Strand Turn

Details...

Helix

129 – 141

13

Helix

146 – 158

13

Helix

162 – 172

11

Helix

173 – 175

3

Helix

180 – 183

4

Helix

185 – 187

3

Helix

190 – 197

8

Helix

202 – 211

10

Helix

213 – 221

9

Helix

224 – 233

10

Helix

237 – 244

8

Beta strand

245 – 247

3

Helix

248 – 251

4

Helix

266 – 285

20

Turn

286 – 288

3

Beta strand

306 – 310

5

Beta strand

313 – 323

11

Beta strand

325 – 332

8

Beta strand

335 – 339

5

Beta strand

346 – 350

5

Beta strand

353 – 360

8

Beta strand

365 – 372

8

Beta strand

375 – 379

5

Beta strand

386 – 390

5

Beta strand

395 – 400

6

Beta strand

405 – 409

5

Beta strand

411 – 414

4

Beta strand

417 – 422

6

Beta strand

429 – 435

7

Beta strand

438 – 443

6

Beta strand

446 – 452

7

Turn

453 – 455

3

Beta strand

458 – 463

6

Beta strand

469 – 475

7

Beta strand

478 – 483

6

Beta strand

488 – 492

5

Turn

493 – 495

3

Beta strand

498 – 502

5

Beta strand

509 – 513

5

Beta strand

516 – 523

8

Beta strand

528 – 532

5

Helix

533 – 536

4

Turn

543 – 546

4

Beta strand

547 – 551

5

Beta strand

561 – 563

3

Beta strand

568 – 570

3

Beta strand

573 – 580

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 4C67F3B7E400FD37	FASTA	605	68,867
	10 20 30 40 50 60 MDPAEAVLQE KALKFMCSMP RSLWLGCSSL ADSMPSLRCL YNPGTGALTA FQNSSEREDC 70 80 90 100 110 120 NNGEPPRKII PEKNSLRQTY NSCARLCLNQ ETVCLASTAM KTENCVAKTK LANGTSSMIV 130 140 150 160 170 180 PKQRKLSASY EKEKELCVKY FEQWSESDQV EFVEHLISQM CHYQHGHINS YLKPMLQRDF 190 200 210 220 230 240 ITALPARGLD HIAENILSYL DAKSLCAAEL VCKEWYRVTS DGMLWKKLIE RMVRTDSLWR 250 260 270 280 290 300 GLAERRGWGQ YLFKNKPPDG NAPPNSFYRA LYPKIIQDIE TIESNWRCGR HSLQRIHCRS 310 320 330 340 350 360 ETSKGVYCLQ YDDQKIVSGL RDNTIKIWDK NTLECKRILT GHTGSVLCLQ YDERVIITGS 370 380 390 400 410 420 SDSTVRVWDV NTGEMLNTLI HHCEAVLHLR FNNGMMVTCS KDRSIAVWDM ASPTDITLRR 430 440 450 460 470 480 VLVGHRAAVN VVDFDDKYIV SASGDRTIKV WNTSTCEFVR TLNGHKRGIA CLQYRDRLVV 490 500 510 520 530 540 SGSSDNTIRL WDIECGACLR VLEGHEELVR CIRFDNKRIV SGAYDGKIKV WDLVAALDPR 550 560 570 580 590 600 APAGTLCLRT LVEHSGRVFR LQFDEFQIVS SSHDDTILIW DFLNDPAAQA EPPRSPSRTY TYISR
	Isoform 2 [UniParc]. Checksum: 6E7C4FBE7BB520BA	FASTA	569	65,049
	10 20 30 40 50 60 MDPAEAVLQE KALKFMNSSE REDCNNGEPP RKIIPEKNSL RQTYNSCARL CLNQETVCLA 70 80 90 100 110 120 STAMKTENCV AKTKLANGTS SMIVPKQRKL SASYEKEKEL CVKYFEQWSE SDQVEFVEHL 130 140 150 160 170 180 ISQMCHYQHG HINSYLKPML QRDFITALPA RGLDHIAENI LSYLDAKSLC AAELVCKEWY 190 200 210 220 230 240 RVTSDGMLWK KLIERMVRTD SLWRGLAERR GWGQYLFKNK PPDGNAPPNS FYRALYPKII 250 260 270 280 290 300 QDIETIESNW RCGRHSLQRI HCRSETSKGV YCLQYDDQKI VSGLRDNTIK IWDKNTLECK 310 320 330 340 350 360 RILTGHTGSV LCLQYDERVI ITGSSDSTVR VWDVNTGEML NTLIHHCEAV LHLRFNNGMM 370 380 390 400 410 420 VTCSKDRSIA VWDMASPTDI TLRRVLVGHR AAVNVVDFDD KYIVSASGDR TIKVWNTSTC 430 440 450 460 470 480 EFVRTLNGHK RGIACLQYRD RLVVSGSSDN TIRLWDIECG ACLRVLEGHE ELVRCIRFDN 490 500 510 520 530 540 KRIVSGAYDG KIKVWDLVAA LDPRAPAGTL CLRTLVEHSG RVFRLQFDEF QIVSSSHDDT 550 560 ILIWDFLNDP AAQAEPPRSP SRTYTYISR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of the receptor component of the IkappaBalpha-ubiquitin ligase." Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M., Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y. Nature 396:590-594(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[2]	"A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif." Margottin F., Bour S.P., Durand H., Selig L., Benichou S., Richard V., Thomas D., Strebel K., Benarous R. Mol. Cell 1:565-574(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH HIV-1 VPU. Tissue: Lymphoid tissue.
[3]	"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] (ISOFORM 2).
[4]	"Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins." Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., Jin S., Liu J., Zhu P., Liu Y. Mol. Cell. Proteomics 9:2517-2528(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Epididymis.
[5]	"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] (ISOFORM 1). Tissue: Testis.
[6]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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). Tissue: Brain.
[9]	"IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2." Suzuki H., Chiba T., Kobayashi M., Takeuchi M., Suzuki T., Ichiyama A., Ikenoue T., Omata M., Furuichi K., Tanaka K. Biochem. Biophys. Res. Commun. 256:127-132(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SCF(BTRC) COMPLEX, FUNCTION IN UBIQUITINATION OF NFKBIA.
[10]	"Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1." Shirane M., Hatakeyama S., Hattori K., Nakayama K., Nakayama K. J. Biol. Chem. 274:28169-28174(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFKBIB AND NFKBIE, FUNCTION IN UBIQUITINATION OF NFKBIB AND NFKBIE.
[11]	"The SCF(beta-TRCP)-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in I-kappa-B-alpha and beta-catenin and stimulates I-kappa-B-alpha ubiquitination in vitro." Winston J.T., Strack P., Beer-Romero P., Chu C.Y., Elledge S.J., Harper J.W. Genes Dev. 13:270-283(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[12]	"SCF(beta)(-TrCP) ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase." Orian A., Gonen H., Bercovich B., Fajerman I., Eytan E., Israel A., Mercurio F., Iwai K., Schwartz A.L., Ciechanover A. EMBO J. 19:2580-2591(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NFKB1, FUNCTION IN UBIQUITINATION OF NFKB1.
[13]	"Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination." Suzuki H., Chiba T., Suzuki T., Fujita T., Ikenoue T., Omata M., Furuichi K., Shikama H., Tanaka K. J. Biol. Chem. 275:2877-2884(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SELF-ASSOCIATION, INTERACTION WITH FBXW11 AND NFKBIA, FUNCTION IN UBIQUITINATION OF NFKBIA.
[14]	"The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome." Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L., Gill G., Howley P.M. Mol. Cell 6:409-419(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBQLN1. Tissue: B-cell.
[15]	"Ligand-dependent degradation of Smad3 by a ubiquitin ligase complex of ROC1 and associated proteins." Fukuchi M., Imamura T., Chiba T., Ebisawa T., Kawabata M., Tanaka K., Miyazono K. Mol. Biol. Cell 12:1431-1443(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED SMAD3, FUNCTION IN SMAD3 UBIQUITINATION.
[16]	"ATF4 degradation relies on a phosphorylation-dependent interaction with the SCF(betaTrCP) ubiquitin ligase." Lassot I., Segeral E., Berlioz-Torrent C., Durand H., Groussin L., Hai T., Benarous R., Margottin-Goguet F. Mol. Cell. Biol. 21:2192-2202(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED ATF4, FUNCTION IN ATF4 UBIQUITINATION.
[17]	"Genetic evidence for the essential role of beta-transducin repeat-containing protein in the inducible processing of NF-kappa B2/p100." Fong A., Sun S.C. J. Biol. Chem. 277:22111-22114(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NFKB2 UBIQUITINATION.
[18]	"Regulation of S33/S37 phosphorylated beta-catenin in normal and transformed cells." Sadot E., Conacci-Sorrell M., Zhurinsky J., Shnizer D., Lando Z., Zharhary D., Kam Z., Ben-Ze'ev A., Geiger B. J. Cell Sci. 115:2771-2780(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED CTNNB1.
[19]	"CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation." Semplici F., Meggio F., Pinna L.A., Oliviero S. Oncogene 21:3978-3987(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDC34 AND UBE2R2.
[20]	"Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase." Margottin-Goguet F., Hsu J.Y., Loktev A., Hsieh H.-M., Reimann J.D.R., Jackson P.K. Dev. Cell 4:813-826(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED FBXO5, FUNCTION IN FBXO5 UBIQUITINATION.
[21]	"SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase." Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W. Genes Dev. 17:3062-3074(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED CDC25A, FUNCTION IN CDC25A UBIQUITINATION.
[22]	"Regulation of the discs large tumor suppressor by a phosphorylation-dependent interaction with the beta-TrCP ubiquitin ligase receptor." Mantovani F., Banks L. J. Biol. Chem. 278:42477-42486(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED DLG1, FUNCTION IN DLG1 UBIQUITINATION.
[23]	"Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage." Busino L., Donzelli M., Chiesa M., Guardavaccaro D., Ganoth D., Dorrello N.V., Hershko A., Pagano M., Draetta G.F. Nature 426:87-91(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED CDC25A, FUNCTION IN CDC25A UBIQUITINATION.
[24]	"Smad4 protein stability is regulated by ubiquitin ligase SCF beta-TrCP1." Wan M., Tang Y., Tytler E.M., Lu C., Jin B., Vickers S.M., Yang L., Shi X., Cao X. J. Biol. Chem. 279:14484-14487(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHOSPHORYLATED SMAD4, FUNCTION IN SMAD4 UBIQUITINATION.
[25]	"Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition." Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C. Nat. Cell Biol. 6:931-940(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SNAI1.
[26]	"Wnt-dependent regulation of the E-cadherin repressor snail." Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J. J. Biol. Chem. 280:11740-11748(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SNAI1.
[27]	"DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases." He Y.J., McCall C.M., Hu J., Zeng Y., Xiong Y. Genes Dev. 20:2949-2954(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CUL4A AND DDB1.
[28]	"Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP." Tempe D., Casas M., Karaz S., Blanchet-Tournier M.F., Concordet J.P. Mol. Cell. Biol. 26:4316-4326(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GLI3.
[29]	"Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing." Wang B., Li Y. Proc. Natl. Acad. Sci. U.S.A. 103:33-38(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[30]	"Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB activity in prostate cancer cells." Zoubeidi A., Ettinger S., Beraldi E., Hadaschik B., Zardan A., Klomp L.W., Nelson C.C., Rennie P.S., Gleave M.E. Mol. Cancer Res. 8:119-130(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CLU.
[31]	"Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase." Wu G., Xu G., Schulman B.A., Jeffrey P.D., Harper J.W., Pavletich N.P. Mol. Cell 11:1445-1456(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 175-605 IN COMPLEX WITH SKP1 AND CTNNB1.
[32]	"Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination." Tang X., Orlicky S., Lin Z., Willems A., Neculai D., Ceccarelli D., Mercurio F., Shilton B.H., Sicheri F., Tyers M. Cell 129:1165-1176(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 128-177, DOMAIN, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF101784 mRNA. Translation: AAD08702.1.
Y14153 mRNA. Translation: CAA74572.1.
AF129530 mRNA. Translation: AAF04464.1.
GU727631 mRNA. Translation: ADU87633.1.
AK313353 mRNA. Translation: BAG36155.1.
AL133387, AL445463, AL627424 Genomic DNA. Translation: CAH70019.1.
AL133387, AL445463, AL627424 Genomic DNA. Translation: CAH70020.1.
AL445463, AL133387, AL627424 Genomic DNA. Translation: CAI12963.1.
AL445463, AL133387, AL627424 Genomic DNA. Translation: CAI12964.1.
AL627424, AL133387, AL445463 Genomic DNA. Translation: CAI41042.1.
AL627424, AL133387, AL445463 Genomic DNA. Translation: CAI41043.1.
CH471066 Genomic DNA. Translation: EAW49772.1.
CH471066 Genomic DNA. Translation: EAW49774.1.
BC027994 mRNA. Translation: AAH27994.1.

IPI

IPI00307418.
IPI00413142.

RefSeq

NP_003930.1. NM_003939.4.
NP_378663.1. NM_033637.3.

UniGene

Hs.643802.
Hs.713753.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1P22	X-ray	2.95	A	175-605	[»]
2P64	X-ray	2.50	A/B	128-177	[»]

ProteinModelPortal

Q9Y297.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31607N.

IntAct

Q9Y297. 42 interactions.

MINT

MINT-108636.

STRING

9606.ENSP00000359206.

PTM databases

PhosphoSite

Q9Y297.

Polymorphism databases

DMDM

13124271.

Proteomic databases

PaxDb

Q9Y297.

PRIDE

Q9Y297.

Protocols and materials databases

DNASU

8945.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370187; ENSP00000359206; ENSG00000166167.
ENST00000408038; ENSP00000385339; ENSG00000166167.

GeneID

8945.

KEGG

hsa:8945.

UCSC

uc001kta.3. human.
uc001ktb.3. human.

Organism-specific databases

CTD

8945.

GeneCards

GC10P103103.

HGNC

HGNC:1144. BTRC.

HPA

CAB032986.

MIM

603482. gene.

neXtProt

NX_Q9Y297.

PharmGKB

PA25465.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2319.

HOGENOM

HOG000006638.

HOVERGEN

HBG002521.

InParanoid

Q9Y297.

KO

K03362.

OMA

NAYLKPM.

OrthoDB

EOG4F1X2M.

PhylomeDB

Q9Y297.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.
REACT_116125. Disease.
REACT_24941. Circadian Clock.
REACT_6900. Immune System.

SignaLink

Q9Y297.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q9Y297.

Bgee

Q9Y297.

CleanEx

HS_BTRC.

Genevestigator

Q9Y297.

Family and domain databases

Gene3D

2.130.10.10. 2 hits.

InterPro

IPR021977. Beta-TrCP_D.
IPR001810. F-box_dom_cyclin-like.
IPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]

Pfam

PF12125. Beta-TrCP_D. 1 hit.
PF00400. WD40. 7 hits.
[Graphical view]

PRINTS

PR00320. GPROTEINBRPT.

SMART

SM01028. Beta-TrCP_D. 1 hit.
SM00256. FBOX. 1 hit.
SM00320. WD40. 7 hits.
[Graphical view]

SUPFAM

SSF81383. F-box_dom_Skp2-like. 1 hit.
SSF50978. WD40_like. 1 hit.

PROSITE

PS50181. FBOX. 1 hit.
PS00678. WD_REPEATS_1. 6 hits.
PS50082. WD_REPEATS_2. 7 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BTRC. human.

EvolutionaryTrace

Q9Y297.

GenomeRNAi

8945.

NextBio

33645.

SOURCE

Search...

Entry information

Entry name

FBW1A_HUMAN

Accession

Primary (citable) accession number: Q9Y297
Secondary accession number(s): B5MD49 , Q5W141, Q5W142, Q9Y213

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1999
Last modified:	May 29, 2013
This is version 137 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.