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Protein

F-box/WD repeat-containing protein 1A

Gene

Btrc

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:10097128, PubMed:16371461, PubMed:18782782, PubMed:9859996, PubMed:9990853, PubMed:21911472). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (By similarity). 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 (PubMed:9859996, PubMed:10097128). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:9859996, PubMed:10097128). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (By similarity). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (PubMed:21911472). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:18782782). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase (By similarity). Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF (By similarity). Required for proteolytic processing of GLI3 (PubMed:16371461).By similarity6 Publications

Caution

PubMed:10531037 wrongly lists the species as human.Curated

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.4 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • beta-catenin binding Source: BHF-UCL
  • protein dimerization activity Source: InterPro
  • protein phosphorylated amino acid binding Source: BHF-UCL
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: MGI

GO - Biological processi

  • branching involved in mammary gland duct morphogenesis Source: MGI
  • cellular response to organic cyclic compound Source: MGI
  • mammary gland epithelial cell proliferation Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of circadian rhythm Source: UniProtKB
  • positive regulation of proteolysis Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein catabolic process Source: MGI
  • protein dephosphorylation Source: UniProtKB
  • protein destabilization Source: UniProtKB
  • protein polyubiquitination Source: BHF-UCL
  • protein ubiquitination Source: MGI
  • regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • regulation of cell cycle Source: MGI
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • regulation of proteasomal protein catabolic process Source: MGI
  • rhythmic process Source: UniProtKB-KW
  • SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Biological processBiological rhythms, Ubl conjugation pathway, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-1169091 Activation of NF-kappaB in B cells
R-MMU-1170546 Prolactin receptor signaling
R-MMU-174113 SCF-beta-TrCP mediated degradation of Emi1
R-MMU-195253 Degradation of beta-catenin by the destruction complex
R-MMU-202424 Downstream TCR signaling
R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-2871837 FCERI mediated NF-kB activation
R-MMU-3769402 Deactivation of the beta-catenin transactivating complex
R-MMU-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-MMU-5607764 CLEC7A (Dectin-1) signaling
R-MMU-5610780 Degradation of GLI1 by the proteasome
R-MMU-5610785 GLI3 is processed to GLI3R by the proteasome
R-MMU-5676590 NIK-->noncanonical NF-kB signaling
R-MMU-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-MMU-8951664 Neddylation
R-MMU-9020702 Interleukin-1 signaling
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
F-box/WD repeat-containing protein 1ABy similarityImported
Alternative name(s):
Beta-TrCP protein E3RS-IkappaBImported
Beta-transducin repeat-containing proteinImported
Short name:
Beta-TrCP1 Publication
E3RSIkappaBBy similarity
Short name:
mE3RS-IkappaB1 Publication
F-box and WD repeats protein beta-TrCPBy similarity
HOS1 Publication
Ubiquitin ligase FWD11 PublicationImported
pIkappaB-E3 receptor subunit1 Publication
Gene namesi
Name:BtrcImported
Synonyms:Fbw1, Fbxw1Imported, Fwd1, Kiaa4123
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:1338871 Btrc

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutants have normal circadian behavior with normal PER2 expression in the suprachiasmatic nucleus.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003935711 – 605F-box/WD repeat-containing protein 1AAdd BLAST605

Proteomic databases

MaxQBiQ3ULA2
PaxDbiQ3ULA2
PeptideAtlasiQ3ULA2
PRIDEiQ3ULA2

PTM databases

iPTMnetiQ3ULA2
PhosphoSitePlusiQ3ULA2

Expressioni

Tissue specificityi

Expressed in heart, brain, liver, skeletal muscle and, most strongly, in testis.1 Publication

Gene expression databases

BgeeiENSMUSG00000025217
GenevisibleiQ3ULA2 MM

Interactioni

Subunit structurei

Homodimer. Self-associates. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. Direct interaction with SKP1 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 the phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (By similarity). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (PubMed:22037600). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (By similarity). Interacts with NFE2L1 (PubMed:21911472). Interacts with INAVA (By similarity).By similarity9 Publications

GO - Molecular functioni

  • beta-catenin binding Source: BHF-UCL
  • protein dimerization activity Source: InterPro
  • protein phosphorylated amino acid binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi198403, 23 interactors
CORUMiQ3ULA2
IntActiQ3ULA2, 16 interactors
MINTiQ3ULA2
STRINGi10090.ENSMUSP00000070728

Structurei

3D structure databases

ProteinModelPortaliQ3ULA2
SMRiQ3ULA2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini182 – 228F-boxPROSITE-ProRule annotationAdd BLAST47
Repeati301 – 338WD 1Sequence analysisAdd BLAST38
Repeati341 – 378WD 2Sequence analysisAdd BLAST38
Repeati381 – 418WD 3Sequence analysisAdd BLAST38
Repeati424 – 461WD 4Sequence analysisAdd BLAST38
Repeati464 – 503WD 5Sequence analysisAdd BLAST40
Repeati505 – 541WD 6Sequence analysisAdd BLAST37
Repeati553 – 590WD 7Sequence analysisAdd BLAST38

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni128 – 177Homodimerization domain DBy similarityAdd BLAST50
Regioni190 – 228Required for down-regulation of SNAI1By similarityAdd BLAST39

Domaini

The N-terminal D domain mediates homodimerization.By similarity

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0281 Eukaryota
ENOG410XTA8 LUCA
GeneTreeiENSGT00760000119106
HOGENOMiHOG000006638
HOVERGENiHBG002521
InParanoidiQ3ULA2
KOiK03362
OMAiTQCCFPQ
OrthoDBiEOG091G0437
PhylomeDBiQ3ULA2
TreeFamiTF105679

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR021977 Beta-TrCP_D
IPR036047 F-box-like_dom_sf
IPR001810 F-box_dom
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF12125 Beta-TrCP_D, 1 hit
PF12937 F-box-like, 1 hit
PF00400 WD40, 6 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM01028 Beta-TrCP_D, 1 hit
SM00256 FBOX, 1 hit
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
SSF81383 SSF81383, 1 hit
PROSITEiView protein in PROSITE
PS50181 FBOX, 1 hit
PS00678 WD_REPEATS_1, 6 hits
PS50082 WD_REPEATS_2, 7 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 12 Publications (identifier: Q3ULA2-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDPAEAVLQE KALKFMCSMP RSLWLGCSSL ADSMPSLRCL YNPGTGALTA
60 70 80 90 100
FQNSSEREDC NNGEPPRKII PEKNSLRQTY NSCARLCINQ ETVCLTSTAM
110 120 130 140 150
KTENCVAKAK LANGTSSMIV PKQRKLSASY EKEKELCVKY FEQWSESDQV
160 170 180 190 200
EFVEHLISQM CHYQHGHINS YLKPMLQRDF ITALPARGLD HIAENILSYL
210 220 230 240 250
DAKSLCAAEL VCKEWYRVTS DGMLWKKLIE RMVRTDSLWR GLAERRGWGQ
260 270 280 290 300
YLFKNKPPDE NAPPNSFYRA LYPKIIQDIE TIESNWRCGR HSLQRIHCRS
310 320 330 340 350
ETSKGVYCLQ YDDQKIVSGL RDNTIKIWDK STLECKRILT GHTGSVLCLQ
360 370 380 390 400
YDERVIITGS SDSTVRVWDV NAGEMLNTLI HHCEAVLHLR FNNGMMVTCS
410 420 430 440 450
KDRSIAVWDM ASPTDITLRR VLVGHRAAVN VVDFDDKYIV SASGDRTIKV
460 470 480 490 500
WNTSTCEFVR TLNGHKRGIA CLQYRDRLVV SGSSDNTIRL WDIECGACLR
510 520 530 540 550
VLEGHEELVR CIRFDNKRIV SGAYDGKIKV WDLMAALDPR APAGTLCLRT
560 570 580 590 600
LVEHSGRVFR LQFDEFQIVS SSHDDTILIW DFLNDPAAHA EPPRSPSRTY

TYISR
Length:605
Mass (Da):68,923
Last modified:April 20, 2010 - v2
Checksum:i9E66D94D1EEEFF1B
GO
Isoform 25 Publications (identifier: Q3ULA2-2) [UniParc]FASTAAdd to basket

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

Show »
Length:569
Mass (Da):65,105
Checksum:iBC7D6544815B2296
GO

Sequence cautioni

The sequence BAD90368 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193A → T in AAD41025 (PubMed:10531037).Curated1
Sequence conflicti226K → E in BAE33798 (PubMed:16141072).Curated1
Sequence conflicti297H → R in BAE26547 (PubMed:16141072).Curated1
Sequence conflicti352D → G in AAD04181 (PubMed:9990853).Curated1
Sequence conflicti377N → D in AAD41025 (PubMed:10531037).Curated1
Sequence conflicti380I → T in AAD41025 (PubMed:10531037).Curated1
Sequence conflicti523A → R in AAD41025 (PubMed:10531037).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05320817 – 52Missing in isoform 2. 5 PublicationsAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF099932 mRNA Translation: AAD08701.1
AF110396 mRNA Translation: AAD41025.1
AF112979 mRNA Translation: AAD04181.1
AF081887 mRNA Translation: AAD17755.1
AF391190
, AF391178, AF391179, AF391180, AF391181, AF391182, AF391183, AF391184, AF391185, AF391186, AF391187, AF391188, AF391189 Genomic DNA Translation: AAL40929.1
AK145624 mRNA Translation: BAE26547.1
AK156660 mRNA Translation: BAE33798.1
AK220183 mRNA Translation: BAD90368.1 Different initiation.
CH466534 Genomic DNA Translation: EDL41951.1
BC003989 mRNA Translation: AAH03989.1
CCDSiCCDS29860.1 [Q3ULA2-1]
CCDS38002.1 [Q3ULA2-2]
RefSeqiNP_001032847.2, NM_001037758.2 [Q3ULA2-1]
NP_001273394.1, NM_001286465.1 [Q3ULA2-1]
NP_001273395.1, NM_001286466.1
NP_033901.1, NM_009771.3 [Q3ULA2-2]
UniGeneiMm.119717
Mm.446448

Genome annotation databases

EnsembliENSMUST00000065601; ENSMUSP00000070728; ENSMUSG00000025217 [Q3ULA2-1]
ENSMUST00000111936; ENSMUSP00000107567; ENSMUSG00000025217 [Q3ULA2-2]
GeneIDi12234
KEGGimmu:12234
UCSCiuc008hqx.2 mouse [Q3ULA2-1]
uc008hqz.2 mouse [Q3ULA2-2]

Keywords - Coding sequence diversityi

Alternative splicing

Entry informationi

Entry nameiFBW1A_MOUSE
AccessioniPrimary (citable) accession number: Q3ULA2
Secondary accession number(s): Q3U0Q4
, Q571K6, Q9QUI5, Q9R1G7, Q9Z159
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 20, 2010
Last sequence update: April 20, 2010
Last modified: May 23, 2018
This is version 129 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways

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