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Protein

F-box/WD repeat-containing protein 1A

Gene

BTRC

Organism
Homo sapiens (Human)
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:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323). 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:10066435, PubMed:10497169, PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25704143, PubMed:25503564). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). 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 (PubMed:16371461).By similarity20 Publications

Pathwayi: protein ubiquitination

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processBiological rhythms, Host-virus interaction, Ubl conjugation pathway, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-1170546 Prolactin receptor signaling
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-202424 Downstream TCR signaling
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-400253 Circadian Clock
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-8951664 Neddylation
R-HSA-9020702 Interleukin-1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9Y297
SIGNORiQ9Y297
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
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 namesi
Name:BTRC
Synonyms:BTRCP, FBW1A, FBXW1A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000166167.17
HGNCiHGNC:1144 BTRC
MIMi603482 gene
neXtProtiNX_Q9Y297

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

Organism-specific databases

DisGeNETi8945
MalaCardsiBTRC
OpenTargetsiENSG00000166167
Orphaneti2440 Split hand-split foot malformation
PharmGKBiPA25465

Polymorphism and mutation databases

BioMutaiBTRC
DMDMi13124271

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509801 – 605F-box/WD repeat-containing protein 1AAdd BLAST605

Proteomic databases

EPDiQ9Y297
PaxDbiQ9Y297
PeptideAtlasiQ9Y297
PRIDEiQ9Y297
ProteomicsDBi85705
85706 [Q9Y297-2]

PTM databases

iPTMnetiQ9Y297
PhosphoSitePlusiQ9Y297

Expressioni

Tissue specificityi

Expressed in epididymis (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000166167 Expressed in 209 organ(s), highest expression level in frontal cortex
CleanExiHS_BTRC
ExpressionAtlasiQ9Y297 baseline and differential
GenevisibleiQ9Y297 HS

Organism-specific databases

HPAiCAB032986
HPA031156

Interactioni

Subunit structurei

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 the phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (PubMed:25704143, PubMed:25503564). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By similarity). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 (By similarity). Interacts with INAVA (PubMed:29420262).By similarity26 Publications
(Microbial infection) Interacts with vaccinia virus A49; this interaction inhibits NF-kappa-B activation.1 Publication
(Microbial infection) Interacts with HIV-1 Vpu.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114457, 396 interactors
CORUMiQ9Y297
DIPiDIP-31607N
IntActiQ9Y297, 84 interactors
MINTiQ9Y297
STRINGi9606.ENSP00000359206

Structurei

Secondary structure

1605
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y297
SMRiQ9Y297
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y297

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini190 – 228F-boxPROSITE-ProRule annotationAdd BLAST39
Repeati301 – 338WD 1Add BLAST38
Repeati341 – 378WD 2Add BLAST38
Repeati381 – 418WD 3Add BLAST38
Repeati424 – 461WD 4Add BLAST38
Repeati464 – 503WD 5Add BLAST40
Repeati505 – 541WD 6Add BLAST37
Repeati553 – 590WD 7Add BLAST38

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni128 – 177Homodimerization domain DAdd BLAST50
Regioni190 – 228Required for down-regulation of SNAI1Add BLAST39

Domaini

The N-terminal D domain mediates homodimerization.1 Publication

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0281 Eukaryota
ENOG410XTA8 LUCA
GeneTreeiENSGT00760000119106
HOGENOMiHOG000006638
HOVERGENiHBG002521
InParanoidiQ9Y297
KOiK03362
OMAiTQCCFPQ
OrthoDBiEOG091G0437
PhylomeDBiQ9Y297
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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y297-1) [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 NSCARLCLNQ ETVCLASTAM
110 120 130 140 150
KTENCVAKTK 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
YLFKNKPPDG NAPPNSFYRA LYPKIIQDIE TIESNWRCGR HSLQRIHCRS
310 320 330 340 350
ETSKGVYCLQ YDDQKIVSGL RDNTIKIWDK NTLECKRILT GHTGSVLCLQ
360 370 380 390 400
YDERVIITGS SDSTVRVWDV NTGEMLNTLI 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 WDLVAALDPR APAGTLCLRT
560 570 580 590 600
LVEHSGRVFR LQFDEFQIVS SSHDDTILIW DFLNDPAAQA EPPRSPSRTY

TYISR
Length:605
Mass (Da):68,867
Last modified:November 1, 1999 - v1
Checksum:i4C67F3B7E400FD37
GO
Isoform 2 (identifier: Q9Y297-2) [UniParc]FASTAAdd to basket

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

Show »
Length:569
Mass (Da):65,049
Checksum:i6E7C4FBE7BB520BA
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7Z3H4B7Z3H4_HUMAN
Beta-transducin repeat containing i...
BTRC hCG_1811016
579Annotation score:
Q5T1W7Q5T1W7_HUMAN
F-box/WD repeat-containing protein ...
BTRC
191Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022027543A → S. Corresponds to variant dbSNP:rs4151060Ensembl.1
Natural variantiVAR_020119592P → H. Corresponds to variant dbSNP:rs2270439Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00676417 – 52Missing in isoform 2. 2 PublicationsAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA No translation available.
AL445463 Genomic DNA No translation available.
AL627424 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49772.1
CH471066 Genomic DNA Translation: EAW49774.1
BC027994 mRNA Translation: AAH27994.1
CCDSiCCDS7511.1 [Q9Y297-2]
CCDS7512.1 [Q9Y297-1]
RefSeqiNP_003930.1, NM_003939.4 [Q9Y297-2]
NP_378663.1, NM_033637.3 [Q9Y297-1]
UniGeneiHs.643802

Genome annotation databases

EnsembliENST00000370187; ENSP00000359206; ENSG00000166167 [Q9Y297-1]
ENST00000408038; ENSP00000385339; ENSG00000166167 [Q9Y297-2]
GeneIDi8945
KEGGihsa:8945
UCSCiuc001kta.5 human [Q9Y297-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 Genomic DNA No translation available.
AL445463 Genomic DNA No translation available.
AL627424 Genomic DNA No translation available.
CH471066 Genomic DNA Translation: EAW49772.1
CH471066 Genomic DNA Translation: EAW49774.1
BC027994 mRNA Translation: AAH27994.1
CCDSiCCDS7511.1 [Q9Y297-2]
CCDS7512.1 [Q9Y297-1]
RefSeqiNP_003930.1, NM_003939.4 [Q9Y297-2]
NP_378663.1, NM_033637.3 [Q9Y297-1]
UniGeneiHs.643802

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1P22X-ray2.95A175-605[»]
2P64X-ray2.50A/B128-177[»]
ProteinModelPortaliQ9Y297
SMRiQ9Y297
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114457, 396 interactors
CORUMiQ9Y297
DIPiDIP-31607N
IntActiQ9Y297, 84 interactors
MINTiQ9Y297
STRINGi9606.ENSP00000359206

PTM databases

iPTMnetiQ9Y297
PhosphoSitePlusiQ9Y297

Polymorphism and mutation databases

BioMutaiBTRC
DMDMi13124271

Proteomic databases

EPDiQ9Y297
PaxDbiQ9Y297
PeptideAtlasiQ9Y297
PRIDEiQ9Y297
ProteomicsDBi85705
85706 [Q9Y297-2]

Protocols and materials databases

DNASUi8945
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370187; ENSP00000359206; ENSG00000166167 [Q9Y297-1]
ENST00000408038; ENSP00000385339; ENSG00000166167 [Q9Y297-2]
GeneIDi8945
KEGGihsa:8945
UCSCiuc001kta.5 human [Q9Y297-1]

Organism-specific databases

CTDi8945
DisGeNETi8945
EuPathDBiHostDB:ENSG00000166167.17
GeneCardsiBTRC
HGNCiHGNC:1144 BTRC
HPAiCAB032986
HPA031156
MalaCardsiBTRC
MIMi603482 gene
neXtProtiNX_Q9Y297
OpenTargetsiENSG00000166167
Orphaneti2440 Split hand-split foot malformation
PharmGKBiPA25465
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0281 Eukaryota
ENOG410XTA8 LUCA
GeneTreeiENSGT00760000119106
HOGENOMiHOG000006638
HOVERGENiHBG002521
InParanoidiQ9Y297
KOiK03362
OMAiTQCCFPQ
OrthoDBiEOG091G0437
PhylomeDBiQ9Y297
TreeFamiTF105679

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-1170546 Prolactin receptor signaling
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-202424 Downstream TCR signaling
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-400253 Circadian Clock
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-8951664 Neddylation
R-HSA-9020702 Interleukin-1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9Y297
SIGNORiQ9Y297

Miscellaneous databases

ChiTaRSiBTRC human
EvolutionaryTraceiQ9Y297
GeneWikiiBTRC_(gene)
GenomeRNAii8945
PROiPR:Q9Y297
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166167 Expressed in 209 organ(s), highest expression level in frontal cortex
CleanExiHS_BTRC
ExpressionAtlasiQ9Y297 baseline and differential
GenevisibleiQ9Y297 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiFBW1A_HUMAN
AccessioniPrimary (citable) accession number: Q9Y297
Secondary accession number(s): B5MD49
, Q5W141, Q5W142, Q9Y213
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: November 1, 1999
Last modified: September 12, 2018
This is version 195 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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