Tbio BTRC F-box/WD repeat-containing protein 1A

Protein Classes

PANTHER Classes

Protein / Receptor / G-protein Coupled Receptor / F-box/wd Repeat-containing Protein 1A

Protein Summary

Description

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). This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]

Uniprot Accession IDs

• Q9Y297
• B5MD49
• Q5W141
• Q5W142
• Q9Y213

Gene Name

• BTRC

Ensembl ID

• ENST00000370187
• ENSP00000359206
• ENSG00000166167
• ENST00000408038
• ENSP00000385339

Symbol

• BTRCP
• FBW1A
• FBXW1A
• FWD1
• FBW1A
• FBXW1
• bTrCP
• FBXW1A
• bTrCP1
• betaTrCP
• BETA-TRCP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
disease perturbation	0.99
biological process	0.97
hub protein	0.92
protein domain	0.92

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 283.8   (req: < 5)

Gene RIFs: 128   (req: <= 3)

Antibodies: 326   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 283.8   (req: >= 5)

Gene RIFs: 128   (req: > 3)

Antibodies: 326   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 38

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (5)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2	2	2		81.7
red blood cell distribution width	EFO_0005192	1	1	1		35
diastolic blood pressure	EFO_0006336	1	1	1		30.8
smoking behavior	EFO_0004318	1	1	1		8.1
erythrocyte count	EFO_0004305	1	1	1		6.9

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
smoking status measurement	EFO_0006527	2		81.7
red blood cell distribution width	EFO_0005192	1		35
diastolic blood pressure	EFO_0006336	1		30.8
smoking behavior	EFO_0004318	1		8.1
erythrocyte count	EFO_0004305	1		6.9

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Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	beta-transducin repeat containing E3 ubiquitin protein ligase		711843
Mouse	beta-transducin repeat containing protein	MGI:1338871	12234
Rat	beta-transducin repeat containing E3 ubiquitin protein ligase	RGD:1359721	361765
Dog	beta-transducin repeat containing E3 ubiquitin protein ligase	VGNC:38564	486851
Horse	beta-transducin repeat containing E3 ubiquitin protein ligase	VGNC:15923	100070200

Species	Name	OMA	EggNOG	Inparanoid
Macaque	beta-transducin repeat containing E3 ubiquitin protein ligase
Mouse	beta-transducin repeat containing protein
Rat	beta-transducin repeat containing E3 ubiquitin protein ligase
Dog	beta-transducin repeat containing E3 ubiquitin protein ligase
Horse	beta-transducin repeat containing E3 ubiquitin protein ligase

Protein Data Bank (2)

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (112)

Reactome (69)

KEGG (9)

PathwayCommons (30)

UniProt (1)

WikiPathways (3)

APC/C-mediated degradation of cell cycle proteins (R-HSA-174143)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
Reactome	Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Name	Explore in Pharos	Explore in Source
APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Gene Ontology Terms (43)

Functions (7)

Components (5)

Processes (31)

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10

1 – 7 of 7

GO Term	Evidence	Assigned by
ubiquitin-protein transferase activity	Inferred from Experiment (EXP)	Reactome
beta-catenin binding	Inferred from Direct Assay (IDA)	ParkinsonsUK-UCL
snoRNA binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ligase activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
protein dimerization activity	Inferred from Electronic Annotation (IEA)	InterPro
protein phosphorylated amino acid binding	Inferred from Electronic Annotation (IEA)	Ensembl
ubiquitin protein ligase activity	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (630)

Explore Interacting Targets

1 – 10 of 630

• See Interactions on String-DB

FBXW11

Tbio

Novelty: 0.0715377

p_int: 1

Score: 0.966

Data Source: BioPlex,STRINGDB

HIVEP1

Tbio

Family: TF

Novelty: 0.03053678

p_int: 1

Score: 0.56

Data Source: BioPlex,STRINGDB

TFAP4

Tbio

Family: TF

Novelty: 0.03155887

p_int: 1

Score: 0.371

Data Source: BioPlex,STRINGDB

MLPH

Tbio

Novelty: 0.01810421

p_int: 0.999999999

Score: 0.188

Data Source: BioPlex,STRINGDB

HIVEP2

Tbio

Family: TF

Novelty: 0.0290218

p_int: 0.999999997

p_wrong: 3e-9

Score: 0.566

Data Source: BioPlex,STRINGDB

FBXO5

Tbio

Novelty: 0.01571484

p_int: 0.999999995

p_ni: 5e-9

Score: 0.969

Data Source: BioPlex,Reactome,STRINGDB

CDC25B

Tchem

Family: Enzyme

Novelty: 0.00378458

p_int: 0.999999992

p_ni: 8e-9

Score: 0.678

Data Source: BioPlex,STRINGDB

EGFLAM

Tbio

Novelty: 0.02955802

p_int: 0.99999998

p_ni: 1.4e-8

p_wrong: 6e-9

Score: 0.177

Data Source: BioPlex,STRINGDB

USP47

Tchem

Family: Enzyme

Novelty: 0.07579226

p_int: 0.999999834

p_ni: 1.66e-7

Score: 0.962

Data Source: BioPlex,STRINGDB

USP37

Tbio

Family: Enzyme

Novelty: 0.05398974

p_int: 0.999999612

p_ni: 8.5e-8

p_wrong: 3.03e-7

Score: 0.473

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  283.80

PubMed score by year

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PubTator Score  175.69

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Biological rhythms
Complete proteome
Cytoplasm
Host-virus interaction
Ligase
Nucleus
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

diastolic blood pressure
erythrocyte count
red blood cell distribution width
smoking behavior
smoking status measurement

MGI Phenotype Find Similar Targets

cellular phenotype
growth/size/body region phenotype
hematopoietic system phenotype
immune system phenotype
reproductive system phenotype
skeleton phenotype