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BTRC beta-transducin repeat containing E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 8945, updated on 3-May-2020

Summary

Official Symbol
BTRCprovided by HGNC
Official Full Name
beta-transducin repeat containing E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:1144
See related
Ensembl:ENSG00000166167 MIM:603482
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FWD1; FBW1A; FBXW1; bTrCP; FBXW1A; bTrCP1; betaTrCP; BETA-TRCP
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 11.6), testis (RPKM 7.3) and 25 other tissues See more
Orthologs

Genomic context

See BTRC in Genome Data Viewer
Location:
10q24.32
Exon count:
21
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 10 NC_000010.11 (101353808..101557321)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (103113790..103317078)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378453 Neighboring gene RNA, U2 small nuclear 43, pseudogene Neighboring gene RNA, U2 small nuclear 59, pseudogene Neighboring gene VISTA enhancer hs326 Neighboring gene DNA polymerase lambda Neighboring gene microRNA 3158-1 Neighboring gene microRNA 3158-2 Neighboring gene deleted in primary ciliary dyskinesia homolog (mouse)

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Vpu vpu Vpu requires BTRC to degrade BST2 (tetherin) but does not require BTRC for Vpu-mediated BST2 (tetherin) antagonism PubMed
vpu HIV-1 Vpu-induced cleavage of IRF3 is largely dependent on the ability of Vpu to interact with beta-TrCP, and mutation of the Vpu phosphorylation sites Ser52 and Ser56 greatly decreases the function of Vpu-induced IRF3 cleavage PubMed
vpu Interaction of HIV-1 Vpu with betaTrCP is required for Vpu ubiquitination and degradation by the proteasome. Amino acid substitutions at serine's 52 and 56 of Vpu abolish the interaction with betaTrCP PubMed
vpu Binding of HIV-1 Vpu to beta-TrCP requires two phosphoserine residues on Vpu (amino acids 52 and 56) and results in recruitment of beta-TrCP to cellular membranes PubMed
vpu Through binding to beta-TrCP, HIV-1 Vpu targets CD4 for degradation in the endoplasmic reticulum and also inhibits IkappaB-alpha degradation as well as NF-kappaB activation PubMed
vpu Chimeras between the TMD of HIV-1 M Vpu and the cytoplasmic domains of SIVcpzPtt, SIVcpzPts, and SIVgor Vpu proteins are capable of binding to human beta-TrCP PubMed
vpu Most HIV-1 Vpu proteins from Cameroonian group N viruses are unable to bind beta-TrCP because of lack of a functional beta-TrCP binding site DSGxxS in Vpu PubMed
vpu HIV-1 Vpu S61A mutant efficiently interacts with endogenous betaTrCP and strongly stabilizes beta-catenin PubMed
vpu HIV-1 Vpu stabilizes cellular Cdc25A and differentially affects betaTrCP-mediated degradation events at different phases of the cell cycle PubMed
vpu Poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP is required for HIV-1 Vpu-induced CD4 degradation PubMed
vpu HIV-1 Vpu interferes with beta-TrCP to inhibit TNF-alpha-induced activation of NFkappaB PubMed
vpu The invariant leucine 63 and the valine 68 within the predicted second alpha-helical domain of the HIV-1 Vpu cytoplasmic tail are required for CD4 down-modulation. L63A and V68A mutants still bind CD4 and retain the ability to interact with beta-TrCP1 PubMed
vpu HIV-1 Vpu and beta-TrCP co-immunoprecipitate with tetherin PubMed
vpu HIV-1 Vpu expression leads to stabilization and upregulation of p53 via inhibiting association of p53 with beta-TrCP and its subsequent ubiquitination PubMed
vpu HIV-1 Vpu interacts with BST-2 in the trans-Golgi network or in early endosomes, leading to lysosomal degradation of BST-2. Vpu-mediated downregulation of BST-2 depends on cellular ubiquitination machinery via betaTrCP PubMed
vpu Co-depletion of beta-TrCP1 and beta-TrCP2 support Vpu's activity to enhance virus release and to downregulate endogenous tetherin in TZM-bl cells PubMed
vpu HIV-1 Vpu is a strong competitive inhibitor of beta-TrCP and impairs the degradation of SCF-beta-TrCP substrates such as IKBalpha, ATF4 and beta-catenin PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC4643

Gene Ontology Provided by GOA

Function Evidence Code Pubs
beta-catenin binding IDA
Inferred from Direct Assay
more info
PubMed 
ligase activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein dimerization activity IEA
Inferred from Electronic Annotation
more info
 
protein phosphorylated amino acid binding IEA
Inferred from Electronic Annotation
more info
 
contributes_to ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
Fc-epsilon receptor signaling pathway TAS
Traceable Author Statement
more info
 
G2/M transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
NIK/NF-kappaB signaling TAS
Traceable Author Statement
more info
 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
T cell receptor signaling pathway TAS
Traceable Author Statement
more info
 
Wnt signaling pathway TAS
Traceable Author Statement
more info
 
branching involved in mammary gland duct morphogenesis IEA
Inferred from Electronic Annotation
more info
 
cellular response to organic cyclic compound IEA
Inferred from Electronic Annotation
more info
 
interleukin-1-mediated signaling pathway TAS
Traceable Author Statement
more info
 
mammary gland epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of DNA-binding transcription factor activity TAS
Traceable Author Statement
more info
PubMed 
negative regulation of smoothened signaling pathway TAS
Traceable Author Statement
more info
PubMed 
negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of circadian rhythm ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of proteolysis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
post-translational protein modification TAS
Traceable Author Statement
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
protein dephosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
protein destabilization IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein polyubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein polyubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein polyubiquitination TAS
Traceable Author Statement
more info
 
protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
regulation of canonical Wnt signaling pathway IC
Inferred by Curator
more info
PubMed 
regulation of circadian rhythm IDA
Inferred from Direct Assay
more info
PubMed 
regulation of mitotic cell cycle phase transition TAS
Traceable Author Statement
more info
 
regulation of proteasomal protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
rhythmic process IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
stimulatory C-type lectin receptor signaling pathway TAS
Traceable Author Statement
more info
 
stress-activated MAPK cascade TAS
Traceable Author Statement
more info
 
ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
SCF ubiquitin ligase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
F-box/WD repeat-containing protein 1A
Names
E3RSIkappaB
F-box and WD repeats protein beta-TrCP
F-box and WD-repeat protein 1B
beta-TrCP1
epididymis tissue protein Li 2a
pIkappaBalpha-E3 receptor subunit

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009234.1 RefSeqGene

    Range
    5098..208246
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001256856.1NP_001243785.1  F-box/WD repeat-containing protein 1A isoform 3

    See identical proteins and their annotated locations for NP_001243785.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
    Source sequence(s)
    AK313417, BC006204, BM680713, CR749295, DA218668
    Consensus CDS
    CCDS73183.1
    UniProtKB/TrEMBL
    B2R8L3, B7Z3H4, Q68DS0
    Related
    ENSP00000377088.5, ENST00000393441.8
    Conserved Domains (4) summary
    cd00200
    Location:277555
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:280315
    7WD40; WD40 repeat [structural motif]
    pfam12125
    Location:113151
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:155202
    F-box-like; F-box-like
  2. NM_003939.5NP_003930.1  F-box/WD repeat-containing protein 1A isoform 2

    See identical proteins and their annotated locations for NP_003930.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AF129530, AK313417, BC006204, CR749295
    Consensus CDS
    CCDS7511.1
    UniProtKB/Swiss-Prot
    Q9Y297
    UniProtKB/TrEMBL
    B2R8L3, Q68DS0
    Related
    ENSP00000385339.2, ENST00000408038.6
    Conserved Domains (4) summary
    cd00200
    Location:267545
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:270305
    7WD40; WD40 repeat [structural motif]
    pfam12125
    Location:103141
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:145192
    F-box-like; F-box-like
  3. NM_033637.4NP_378663.1  F-box/WD repeat-containing protein 1A isoform 1

    See identical proteins and their annotated locations for NP_378663.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    BC006204, BC027994, CR749295
    Consensus CDS
    CCDS7512.1
    UniProtKB/Swiss-Prot
    Q9Y297
    UniProtKB/TrEMBL
    A0A0S2Z4P6, B2R8L3, Q68DS0
    Related
    ENSP00000359206.3, ENST00000370187.8
    Conserved Domains (4) summary
    cd00200
    Location:303581
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:306341
    7WD40; WD40 repeat [structural motif]
    pfam12125
    Location:139177
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:181228
    F-box-like; F-box-like

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p13 Primary Assembly

    Range
    101353808..101557321
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017016872.1XP_016872361.1  F-box/WD repeat-containing protein 1A isoform X3

    Conserved Domains (5) summary
    COG2319
    Location:272568
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:285563
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:121159
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:163210
    F-box-like; F-box-like
    sd00039
    Location:288323
    7WD40; WD40 repeat [structural motif]
  2. XM_017016874.1XP_016872363.1  F-box/WD repeat-containing protein 1A isoform X4

    Conserved Domains (5) summary
    COG2319
    Location:228524
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:241519
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:77115
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:119166
    F-box-like; F-box-like
    sd00039
    Location:244279
    7WD40; WD40 repeat [structural motif]
  3. XM_006718054.2XP_006718117.1  F-box/WD repeat-containing protein 1A isoform X1

    Conserved Domains (5) summary
    COG2319
    Location:417713
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:430708
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:266304
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:308355
    F-box-like; F-box-like
    sd00039
    Location:433468
    7WD40; WD40 repeat [structural motif]
  4. XM_017016870.1XP_016872359.1  F-box/WD repeat-containing protein 1A isoform X2

  5. XM_024448246.1XP_024304014.1  F-box/WD repeat-containing protein 1A isoform X6

    Conserved Domains (4) summary
    cd00200
    Location:204482
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:207242
    7WD40; WD40 repeat [structural motif]
    pfam12125
    Location:4078
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:82129
    F-box-like; F-box-like
  6. XM_017016871.1XP_016872360.1  F-box/WD repeat-containing protein 1A isoform X3

    Conserved Domains (5) summary
    COG2319
    Location:272568
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:285563
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:121159
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:163210
    F-box-like; F-box-like
    sd00039
    Location:288323
    7WD40; WD40 repeat [structural motif]
  7. XM_017016873.2XP_016872362.1  F-box/WD repeat-containing protein 1A isoform X3

    Conserved Domains (5) summary
    COG2319
    Location:272568
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:285563
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:121159
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:163210
    F-box-like; F-box-like
    sd00039
    Location:288323
    7WD40; WD40 repeat [structural motif]
  8. XM_024448247.1XP_024304015.1  F-box/WD repeat-containing protein 1A isoform X6

    Conserved Domains (4) summary
    cd00200
    Location:204482
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    sd00039
    Location:207242
    7WD40; WD40 repeat [structural motif]
    pfam12125
    Location:4078
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:82129
    F-box-like; F-box-like
  9. XM_011540320.2XP_011538622.1  F-box/WD repeat-containing protein 1A isoform X5

    Conserved Domains (5) summary
    COG2319
    Location:222518
    WD40; WD40 repeat [General function prediction only]
    cd00200
    Location:235513
    WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
    pfam12125
    Location:71109
    Beta-TrCP_D; D domain of beta-TrCP
    pfam12937
    Location:113160
    F-box-like; F-box-like
    sd00039
    Location:238273
    7WD40; WD40 repeat [structural motif]

RNA

  1. XR_001747256.1 RNA Sequence

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