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

Gene ID: 8945, updated on 26-Aug-2014
Official Symbol
BTRCprovided by HGNC
Official Full Name
beta-transducin repeat containing E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:1144
Locus tag
RP11-529I10.2
See related
Ensembl:ENSG00000166167; HPRD:04596; MIM:603482; Vega:OTTHUMG00000018932
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]
See BTRC in Epigenomics, MapViewer
Location:
10q24.32
Exon count:
15
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 10 NC_000010.11 (101354033..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 LBX1 antisense RNA 1 (head to head) Neighboring gene uncharacterized LOC101927419 Neighboring gene ladybird homeobox 1 Neighboring gene uncharacterized LOC102724260 Neighboring gene microRNA 3158-1 Neighboring gene microRNA 3158-2 Neighboring gene polymerase (DNA directed), lambda Neighboring gene deleted in primary ciliary dyskinesia homolog (mouse)

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2011-12-21)

ISCA Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2011-12-21)

ISCA Genome Curation Page

Protein interactions

Protein Gene Interaction Pubs
Vpu 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 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 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
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

Go to the HIV-1, Human Protein Interaction Database

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC4643

Gene Ontology Provided by GOA

Function Evidence Code Pubs
beta-catenin binding IEA
Inferred from Electronic Annotation
more info
 
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 transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
G2/M transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
 
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process 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
 
mammary gland epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
mitotic cell cycle TAS
Traceable Author Statement
more info
 
negative regulation of sequence-specific 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
 
positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle 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 IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
regulation of I-kappaB kinase/NF-kappaB signaling IEA
Inferred from Electronic Annotation
more info
 
regulation of cell cycle IEA
Inferred from Electronic Annotation
more info
 
regulation of circadian rhythm IDA
Inferred from Direct Assay
more info
PubMed 
regulation of proteasomal protein catabolic process IEA
Inferred from Electronic Annotation
more info
 
regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle TAS
Traceable Author Statement
more info
 
rhythmic process IEA
Inferred from Electronic Annotation
more info
 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
viral process TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
SCF ubiquitin ligase complex IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
nucleus IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
F-box/WD repeat-containing protein 1A
Names
F-box/WD repeat-containing protein 1A
beta-TrCP1
E3RSIkappaB
F-box and WD-repeat protein 1B
epididymis tissue protein Li 2a
pIkappaBalpha-E3 receptor subunit
F-box and WD repeats protein beta-TrCP

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 

    Range
    4966..208254
    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 proteins identical to 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
    UniProtKB/TrEMBL
    B7Z3H4
    UniProtKB/TrEMBL
    Q68DS0
    Related
    ENSP00000377088, ENST00000393441
    Conserved Domains (4) summary
    pfam12125
    Location:112151
    Blast Score: 231
    Beta-TrCP_D; D domain of beta-TrCP
    COG2319
    Location:264560
    Blast Score: 388
    COG2319; FOG: WD40 repeat [General function prediction only]
    cd00200
    Location:277555
    Blast Score: 654
    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 ...
    pfam12937
    Location:155202
    Blast Score: 127
    F-box-like; F-box-like
  2. NM_003939.4NP_003930.1  F-box/WD repeat-containing protein 1A isoform 2

    See proteins identical to 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, BM680713, CR749295, DA218668
    Consensus CDS
    CCDS7511.1
    UniProtKB/TrEMBL
    B2R8L3
    UniProtKB/TrEMBL
    Q68DS0
    UniProtKB/Swiss-Prot
    Q9Y297
    Related
    ENSP00000385339, OTTHUMP00000020315, ENST00000408038, OTTHUMT00000049937
    Conserved Domains (4) summary
    pfam12125
    Location:102141
    Blast Score: 231
    Beta-TrCP_D; D domain of beta-TrCP
    COG2319
    Location:254550
    Blast Score: 385
    COG2319; FOG: WD40 repeat [General function prediction only]
    cd00200
    Location:267545
    Blast Score: 661
    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 ...
    pfam12937
    Location:145192
    Blast Score: 128
    F-box-like; F-box-like
  3. NM_033637.3NP_378663.1  F-box/WD repeat-containing protein 1A isoform 1

    See proteins identical to NP_378663.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AK313417, BC006204, BC027994, BM680713, CR749295, DA218668
    Consensus CDS
    CCDS7512.1
    UniProtKB/TrEMBL
    B2R8L3
    UniProtKB/TrEMBL
    Q68DS0
    UniProtKB/Swiss-Prot
    Q9Y297
    Related
    ENSP00000359206, OTTHUMP00000020314, ENST00000370187, OTTHUMT00000049936
    Conserved Domains (4) summary
    pfam12125
    Location:138177
    Blast Score: 232
    Beta-TrCP_D; D domain of beta-TrCP
    COG2319
    Location:290586
    Blast Score: 388
    COG2319; FOG: WD40 repeat [General function prediction only]
    cd00200
    Location:303581
    Blast Score: 660
    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 ...
    pfam12937
    Location:181228
    Blast Score: 128
    F-box-like; F-box-like

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000010.11 

    Range
    101354033..101557321
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006718054.1XP_006718117.1  

    Conserved Domains (4) summary
    pfam12125
    Location:265304
    Blast Score: 234
    Beta-TrCP_D; D domain of beta-TrCP
    COG2319
    Location:417713
    Blast Score: 401
    COG2319; FOG: WD40 repeat [General function prediction only]
    cd00200
    Location:430708
    Blast Score: 664
    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 ...
    pfam12937
    Location:308355
    Blast Score: 128
    F-box-like; F-box-like
  2. XM_005270264.1XP_005270321.1  

    See proteins identical to XP_005270321.1

    Conserved Domains (2) summary
    COG2319
    Location:11307
    Blast Score: 355
    COG2319; FOG: WD40 repeat [General function prediction only]
    cd00200
    Location:24302
    Blast Score: 620
    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 ...

RNA

  1. XR_428727.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000142.1 

    Range
    96743700..96947675
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018921.2 

    Range
    103397663..103600757
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)