Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009749
UniProt IDQ9Y297
Primary gene name(s)BTRC
Synonym gene name(s)BTRCP, FBW1A, FBXW1A
Protein nameF-box/WD repeat-containing protein 1A
Protein functionSubstrate 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. SCF(BTRC mediates the ubiquitination of CTNNB1 and participates in Wnt signaling. 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. Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22'. SCF(BTRC mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis, PubMed:25704143, PubMed:25503564. SCF(BTRC mediates the ubiquitination of phosphorylated NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2. Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2. 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. {ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10497169, ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:11359933, ECO:0000269|PubMed:11994270, ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:12902344, ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:9859996}.
Subcellular locationCytoplasm {ECO:0000250|UniProtKB:Q3ULA2}. Nucleus {ECO:0000250|UniProtKB:Q3ULA2}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y297
Gene Ontology
(Biological Process)
Complete annatation
branching involved in mammary gland duct morphogenesis [GO:0060444];
cellular response to organic cyclic compound [GO:0071407];
Fc-epsilon receptor signaling pathway [GO:0038095];
G2/M transition of mitotic cell cycle [GO:0000086];
mammary gland epithelial cell proliferation [GO:0033598];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
negative regulation of smoothened signaling pathway [GO:0045879];
negative regulation of transcription, DNA-templated [GO:0045892];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of circadian rhythm [GO:0042753];
positive regulation of proteolysis [GO:0045862];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition [GO:0051437];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein dephosphorylation [GO:0006470];
protein destabilization [GO:0031648];
protein polyubiquitination [GO:0000209];
protein ubiquitination [GO:0016567];
regulation of canonical Wnt signaling pathway [GO:0060828];
regulation of circadian rhythm [GO:0042752];
regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043122];
regulation of proteasomal protein catabolic process [GO:0061136];
rhythmic process [GO:0048511];
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process [GO:0031146];
signal transduction [GO:0007165];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
ubiquitin-dependent protein catabolic process [GO:0006511];
viral process [GO:0016032];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
beta-catenin binding [GO:0008013];
ligase activity [GO:0016874];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-protein transferase activity [GO:0004842]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
SCF ubiquitin ligase complex [GO:0019005]
Protein-protein interaction114457
Phylogenetic treeQ9Y297
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.433942809531760.1877794102978270.290427016111735
AZA vs. DISU0.1642247701134280.5201457472791940.940467433667575
AZA vs. IL7-0.07270394930596320.709646386037090.999311006273513
AZA vs. SAHA0.06222788509933890.8005170398748580.947843363370797
DISU vs. CD3-0.2819926882236780.4411629365069410.572592569735287
DISU vs. IL7-0.2459929165093130.3332717924173620.714052340916961
DISU vs. SAHA-0.1005581253072710.7325093434619080.921843630661778
DMSO vs. AZA-0.02282410503561370.8938564317169591
DMSO vs. CD3-0.4673803166614180.1464634194737510.232578414079484
DMSO vs. DISU-0.1886242731569940.4436384888833720.884953831766437
DMSO vs. IL7-0.04281043320733940.8147890734228950.962538241700332
DMSO vs. SAHA0.07831901103902810.7420623746122780.92450038820069
HIV vs. Mock in Activation0.05718639236503890.9269849151791250.999983755607037
HIV vs. Mock in Latency0.0494561561323590.7681930767155030.999834320637052
IL7 vs. CD3-0.4994278392353150.122726757066870.221621148212853
SAHA vs. CD3-0.3963036282314660.2637014520241770.375080781689887
SAHA vs. IL70.1318197544957120.5918000283153520.792184852750699
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.458808 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1P22 X-ray 2.9Å A=175-605.
2P64 X-ray 2.5Å A/B=128-177.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)