Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000274
UniProt IDO43683
Primary gene name(s)BUB1
Synonym gene name(s)BUB1L
Protein nameMitotic checkpoint serine/threonine-protein kinase BUB1
Protein functionSerine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Acts as a substrate for anaphase-promoting complex or cyclosome, APC/C in complex with its activator CDH1, APC/C-Cdh1. Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936}.
Subcellular locationNucleus. Chromosome, centromere, kinetochore. Note=Nuclear in interphase cells. Accumulates gradually during G1 and S phase of the cell cycle, peaks at G2/M, and drops dramatically after mitosis. Localizes to the outer kinetochore. Kinetochore localization is required for normal mitotic timing and checkpoint response to spindle damage and occurs very early in prophase. AURKB, CASC5 and INCENP are required for kinetochore localization, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O43683
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cell division [GO:0051301];
cell proliferation [GO:0008283];
mitotic cell cycle checkpoint [GO:0007093];
mitotic nuclear division [GO:0007067];
mitotic spindle assembly checkpoint [GO:0007094];
regulation of chromosome segregation [GO:0051983];
regulation of sister chromatid cohesion [GO:0007063];
sister chromatid cohesion [GO:0007062];
spindle assembly checkpoint [GO:0071173];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
condensed chromosome kinetochore [GO:0000777];
condensed nuclear chromosome outer kinetochore [GO:0000942];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
kinetochore [GO:0000776];
membrane [GO:0016020];
nucleoplasm [GO:0005654]
Protein-protein interaction107164
Phylogenetic treeO43683
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. CD3-0.1113131724374360.9220155568619690.950131168673841
AZA vs. DISU0.6543135213939480.1869027058281110.773309079601727
AZA vs. IL70.1957658401895270.6368015414694110.999311006273513
AZA vs. SAHA0.1896309662829330.505325620731520.824380779968283
DISU vs. CD30.7548137361141040.5004851829342110.625928287360017
DISU vs. IL7-0.467567780071780.3769897287251110.747975804228883
DISU vs. SAHA-0.4632500096586320.3105730218459310.693619068609396
DMSO vs. AZA0.02353852419066890.9468069646448531
DMSO vs. CD30.120332005326910.9154451095716790.942277984127996
DMSO vs. DISU-0.6336808953056180.1916933506686130.708043822200001
DMSO vs. IL70.1798897650398480.654984175544140.927841690011581
DMSO vs. SAHA0.1596411151696440.5469280148160570.836857507789066
HIV vs. Mock in Activation-0.1269256285096240.9505488393246220.999983755607037
HIV vs. Mock in Latency0.2143670410228970.4386980070455530.999834320637052
IL7 vs. CD30.3165557346932950.7792356277729110.853666105277106
SAHA vs. CD30.2770055712417040.824111469028680.87530919212081
SAHA vs. IL7-0.0083362851137530.9813332513751360.993505663857807
(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) FALSE
(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 0.561248 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
0.908 1.721 1.462 1.487 1.338
(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
209642_at 2.78 Yes upregulated in CD4+ cells

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
2LAH NMR - A=1-150.
4A1G X-ray 2.6Å A/B/C/D=1-150.
4QPM X-ray 2.2Å A/B=740-1085.
4R8Q X-ray 2.3Å A=724-1085.
5DMZ X-ray 2.4Å A/B=726-1085.

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

HIV Partner Interaction Type PubMed
Tat activates 24488929

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04110 Cell cycle - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)