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FLASH GENE
Symbol BUB1B contributors: mct/pgu - updated : 28-02-2015
HGNC name budding uninhibited by benzimidazoles 1 homolog beta (yeast)
HGNC id 1149
Corresponding disease
MVA mosaic variegated aneuploidy
Location 15q15.1      Physical location : 40.453.209 - 40.513.335
Synonym name
  • spindle assembly checkpoint gene
  • kinetochore-associated checkpoint kinase 1b
  • MAD3/BUB1-related protein kinase
  • mitotic checkpoint kinase MAD3L
  • protein SSK1
  • budding uninhibited by benzimidazole-related 1
  • Synonym symbol(s) SSK1, BUBR1, Bub1A, MAD3L, hBUBR1, BUB1beta, MAD3
    EC.number 2.7.1.37, 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 60.13 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    THBS1 15q15 thrombospondin 1 FLJ35989 15q14 hypothetical protein FLJ35989 GPR 15q14 putative G protein coupled receptor LOC388113 15 hypothetical gene supported by BC035481 MGC10997 15q13-q14 pseudogene MGC10997 SRP14 15q15.1-q21.1 signal recognition particle 14kDa (homologous Alu RNA binding protein) BMF 15q14 Bcl2 modifying factor BUB1B 15q15 BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) PAK6 15q14 p21(CDKN1A)-activated kinase 6 LOC390577 15 similar to KIAA1728 protein PLCB2 15q15 phospholipase C, beta 2 LOC390578 15 similar to BLOCK 23 LOC388114 15 LOC388114 LOC388115 15 similar to RIKEN cDNA 2600011L02 LOC146071 15q14 similar to RIKEN cDNA 1810007E14; EST AA238765 DISP2 15q14 dispatched homolog 2 (Drosophila) FLJ14502 15q14 TRAF4 associated factor 1 IVD 15q14-q15 isovaleryl Coenzyme A dehydrogenase KIAA0945 D4ST-1 15q14 isovaleryl Coenzyme A dehydrogenase MGC20481 15q14 hypothetical protein MGC20481 C18B11 15q13.3 C18B11 homolog (44.9kD) AF15Q14 15q14 AF15q14 protein RAD51 15q15.1 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) FLJ10579 15q14 hypothetical protein FLJ10579 GCHFR 15q15 GTP cyclohydrolase I feedback regulatory protein FLJ10634 15q14 hypothetical protein FLJ10634 ZFYVE19 15q14 zinc finger, FYVE domain containing 19 PPP1R14D 15q13.3 protein phosphatase 1, regulatory (inhibitor) subunit 14D SPINT1 15q15 serine protease inhibitor, Kunitz type 1 ARHV 15q13.3 ras homolog gene family, member V VPS18 15q14-q15 vacuolar protein sorting protein 18 DLL4 15q14 delta-like 4 (Drosophila) MGC4504 15q14 hypothetical protein MGC4504 KIAA1259 15q14 hypothetical protein MGC4504
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 3749 - 1050 - 1999 9889005
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
     thymus   highly
    Digestiveintestinesmall intestine   
     mouthtongue  highly
    Lymphoid/Immunelymph node    
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint, G2M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • conserved N-terminal region, comprising residues 1-204, a globular domain of high alpha-helical content, involved in direct protein-protein interactions and/or protein-lipid interactions
  • two conserved domains, CD1 directing kinetochore localization and CD2 encoding a serine/threonine kinase activity
  • a conserved and highly phosphorylated domain (KARD) crucial for formation of kinetochore-microtubule attachments
  • a putative nuclear localization signal (NLS) between CD1 and CD2
  • a unique C-terminal extension that contains a serine-threonine kinase domain
  • conjugated Acetylated , sumoylated
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae Bub1p
    ortholog to murine Bub1b
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • BUB1 subfamily
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • localize to kinetochores with MAD1L1 and MAD2L1
  • localize to centrosome where it physically interacts with PLK1
  • helps promote the establishment of stable kinetochore-microtubule attachments during prometaphase
  • basic FUNCTION
  • multidomain protein kinase playing an important role in cell division
  • modulating the timing of anaphase initiation in mitotic cells with improperly aligned chromosomes
  • contributing to a specific driving force in tumor metastasis and progression as a result of nonmutational, as well as mutational inactivation
  • playing a role in regulating aging and infertility
  • acting as a crucial meiotic timer, mediating a prophase delay in every meiosis
  • playing an essential role for early embryonic development and normal hematopoiesis
  • plays an essential role in kinetochore localization and assembly of other spindle assembly checkpoint components
  • plays an important role in the DNA damage response
  • having functions in the spindle checkpoint remarkably dosage-dependent and reduction of BUB1B expression resulting in premature chromatid separation and aneuploidy
  • may play an important role in mediating the cross-talk, between spindle checkpoint components and ERKs and MEK
  • involved in the mitotic spindle checkpoint pathway
  • at centrosome, inhibits PLK1 phosphorylation and its kinase activty during interphase, thus preventing centrosome reduplication
  • required for ubiquitin-mediated proteasomal degradation of CDC20 in the G0 phase and maintains anaphase-promoting complex/cyclosome-CDC20 homolog 1 activity that regulates the optimal level of dishevelled for ciliogenesis
  • cell cycle regulator, plays a crucial role in cilia formation through the quantitative regulation of ciliary protein
  • functions as a crucial component that monitors proper chromosome congression and mitotic timing during cell division
  • its sumoylation plays an important role in its timely removal from the kinetochores and the checkpoint inactivation, thus allowing normal anaphase entry and chromosome segregation
  • vertebrate mitotic checkpoint protein that is an unusual pseudokinase
  • counteracts AURKB activity at improperly attached kinetochores by recruiting B56-PP2A phosphatase complexes
  • critical component of the spindle assembly checkpoint, the surveillance mechanism that helps maintain the high fidelity of mitotic chromosome segregation by preventing cells from initiating anaphase if one or more kinetochores are not attached to the spindle
  • potentially contributes to enhanced polyploidization by a mechanism other than its spindle assembly checkpoint (SAC) function
  • MAD2L1 is one of the key components of the spindle and mitotic checkpoint complex that regulates the fidelity of cell division along with MAD1L1, CDC20, BUB1B
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with BUB3, anaphase promoting complex
  • component of the mitotic spindle checkpoint
  • member of the SAC complex (spindle assembly checkpoint)
  • complexing with CDC20
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • BUB3, CENPE
  • directly links spindle checkpoint proteins BUB1B and BUB1 to kinetochores and is required for spindle checkpoint and chromosome alignment (association of the amino and middle domain of CASK5 with the TPR domains in the N- termini of BUB1B and BUB1 is essential for BUB1B and BUB1 to execute their distinct mitotic functions)
  • interacting with TP73 (has a role in regulating SAC functions during meiosis and mitosis)
  • functional interaction between BUB1B and PTTG1 in an anaphase-promoting complex/cyclosome CDC20-independent manner
  • physically interacts with Plk1
  • KIF18A physically interacted with CENPE and BUB1B during mitosis
  • in early M phase, binds to cell division cycle protein 20 (CDC20), a co-activator of the anaphase-promoting complex/cyclosome
  • direct interaction between BUB1B and MAD2L1 and the interaction plays critical roles in mitotic checkpoint complex-mediated inhibition of anaphase-promoting complex/cyclosome (APC/C)
  • binding of MAD2L1BP to MAD2L1 in mitotic checkpoint complex (MCC) may trigger a conformational change in CDC20 that facilitates its phosphorylation by CDK, and the latter process may promote its dissociation from BUB1B
  • CENPE-dependent BUB1B autophosphorylation at unattached kinetochores is important for a full-strength mitotic checkpoint to prevent single chromosome loss
  • PLK1 and BUB1B cooperate to stabilize kinetochore-microtubule interactions by regulating PP2A-B56alpha-mediated dephosphorylation of AURKB substrates at the kinetochore-microtubule interface
  • TP53 counteracts tissue destruction in response to BUB1B insufficiency through diverse mechanisms and uncover a causal link between senescence of the progenitor cell compartment and age-related dysfunction
  • direct interaction between BUB1B and MAD2L1 is critical for assembly and function of the human mitotic checkpoint complex (MCC), the spindle assembly checkpoint (SAC) effector
  • TP53 deficiency may lead to the failure of BUB1B downregulation by Oxidative stress (OS) and TP53 deficiency and BUB1B accumulation could contribute to gastric carcinogenesis associated with aneuploidy
  • USP16 deubiquitinates PLK1, resulting in an enhanced interaction with kinetochore-localized proteins such as BUB1B, and thereby retains PLK1 on the kinetochores to promote proper chromosome alignment in early mitosis
  • MAD2L1BP blocks the MAD2L1-BUB1B interaction and prevents spontaneous clathrin-mediated INSR endocytosis
  • cell & other
    REGULATION
    activated by disruption of microtubules that activates the spindle checkpoint, of which BUB1B is a major component
    in response to kinetochore tension
    induced by ZNF143
    inhibited by budding uninhibited by benzimidazoles
    during late mitosis via both proteasome- and caspase-mediated degradation
    Other mitotic phosphorylation of BUB1B is also affected by TTK inhibition but seems dispensable for mitotic checkpoint complex (MCC) assembly
    loss of BUB1B acetylation causes defects in spindle assembly checkpoint signaling and promotes tumor formation
    is modified via sumoylation and BUB1B sumoylation is important for regulating normal chromosome segregation
    ASSOCIATED DISORDERS
    corresponding disease(s) MVA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in colorectal, intestinal cancers and in glioblastoma, rarely in lung carcinoma
    tumoral     --low  
    in colorectal, intestinal cancers and in glioblastoma, rarely in lung carcinomain colon carcinoma with lymph node metastasis
    constitutional germinal mutation      
    cause premature chromatid separation (mosaic variegated aneuploidy) (MVA)syndrome, which is characterized by constitutional aneuploidy and a high risk of childhood cancer
    tumoral       loss of function
    may be involved in the initiation stage of tumorigenesis
    constitutional       loss of function
    correlated with enhanced activation of MEK and ERKs after disruption of microtubule dynamics
    tumoral     --over  
    in breast carcinoma (
    tumoral     --over  
    associated with poor survival in early stage breast cancer patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • BubR1+/- mouse embryonic fibroblasts are defective in spindle checkpoint activation, contain a significantly reduced amount of securin and Cdc20, and exhibit a greater level of micronuclei than wild-type cells