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MYBBP1A (MYB binding protein (P160) 1a)

Written2011-01Claudia Perrera, Riccardo Colombo
Department of Cell Biology-Oncology, Nerviano Medical Sciences, Viale Pasteur 10, Nerviano 20014, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMYB binding protein (P160) 1a
Alias_symbol (synonym)P160
PAP2
FLJ37886
Other alias
HGNC (Hugo) MYBBP1A
LocusID (NCBI) 10514
Atlas_Id 41467
Location 17p13.2  [Link to chromosome band 17p13]
Location_base_pair Starts at 4442191 and ends at 4458681 bp from pter ( according to hg19-Feb_2009)  [Mapping MYBBP1A.png]
Fusion genes
(updated 2016)
MYBBP1A (17p13.2) / BAG6 (6p21.33)MYBBP1A (17p13.2) / EPC2 (2q23.1)

DNA/RNA

Note Total gene length 16491 bp, mRNA length 4122 bp, telomeric to SPNS2 and centromeric to GGT6. Two variants described. MYBBP1A gene is composed by 26 exones and 28 introns.
Description The human MYBBP1A gene is located on chromosome 17p13.3 (Keough et al., 1999).
Transcription The complete MYBBP1A cDNA is 4518 bp, including 25 bp of 5' UTR and 506 bp of 3' UTR up to the polyA tail.

Protein

 
  Schematic representation of Mybbp1A protein. aa 1-582 is the domain reported to interact in vitro with Myb. NLS: Nuclear and nucleolar localisation signal. The indicated S, T and Y are phosphorylated residues identified in several phospho-proteomic studies.
Description Human MYBBP1A is a 1328 aa long protein. Murine MYBBP1A was originally identified as a protein interacting with the leucine zipper of c-Myb (Favier et al., 1994). Subsequently, in 1998, the human gene homologue of MYBBP1A was cloned and its chromosomal location mapped to 17p13.3 (Keough et al., 1999).
Expression MYBBP1A is ubiquitously expressed (Tavner et al., 1998).
Localisation MYBBP1A is a nuclear protein, predominantly localized in the nucleolus (Keough et al., 2003). MYBBP1A has been confirmed as a resident protein of the nucleolus by three large-scale proteomic studies that have established a protein inventory of this sub-nuclear compartment (Andersen et al., 2002; Scherl et al., 2002; Andersen et al., 2005). The nuclear/nucleolar localization signals are present in the C-terminal tail of MYBBP1A.
Function MYBBP1A functions have not yet been completely clarified. It was originally identified as a protein able to interact with the negative regulatory domain (NRD) of c-Myb; however, it was later shown to lack any significant effect in a Myb-dependent transcription reporter assay (Favier et al., 1994). MYBBP1A has been found to interact with and regulate several transcription factors: it binds and represses both Prep1-Pbx1, involved in development and organogenesis, and also PGC-1a, a key regulator of metabolic processes such as mitochondrial biogenesis and respiration and gluconeogenesis in liver (Fan et al., 2004; Diaz et al., 2007). MYBBP1A acts as a co-repressor for RelA/p65, a member of the NFkB family, by competing with the co-activator p300 histone acetyltrasferase for interaction with the transcription activation domain (TAD) of RelA/p65. It is also a co-repressor on the Period2 promoter, repressing the expression of Per2, an essential gene in the regulation of the circadian clock (Owen et al., 2007; Hara et al., 2009). Conversely, MYBBP1A is a positive regulator of the aromatic hydrocarbon receptor (AhR) which mediates transcriptional responses to certain hydrophobic ligands, such as dioxin, by enhancing the ability of AhR to activate transcription (Jones et al., 2002).
MYBBP1A has also been reported to be a component of macromolecular complexes such as the B-WICH complex, a 3 MDa assembly made of proteins and RNAs, formed during active transcription (Cavellan et al., 2006) or part of large interactomes such as the SMN interactome (Fuller et al., 2010).
MYBBP1A can be post-translationally processed in some type of cells to generate an amino-terminal fragments of 67 kDa (p67). Ribosomal stress induced by Actinomycin D (an inhibitor of ribosome biogenesis) treatment causes MYBBP1A processing and translocation from the nucleolus to the nucloplasm (Diaz et al., 2007; Yamauchi et al., 2008), indicating a possible MYBBP1A role in ribosome biogenesis.
Several post-translational modifications have been described for MYBBP1A, even if their biological significance is not yet clarified. MYBBP1A is reported to be a heavily phosphorylated protein in cells, according to several large-scale mass spectrometry-based phosphoproteomic studies (Beausoleil et al., 2004; Beausoleil et al., 2006; Nousiainen et al., 2006; Olsen et al., 2006; Cantin et al., 2008; Daub et al., 2008; Dephoure et al., 2008; Imami et al., 2008). The majority of the phosphosites mapped in MYBBP1A in these studies (18 out of a total of 21) reside within the ~200 amino-acid long C-terminal portion of the protein, which has been shown to be relevant for its nuclear and nucleolar localization (Keough et al., 2003). Notably, MYBBP1A was also found to be also a component of the proteome as well as the phospho-proteome of the human mitotic spindle. MYBBP1A contains several consensus motifs for several kinases, but until now, only Ser1303 has been proven in vitro and in HeLa cells to be indeed phosphorylated by Aurora B kinase (Perrera et al., 2010). In this work, it has been shown that MYBBP1A depletion by RNAi causes a delay in progression through mitosis and defects in mitotic spindle assembly and stability, indicating that, like other nucleolar proteins, MYBBP1A may have a role in insuring correct mitotic progression (Perrera et al., 2010).
MYBBP1A has been reported to be also sumoylated upon MG132 treatment (Matafora et al., 2009).
Homology Orthologous genes for MYBBP1A sharing a high degree of similarity are present in rat and mice. Protein homologues have also been recognized in dog, bovine, and chicken and a MYBBP1A-like protein spanning 1269 residues and showing a 60% similarity to the human protein has been identified in zebrafish, suggesting that MYBBP1A is significantly conserved across vertebrate species (Amsterdam et al., 2004). MYBBP1A shares some homology to a yeast protein called POL5, reported to be an essential DNA polymerase in Saccharomyces cerevisiae (Yang et al., 2003).

Implicated in

Note
  
Entity Various cancers
Disease MYBBP1A maps at 17p13.3, a region frequently lost in many solid and haematological tumors, such as breast and ovarian cancer, medulloblastoma, astrocytoma, leukemias, etc. This indicates that this chromosomal band contains one or more tumor suppressor genes. However, MYBBP1A is unlikely a candidate for being a tumor suppressor gene, as it lies centromeric to the regions of LOH described (Keough et al., 1999).
  

Bibliography

Identification of 315 genes essential for early zebrafish development.
Amsterdam A, Nissen RM, Sun Z, Swindell EC, Farrington S, Hopkins N.
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12792-7. Epub 2004 Jul 15.
PMID 15256591
 
Nucleolar proteome dynamics.
Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M.
Nature. 2005 Jan 6;433(7021):77-83.
PMID 15635413
 
A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP.
Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10.
PMID 16964243
 
Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd.
J Proteome Res. 2008 Mar;7(3):1346-51. Epub 2008 Jan 26.
PMID 18220336
 
The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear proteins in transcription.
Cavellan E, Asp P, Percipalle P, Farrants AK.
J Biol Chem. 2006 Jun 16;281(24):16264-71. Epub 2006 Apr 9.
PMID 16603771
 
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M.
Mol Cell. 2008 Aug 8;31(3):438-48.
PMID 18691976
 
A quantitative atlas of mitotic phosphorylation.
Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP.
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. Epub 2008 Jul 31.
PMID 18669648
 
p160 Myb-binding protein interacts with Prep1 and inhibits its transcriptional activity.
Diaz VM, Mori S, Longobardi E, Menendez G, Ferrai C, Keough RA, Bachi A, Blasi F.
Mol Cell Biol. 2007 Nov;27(22):7981-90. Epub 2007 Sep 17.
PMID 17875935
 
Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK.
Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, Jaeger S, Erdjument-Bromage H, Tempst P, Spiegelman BM.
Genes Dev. 2004 Feb 1;18(3):278-89. Epub 2004 Jan 26.
PMID 14744933
 
Detection of proteins that bind to the leucine zipper motif of c-Myb.
Favier D, Gonda TJ.
Oncogene. 1994 Jan;9(1):305-11.
PMID 8302594
 
The SMN interactome includes Myb-binding protein 1a.
Fuller HR, Man NT, Lam le T, Thanh le T, Keough RA, Asperger A, Gonda TJ, Morris GE.
J Proteome Res. 2010 Jan;9(1):556-63.
PMID 19928837
 
Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter.
Hara Y, Onishi Y, Oishi K, Miyazaki K, Fukamizu A, Ishida N.
Nucleic Acids Res. 2009 Mar;37(4):1115-26. Epub 2009 Jan 7.
PMID 19129230
 
Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.
Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y.
Anal Sci. 2008 Jan;24(1):161-6.
PMID 18187866
 
Myb-binding protein 1a augments AhR-dependent gene expression.
Jones LC, Okino ST, Gonda TJ, Whitlock JP Jr.
J Biol Chem. 2002 Jun 21;277(25):22515-9. Epub 2002 Apr 15.
PMID 11956195
 
Molecular cloning and chromosomal mapping of the human homologue of MYB binding protein (P160) 1A (MYBBP1A) to 17p13.3.
Keough R, Woollatt E, Crawford J, Sutherland GR, Plummer S, Casey G, Gonda TJ.
Genomics. 1999 Dec 15;62(3):483-9.
PMID 10644447
 
Myb-binding protein 1a is a nucleocytoplasmic shuttling protein that utilizes CRM1-dependent and independent nuclear export pathways.
Keough RA, Macmillan EM, Lutwyche JK, Gardner JM, Tavner FJ, Jans DA, Henderson BR, Gonda TJ.
Exp Cell Res. 2003 Sep 10;289(1):108-23.
PMID 12941609
 
Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition.
Matafora V, D'Amato A, Mori S, Blasi F, Bachi A.
Mol Cell Proteomics. 2009 Oct;8(10):2243-55. Epub 2009 Jul 12.
PMID 19596686
 
Phosphoproteome analysis of the human mitotic spindle.
Nousiainen M, Sillje HH, Sauer G, Nigg EA, Korner R.
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5391-6. Epub 2006 Mar 24.
PMID 16565220
 
Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M.
Cell. 2006 Nov 3;127(3):635-48.
PMID 17081983
 
MYBBP1a is a novel repressor of NF-kappaB.
Owen HR, Elser M, Cheung E, Gersbach M, Kraus WL, Hottiger MO.
J Mol Biol. 2007 Feb 23;366(3):725-36. Epub 2006 Dec 15.
PMID 17196614
 
Identification of Myb-binding protein 1A (MYBBP1A) as a novel substrate for aurora B kinase.
Perrera C, Colombo R, Valsasina B, Carpinelli P, Troiani S, Modugno M, Gianellini L, Cappella P, Isacchi A, Moll J, Rusconi L.
J Biol Chem. 2010 Apr 16;285(16):11775-85. Epub 2010 Feb 22.
PMID 20177074
 
Functional proteomic analysis of human nucleolus.
Scherl A, Coute Y, Deon C, Calle A, Kindbeiter K, Sanchez JC, Greco A, Hochstrasser D, Diaz JJ.
Mol Biol Cell. 2002 Nov;13(11):4100-9.
PMID 12429849
 
Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb.
Tavner FJ, Simpson R, Tashiro S, Favier D, Jenkins NA, Gilbert DJ, Copeland NG, Macmillan EM, Lutwyche J, Keough RA, Ishii S, Gonda TJ.
Mol Cell Biol. 1998 Feb;18(2):989-1002.
PMID 9447996
 
Ribosomal stress induces processing of Mybbp1a and its translocation from the nucleolus to the nucleoplasm.
Yamauchi T, Keough RA, Gonda TJ, Ishii S.
Genes Cells. 2008 Jan;13(1):27-39.
PMID 18173745
 
Yeast POL5 is an evolutionarily conserved regulator of rDNA transcription unrelated to any known DNA polymerases.
Yang W, Rogozin IB, Koonin EV.
Cell Cycle. 2003 Mar-Apr;2(2):120-2.
PMID 12695662
 

Citation

This paper should be referenced as such :
Perrera, C ; Colombo, R
MYBBP1A (MYB binding protein (P160) 1a)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(8):667-669.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MYBBP1AID41467ch17p13.html


External links

Nomenclature
HGNC (Hugo)MYBBP1A   7546
Cards
AtlasMYBBP1AID41467ch17p13
Entrez_Gene (NCBI)MYBBP1A  10514  MYB binding protein 1a
AliasesP160; PAP2
GeneCards (Weizmann)MYBBP1A
Ensembl hg19 (Hinxton)ENSG00000132382 [Gene_View]  chr17:4442191-4458681 [Contig_View]  MYBBP1A [Vega]
Ensembl hg38 (Hinxton)ENSG00000132382 [Gene_View]  chr17:4442191-4458681 [Contig_View]  MYBBP1A [Vega]
ICGC DataPortalENSG00000132382
TCGA cBioPortalMYBBP1A
AceView (NCBI)MYBBP1A
Genatlas (Paris)MYBBP1A
WikiGenes10514
SOURCE (Princeton)MYBBP1A
Genetics Home Reference (NIH)MYBBP1A
Genomic and cartography
GoldenPath hg19 (UCSC)MYBBP1A  -     chr17:4442191-4458681 -  17p13.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MYBBP1A  -     17p13.3   [Description]    (hg38-Dec_2013)
EnsemblMYBBP1A - 17p13.3 [CytoView hg19]  MYBBP1A - 17p13.3 [CytoView hg38]
Mapping of homologs : NCBIMYBBP1A [Mapview hg19]  MYBBP1A [Mapview hg38]
OMIM604885   
Gene and transcription
Genbank (Entrez)AF147709 AK095205 AK293458 AK301622 AK303150
RefSeq transcript (Entrez)NM_001105538 NM_014520
RefSeq genomic (Entrez)NC_000017 NC_018928 NT_010718 NW_004929405
Consensus coding sequences : CCDS (NCBI)MYBBP1A
Cluster EST : UnigeneHs.701718 [ NCBI ]
CGAP (NCI)Hs.701718
Alternative Splicing GalleryENSG00000132382
Gene ExpressionMYBBP1A [ NCBI-GEO ]   MYBBP1A [ EBI - ARRAY_EXPRESS ]   MYBBP1A [ SEEK ]   MYBBP1A [ MEM ]
Gene Expression Viewer (FireBrowse)MYBBP1A [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10514
GTEX Portal (Tissue expression)MYBBP1A
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9BQG0   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9BQG0  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9BQG0
Splice isoforms : SwissVarQ9BQG0
PhosPhoSitePlusQ9BQG0
Domains : Interpro (EBI)ARM-type_fold    DNA_pol_V   
Domain families : Pfam (Sanger)DNA_pol_phi (PF04931)   
Domain families : Pfam (NCBI)pfam04931   
Conserved Domain (NCBI)MYBBP1A
DMDM Disease mutations10514
Blocks (Seattle)MYBBP1A
SuperfamilyQ9BQG0
Human Protein AtlasENSG00000132382
Peptide AtlasQ9BQG0
HPRD05349
IPIIPI00005024   IPI00607584   IPI00908888   IPI00168774   
Protein Interaction databases
DIP (DOE-UCLA)Q9BQG0
IntAct (EBI)Q9BQG0
FunCoupENSG00000132382
BioGRIDMYBBP1A
STRING (EMBL)MYBBP1A
ZODIACMYBBP1A
Ontologies - Pathways
QuickGOQ9BQG0
Ontology : AmiGOcore promoter binding  osteoblast differentiation  transcription corepressor activity  DNA-directed DNA polymerase activity  protein binding  nucleus  nucleus  nucleoplasm  nucleolus  nucleolus  cytoplasm  transcription, DNA-templated  regulation of transcription, DNA-templated  nucleocytoplasmic transport  transcription factor binding  membrane  respiratory electron transport chain  circadian regulation of gene expression  cellular response to glucose starvation  NLS-dependent protein nuclear import complex  intracellular membrane-bounded organelle  sequence-specific DNA binding  poly(A) RNA binding  positive regulation of gene expression, epigenetic  negative regulation of transcription, DNA-templated  positive regulation of cell cycle arrest  DNA biosynthetic process  intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of anoikis  
Ontology : EGO-EBIcore promoter binding  osteoblast differentiation  transcription corepressor activity  DNA-directed DNA polymerase activity  protein binding  nucleus  nucleus  nucleoplasm  nucleolus  nucleolus  cytoplasm  transcription, DNA-templated  regulation of transcription, DNA-templated  nucleocytoplasmic transport  transcription factor binding  membrane  respiratory electron transport chain  circadian regulation of gene expression  cellular response to glucose starvation  NLS-dependent protein nuclear import complex  intracellular membrane-bounded organelle  sequence-specific DNA binding  poly(A) RNA binding  positive regulation of gene expression, epigenetic  negative regulation of transcription, DNA-templated  positive regulation of cell cycle arrest  DNA biosynthetic process  intrinsic apoptotic signaling pathway by p53 class mediator  positive regulation of anoikis  
REACTOMEQ9BQG0 [protein]
REACTOME Pathways5250924 [pathway]   
NDEx NetworkMYBBP1A
Atlas of Cancer Signalling NetworkMYBBP1A
Wikipedia pathwaysMYBBP1A
Orthology - Evolution
OrthoDB10514
GeneTree (enSembl)ENSG00000132382
Phylogenetic Trees/Animal Genes : TreeFamMYBBP1A
HOVERGENQ9BQG0
HOGENOMQ9BQG0
Homologs : HomoloGeneMYBBP1A
Homology/Alignments : Family Browser (UCSC)MYBBP1A
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMYBBP1A [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MYBBP1A
dbVarMYBBP1A
ClinVarMYBBP1A
1000_GenomesMYBBP1A 
Exome Variant ServerMYBBP1A
ExAC (Exome Aggregation Consortium)MYBBP1A (select the gene name)
Genetic variants : HAPMAP10514
Genomic Variants (DGV)MYBBP1A [DGVbeta]
DECIPHER (Syndromes)17:4442191-4458681  ENSG00000132382
CONAN: Copy Number AnalysisMYBBP1A 
Mutations
ICGC Data PortalMYBBP1A 
TCGA Data PortalMYBBP1A 
Broad Tumor PortalMYBBP1A
OASIS PortalMYBBP1A [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMYBBP1A  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMYBBP1A
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MYBBP1A
DgiDB (Drug Gene Interaction Database)MYBBP1A
DoCM (Curated mutations)MYBBP1A (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MYBBP1A (select a term)
intoGenMYBBP1A
NCG5 (London)MYBBP1A
Cancer3DMYBBP1A(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604885   
Orphanet
MedgenMYBBP1A
Genetic Testing Registry MYBBP1A
NextProtQ9BQG0 [Medical]
TSGene10514
GENETestsMYBBP1A
Huge Navigator MYBBP1A [HugePedia]
snp3D : Map Gene to Disease10514
BioCentury BCIQMYBBP1A
ClinGenMYBBP1A
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10514
Chemical/Pharm GKB GenePA31346
Clinical trialMYBBP1A
Miscellaneous
canSAR (ICR)MYBBP1A (select the gene name)
Probes
Litterature
PubMed84 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMYBBP1A
EVEXMYBBP1A
GoPubMedMYBBP1A
iHOPMYBBP1A
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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