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MAPRE1 (Microtubule-associated protein, RP/EB family, member 1)

Identity

Other namesEB1
HGNC (Hugo) MAPRE1
LocusID (NCBI) 22919
Location 20q11.21
Location_base_pair Starts at 31407699 and ends at 31438211 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  EB1-GFP fluorescence on polymerizing microtubule plus ends in a living PtK1 cell.
Note The original name EB1 came from a yeast two hybrid screen "End Binding 1" is a nickname that was later applied when the protein was found to target to microtubule plus ends.

DNA/RNA

Description 22 Kb genomic locus, 5 introns
Transcription 2540 bp open reading frame

Protein

 
Description 268 amino acids; 35 kDa; EB1 was cloned in yeast two-hybrid screen as binding partner for the tumor suppressor APC (Adenomatous Polyposis Coli); EB1 is a microtubule plus end tracking protein (+tip). It contains a calponin homology domain and a leucine zipper
Expression EB1 is ubiquitously expressed. Protein levels remain similar throughout the cell cycle.
Localisation EB1 targets to the plus ends of microtubules when they are polymerizing, producing a "comet tail" pattern. (Figure 1). The mechanism is treadmilling, in which new subunits are continually added at the tip. EB1 also shows additional weak binding to the microtubule lattice (along the length of the microtubule). EB1 targets to kinetochores moving anti-poleward. This is suspected to be due to binding to kinetochore microtubule plus ends rather than the kinetochore itself. Through its carboxyl terminus, EB1 localizes to centrosomes and spindle poles.
Function
  • The primary function identified to date is regulation of microtubule dynamic instability. Microtubules dynamically convert between growth (polymerization) and shrinkage (depolymerization). The transition from growth to shrinkage is called catastrophe, while the conversion from shrinkage to growth is called rescue. Microtubules also pause in their polymerization. EB1 reduces these pauses and reduces the frequency of catastrophes. EB1 increases the frequency of rescues. The net result is more stable, longer microtubules. This effect is predominantly seen during mitosis.
  • EB1 is important in maintaining the structure of the mitotic spindle. This is thought to be mediated by its effects on spindle microtubule dynamic instability.
  • EB1 is important in spindle positioning within the cell. This is thought to be due to its effects on astral microtubule dynamic instability. In budding yeast, EB1 also plays a role in positioning the mitotic spindle through the bud neck. In this case, it is through microtubule dynamics as well direct binding to a protein at the bud tip, creating a physical link between the microtubule end and the cell cortex.
  • EB1 plays a role in linking kinetochores to kinetochore microtubules, which is important for chromosome stability. It is not known whether it regulates kinetochore microtubule dynamics or end-on attachment.
  • EB1 also has an independent role in anchoring microtubule minus ends to centrosomes
  • Protein-protein interactions: Adenomatous Polyposis Coli (APC) tumor suppressor, polymerized tubulin (microtubules), p150glued/dynactin, CLIP-170, mDia, Pin2/TRF1, RhoGEF2 (drosophila), shortstop (drosophila)
  • Homology MAPRE2, MAPRE3

    Mutations

    Note none known

    Implicated in

    Entity Colon cancer
    Disease Truncation of the Adenomatous Polyposis Coli (APC) protein is seen in Familial Adenomatous Polyposis (FAP) as well as most sporadic colon cancers. EB1 binds to the APC C-terminus, so its binding is lost in most truncations. Also lost are other APC binding partners including the transcription factor beta-catenin. The role of APC as a tumor suppressor is thought to be through the beta-catenin pathway. Some evidence in the mouse suggests that this is true.
    However, there is increasing evidence that connections between APC and the cytoskeleton are important in cell migration, which could have an important role in colon cancer. One Italian FAP family has been reported in which APC is truncated distal to the beta-catenin binding site but including the EB1 binding site. There is no direct evidence of EB1 mutation in colon cancer, and a single report found no evidence of somatic mutations by reverse transcriptase single-strand conformational polymorphism (SSCP) analysis in 21 sporadic colorectal cancers and seven colorectal adenomas.
      
    Entity Meduloblastoma
    Disease A single report showed that EB1 is transcriptionally elevated in pediatric meduloblastoma. There is no direct evidence of EB1 mutation in meduloblastoma.
      

    Breakpoints

    Note none known

    External links

    Nomenclature
    HGNC (Hugo)MAPRE1   6890
    Cards
    AtlasMAPRE1ID455ch20q11
    Entrez_Gene (NCBI)MAPRE1  22919  microtubule-associated protein, RP/EB family, member 1
    GeneCards (Weizmann)MAPRE1
    Ensembl (Hinxton)ENSG00000101367 [Gene_View]  chr20:31407699-31438211 [Contig_View]  MAPRE1 [Vega]
    AceView (NCBI)MAPRE1
    Genatlas (Paris)MAPRE1
    WikiGenes22919
    SOURCE (Princeton)NM_012325
    Genomic and cartography
    GoldenPath (UCSC)MAPRE1  -  20q11.21   chr20:31407699-31438211 +  20q11.1-q11.3   [Description]    (hg19-Feb_2009)
    EnsemblMAPRE1 - 20q11.1-q11.3 [CytoView]
    Mapping of homologs : NCBIMAPRE1 [Mapview]
    OMIM603108   
    Gene and transcription
    Genbank (Entrez)AK297273 AK310817 AK312590 BC040410 BC106068
    RefSeq transcript (Entrez)NM_012325
    RefSeq genomic (Entrez)AC_000152 NC_000020 NC_018931 NT_011362 NW_001838664 NW_004929418
    Consensus coding sequences : CCDS (NCBI)MAPRE1
    Cluster EST : UnigeneHs.472437 [ NCBI ]
    CGAP (NCI)Hs.472437
    Alternative Splicing : Fast-db (Paris)GSHG0018674
    Alternative Splicing GalleryENSG00000101367
    Gene ExpressionMAPRE1 [ NCBI-GEO ]     MAPRE1 [ SEEK ]   MAPRE1 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ15691 (Uniprot)
    NextProtQ15691  [Medical]
    With graphics : InterProQ15691
    Splice isoforms : SwissVarQ15691 (Swissvar)
    Domaine pattern : Prosite (Expaxy)CH (PS50021)    EB1_C (PS51230)   
    Domains : Interpro (EBI)CH-domain    EB1    EB1_C    MAPRE   
    Related proteins : CluSTrQ15691
    Domain families : Pfam (Sanger)CH (PF00307)    EB1 (PF03271)   
    Domain families : Pfam (NCBI)pfam00307    pfam03271   
    DMDM Disease mutations22919
    Blocks (Seattle)Q15691
    PDB (SRS)1PA7    1TXQ    1UEG    1VKA    1WU9    1YIB    1YIG    2HKQ    2HL3    2HL5    2QJZ    2R8U    3GJO    3TQ7   
    PDB (PDBSum)1PA7    1TXQ    1UEG    1VKA    1WU9    1YIB    1YIG    2HKQ    2HL3    2HL5    2QJZ    2R8U    3GJO    3TQ7   
    PDB (IMB)1PA7    1TXQ    1UEG    1VKA    1WU9    1YIB    1YIG    2HKQ    2HL3    2HL5    2QJZ    2R8U    3GJO    3TQ7   
    PDB (RSDB)1PA7    1TXQ    1UEG    1VKA    1WU9    1YIB    1YIG    2HKQ    2HL3    2HL5    2QJZ    2R8U    3GJO    3TQ7   
    Human Protein AtlasENSG00000101367
    Peptide AtlasQ15691
    HPRD04379
    IPIIPI00017596   IPI00910350   
    Protein Interaction databases
    DIP (DOE-UCLA)Q15691
    IntAct (EBI)Q15691
    FunCoupENSG00000101367
    BioGRIDMAPRE1
    InParanoidQ15691
    Interologous Interaction database Q15691
    IntegromeDBMAPRE1
    STRING (EMBL)MAPRE1
    Ontologies - Pathways
    Ontology : AmiGOG2/M transition of mitotic cell cycle  mitotic cell cycle  protein binding  cytoplasm  Golgi apparatus  centrosome  spindle  cytosol  microtubule  cytoplasmic microtubule  mitosis  protein C-terminus binding  cell proliferation  cortical microtubule cytoskeleton  negative regulation of microtubule polymerization  cell projection membrane  microtubule plus-end  protein localization to microtubule  microtubule plus-end binding  cell division  
    Ontology : EGO-EBIG2/M transition of mitotic cell cycle  mitotic cell cycle  protein binding  cytoplasm  Golgi apparatus  centrosome  spindle  cytosol  microtubule  cytoplasmic microtubule  mitosis  protein C-terminus binding  cell proliferation  cortical microtubule cytoskeleton  negative regulation of microtubule polymerization  cell projection membrane  microtubule plus-end  protein localization to microtubule  microtubule plus-end binding  cell division  
    REACTOMEMAPRE1
    Protein Interaction DatabaseMAPRE1
    Wikipedia pathwaysMAPRE1
    Gene fusion - rearrangments
    Rearrangement : TICdbKMT2A [11q23.3]  -  MAPRE1 [20q11.21]
    Rearrangement : TICdbMAPRE1 [20q11.21]  -  KMT2A [11q23.3]
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)MAPRE1
    SNP (GeneSNP Utah)MAPRE1
    SNP : HGBaseMAPRE1
    Genetic variants : HAPMAPMAPRE1
    1000_GenomesMAPRE1 
    ICGC programENSG00000101367 
    Somatic Mutations in Cancer : COSMICMAPRE1 
    CONAN: Copy Number AnalysisMAPRE1 
    Mutations and Diseases : HGMDMAPRE1
    OMIM603108   
    GENETestsMAPRE1
    Disease Genetic AssociationMAPRE1
    Huge Navigator MAPRE1 [HugePedia]  MAPRE1 [HugeCancerGEM]
    Genomic VariantsMAPRE1  MAPRE1 [DGVbeta]
    Exome VariantMAPRE1
    dbVarMAPRE1
    ClinVarMAPRE1
    snp3D : Map Gene to Disease22919
    General knowledge
    Homologs : HomoloGeneMAPRE1
    Homology/Alignments : Family Browser (UCSC)MAPRE1
    Phylogenetic Trees/Animal Genes : TreeFamMAPRE1
    Chemical/Protein Interactions : CTD22919
    Chemical/Pharm GKB GenePA30634
    Clinical trialMAPRE1
    Cancer Resource (Charite)ENSG00000101367
    Other databases
    Probes
    Litterature
    PubMed79 Pubmed reference(s) in Entrez
    CoreMineMAPRE1
    iHOPMAPRE1

    Bibliography

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    PMID 7606712
     
    RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells.
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    Journal of immunology (Baltimore, Md. : 1950). 1997 ; 159 (3) : 1276-1283.
    PMID 9233623
     
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    Schwartz K, Richards K, Botstein D
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    PMID 9398684
     
    The adenomatous polyposis coli-binding protein EB1 is associated with cytoplasmic and spindle microtubules.
    Berrueta L, Kraeft SK, Tirnauer JS, Schuyler SC, Chen LB, Hill DE, Pellman D, Bierer BE
    Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (18) : 10596-10601.
    PMID 9724749
     
    Absence of somatic alterations of the EB1 gene adenomatous polyposis coli-associated protein in human sporadic colorectal cancers.
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    British journal of cancer. 1998 ; 78 (10) : 1356-1360.
    PMID 9823979
     
    EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle.
    Morrison EE, Wardleworth BN, Askham JM, Markham AF, Meredith DM
    Oncogene. 1998 ; 17 (26) : 3471-3477.
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    A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein.
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    PMID 9624007
     
    The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain.
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    PMID 10226031
     
    EB/RP gene family encodes tubulin binding proteins.
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    Yeast Bim1p promotes the G1-specific dynamics of microtubules.
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    The Journal of cell biology. 1999 ; 145 (5) : 993-1007.
    PMID 10352017
     
    Regulation and function of the interaction between the APC tumour suppressor protein and EB1.
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    PMID 10773885
     
    Molecular linkage underlying microtubule orientation toward cortical sites in yeast.
    Korinek WS, Copeland MJ, Chaudhuri A, Chant J
    Science (New York, N.Y.). 2000 ; 287 (5461) : 2257-2259.
    PMID 10731146
     
    Positioning of the mitotic spindle by a cortical-microtubule capture mechanism.
    Lee L, Tirnauer JS, Li J, Schuyler SC, Liu JY, Pellman D
    Science (New York, N.Y.). 2000 ; 287 (5461) : 2260-2262.
    PMID 10731147
     
    The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules.
    Mimori-Kiyosue Y, Shiina N, Tsukita S
    Current biology : CB. 2000 ; 10 (14) : 865-868.
    PMID 10899006
     
    EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability.
    Tirnauer JS, Bierer BE
    The Journal of cell biology. 2000 ; 149 (4) : 761-766.
    PMID 10811817
     
    Critical role for the EB1 and APC interaction in the regulation of microtubule polymerization.
    Nakamura M, Zhou XZ, Lu KP
    Current biology : CB. 2001 ; 11 (13) : 1062-1067.
    PMID 11470413
     
    Characterization of human MAPRE genes and their proteins.
    Su LK, Qi Y
    Genomics. 2001 ; 71 (2) : 142-149.
    PMID 11161807
     
    Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome.
    Askham JM, Vaughan KT, Goodson HV, Morrison EE
    Molecular biology of the cell. 2002 ; 13 (10) : 3627-3645.
    PMID 12388762
     
    Dissecting interactions between EB1, microtubules and APC in cortical clusters at the plasma membrane.
    Barth AI, Siemers KA, Nelson WJ
    Journal of cell science. 2002 ; 115 (Pt 8) : 1583-1590.
    PMID 11950877
     
    Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle.
    Rogers SL, Rogers GC, Sharp DJ, Vale RD
    The Journal of cell biology. 2002 ; 158 (5) : 873-884.
    PMID 12213835
     
    EB1 targets to kinetochores with attached, polymerizing microtubules.
    Tirnauer JS, Canman JC, Salmon ED, Mitchison TJ
    Molecular biology of the cell. 2002 ; 13 (12) : 4308-4316.
    PMID 12475954
     
    EB1-microtubule interactions in Xenopus egg extracts: role of EB1 in microtubule stabilization and mechanisms of targeting to microtubules.
    Tirnauer JS, Grego S, Salmon ED, Mitchison TJ
    Molecular biology of the cell. 2002 ; 13 (10) : 3614-3626.
    PMID 12388761
     
    Characterization of functional domains of human EB1 family proteins.
    Bu W, Su LK
    The Journal of biological chemistry. 2003 ; 278 (50) : 49721-49731.
    PMID 14514668
     
    CLIP-170 interacts with dynactin complex and the APC-binding protein EB1 by different mechanisms.
    Goodson HV, Skube SB, Stalder R, Valetti C, Kreis TE, Morrison EE, Schroer TA
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    Crystal structure of the amino-terminal microtubule-binding domain of end-binding protein 1 (EB1).
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    The microtubule plus-end proteins EB1 and dynactin have differential effects on microtubule polymerization.
    Ligon LA, Shelly SS, Tokito M, Holzbaur EL
    Molecular biology of the cell. 2003 ; 14 (4) : 1405-1417.
    PMID 12686597
     
    A novel localization pattern for an EB1-like protein links microtubule dynamics to endomembrane organization.
    Mathur J, Mathur N, Kernebeck B, Srinivas BP, Hˆºlskamp M
    Current biology : CB. 2003 ; 13 (22) : 1991-1997.
    PMID 14614826
     
    Shortstop recruits EB1/APC1 and promotes microtubule assembly at the muscle-tendon junction.
    Subramanian A, Prokop A, Yamamoto M, Sugimura K, Uemura T, Betschinger J, Knoblich JA, Volk T
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    PMID 12842007
     
    Adenomatous polyposis coli and EB1 localize in close proximity of the mother centriole and EB1 is a functional component of centrosomes.
    Louie RK, Bahmanyar S, Siemers KA, Votin V, Chang P, Stearns T, Nelson WJ, Barth AI
    Journal of cell science. 2004 ; 117 (Pt 7) : 1117-1128.
    PMID 14970257
     
    Drosophila RhoGEF2 associates with microtubule plus ends in an EB1-dependent manner.
    Rogers SL, Wiedemann U, Hˆ§cker U, Turck C, Vale RD
    Current biology : CB. 2004 ; 14 (20) : 1827-1833.
    PMID 15498490
     
    EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration.
    Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, Wallar BJ, Alberts AS, Gundersen GG
    Nature cell biology. 2004 ; 6 (9) : 820-830.
    PMID 15311282
     
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    Contributor(s)

    Written11-2004Jennifer S Tirnauer
    Center for Molecular Medicine, University of Connecticut Health Center, 263 Farmington Avenue, E1032, Farmington, CT 06030-3101, USA

    Citation

    This paper should be referenced as such :
    Tirnauer JS . MAPRE1 (Microtubule-associated protein, RP/EB family, member 1). Atlas Genet Cytogenet Oncol Haematol. November 2004 .
    URL : http://AtlasGeneticsOncology.org/Genes/MAPRE1ID455ch20q11.html

    The various updated versions of this paper are referenced and archived by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/38147/1/11-2004-MAPRE1ID455ch20q11.pdf   [ Bibliographic record ]

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Apr 16 11:40:28 CEST 2014

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