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NIN ninein (GSK3B interacting protein)

Identity

Other namesGSK3B-interacting protein
Glycogen synthase kinase 3 beta-interacting protein
KIAA1565
Ninein centrosomal protein.
HGNC (Hugo) NIN
Location 14q22.1
Location_base_pair Starts at 50262297 and ends at 50360106 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order SAV1 (SAlvador homolog 1 Drosophila) is more centromeric.
C14orf29 (Chromosome 14 Open Reading Frame 29) is more telomeric.
 
  Genomic structure of NIN. Black boxes indicate exons.

DNA/RNA

Description 31 exons spanning 111.3 Kb on 14q22.1. Transcription is from telomere to centromere.
Transcription 5 alternative transcripts:
  • Variant 2 encodes de longest isoform
  • Variant 1 contains a different 3' terminal region and the resulting protein has a distinct and shorter C-terminus.
  • Variant 3 contains also a different 3' terminal region and it encodes isoform 3 , with a shorter and distinct C-terminus than variant 2.
  • Variant 4 differs in the 5' and 3' UTRs, and has multiple differences in the coding region. The resulting isoform 4 contains an additional internal segment, when compared to isoform 2, has a longer and distinct N-terminus, and has a shorter and distinct C-terminus.
  • Variant 5 has multiple differences in the coding region and 3' UTR, the resulting isoform 5 contains an additional internal segment and has a distinct and shorter C-terminus. Isoform 5 has also been referred to as hNinein-Lm.

    4 alternative transcripts in EnsEMBL 1:

  • Q9HCK7 corresponding to RefSeq variant 4.
  • NIN corresponding to RefSeq variant 5.
  • NIN corresponding to RefSeq variant 4.
  • NM_182944 corresponding to RefSeq variant 1.
  • Protein

    Note Ninein (GSK3B interacting protein)
     
      Schematic representation of NIN. LZ: leuzine-zipper domain. Coiled-coil domains are indicated with asterisks.
    Description Homooligomer. Interacts with GSK3B (GSK3-beta) via its C-terminus domain, ait also interacts with C14ORF166 preventing its phosphorylation by GSK3-beta. NIN is a component of the core centrosome. Arranged in a tubular conformation with an open and a closed end within the centrosome. In the mother centrosome, it localizes at both ends of the centrosome tube, including the site of centrosome duplication, while in the daughter centrosome it is present only at the closed end. Requires PCM1 for centrosome localization. In interphase cells, it is localized in the centrosome. Decreases in metaphase and anaphase and reappears in telophase.
    Expression Ubiquitous. Highly expressed in heart and skeletal muscle.
    Localisation Centrosome.
    Function The centrosome is the major microtubulin-organizing center (MTOC) in most vertebrate cells. In a typical somatic cell, the centrosome is composed of a pair of centrioles surrounded by a mass of amorphous pericentriolar material (PCM) that may be involved in the complex of Y-tubulin, centrin, pericentrin and ninein. This protein play an important role as a microtubule minus-end capping, centriole position, anchoring factor and as a centrosome maturation factor. Localization of this protein to the centrosome requires three of its four leucine zippers in the central coiled-coil domain. In addition it has been suggested that ninein could play a role to ensure equal chromosome segregation prior to telophase/cytokinesis in the division cycle.
    Homology It presents homology in various species. It also belongs to ENSF00000001557 protein family.

    Mutations

    Somatic t(5;14)(q33;q24) 5' NIN-PDGFRB 3' fusion in a chronic myeloprolifetrative disorder with eosinophilia

    Implicated in

    Entity t(5;14)(q33;q24) , 5q33 myeloproliferative disease.
    Disease Chronic myeloproliferative disorder with eosinophilia and skin lesions ( "Atypical CML").
    Prognosis Good. Relative mild disease course over at least 13 years. Imatinib mesylate responsive disease.
    Cytogenetics t(5;14)(q33;q24)
    Hybrid/Mutated Gene 5' NIN-PDGFRB 3'
    Abnormal Protein NIN-PDGFRB
     
    Schematic representation of the fusion NIN-PDGFRB consecuence of the t(5;14)(q33;q24) in a chronic myeloprolifetrative disorder with eosinophilia. From up to down: PDGFRB, NIN and the putative chimeric NIN-PDGFRB structure. TM, transmembrane domain; TK, tyrosine kinase domain; LZ, leuzine-zipper domain. Coiled coil domains on NIN and NIN-PDGFRB are indicated with asterisks.
      

    External links

    Nomenclature
    HGNC (Hugo)NIN   14906
    Entrez_Gene (NCBI)NIN  51199  ninein (GSK3B interacting protein)
    Cards
    AtlasNINID176
    GeneCards (Weizmann)NIN
    Ensembl (Hinxton)ENSG00000100503 [Gene_View]  NIN [Vega]
    AceView (NCBI)NIN
    Genatlas (Paris)NIN
    euGene (Indiana)51199
    SOURCE (Stanford)NM_016350 NM_020921 NM_182944 NM_182946
    Gene Expression (Array Express) ENSG00000100503
    Genomic and cartography
    GoldenPath (UCSC)NIN  -  14q22.1   chr14:50262297-50360106 -  14q22.1   [Description]    (hg18-Mar_2006)
    EnsemblNIN - 14q22.1 [CytoView]
    Mapping of homologs : NCBININ [Mapview]
    OMIM608684   
    Gene and transcription
    Gene : Genbank (Entrez)AA742651 AB046785 AF186776 AF212162 AF223937
    Reference sequence (RefSeq transcript) :SRSNM_016350 NM_020921 NM_182944 NM_182946
    Reference transcript : EntrezNM_016350 NM_020921 NM_182944 NM_182946
    RefSeq genomic : SRSAC_000057 AC_000146 NC_000014 NT_026437 NW_001838111 NW_925539
    RefSeq genomic : EntrezAC_000057 AC_000146 NC_000014 NT_026437 NW_001838111 NW_925539
    Consensus coding sequences : CCDS NCBININ
    Cluster EST : UnigeneHs.310429 [ SRS ] Hs.310429 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)209
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtQ8N4C6 (SRS) Q8N4C6 (Expasy) Q8N4C6 (Uniprot)
    With graphics : InterProQ8N4C6
    Splice isoforms : VarSplice FASTAQ8N4C6(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)EF_HAND_2 (PS50222)   
    Domain pattern : Prosite (Expaxy)EF_HAND_2 (PS50222)   
    Domains : Interpro (SRS)EF_HAND_2   
    Domains : Interpro (EBI)EF_HAND_2   
    Related proteins : CluSTrQ8N4C6
    Domain families : Pfam SRS
    Domain families : Pfam Sanger
    Domain families : Pfam NCBI
    Blocks (Seattle)Q8N4C6
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    HPRD09785
    Protein Interaction databases
    DIP (DOE-UCLA)Q8N4C6
    IntAct (EBI)Q8N4C6
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBININ
    SNP : GeneSNP UtahNIN
    SNP : HGBaseNIN
    Genetic variants : HAPMAPNIN
    Cancer Gene: CensusNIN 
    Somatic Mutations in Cancer : COSMICNIN 
    Translocation Breakpoints in Cancer : TICdbNIN 
    Mutations and Diseases : HGMDNIN
    Hereditary diseases : OMIM608684   
    Hereditary diseases : GENETests608684   
    Diseases : Genetic AssociationNIN
    General knowledge
    Homologs : HomoloGeneNIN
    Homology/Alignments : Family Browser UCSCNIN
    Phylogenetic Trees/Animal Genes : TreeFamNIN
    Chemical/Protein Interactions : CTD51199
    Keywords Ontology : AmiGOnucleotide binding  protein binding  GTP binding  cytoplasm  centrosome  cytoskeleton  microtubule  centrosome localization  
    Keywords Ontology : EGO-EBInucleotide binding  protein binding  GTP binding  cytoplasm  centrosome  cytoskeleton  microtubule  centrosome localization  
    Pathways : BIOCARTA
    Pathways : KEGG
    Other databases
    Probes
    Probes : ImagenesNIN Related clones (RZPD - Berlin)
    Literature
    PubMed25 Pubmed reference(s) in Entrez
    PubGeneNIN

    Bibliography

    Pericentrin, a highly conserved centrosome protein involved in microtubule organization.
    Doxsey SJ, Stein P, Evans L, Calarco PD, Kirschner M
    Cell. 1994 ; 76 (4) : 639-650.
    PMID 8124707
     
    Molecular characterisation of ninein, a new coiled-coil protein of the centrosome.
    Bouckson-Castaing V, Moudjou M, Ferguson DJ, Mucklow S, Belkaid Y, Milon G, Crocker PR
    Journal of cell science. 1996 ; 109 ( Pt 1) : 179-190.
    PMID 8834802
     
    Cloning and characterization of a novel human ninein protein that interacts with the glycogen synthase kinase 3beta.
    Hong YR, Chen CH, Chang JH, Wang S, Sy WD, Chou CK, Howng SL
    Biochimica et biophysica acta. 2000 ; 1492 (2-3) : 513-516.
    PMID 11004522
     
    Genomic organization and molecular characterization of the human ninein gene.
    Hong YR, Chen CH, Chuo MH, Liou SY, Howng SL
    Biochemical and biophysical research communications. 2000 ; 279 (3) : 989-995.
    PMID 11162463
     
    Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the role of ninein.
    Mogensen MM, Malik A, Piel M, Bouckson-Castaing V, Bornens M
    Journal of cell science. 2000 ; 113 ( Pt 17) : 3013-3023.
    PMID 10934040
     
    A subset of centrosomal proteins are arranged in a tubular conformation that is reproduced during centrosome duplication.
    Ou Y, Rattner JB
    Cell motility and the cytoskeleton. 2000 ; 47 (1) : 13-24.
    PMID 11002307
     
    Re-evaluating centrosome function.
    Doxsey S
    Nature reviews. Molecular cell biology. 2001 ; 2 (9) : 688-698.
    PMID 11533726
     
    Assembly of centrosomal proteins and microtubule organization depends on PCM-1.
    Dammermann A, Merdes A
    The Journal of cell biology. 2002 ; 159 (2) : 255-266.
    PMID 12403812
     
    CEP110 and ninein are located in a specific domain of the centrosome associated with centrosome maturation.
    Ou YY, Mack GJ, Zhang M, Rattner JB
    Journal of cell science. 2002 ; 115 (Pt 9) : 1825-1835.
    PMID 11956314
     
    Molecular characterization of human ninein protein: two distinct subdomains required for centrosomal targeting and regulating signals in cell cycle.
    Chen CH, Howng SL, Cheng TS, Chou MH, Huang CY, Hong YR
    Biochemical and biophysical research communications. 2003 ; 308 (4) : 975-983.
    PMID 12927815
     
    A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3beta and is highly expressed in brain tumors.
    Howng SL, Hsu HC, Cheng TS, Lee YL, Chang LK, Lu PJ, Hong YR
    FEBS letters. 2004 ; 566 (1-3) : 162-168.
    PMID 15147888
     
    Human ninein is a centrosomal autoantigen recognized by CREST patient sera and plays a regulatory role in microtubule nucleation.
    Stillwell EE, Zhou J, Joshi HC
    Cell cycle (Georgetown, Tex.). 2004 ; 3 (7) : 923-930.
    PMID 15190203
     
    NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.
    Vizmanos JL, Novo FJ, Romˆ°n JP, Baxter EJ, Lahortiga I, Larrˆ°yoz MJ, Odero MD, Giraldo P, Calasanz MJ, Cross NC
    Cancer research. 2004 ; 64 (8) : 2673-2676.
    PMID 15087377
     
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    Contributor(s)

    Written09-2004José Luis Vizmanos

    Citation

    This paper should be referenced as such :
    Vizmanos JL . NIN ninein (GSK3B interacting protein). Atlas Genet Cytogenet Oncol Haematol. September 2004 .
    URL : http://AtlasGeneticsOncology.org/Genes/NINID176.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Feb 27 10:50:18 CET 2010

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