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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
LocusID (NCBI) 51199
Location 14q22.1
Location_base_pair Starts at 51192546 and ends at 51297839 bp from pter ( according to hg19-Feb_2009)  [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.
      

    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias 11q23ChildAMLID1615 11q23ID1030

    External links

    Nomenclature
    HGNC (Hugo)NIN   14906
    Cards
    AtlasNINID176
    Entrez_Gene (NCBI)NIN  51199  ninein (GSK3B interacting protein)
    GeneCards (Weizmann)NIN
    Ensembl hg19 (Hinxton)ENSG00000100503 [Gene_View]  chr14:51192546-51297839 [Contig_View]  NIN [Vega]
    Ensembl hg38 (Hinxton)ENSG00000100503 [Gene_View]  chr14:51192546-51297839 [Contig_View]  NIN [Vega]
    ICGC DataPortalENSG00000100503
    cBioPortalNIN
    AceView (NCBI)NIN
    Genatlas (Paris)NIN
    WikiGenes51199
    SOURCE (Princeton)NIN
    Genomic and cartography
    GoldenPath hg19 (UCSC)NIN  -     chr14:51192546-51297839 -  14q21-q22   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)NIN  -     14q21-q22   [Description]    (hg38-Dec_2013)
    EnsemblNIN - 14q21-q22 [CytoView hg19]  NIN - 14q21-q22 [CytoView hg38]
    Mapping of homologs : NCBININ [Mapview hg19]  NIN [Mapview hg38]
    OMIM608684   614851   
    Gene and transcription
    Genbank (Entrez)AA742651 AB046785 AF186776 AF212162 AF223937
    RefSeq transcript (Entrez)NM_016350 NM_020921 NM_182944 NM_182945 NM_182946
    RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_032968 NT_026437 NW_001838111 NW_004929393
    Consensus coding sequences : CCDS (NCBI)NIN
    Cluster EST : UnigeneHs.569387 [ NCBI ]
    CGAP (NCI)Hs.569387
    Alternative Splicing : Fast-db (Paris)GSHG0009357
    Alternative Splicing GalleryENSG00000100503
    Gene ExpressionNIN [ NCBI-GEO ]     NIN [ SEEK ]   NIN [ MEM ]
    SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ8N4C6 (Uniprot)
    NextProtQ8N4C6  [Medical]
    With graphics : InterProQ8N4C6
    Splice isoforms : SwissVarQ8N4C6 (Swissvar)
    Domaine pattern : Prosite (Expaxy)EF_HAND_2 (PS50222)   
    Domains : Interpro (EBI)EF-hand-dom_pair    EF_hand_dom   
    Related proteins : CluSTrQ8N4C6
    Domain families : Pfam (Sanger)EF-hand_6 (PF13405)   
    Domain families : Pfam (NCBI)pfam13405   
    DMDM Disease mutations51199
    Blocks (Seattle)Q8N4C6
    Human Protein AtlasENSG00000100503
    Peptide AtlasQ8N4C6
    HPRD09785
    IPIIPI00441952   IPI00171791   IPI00329695   IPI00921003   IPI00441955   IPI00441959   IPI00971005   IPI00984029   IPI00441960   IPI00982681   IPI00883941   IPI00978213   
    Protein Interaction databases
    DIP (DOE-UCLA)Q8N4C6
    IntAct (EBI)Q8N4C6
    FunCoupENSG00000100503
    BioGRIDNIN
    IntegromeDBNIN
    STRING (EMBL)NIN
    Ontologies - Pathways
    QuickGOQ8N4C6
    Ontology : AmiGOspindle pole  calcium ion binding  protein binding  GTP binding  nucleolus  centrosome  centriole  microtubule  microtubule anchoring at centrosome  centrosome localization  centrosome-templated microtubule nucleation  
    Ontology : EGO-EBIspindle pole  calcium ion binding  protein binding  GTP binding  nucleolus  centrosome  centriole  microtubule  microtubule anchoring at centrosome  centrosome localization  centrosome-templated microtubule nucleation  
    Protein Interaction DatabaseNIN
    DoCM (Curated mutations)NIN
    Wikipedia pathwaysNIN
    Gene fusion - rearrangements
    Rearrangement : TICdbNIN [14q22.1]  -  PDGFRB [2q31.1]
    Polymorphisms : SNP, variants
    NCBI Variation ViewerNIN [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)NIN
    dbVarNIN
    ClinVarNIN
    1000_GenomesNIN 
    Exome Variant ServerNIN
    SNP (GeneSNP Utah)NIN
    SNP : HGBaseNIN
    Genetic variants : HAPMAPNIN
    Genomic VariantsNIN  NIN [DGVbeta]
    Mutations
    ICGC Data PortalENSG00000100503 
    Cancer Gene: CensusNIN 
    Somatic Mutations in Cancer : COSMICNIN 
    CONAN: Copy Number AnalysisNIN 
    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
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)14:51192546-51297839
    Mutations and Diseases : HGMDNIN
    OMIM608684    614851   
    MedgenNIN
    NextProtQ8N4C6 [Medical]
    GENETestsNIN
    Disease Genetic AssociationNIN
    Huge Navigator NIN [HugePedia]  NIN [HugeCancerGEM]
    snp3D : Map Gene to Disease51199
    DGIdb (Drug Gene Interaction db)NIN
    General knowledge
    Homologs : HomoloGeneNIN
    Homology/Alignments : Family Browser (UCSC)NIN
    Phylogenetic Trees/Animal Genes : TreeFamNIN
    Chemical/Protein Interactions : CTD51199
    Chemical/Pharm GKB GenePA31630
    Clinical trialNIN
    Cancer Resource (Charite)ENSG00000100503
    Other databases
    Probes
    Litterature
    PubMed38 Pubmed reference(s) in Entrez
    CoreMineNIN
    GoPubMedNIN
    iHOPNIN

    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. 2004;8(4):300-302.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/NINID176.html

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