NIN ninein (GSK3B interacting protein)

2004-09-01   José Luis Vizmanos  

Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, 31008 Pamplona, Navarra, Espana

Identity

HGNC
LOCATION
14q22.1
IMAGE
Atlas Image
LEGEND
Genomic structure of NIN. Black boxes indicate exons.
LOCUSID
ALIAS
SCKL7
FUSION GENES

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.
  • Proteins

    Note

    Ninein (GSK3B interacting protein)
    Atlas Image
    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 name
    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 gene
    5 NIN-PDGFRB 3
    Fusion protein
    NIN-PDGFRB
    Atlas Image
    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.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    88348021996Molecular characterisation of ninein, a new coiled-coil protein of the centrosome.Bouckson-Castaing V et al
    129278152003Molecular characterization of human ninein protein: two distinct subdomains required for centrosomal targeting and regulating signals in cell cycle.Chen CH et al
    124038122002Assembly of centrosomal proteins and microtubule organization depends on PCM-1.Dammermann A et al
    115337262001Re-evaluating centrosome function.Doxsey S et al
    81247071994Pericentrin, a highly conserved centrosome protein involved in microtubule organization.Doxsey SJ et al
    111624632000Genomic organization and molecular characterization of the human ninein gene.Hong YR et al
    151478882004A novel ninein-interaction protein, CGI-99, blocks ninein phosphorylation by GSK3beta and is highly expressed in brain tumors.Howng SL et al
    109340402000Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the role of ninein.Mogensen MM et al
    110023072000A subset of centrosomal proteins are arranged in a tubular conformation that is reproduced during centrosome duplication.Ou Y et al
    119563142002CEP110 and ninein are located in a specific domain of the centrosome associated with centrosome maturation.Ou YY et al
    151902032004Human ninein is a centrosomal autoantigen recognized by CREST patient sera and plays a regulatory role in microtubule nucleation.Stillwell EE et al
    150873772004NIN, 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 et al

    Other Information

    Locus ID:

    NCBI: 51199
    MIM: 608684
    HGNC: 14906
    Ensembl: ENSG00000100503

    Variants:

    dbSNP: 51199
    ClinVar: 51199
    TCGA: ENSG00000100503
    COSMIC: NIN

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000100503ENST00000245441Q8N4C6
    ENSG00000100503ENST00000324330Q8N4C6
    ENSG00000100503ENST00000382041Q8N4C6
    ENSG00000100503ENST00000382043Q8N4C6
    ENSG00000100503ENST00000389869H9KV85
    ENSG00000100503ENST00000453196C9J066
    ENSG00000100503ENST00000453401H7C162
    ENSG00000100503ENST00000476352E9PN67
    ENSG00000100503ENST00000485005A0A0B4J215
    ENSG00000100503ENST00000486950R4GN85
    ENSG00000100503ENST00000496749E9PJH9
    ENSG00000100503ENST00000530853H0YDJ4
    ENSG00000100503ENST00000530997Q8N4C6

    Expression (GTEx)

    0
    10
    20
    30
    40
    50
    60

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    381175882024Ninein promotes F-actin cup formation and inward phagosome movement during phagocytosis in macrophages.1
    381175882024Ninein promotes F-actin cup formation and inward phagosome movement during phagocytosis in macrophages.1
    341185942021β3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis.2
    341185942021β3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis.2
    307657892019Genetic susceptibility of common polymorphisms in NIN and SIGLEC5 to chronic periodontitis.8
    307657892019Genetic susceptibility of common polymorphisms in NIN and SIGLEC5 to chronic periodontitis.8
    253322392015JAK2 tyrosine kinase phosphorylates and is negatively regulated by centrosomal protein Ninein.10
    257417252015Sip1 downstream Effector ninein controls neocortical axonal growth, ipsilateral branching, and microtubule growth and stability.28
    253322392015JAK2 tyrosine kinase phosphorylates and is negatively regulated by centrosomal protein Ninein.10
    257417252015Sip1 downstream Effector ninein controls neocortical axonal growth, ipsilateral branching, and microtubule growth and stability.28
    236654822013Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype.10
    236654822013Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype.10
    229377432012Positive selection on NIN, a gene involved in neurogenesis, and primate brain evolution.11
    230471842012Differential expression of centrosome-associated proteins in human brain tumors: a possible role of hNinein isoform 6 in cell differentiation.2
    229377432012Positive selection on NIN, a gene involved in neurogenesis, and primate brain evolution.11

    Citation

    José Luis Vizmanos

    NIN ninein (GSK3B interacting protein)

    Atlas Genet Cytogenet Oncol Haematol. 2004-09-01

    Online version: http://atlasgeneticsoncology.org/gene/176/favicon/js/gene-fusions/?id=176