NIN

Identity

Other names	GSK3B-interacting protein
	Glycogen synthase kinase 3 beta-interacting protein
	KIAA1565
	Ninein centrosomal protein.
HGNC	NIN
Location	14q22.1
Location_base_pair	Starts at 50262297 and ends at 50360106 bp from pter (hg18-Mar_2006).
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

	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	NIN   14906
Entrez_Gene	NIN  51199  ninein (GSK3B interacting protein)
	Cards
Atlas	NINID176
GeneCards	NIN
Ensembl	NIN [Search_View]   ENSG00000100503 [Gene_View]
Genatlas	NIN
GeneLynx	NIN
eGenome	NIN
euGene	51199
	Genomic and cartography
GoldenPath	NIN  -  14q22.1   chr14:50262297-50360106 -  14q21-q22   [Description]    (hg18-Mar_2006)
Ensembl	NIN - 14q21-q22 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	NIN
	Gene and transcription
Genbank	AA742651 [ ENTREZ ]
Genbank	AB046785 [ ENTREZ ]
Genbank	AF186776 [ ENTREZ ]
Genbank	AF212162 [ ENTREZ ]
Genbank	AF223937 [ ENTREZ ]
RefSeq	NM_016350 [ SRS ]    NM_016350 [ ENTREZ ]
RefSeq	NM_020921 [ SRS ]    NM_020921 [ ENTREZ ]
RefSeq	NM_182944 [ SRS ]    NM_182944 [ ENTREZ ]
RefSeq	NM_182946 [ SRS ]    NM_182946 [ ENTREZ ]
RefSeq	AC_000057 [ SRS ]    AC_000057 [ ENTREZ ]
RefSeq	AC_000146 [ SRS ]    AC_000146 [ ENTREZ ]
RefSeq	NC_000014 [ SRS ]    NC_000014 [ ENTREZ ]
RefSeq	NT_026437 [ SRS ]    NT_026437 [ ENTREZ ]
RefSeq	NW_001838111 [ SRS ]    NW_001838111 [ ENTREZ ]
RefSeq	NW_925539 [ SRS ]    NW_925539 [ ENTREZ ]
AceView	NIN AceView - NCBI
Unigene	Hs.310429 [ SRS ]    Hs.310429 [ NCBI ]     HS310429 [ spliceNest ]
Fast-db	209 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q5BKU3 [ SRS]    Q5BKU3 [ EXPASY ]     Q5BKU3 [ INTERPRO ]     Q5BKU3 [ UNIPROT ]
Prosite	PS50222 EF_HAND_2 [ SRS ]    PS50222 EF_HAND_2 [ Expasy ]
Interpro	IPR002048 EF_hand_Ca_bd [ SRS ]    IPR002048 EF_hand_Ca_bd [ EBI ]
CluSTr	Q5BKU3
Pfam	PF00036 efhand [ SRS ]    PF00036 efhand [ Sanger ]    pfam00036 [ NCBI-CDD ]
Blocks	Q5BKU3
HPRD	09785
	Protein Interaction databases
DIP	Q5BKU3
IntAct	Q5BKU3
	Polymorphism : SNP, mutations, diseases
OMIM	608684    [ map ]
GENECLINICS	608684
SNP	NIN [dbSNP-NCBI]
SNP	NM_016350 [SNP-NCI]
SNP	NM_020921 [SNP-NCI]
SNP	NM_182944 [SNP-NCI]
SNP	NM_182946 [SNP-NCI]
SNP	NIN [GeneSNPs - Utah]  NIN] [HGBASE - SRS]
HAPMAP	NIN [HAPMAP]
COSMIC	NIN [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	NIN [Translocation breakpoints In Cancer]
HGMD	NIN
	General knowledge
Family Browser	NIN [UCSC Family Browser]
SOURCE	NM_016350
SOURCE	NM_020921
SOURCE	NM_182944
SOURCE	NM_182946
SMD	Hs.310429
SAGE	Hs.310429
GO	nucleotide binding [Amigo]  nucleotide binding
GO	transmembrane receptor protein tyrosine kinase activity [Amigo]  transmembrane receptor protein tyrosine kinase activity
GO	calcium ion binding [Amigo]  calcium ion binding
GO	protein binding [Amigo]  protein binding
GO	ATP binding [Amigo]  ATP binding
GO	GTP binding [Amigo]  GTP binding
GO	centrosome [Amigo]  centrosome
GO	microtubule [Amigo]  microtubule
GO	protein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GO	transmembrane receptor protein tyrosine kinase signaling pathway [Amigo]  transmembrane receptor protein tyrosine kinase signaling pathway
GO	membrane [Amigo]  membrane
GO	centrosome localization [Amigo]  centrosome localization
PubGene	NIN
TreeFam	NIN
CTD	51199 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	NIN Related clones (RZPD - Berlin)
	PubMed
PubMed	23 Pubmed reference(s) in Entrez

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)

Written	09-2004	José Luis Vizmanos

Citation

This paper should be referenced as such :

Vizmanos JL . NIN. 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 Oct 11 12:54:28 2008