MIB2 (mindbomb homolog 2 (Drosophila))

Identity

Other names	FLJ20648
	FLJ39787
	ZZANK1
	ZZZ5
	Skeletrophin
	novelzin
HGNC	MIB2
Location	1p36.33
Local_order	ATAD3A (ATPase family, AAA domain containing 3B), is more telomeric, CDC2L2 (cell division cycle 2-like 2) is more centromeric.

Note	Orientation: plus strand.

DNA/RNA

Note	There are at least six alternative splicing forms.
	Genomic structure of Mib2/skeletrophin
Description	20 Exons spanning 14kb on 1p36.33.

Protein

	Schematic illustrating of mib2/skeletrophin.

Note	The number of amino acids are varied in each splicing form.
Expression	Human mib2/skeletrophin is strongly expressed in adult brain, heart and skeletal muscles.
Localisation	Cytoplasmic
Function	Ubiquitin ligase to cytoplasmic domain of Notch ligands and NMDA receptor GRIN2B/NR2B subunit. Putative positive regulation of I-kappaB kinase/NF-kappaB cascade.
Homology	The protein structure of mib2/skeletrophin is closely related to MIB1 (mind bomb-1 homolog).

Implicated in

Entity	Malignant melanoma, vertical growth phase.
Oncogenesis	Putative suppressor factor against malignant melanoma invasion. In invasive malignant melanoma, Mib2/skeletrophin gene expression is down-regulated by various epigenetic events described below. The promoter region of Mib2/skeletrophin gene contains typical CpG islands, which is hypermethylated in invasive malignant melanoma. A zinc-finger transcriptional factor Snail, which is overexpressed in many melanoma cells, repressed the Mib2/skeletrophin promoter activity via an E-box-related element. An activator protein-2, which has a tumor suppressor-like role in melanoma, increased Mib2/skeletrophin expression.
Entity	Multiple myeloma, especially at advanced stage with osteolytic lesion.
Oncogenesis	Putative oncogenic factor for multiple myeloma thorough bone marrow microenvironments. In multiple myeloma, Mib2/skeletrophin and its substrates, Jagged-1 and Jagged-2, are both overexpressed in bone marrow microenvironments. Ligands-dependent Notch activation is occurred by direct cell-cell interaction between multiple myeloma cells and bone marrow stromal cells and contribute the myeloma niche, which is known as microenvironment suitable for myelomagenesis.

External links

	Nomenclature
HGNC	MIB2   30577
Entrez_Gene	MIB2  142678  mindbomb homolog 2 (Drosophila)
	Cards
Atlas	MIB2ID44179ch1p36
GeneCards	MIB2
Ensembl	MIB2 [Search_View]   ENSG00000197530 [Gene_View]
Genatlas	MIB2
GeneLynx	MIB2
eGenome	MIB2
euGene	142678
	Genomic and cartography
GoldenPath	MIB2  -  1p36.33   chr1:1540747-1555848 +  1p36.33   [Description]    (hg18-Mar_2006)
Ensembl	MIB2 - 1p36.33 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	MIB2
	Gene and transcription
Genbank	AB064367 [ ENTREZ ]
Genbank	AB074480 [ ENTREZ ]
Genbank	AB076691 [ ENTREZ ]
Genbank	AB076692 [ ENTREZ ]
Genbank	AB076693 [ ENTREZ ]
RefSeq	NM_080875 [ SRS ]    NM_080875 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_004350 [ SRS ]    NT_004350 [ ENTREZ ]
RefSeq	NW_001838585 [ SRS ]    NW_001838585 [ ENTREZ ]
RefSeq	NW_921350 [ SRS ]    NW_921350 [ ENTREZ ]
AceView	MIB2 AceView - NCBI
Unigene	Hs.593430 [ SRS ]    Hs.593430 [ NCBI ]     HS593430 [ spliceNest ]
Fast-db	489 (alternative variants)
	Protein : pattern, domain, 3D structure
HPRD	15905
	Protein Interaction databases
	Polymorphism : SNP, mutations, diseases
OMIM	611141    [ map ]
GENECLINICS	611141
SNP	MIB2 [dbSNP-NCBI]
SNP	NM_080875 [SNP-NCI]
SNP	MIB2 [GeneSNPs - Utah]  MIB2] [HGBASE - SRS]
HAPMAP	MIB2 [HAPMAP]
HGMD	MIB2
	General knowledge
Family Browser	MIB2 [UCSC Family Browser]
SOURCE	NM_080875
SMD	Hs.593430
SAGE	Hs.593430
GO	actin binding [Amigo]  actin binding
GO	signal transducer activity [Amigo]  signal transducer activity
GO	protein binding [Amigo]  protein binding
GO	cytoplasm [Amigo]  cytoplasm
GO	endosome [Amigo]  endosome
GO	Notch signaling pathway [Amigo]  Notch signaling pathway
GO	zinc ion binding [Amigo]  zinc ion binding
GO	ligase activity [Amigo]  ligase activity
GO	positive regulation of I-kappaB kinase/NF-kappaB cascade [Amigo]  positive regulation of I-kappaB kinase/NF-kappaB cascade
GO	metal ion binding [Amigo]  metal ion binding
PubGene	MIB2
TreeFam	MIB2
CTD	142678 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	MIB2 Related clones (RZPD - Berlin)
	PubMed
PubMed	14 Pubmed reference(s) in LocusLink

Bibliography

Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma.

Takeuchi T, Heng HH, Ye CJ, Liang SB, Iwata J, Sonobe H, Ohtsuki Y

The American journal of pathology. 2003 ; 163 (4) : 1395-1404.

PMID 14507647

Mind bomb-2 is an E3 ligase for Notch ligand.

Koo BK, Yoon KJ, Yoo KW, Lim HS, Song R, So JH, Kim CH, Kong YY

The Journal of biological chemistry. 2005 ; 280 (23) : 22335-22342.

PMID 15824097

Skeletrophin, a novel RING molecule controlled by the chromatin remodeling complex, is downregulated in malignant melanoma.

Takeuchi T, Adachi Y, Ohtsuki Y

DNA and cell biology. 2005 ; 24 (5) : 339-344.

PMID 15869411

Skeletrophin, a novel ubiquitin ligase to the intracellular region of Jagged-2, is aberrantly expressed in multiple myeloma.

Takeuchi T, Adachi Y, Ohtsuki Y

The American journal of pathology. 2005 ; 166 (6) : 1817-1826.

PMID 15920166

A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion.

Takeuchi T, Adachi Y, Sonobe H, Furihata M, Ohtsuki Y

Oncogene. 2006 ; 25 (53) : 7059-7069.

PMID 16715130

Mind bomb-2 is an E3 ligase that ubiquitinates the N-methyl-D-aspartate receptor NR2B subunit in a phosphorylation-dependent manner.

Jurd R, Thornton C, Wang J, Luong K, Phamluong K, Kharazia V, Gibb SL, Ron D

The Journal of biological chemistry. 2008 ; 283 (1) : 301-310.

PMID 17962190

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	01-2008	Tamotsu Takeuchi
		Department of Pathology, Kochi Medical School, Kohasu, Okou, Nankoku, Kochi 783 8505, Japan

Citation

This paper should be referenced as such :

Takeuchi T . MIB2 (mindbomb homolog 2 (Drosophila)). Atlas Genet Cytogenet Oncol Haematol. January 2008 . URL : http://AtlasGeneticsOncology.org/Genes/MIB2ID44179ch1p36.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:15:19 2008