The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017] See more...

Aliases for MIB2 Gene

Aliases for MIB2 Gene

  • Mindbomb E3 Ubiquitin Protein Ligase 2 2 3 5
  • Skeletrophin 2 3 4
  • Zinc Finger ZZ Type With Ankyrin Repeat Domain Protein 1 3 4
  • Zinc Finger, ZZ Type With Ankyrin Repeat Domain 1 2 3
  • Putative NF-Kappa-B-Activating Protein 002N 3 4
  • RING-Type E3 Ubiquitin Transferase MIB2 3 4
  • E3 Ubiquitin-Protein Ligase MIB2 3 4
  • Novel Zinc Finger Protein 3 4
  • Mind Bomb Homolog 2 3 4
  • Novelzin 3 4
  • ZZANK1 3 4
  • ZZZ5 2 3
  • Mindbomb Homolog 2 (Drosophila) 2
  • Mindbomb Homolog 2 3
  • EC 6.3.2.13 51
  • EC 2.3.2.27 4
  • FLJ39787 2
  • EC 6.3.2 51
  • MIB2 5
  • SKD 4

External Ids for MIB2 Gene

Previous HGNC Symbols for MIB2 Gene

  • ZZANK1

Previous GeneCards Identifiers for MIB2 Gene

  • GC01P9N0043
  • GC01P001540
  • GC01P000824
  • GC01P001550

Summaries for MIB2 Gene

Entrez Gene Summary for MIB2 Gene

  • The protein encoded by this gene is an E3 ubiquitin protein ligase that mediates ubiquitination of proteins in the Notch signaling pathway. The encoded protein may be a suppressor of melanoma invasion. [provided by RefSeq, Mar 2017]

GeneCards Summary for MIB2 Gene

MIB2 (Mindbomb E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Diseases associated with MIB2 include Left Ventricular Noncompaction and Akinetopsia. Among its related pathways are Signaling by GPCR and NOTCH2 Activation and Transmission of Signal to the Nucleus. Gene Ontology (GO) annotations related to this gene include actin binding and ubiquitin-protein transferase activity. An important paralog of this gene is MIB1.

UniProtKB/Swiss-Prot Summary for MIB2 Gene

  • E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors.

Gene Wiki entry for MIB2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MIB2 Gene

Genomics for MIB2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MIB2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MIB2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MIB2

Top Transcription factor binding sites by QIAGEN in the MIB2 gene promoter:
  • AP-1
  • AREB6
  • c-Fos
  • c-Jun
  • FosB
  • Fra-1
  • GATA-1
  • JunB
  • JunD
  • Max1

Genomic Locations for MIB2 Gene

Genomic Locations for MIB2 Gene
chr1:1,613,730-1,630,610
(GRCh38/hg38)
Size:
16,881 bases
Orientation:
Plus strand
chr1:1,550,795-1,565,990
(GRCh37/hg19)
Size:
15,196 bases
Orientation:
Plus strand

Genomic View for MIB2 Gene

Genes around MIB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MIB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MIB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MIB2 Gene

Proteins for MIB2 Gene

  • Protein details for MIB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96AX9-MIB2_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase MIB2
    Protein Accession:
    Q96AX9
    Secondary Accessions:
    • A2AGM5
    • A2AGM6
    • B3KV93
    • B3KVF4
    • B3KXY1
    • B4DZ57
    • E9PGU1
    • E9PHQ1
    • F8WA73
    • J3KNZ7
    • Q7Z437
    • Q8IY62
    • Q8N786
    • Q8N897
    • Q8N8R2
    • Q8N911
    • Q8NB36
    • Q8NCY1
    • Q8NG59
    • Q8NG60
    • Q8NG61
    • Q8NI59
    • Q8WYN1

    Protein attributes for MIB2 Gene

    Size:
    1013 amino acids
    Molecular mass:
    109939 Da
    Quaternary structure:
    • Interacts with actin monomer.
    SequenceCaution:
    • Sequence=AAH16490.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB82979.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAC03707.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC04646.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC04752.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAC04952.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for MIB2 Gene

neXtProt entry for MIB2 Gene

Selected DME Specific Peptides for MIB2 Gene

Q96AX9:
  • FQGAKVVRGPDWEWG
  • LVFQCGHG
  • KILARARQLVD
  • AVQRGFL
  • RGMRWKC
  • KKEDGFTALHLAALNNH
  • TVVVQWDQG
  • ETRWTFHPGALTK
  • RRMKKCI
  • RVVRGVDW
  • KNQGRTALQ
  • RYRQMEERITCPICID

Post-translational modifications for MIB2 Gene

  • Ubiquitinated. Possibly via autoubiquitination (By similarity).
  • Ubiquitination at Lys427 and Lys842
  • Modification sites at PhosphoSitePlus

Domains & Families for MIB2 Gene

Gene Families for MIB2 Gene

Protein Domains for MIB2 Gene

Suggested Antigen Peptide Sequences for MIB2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ46290 fis, clone TESTI4032913, highly similar to Ubiquitin ligase protein MIB2 (EC 6.3.2.-) (B3KXY1_HUMAN)
  • Zinc finger ZZ type with ankyrin repeat domain protein 1 (MIB2_HUMAN)
genes like me logo Genes that share domains with MIB2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for MIB2 Gene

Function for MIB2 Gene

Molecular function for MIB2 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;.
UniProtKB/Swiss-Prot Induction:
Down-regulated in many primary skin melanomas. Treatment with a demethylating agent, 5'-aza-2-deoxycytidine, restores expression, suggesting that down-regulation is the result of methylation of the gene.

Enzyme Numbers (IUBMB) for MIB2 Gene

Phenotypes From GWAS Catalog for MIB2 Gene

Gene Ontology (GO) - Molecular Function for MIB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IEA --
GO:0004842 ubiquitin-protein transferase activity IEA,IBA 21873635
GO:0005515 protein binding IEA,IPI 21903422
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with MIB2: view
genes like me logo Genes that share phenotypes with MIB2: view

Animal Models for MIB2 Gene

MGI Knock Outs for MIB2:
  • Mib2 Mib2<tm1a(EUCOMM)Wtsi>
  • Mib2 Mib2<tm1Art>
  • Mib2 Mib2<tm1Kong>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MIB2

Clone Products

  • Addgene plasmids for MIB2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MIB2 Gene

Localization for MIB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MIB2 Gene

Cytoplasm. Endosome. Note=Colocalizes with endosomal compartments.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MIB2 gene
Compartment Confidence
cytosol 5
endosome 3
mitochondrion 2
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1
peroxisome 0

Gene Ontology (GO) - Cellular Components for MIB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex IEA --
GO:0005737 cytoplasm IBA 21873635
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MIB2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MIB2 Gene

Pathways & Interactions for MIB2 Gene

genes like me logo Genes that share pathways with MIB2: view

UniProtKB/Swiss-Prot Q96AX9-MIB2_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for MIB2 Gene

Activates:

Gene Ontology (GO) - Biological Process for MIB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination TAS --
GO:0007219 Notch signaling pathway IEA --
GO:0016567 protein ubiquitination IEA,IBA 21873635
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling HMP 12761501
genes like me logo Genes that share ontologies with MIB2: view

Drugs & Compounds for MIB2 Gene

No Compound Related Data Available

Transcripts for MIB2 Gene

mRNA/cDNA for MIB2 Gene

5 REFSEQ mRNAs :
28 NCBI additional mRNA sequence :
32 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MIB2

Clone Products

  • Addgene plasmids for MIB2

Alternative Splicing Database (ASD) splice patterns (SP) for MIB2 Gene

No ASD Table

Relevant External Links for MIB2 Gene

GeneLoc Exon Structure for
MIB2

Expression for MIB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MIB2 Gene

Protein differential expression in normal tissues from HIPED for MIB2 Gene

This gene is overexpressed in Pancreas (24.2), Bone (18.2), Heart (10.8), and Liver, secretome (10.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MIB2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MIB2

SOURCE GeneReport for Unigene cluster for MIB2 Gene:

Hs.135805

mRNA Expression by UniProt/SwissProt for MIB2 Gene:

Q96AX9-MIB2_HUMAN
Tissue specificity: Expressed in skeletal muscle, and to a lesser extent in heart, brain and kidney.

Evidence on tissue expression from TISSUES for MIB2 Gene

  • Nervous system(4.8)
  • Lung(4.5)
  • Spleen(4.4)
  • Heart(4.4)
  • Liver(4.3)
  • Pancreas(3.4)
  • Skin(2.5)
  • Blood(2.2)
  • Kidney(2.1)
  • Intestine(2)
genes like me logo Genes that share expression patterns with MIB2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for MIB2 Gene

Orthologs for MIB2 Gene

This gene was present in the common ancestor of animals.

Orthologs for MIB2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MIB2 30
  • 93.31 (n)
Dog
(Canis familiaris)
Mammalia MIB2 30 31
  • 89.39 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MIB2 30 31
  • 86.99 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Mib2 30 17 31
  • 85.49 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Mib2 30
  • 85.1 (n)
Oppossum
(Monodelphis domestica)
Mammalia MIB2 31
  • 72 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 68 (a)
OneToMany
-- 31
  • 64 (a)
OneToMany
Chicken
(Gallus gallus)
Aves MIB2 30 31
  • 67.16 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MIB2 31
  • 81 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia mib2 30
  • 63.82 (n)
Zebrafish
(Danio rerio)
Actinopterygii mib2 30
  • 66.9 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008851 30
  • 56.26 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta mib2 30 31
  • 53.3 (n)
OneToOne
Species where no ortholog for MIB2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for MIB2 Gene

ENSEMBL:
Gene Tree for MIB2 (if available)
TreeFam:
Gene Tree for MIB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MIB2: view image

Paralogs for MIB2 Gene

Paralogs for MIB2 Gene

(8) SIMAP similar genes for MIB2 Gene using alignment to 13 proteins:

  • MIB2_HUMAN
  • D6R9Q6_HUMAN
  • D6RAZ0_HUMAN
  • D6RDI1_HUMAN
  • D6RE96_HUMAN
  • D6RED3_HUMAN
  • D6RFJ2_HUMAN
  • D6RHY5_HUMAN
  • E9PD12_HUMAN
  • F2Z2L2_HUMAN
  • H0YAM8_HUMAN
  • J3QLE0_HUMAN
  • J3QR95_HUMAN
genes like me logo Genes that share paralogs with MIB2: view

Variants for MIB2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MIB2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
709352 Benign: not provided 1,625,341(+) C/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
709684 Likely Benign: not provided 1,627,388(+) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
714061 Likely Benign: not provided 1,626,827(+) C/T INTRON_VARIANT
714062 Benign: not provided 1,627,168(+) A/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
720977 Benign: not provided 1,616,568(+) C/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for MIB2 Gene

Structural Variations from Database of Genomic Variants (DGV) for MIB2 Gene

Variant ID Type Subtype PubMed ID
dgv5n111 CNV deletion 26073780
dgv8n100 CNV loss 25217958
esv2659399 CNV deletion 23128226
esv2661270 CNV deletion 23128226
esv2758913 CNV gain+loss 17122850
esv2760410 CNV gain+loss 21179565
esv3575582 CNV gain 25503493
nsv10161 CNV gain+loss 18304495
nsv1074054 CNV deletion 25765185
nsv1074993 CNV deletion 25765185
nsv1136057 CNV deletion 24896259
nsv1160797 CNV duplication 26073780
nsv482937 CNV loss 15286789
nsv545017 CNV loss 21841781
nsv822031 CNV loss 20364138
nsv950452 CNV deletion 24416366

Variation tolerance for MIB2 Gene

Residual Variation Intolerance Score: 85.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.26; 85.06% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MIB2 Gene

Human Gene Mutation Database (HGMD)
MIB2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MIB2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MIB2 Gene

Disorders for MIB2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for MIB2 Gene - From: Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
left ventricular noncompaction
  • left ventricular hypertrabeculation
akinetopsia
melanoma
  • malignant melanoma
gastritis, familial giant hypertrophic
  • menetrier disease
autosomal recessive alport syndrome
  • alport syndrome autosomal recessive
- elite association - COSMIC cancer census association via MalaCards
Search MIB2 in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with MIB2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MIB2 Gene

Publications for MIB2 Gene

  1. Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. (PMID: 12761501) Matsuda A … Sugano S (Oncogene 2003) 2 3 4
  2. Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. (PMID: 14507647) Takeuchi T … Ohtsuki Y (The American journal of pathology 2003) 3 4 23
  3. A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion. (PMID: 16715130) Takeuchi T … Ohtsuki Y (Oncogene 2006) 3 23
  4. Skeletrophin, a novel ubiquitin ligase to the intracellular region of Jagged-2, is aberrantly expressed in multiple myeloma. (PMID: 15920166) Takeuchi T … Ohtsuki Y (The American journal of pathology 2005) 3 23
  5. Skeletrophin, a novel RING molecule controlled by the chromatin remodeling complex, is downregulated in malignant melanoma. (PMID: 15869411) Takeuchi T … Ohtsuki Y (DNA and cell biology 2005) 3 23

Products for MIB2 Gene

Sources for MIB2 Gene