MIB1
E3 ubiquitin-protein ligase MIB1
Also known as: DIP-1, KIAA1323, MIB, MIB1_HUMAN, ZZANK2, ZZZ6
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q86YT6
- Gene
- MIB1
- Ensembl
- ENSG00000101752
- Chromosome
- 18
- Canonical length
- 1006 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Microtubules,Mitotic spindle,Primary cilium,Centriolar satellite,Basal body
OverviewNCBI Gene
This gene encodes a protein containing multiple ankyrin repeats and RING finger domains that functions as an E3 ubiquitin ligase. The encoded protein positively regulates Notch signaling by ubiquitinating the Notch receptors, thereby facilitating their endocytosis. This protein may also promote the ubiquitination and degradation of death-associated protein kinase 1 (DAPK1). [provided by RefSeq, Jun 2013]
Canonical amino-acid sequenceUniProt
1006 residues, UniProt reviewed canonical sequence.
>Q86YT6|MIB1
1 MSNSRNNRVM VEGVGARVVR GPDWKWGKQD GGEGHVGTVR SFESPEEVVV VWDNGTAANY
61 RCSGAYDLRI LDSAPTGIKH DGTMCDTCRQ QPIIGIRWKC AECTNYDLCT VCYHGDKHHL
121 RHRFYRITTP GSERVLLESR RKSKKITARG IFAGARVVRG VDWQWEDQDG GNGRRGKVTE
181 IQDWSASSPH SAAYVLWDNG AKNLYRVGFE GMSDLKCVQD AKGGSFYRDH CPVLGEQNGN
241 RNPGGLQIGD LVNIDLDLEI VQSLQHGHGG WTDGMFETLT TTGTVCGIDE DHDIVVQYPS
301 GNRWTFNPAV LTKANIVRSG DAAQGAEGGT SQFQVGDLVQ VCYDLERIKL LQRGHGEWAE
361 AMLPTLGKVG RVQQIYSDSD LKVEVCGTSW TYNPAAVSKV ASAGSAISNA SGERLSQLLK
421 KLFETQESGD LNEELVKAAA NGDVAKVEDL LKRPDVDVNG QCAGHTAMQA ASQNGHVDIL
481 KLLLKQNVDV EAEDKDGDRA VHHAAFGDEG AVIEVLHRGS ADLNARNKRR QTPLHIAVNK
541 GHLQVVKTLL DFGCHPSLQD SEGDTPLHDA ISKKRDDILA VLLEAGADVT ITNNNGFNAL
601 HHAALRGNPS AMRVLLSKLP RPWIVDEKKD DGYTALHLAA LNNHVEVAEL LVHQGNANLD
661 IQNVNQQTAL HLAVERQHTQ IVRLLVRAGA KLDIQDKDGD TPLHEALRHH TLSQLRQLQD
721 MQDVGKVDAA WEPSKNTLIM GLGTQGAEKK SAASIACFLA ANGADLSIRN KKGQSPLDLC
781 PDPNLCKALA KCHKEKVSGQ VGSRSPSMIS NDSETLEECM VCSDMKRDTL FGPCGHIATC
841 SLCSPRVKKC LICKEQVQSR TKIEECVVCS DKKAAVLFQP CGHMCACENC ANLMKKCVQC
901 RAVVERRVPF IMCCGGKSSE DATDDISSGN IPVLQKDKDN TNVNADVQKL QQQLQDIKEQ
961 TMCPVCLDRL KNMIFLCGHG TCQLCGDRMS ECPICRKAIE RRILLYLocalizationUniProt · AlphaFold · HPA
Whether an antibody against MIB1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.31
- Highest tissue expression
- 13 nTPM
Expression across tissuesHPA
Tissue
- thyroid gland: 13 nTPM
- endometrium: 12 nTPM
- blood vessel: 11 nTPM
- thymus: 11 nTPM
- ovary: 11 nTPM
- breast: 11 nTPM
Single-cell type
- cardiomyocytes: 2,577 nCPM
- myonuclei: 980 nCPM
- podocytes: 526 nCPM
- choroid plexus epithelial cells: 307 nCPM
- ependymal cells: 260 nCPM
- gonadotrophs: 233 nCPM
Immune cell
- basophil: 0.7 nTPM
- NK-cell: 0.5 nTPM
- T-reg: 0.4 nTPM
- classical monocyte: 0.3 nTPM
- memory CD4 T-cell: 0.3 nTPM
- neutrophil: 0.3 nTPM
Brain region
- thalamus: 27 nTPM
- midbrain: 27 nTPM
- spinal cord: 27 nTPM
- hypothalamus: 26 nTPM
- medulla oblongata: 25 nTPM
- white matter: 24 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about MIB1.
Disease | AllUniProt
Conditions MIB1 is implicated in, by any mechanism.
- Left ventricular non-compaction 7 (LVNC7) MIM:615092
Disease | GeneticClinVar
28 pathogenic / likely-pathogenic of 675 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Left ventricular noncompaction 7
- MIB1-related disorder
- Hypercholesterolemia, familial, 1
Disease | AutoantibodyPubMed
Conditions in which antibodies against MIB1 are reported. Each links to that disease's full target list.
Showing 2 of 5 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for MIB1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
32 publications
- The Ki-67 proliferation antigen in meningiomas. Experience in 600 cases.
2004 · Acta Neurochir (Wien) · RCR 3.6 · 102 citations - Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review.
2003 · J Clin Oncol · RCR 2.9 · 127 citations - Cell membrane reactivity of MIB-1 antibody to Ki67 in human tumors: fact or artifact?
2007 · Appl Immunohistochem Mol Morphol · RCR 2 · 57 citations - Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma.
2004 · Am J Surg Pathol · RCR 1.9 · 68 citations - CytoLyt fixation significantly inhibits MIB1 immunoreactivity whereas alternative Ki-67 clone 30-9 is not susceptible to the inhibition: Critical diagnostic implications.
2019 · Cancer Cytopathol · RCR 1.8 · 33 citations
Show 20 more of 32 total
- Measurement of Ki-67 antigen in 159 pituitary adenomas using the MIB-1 monoclonal antibody.
2004 · Braz J Med Biol Res · RCR 1.7 · 59 citations - Aggressiveness and quantification of epithelial proliferation of middle ear cholesteatoma by MIB1.
2003 · Laryngoscope · RCR 1.4 · 32 citations - Techniques to assess the proliferative potential of brain tumors.
2005 · J Neurooncol · RCR 1.3 · 49 citations - Analysis of Ki-67 antigen expression, DNA proliferative fraction, and survival in resected cancer of the pancreas.
2003 · Am J Surg · RCR 1.1 · 51 citations - Immunohistochemical detection of metallothionein and MIB1 in uterine cervical squamous lesions.
1998 · Int J Gynecol Pathol · RCR 1.1 · 31 citations - Proliferation index determined by MIB-1 and recurrence in endometrial cancer.
1996 · Gynecol Oncol · RCR 1 · 26 citations - Apoptotic and proliferating cells in cutaneous lymphoproliferative diseases.
1997 · Arch Dermatol · RCR 0.9 · 33 citations - Diagnostic validity of the Ki-67 labeling index using the MIB-1 monoclonal antibody in the grading of meningiomas.
2003 · Neurol India · RCR 0.8 · 24 citations - A simple digital image analysis system for automated Ki67 assessment in primary breast cancer.
2021 · Histopathology · RCR 0.8 · 15 citations - Scoring the percentage of Ki67 positive nuclei is superior to mitotic count and the mitosis marker phosphohistone H3 (PHH3) in terms of differentiating flat lesions of the bladder mucosa.
2012 · J Clin Pathol · RCR 0.8 · 20 citations - Multiple regression analysis for assessing the growth of small hepatocellular carcinoma: the MIB-1 labeling index is the most effective parameter.
1998 · J Gastroenterol · RCR 0.7 · 20 citations - Expression of RCAS1 in female genital organs.
2005 · Int J Gynecol Pathol · RCR 0.7 · 20 citations - Correlation of MIB-1 antigen expression with transcription factors Skn-1, Oct-1, AP-2, and HPV type in cervical intraepithelial neoplasia.
1997 · J Pathol · RCR 0.5 · 20 citations - Labeling of cycling corneal endothelial cells during healing with a monoclonal antibody to the Ki67 antigen (MIB-1).
1999 · Cornea · RCR 0.5 · 17 citations - Immunohistochemical assessment of Ki67 with antibodies SP6 and MIB1 in primary breast cancer: a comparison of prognostic value and reproducibility.
2014 · Histopathology · RCR 0.5 · 14 citations - Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker.
2009 · Neuropathology · RCR 0.5 · 18 citations - Small lesions of porokeratosis show a normal proliferation rate with MIB-1.
2008 · Acta Dermatovenerol Alp Pannonica Adriat · RCR 0.5 · 8 citations - Mitosis in dermatofibroma: a worrisome histopathologic sign that does not necessarily equal recurrence.
2008 · J Cutan Pathol · RCR 0.4 · 7 citations - p53 expression in uveal malignant melanomas.
1996 · Pathology · RCR 0.4 · 12 citations - LCN2 Promoter Methylation Status as Novel Predictive Marker for Microvessel Density and Aggressive Tumor Phenotype in Breast Cancer Patients.
2015 · Asian Pac J Cancer Prev · RCR 0.3 · 10 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.97
- gnomAD pLI
- 0
- gnomAD missense Z
- 3.21
- DepMap mean gene effect
- -0.26
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- blood vessel development
- central nervous system neuron differentiation
- endocytosis
- heart looping
- in utero embryonic development
- negative regulation of neuron differentiation
- neural tube formation
- Notch signaling pathway
- positive regulation of endocytosis
- protein ubiquitination
- somitogenesis
- ubiquitin-dependent protein catabolic process
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Zinc finger, ZZ-type
- Zinc finger, RING-type
- Ankyrin repeat
- Mib-herc2
- Zinc finger, RING/FYVE/PHD-type
- Ankyrin repeat-containing domain superfamily
- Mib/herc2 domain superfamily
- Mind bomb, SH3 repeat domain
- E3 ubiquitin-protein ligase MIB1/2, zinc finger, ZZ-type
- Zinc finger, ZZ-type superfamily
- Ankyrin repeat
- Zinc finger, ZZ type
- Mib_herc2
- Ankyrin repeats (3 copies)
- Zinc finger, C3HC4 type (RING finger)
- Mind bomb SH3 repeat domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MIB1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads MIB1 as an antibody target. Whether an autoantibody or antibody against MIB1 could matter depends on whether native MIB1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MIB1 is annotated at the cell surface, where native MIB1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label MIB1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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