Property Summary

NCBI Gene PubMed Count 56
PubMed Score 222.23
PubTator Score 244.63

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (4)

Disease Target Count
IGA Glomerulonephritis 454
Myotonia 3
Disease Target Count P-value
lung carcinoma 2844 1.2e-35
breast carcinoma 1614 7.2e-19
non-small cell lung cancer 2798 2.9e-13
Breast cancer 3098 7.0e-08
Pick disease 1893 7.4e-06
medulloblastoma, large-cell 6234 2.1e-05
lung cancer 4473 2.5e-05
group 4 medulloblastoma 1875 3.5e-05
ovarian cancer 8491 5.4e-05
juvenile dermatomyositis 1189 6.9e-05
atypical teratoid / rhabdoid tumor 4369 1.0e-04
invasive ductal carcinoma 2950 1.2e-04
osteosarcoma 7933 1.8e-04
psoriasis 6685 2.3e-04
glioblastoma 5572 5.7e-04
acute quadriplegic myopathy 1157 5.9e-04
astrocytic glioma 2241 6.5e-04
colon cancer 1475 1.0e-03
ulcerative colitis 2087 1.2e-03
pancreatic cancer 2300 1.2e-03
primary Sjogren syndrome 788 1.3e-03
interstitial cystitis 2299 2.8e-03
dermatomyositis 966 2.9e-03
adult high grade glioma 2148 3.0e-03
ependymoma 2514 3.5e-03
cystic fibrosis 1670 4.5e-03
progressive supranuclear palsy 674 5.6e-03
Amyotrophic Lateral Sclerosis 432 5.8e-03
pancreatic ductal adenocarcinoma liver metastasis 1795 5.9e-03
Waldenstrons macroglobulinemia 764 7.1e-03
Gaucher disease type 1 171 1.2e-02
limb girdle muscular dystrophy 2B 74 1.3e-02
intraductal papillary-mucinous adenoma (IPMA) 2956 1.4e-02
oligodendroglioma 2849 1.4e-02
hereditary spastic paraplegia 313 1.5e-02
lung adenocarcinoma 2714 1.5e-02
aldosterone-producing adenoma 664 2.8e-02
intraductal papillary-mucinous carcinoma (IPMC) 2988 3.3e-02
Rheumatoid Arthritis 1170 3.4e-02
subependymal giant cell astrocytoma 2287 4.4e-02
pituitary cancer 1972 4.6e-02

Expression

  Differential Expression (41)

Disease log2 FC p
Rheumatoid Arthritis 2.600 3.4e-02
Waldenstrons macroglobulinemia 1.589 7.1e-03
astrocytic glioma 3.000 6.5e-04
ependymoma 2.700 3.5e-03
oligodendroglioma 2.300 1.4e-02
psoriasis -2.300 2.3e-04
osteosarcoma 2.479 1.8e-04
cystic fibrosis -1.195 4.5e-03
atypical teratoid / rhabdoid tumor -1.300 1.0e-04
glioblastoma 1.300 5.7e-04
group 4 medulloblastoma -1.900 3.5e-05
medulloblastoma, large-cell -1.500 2.1e-05
hereditary spastic paraplegia -1.716 1.5e-02
limb girdle muscular dystrophy 2B -1.087 1.3e-02
Amyotrophic Lateral Sclerosis 1.204 5.8e-03
juvenile dermatomyositis 1.262 6.9e-05
acute quadriplegic myopathy 2.242 5.9e-04
pancreatic ductal adenocarcinoma liver m... 1.431 5.9e-03
non-small cell lung cancer -1.461 2.9e-13
intraductal papillary-mucinous adenoma (... 1.600 1.4e-02
intraductal papillary-mucinous carcinoma... 1.300 3.3e-02
lung cancer -1.800 2.5e-05
colon cancer -2.100 1.0e-03
interstitial cystitis 1.600 2.8e-03
adult high grade glioma 1.800 3.0e-03
primary Sjogren syndrome 1.400 1.3e-03
aldosterone-producing adenoma -1.837 2.8e-02
subependymal giant cell astrocytoma 2.465 4.4e-02
lung adenocarcinoma 1.054 1.5e-02
lung carcinoma -1.200 1.2e-35
breast carcinoma -1.800 7.2e-19
Pick disease 1.900 7.4e-06
progressive supranuclear palsy -1.100 5.6e-03
Breast cancer -1.300 7.0e-08
invasive ductal carcinoma -1.400 1.2e-04
ulcerative colitis -1.200 1.2e-03
ovarian cancer 1.900 5.4e-05
Gaucher disease type 1 -1.300 1.2e-02
pituitary cancer -1.100 4.6e-02
pancreatic cancer 1.200 1.2e-03
dermatomyositis -1.600 2.9e-03

MLP Assay (4)

AID Type Active / Inconclusive / Inactive Description
2675 confirmatory 100 / 29714 / 248993 qHTS Assay for Inhibitors of MBNL1-poly(CUG) RNA binding
2700 summary 0 / 0 / 0 qHTS Assay for Inhibitors of MBNL1-poly(CUG) RNA binding: Summary
493199 confirmatory 66 / 39 / 30 qHTS Assay for Inhibitors of MBNL1-poly(CUG) RNA binding: Initial hit validation from the primary screen
493205 confirmatory 45 / 29 / 61 qHTS Assay for Inhibitors of MBNL1-poly(CUG) RNA binding: Initial hit validation in AlphaScreen assay for MBNL1-(CUG)12 binding

Gene RIF (44)

PMID Text
26883358 muscleblind-like 1 (MBNL1) is a robust suppressor of multiorgan breast cancer metastasis. It binds the 3' untranslated regions of DBNL and TACC1 -two genes that are implicated as metastasis suppressors.
26339785 Sense DMPK RNA foci clearly co-localize with MBNL1 and MBNL2 proteins and accumulate in myotonic dystrophy 1 tissues during development.
26218986 Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65
26018658 abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform.
25977444 MBNL1 binds with C allelic pre-miR-1307 leading to low expression of miR-1307-3p in colorectal cancer.
25403273 The result is consistent with the hypothesis that MBNL proteins are trapped by expanded CUG repeats and inactivated in myotonic dystrophy type 1 (DM1) and that CELF1 is activated in DM1.
25274774 Results show that nuclear localization is a major determinant of MBNL1 function. It promotes the nuclear retention of repeat-containing transcripts, which results in repression of aberrant protein expression from the expanded repeats.
25211016 Reduced RBFOX1 activity in myotonic dystrophy type 1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1.
24440524 both MBNL1 and MBNL2 are involved in the regulation of Tau exon 2 splicing and the mis-splicing of Tau in DM1 is due to the combined inactivation of both.
24373687 Results highlight the importance of RNA binding by MBNL Zinc Finger domains 1 and 2 for splicing regulatory activity, even when the protein is artificially recruited to its regulatory location on target RNAs.
24354850 MBNL1 is highly mobile and changes localization in response to altered transcription and splicing activity, providing an insight into the sensitivity of the lens to changes in MBNL1 distribution.
24048253 MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation.
23949219 MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via their proline-rich motifs.
23807294 in both dystrophic and sarcopenic muscles MBNL1 undergoes intranuclear relocation, accumulating in its usual functional sites but also ectopically moving to domains which are usually devoid of this protein in healthy adults
23739326 consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming
23166594 MBNL1 loss shows a graded effect on the number and severity of the ensuing RNA splice defects.
23161457 This report demonistrated that the association of several genetic variants of the MBNL1 gene with DM1 or with the severity of the disease.
22890842 It was demonstrated that functionally distinct classes of MBNL1-mediated splicing events exist as defined by requirements for zinc finger-RNA interactions.
22520280 The present results show that the MBNL1 protein is expressed and more or less sequestered into the CCUGexp nuclear foci also in analyzed non-muscle tissues of DM2 patients.
22355723 study suggests that regulation of CUGBP1 and MBNL1 is essential for accurate control of destabilization of a broad spectrum of mRNAs as well as of alternative splicing events
22306654 Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
22113158 congenital myotonic dystrophy muscle has nuclear foci that contain muscleblind-like 1 (MBNL1) protein.
22106026 The removal of one pair of zinc fingers greatly impairs the binding affinity of MBNL1, which indicates that the two pairs of zinc fingers might possibly interact with RNA targets cooperatively.
21900255 Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex
21832083 Deletion of the MBNL1 response element eliminated MBNL1 splicing regulation and led to complete inclusion of exon 5, which is consistent with the suppressive effect of MBNL1 on splicing.
21685920 MBNL1 regulates pre-miR-1 biogenesis.
21548961 Although MBNL1 contains four Zn fingers, it appears that only two Zn fingers binding GC motifs are necessary for high affinity RNA binding.
21454535 the abnormally high inclusion of the exon 5 and 7 regions in DM1 is expected to enhance the potential of MBNL1 of being sequestered with nuclear CUG expansions, which provides new insight into DM1 pathophysiology.
21439371 results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1
20519504 Findings demonstrate a role for Mbnl1 in controlling insulin receptor exon 11 inclusion via binding to a downstream intronic enhancer element.
19805260 Data show that ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex.
19345584 Our data seem indicate that the presence of ribonuclear inclusions and MBNL1 nuclear foci are involved in alteration of alternative splicing but do not impair DM2 myogenic differentiation.
19095965 MBNL1 and MBNL2 always co-distributed. Functional differences between MBNL1 and MBNL2 have not yet been found
19043415 Both the ZnF3 and the ZnF4 zinc-finger domains target GC steps, with site-specific recognition mediated by a network of hydrogen bonds formed primarily with main chain groups of the protein.
18335541 Examination of dynamics of MBNL1 in response to stress, and suggestion of a role for MBNL1 in mRNA metabolism in the cytoplasm.
17942744 MBNL may bind all of its RNA substrates, both normal and pathogenic, as structured stem-loops containing pyrimidine mismatches.
17846170 MBNL1 (muscleblind-like protein 1) is an alternative splicing factor that becomes highly concentrated with mutant RNA foci.
16946708 Elevated levels of MBNL1 show RNA-independent interaction with hnRNP H and dampen the inhibitory activity of increased hnRNP H levels on IR splicing in normal myoblasts.
16920640 findings show that MBNL1 nuclear sequestration in protein foci is a molecular pathology marker of DM1 and DM2 patients where ribonuclear inclusions of transcripts with expanded CUG/CCUG repeats are also present
16394256 The fact that a human protein works in a Drosophila cellular context illustrates the use of an in vivo test to prove functional conservation.
16273094 localized expression of the integrin alpha3 protein is regulated at the level of RNA localization by MBNL1; integrin alpha3 transcripts are physically associated with MLP1 in cells and MLP1 binds to a specific ACACCC motif in the integrin alpha3 3' UTR
15961406 The GFP-MBNL1 in CUG and CAG foci have similar half-times of recovery and fractions of immobile molecules, suggesting GFP-MBNL1 is bound by both CUG and CAG repeats and formation of RNA foci and disruption of MBNL1-regulated splicing are separable events.
15546872 small interfering RNA-mediated down-regulation of MBNL1 in normal myoblasts results in abnormal insulin receptor splicing
15257297 MBNL proteins promote opposite splicing patterns for cardiac troponin T and insulin receptor alternative exons

AA Sequence

MAVSVTPIRDTKWLTLEVCREFQRGTCSRPDTECKFAHPSKSCQVENGRVIACFDSLKGRCSRENCKYLH      1 - 70
PPPHLKTQLEINGRNNLIQQKNMAMLAQQMQLANAMMPGAPLQPVPMFSVAPSLATNASAAAFNPYLGPV     71 - 140
SPSLVPAEILPTAPMLVTGNPGVPVPAAAAAAAQKLMRTDRLEVCREYQRGNCNRGENDCRFAHPADSTM    141 - 210
IDTNDNTVTVCMDYIKGRCSREKCKYFHPPAHLQAKIKAAQYQVNQAAAAQAAATAAAMTQSAVKSLKRP    211 - 280
LEATFDLGIPQAVLPPLPKRPALEKTNGATAVFNTGIFQYQQALANMQLQQHTAFLPPVPMVHGATPATV    281 - 350
SAATTSATSVPFAATATANQIPIISAEHLTSHKYVTQM                                    351 - 388
//

Text Mined References (63)

PMID Year Title
27222292 2016 Identification of variants in MBNL1 in patients with a myotonic dystrophy-like phenotype.
26883358 2016 Muscleblind-like 1 suppresses breast cancer metastatic colonization and stabilizes metastasis suppressor transcripts.
26339785 2015 Sense and Antisense DMPK RNA Foci Accumulate in DM1 Tissues during Development.
26218986 2015 Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.
26018658 2015 Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.
25977444 2015 The polymorphic terminal-loop of pre-miR-1307 binding with MBNL1 contributes to colorectal carcinogenesis via interference with Dicer1 recruitment.
25593321 2015 RNA toxicity and missplicing in the common eye disease fuchs endothelial corneal dystrophy.
25416956 2014 A proteome-scale map of the human interactome network.
25403273 2015 ABLIM1 splicing is abnormal in skeletal muscle of patients with DM1 and regulated by MBNL, CELF and PTBP1.
25274774 2015 Nuclear localization of MBNL1: splicing-mediated autoregulation and repression of repeat-derived aberrant proteins.
25211016 2014 RBFOX1 cooperates with MBNL1 to control splicing in muscle, including events altered in myotonic dystrophy type 1.
24440524 2014 Tau exon 2 responsive elements deregulated in myotonic dystrophy type I are proximal to exon 2 and synergistically regulated by MBNL1 and MBNL2.
24373687 2013 Dissecting domains necessary for activation and repression of splicing by Muscleblind-like protein 1.
24354850 2014 Transcriptionally correlated subcellular dynamics of MBNL1 during lens development and their implication for the molecular pathology of myotonic dystrophy type 1.
24048253 2013 MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation.
23949219 2013 MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases.
23807294 2013 Muscleblind-like1 undergoes ectopic relocation in the nuclei of skeletal muscles in myotonic dystrophy and sarcopenia.
23739326 2013 MBNL proteins repress ES-cell-specific alternative splicing and reprogramming.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23166594 2012 RNA splicing is responsive to MBNL1 dose.
23161457 2013 MBNL1 gene variants as modifiers of disease severity in myotonic dystrophy type 1.
22890842 2012 Combinatorial mutagenesis of MBNL1 zinc fingers elucidates distinct classes of regulatory events.
22681889 2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
22658674 2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
22520280 2012 Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2.
22355723 2012 CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
22306654 2012 Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
22113158 2012 A rapid immunohistochemical test to distinguish congenital myotonic dystrophy from X-linked myotubular myopathy.
22106026 2012 MBNL1-RNA recognition: contributions of MBNL1 sequence and RNA conformation.
21900255 2011 Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex.
21832083 2011 Autoregulated splicing of muscleblind-like 1 (MBNL1) Pre-mRNA.
21685920 2011 Misregulation of miR-1 processing is associated with heart defects in myotonic dystrophy.
21548961 2011 The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements.
21454535 2011 Analysis of exonic regions involved in nuclear localization, splicing activity, and dimerization of Muscleblind-like-1 isoforms.
21439371 2011 Mis-splicing of Tau exon 10 in myotonic dystrophy type 1 is reproduced by overexpression of CELF2 but not by MBNL1 silencing.
21269460 2011 Initial characterization of the human central proteome.
20519504 2010 Muscleblind-like 1 (Mbnl1) promotes insulin receptor exon 11 inclusion via binding to a downstream evolutionarily conserved intronic enhancer.
19805260 2009 A simple ligand that selectively targets CUG trinucleotide repeats and inhibits MBNL protein binding.
19470458 2009 The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing.
19345584 2009 Ribonuclear inclusions and MBNL1 nuclear sequestration do not affect myoblast differentiation but alter gene splicing in myotonic dystrophy type 2.
19095965 2009 Muscleblind-like proteins: similarities and differences in normal and myotonic dystrophy muscle.
19043415 2008 Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1.
18335541 2008 MBNL1 associates with YB-1 in cytoplasmic stress granules.
17942744 2007 MBNL binds similar RNA structures in the CUG repeats of myotonic dystrophy and its pre-mRNA substrate cardiac troponin T.
17846170 2007 Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains.
16946708 2006 Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing.
16920640 Muscleblind-like protein 1 nuclear sequestration is a molecular pathology marker of DM1 and DM2.
16717059 2006 Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy.
16641997 2006 The DNA sequence, annotation and analysis of human chromosome 3.
16394256 An interspecific functional complementation test in Drosophila for introductory genetics laboratory courses.
16273094 2005 RNA-dependent integrin alpha3 protein localization regulated by the Muscleblind-like protein MLP1.
15961406 2005 Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy.
15546872 2005 MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15257297 2004 Muscleblind proteins regulate alternative splicing.
14722159 2004 Muscleblind protein, MBNL1/EXP, binds specifically to CHHG repeats.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11929853 2002 Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells.
11590133 2001 Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2.
11433021 2001 In vivo co-localisation of MBNL protein with DMPK expanded-repeat transcripts.
10970838 2000 Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy.
9455477 1997 Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.