UniProtKB - Q9NR56 (MBNL1_HUMAN)
Protein
Muscleblind-like protein 1
Gene
MBNL1
Organism
Homo sapiens (Human)
Status
Functioni
Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues.5 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 13 – 41 | C3H1-type 1PROSITE-ProRule annotationAdd BLAST | 29 | |
Zinc fingeri | 47 – 73 | C3H1-type 2PROSITE-ProRule annotationAdd BLAST | 27 | |
Zinc fingeri | 179 – 207 | C3H1-type 3PROSITE-ProRule annotationAdd BLAST | 29 | |
Zinc fingeri | 215 – 241 | C3H1-type 4PROSITE-ProRule annotationAdd BLAST | 27 |
GO - Molecular functioni
- double-stranded RNA binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- RNA binding Source: UniProtKB
GO - Biological processi
- embryonic limb morphogenesis Source: UniProtKB
- in utero embryonic development Source: UniProtKB
- mRNA processing Source: UniProtKB-KW
- myoblast differentiation Source: UniProtKB
- nervous system development Source: UniProtKB
- regulation of alternative mRNA splicing, via spliceosome Source: GO_Central
- regulation of RNA splicing Source: UniProtKB
- RNA splicing Source: UniProtKB
Keywordsi
Molecular function | RNA-binding |
Biological process | mRNA processing, mRNA splicing |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9NR56 |
Names & Taxonomyi
Protein namesi | Recommended name: Muscleblind-like protein 1Alternative name(s): Triplet-expansion RNA-binding protein |
Gene namesi | Name:MBNL1 Synonyms:EXP, KIAA0428, MBNL |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6923, MBNL1 |
MIMi | 606516, gene |
neXtProti | NX_Q9NR56 |
VEuPathDBi | HostDB:ENSG00000152601.17 |
Subcellular locationi
Nucleus
- Nucleus 3 Publications
Other locations
- Cytoplasm 1 Publication
- Cytoplasmic granule 1 Publication
Note: Localized with DDX1, TIAL1 and YBX1 in stress granules upon stress (PubMed:18335541). Localized in the cytoplasm of multinucleated myotubes (PubMed:18335541). Colocalizes with nuclear foci of retained expanded-repeat transcripts in myotubes from patients affected by myotonic dystrophy (PubMed:10970838, PubMed:11590133, PubMed:11929853).
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- cytoplasmic stress granule Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Dystrophia myotonica 1 (DM1)2 Publications
The protein represented in this entry may be involved in disease pathogenesis. In muscle cells from patients, MBNL1 is sequestered by DMPK RNAs containing pathogenic CUG triplet repeat expansions. MBNL1 binding is proportional to repeat length consistent with the direct correlation between the length of repeat expansion and disease severity.
Disease descriptionA muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076508 | 32 | T → M in DM1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs185894411Ensembl. | 1 | |
Natural variantiVAR_076509 | 171 – 173 | Missing in DM1; unknown pathological significance. 1 Publication | 3 | |
Natural variantiVAR_076510 | 338 | P → S in DM1; unknown pathological significance. 1 Publication | 1 |
Corneal dystrophy, Fuchs endothelial, 3 (FECD3)1 Publication
The protein represented in this entry is involved in disease pathogenesis. In corneal endothelial cells from patients, MBNL1 is sequestered by TCF4 RNAs containing pathogenic CUG triplet repeat expansions. This results in missplicing of essential MBNL1-regulated mRNAs.1 Publication
Disease descriptionA late-onset form of Fuchs endothelial corneal dystrophy, a disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition.
Related information in OMIMKeywords - Diseasei
Corneal dystrophy, Disease variantOrganism-specific databases
DisGeNETi | 4154 |
MIMi | 160900, phenotype 613267, phenotype |
OpenTargetsi | ENSG00000152601 |
PharmGKBi | PA30666 |
Miscellaneous databases
Pharosi | Q9NR56, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1293317 |
Genetic variation databases
BioMutai | MBNL1 |
DMDMi | 17369313 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000089178 | 1 – 388 | Muscleblind-like protein 1Add BLAST | 388 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 6 | PhosphothreonineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9NR56 |
jPOSTi | Q9NR56 |
MassIVEi | Q9NR56 |
MaxQBi | Q9NR56 |
PaxDbi | Q9NR56 |
PeptideAtlasi | Q9NR56 |
PRIDEi | Q9NR56 |
ProteomicsDBi | 19310 82279 [Q9NR56-1] 82280 [Q9NR56-2] 82281 [Q9NR56-3] 82282 [Q9NR56-4] 82283 [Q9NR56-5] 82284 [Q9NR56-6] |
PTM databases
iPTMneti | Q9NR56 |
PhosphoSitePlusi | Q9NR56 |
SwissPalmi | Q9NR56 |
Expressioni
Tissue specificityi
Highly expressed in cardiac, skeletal muscle and during myoblast differentiation. Weakly expressed in other tissues (at protein level). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.2 Publications
Gene expression databases
Bgeei | ENSG00000152601, Expressed in calcaneal tendon and 259 other tissues |
ExpressionAtlasi | Q9NR56, baseline and differential |
Genevisiblei | Q9NR56, HS |
Organism-specific databases
HPAi | ENSG00000152601, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with DDX1 and YBX1.
Interacts with HNRNPH1; the interaction in RNA-independent.
3 PublicationsBinary interactionsi
Hide detailsQ9NR56
With | #Exp. | IntAct |
---|---|---|
DAB1 [O75553] | 4 | EBI-2805004,EBI-7875264 |
HNRNPH1 [P31943] | 2 | EBI-2805004,EBI-351590 |
Isoform 5 [Q9NR56-5]
With | #Exp. | IntAct |
---|---|---|
ATXN1 [P54253] | 6 | EBI-25978262,EBI-930964 |
Protein-protein interaction databases
BioGRIDi | 110324, 44 interactors |
IntActi | Q9NR56, 28 interactors |
MINTi | Q9NR56 |
STRINGi | 9606.ENSP00000282486 |
Miscellaneous databases
RNActi | Q9NR56, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9NR56 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9NR56 |
Family & Domainsi
Sequence similaritiesi
Belongs to the muscleblind family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 13 – 41 | C3H1-type 1PROSITE-ProRule annotationAdd BLAST | 29 | |
Zinc fingeri | 47 – 73 | C3H1-type 2PROSITE-ProRule annotationAdd BLAST | 27 | |
Zinc fingeri | 179 – 207 | C3H1-type 3PROSITE-ProRule annotationAdd BLAST | 29 | |
Zinc fingeri | 215 – 241 | C3H1-type 4PROSITE-ProRule annotationAdd BLAST | 27 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG2494, Eukaryota |
GeneTreei | ENSGT00950000182897 |
HOGENOMi | CLU_053536_0_0_1 |
InParanoidi | Q9NR56 |
OrthoDBi | 1543798at2759 |
PhylomeDBi | Q9NR56 |
TreeFami | TF321931 |
Family and domain databases
InterProi | View protein in InterPro IPR000571, Znf_CCCH |
Pfami | View protein in Pfam PF00642, zf-CCCH, 1 hit |
SMARTi | View protein in SMART SM00356, ZnF_C3H1, 4 hits |
PROSITEi | View protein in PROSITE PS50103, ZF_C3H1, 4 hits |
s (7+)i Sequence
Sequence statusi: Complete.
This entry describes 7 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 7 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9NR56-1) [UniParc]FASTAAdd to basket
Also known as: EXP42
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAVSVTPIRD TKWLTLEVCR EFQRGTCSRP DTECKFAHPS KSCQVENGRV
60 70 80 90 100
IACFDSLKGR CSRENCKYLH PPPHLKTQLE INGRNNLIQQ KNMAMLAQQM
110 120 130 140 150
QLANAMMPGA PLQPVPMFSV APSLATNASA AAFNPYLGPV SPSLVPAEIL
160 170 180 190 200
PTAPMLVTGN PGVPVPAAAA AAAQKLMRTD RLEVCREYQR GNCNRGENDC
210 220 230 240 250
RFAHPADSTM IDTNDNTVTV CMDYIKGRCS REKCKYFHPP AHLQAKIKAA
260 270 280 290 300
QYQVNQAAAA QAAATAAAMT QSAVKSLKRP LEATFDLGIP QAVLPPLPKR
310 320 330 340 350
PALEKTNGAT AVFNTGIFQY QQALANMQLQ QHTAFLPPVP MVHGATPATV
360 370 380
SAATTSATSV PFAATATANQ IPIISAEHLT SHKYVTQM
Computationally mapped potential isoform sequencesi
There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ86VM6 | Q86VM6_HUMAN | MBNL1 protein | MBNL1 hCG_28028 | 343 | Annotation score: | ||
A0A0A0MQX8 | A0A0A0MQX8_HUMAN | Muscleblind-like protein 1 | MBNL1 | 400 | Annotation score: | ||
C9JP00 | C9JP00_HUMAN | Muscleblind-like protein 1 | MBNL1 | 348 | Annotation score: | ||
H7C4Y1 | H7C4Y1_HUMAN | Muscleblind-like protein 1 | MBNL1 | 210 | Annotation score: | ||
C9JCX1 | C9JCX1_HUMAN | Muscleblind-like protein 1 | MBNL1 | 155 | Annotation score: | ||
H7C4T5 | H7C4T5_HUMAN | Muscleblind-like protein 1 | MBNL1 | 329 | Annotation score: | ||
C9J7P7 | C9J7P7_HUMAN | Muscleblind-like protein 1 | MBNL1 | 90 | Annotation score: | ||
C9J4T8 | C9J4T8_HUMAN | Muscleblind-like protein 1 | MBNL1 | 58 | Annotation score: |
Sequence cautioni
The sequence BAA24858 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Isoform 7 (identifier: Q9NR56-7) | |||||
Sequence conflicti | 317 | A → AA in AAP30726 (Ref. 6) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076508 | 32 | T → M in DM1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs185894411Ensembl. | 1 | |
Natural variantiVAR_076509 | 171 – 173 | Missing in DM1; unknown pathological significance. 1 Publication | 3 | |
Natural variantiVAR_076510 | 338 | P → S in DM1; unknown pathological significance. 1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_006429 | 116 – 183 | Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST | 68 | |
Alternative sequenceiVSP_044903 | 270 – 370 | TQSAV…ATANQ → FPWCTVLRQPLCPQQQHLPQ VFPSLQQPQPTSPILDASTL LGATSCPAAAGKM in isoform 7. 1 PublicationAdd BLAST | 101 | |
Alternative sequenceiVSP_006430 | 270 – 287 | Missing in isoform 2, isoform 3, isoform 4, isoform 5 and isoform 6. 6 PublicationsAdd BLAST | 18 | |
Alternative sequenceiVSP_043799 | 338 | P → PGSILCMTPATSV in isoform 4, isoform 5 and isoform 6. 5 Publications | 1 | |
Alternative sequenceiVSP_043800 | 339 – 388 | VPMVH…YVTQM → DTHNICRTSD in isoform 6. 1 PublicationAdd BLAST | 50 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3D2N | X-ray | 2.70 | A | 9-90 | [»] | |
3D2Q | X-ray | 1.50 | A/B/C/D | 178-246 | [»] | |
3D2S | X-ray | 1.70 | A/B/C/D | 178-246 | [»] | |
5U6H | NMR | - | A | 1-92 | [»] | |
5U6L | NMR | - | A | 173-255 | [»] | |
5U9B | NMR | - | A | 1-92 | [»] | |
SMRi | Q9NR56 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110324, 44 interactors |
IntActi | Q9NR56, 28 interactors |
MINTi | Q9NR56 |
STRINGi | 9606.ENSP00000282486 |
Chemistry databases
ChEMBLi | CHEMBL1293317 |
PTM databases
iPTMneti | Q9NR56 |
PhosphoSitePlusi | Q9NR56 |
SwissPalmi | Q9NR56 |
Genetic variation databases
BioMutai | MBNL1 |
DMDMi | 17369313 |
Proteomic databases
EPDi | Q9NR56 |
jPOSTi | Q9NR56 |
MassIVEi | Q9NR56 |
MaxQBi | Q9NR56 |
PaxDbi | Q9NR56 |
PeptideAtlasi | Q9NR56 |
PRIDEi | Q9NR56 |
ProteomicsDBi | 19310 82279 [Q9NR56-1] 82280 [Q9NR56-2] 82281 [Q9NR56-3] 82282 [Q9NR56-4] 82283 [Q9NR56-5] 82284 [Q9NR56-6] |
Protocols and materials databases
Antibodypediai | 4292, 337 antibodies |
DNASUi | 4154 |
Genome annotation databases
Organism-specific databases
CTDi | 4154 |
DisGeNETi | 4154 |
GeneCardsi | MBNL1 |
HGNCi | HGNC:6923, MBNL1 |
HPAi | ENSG00000152601, Low tissue specificity |
MIMi | 160900, phenotype 606516, gene 613267, phenotype |
neXtProti | NX_Q9NR56 |
OpenTargetsi | ENSG00000152601 |
PharmGKBi | PA30666 |
VEuPathDBi | HostDB:ENSG00000152601.17 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2494, Eukaryota |
GeneTreei | ENSGT00950000182897 |
HOGENOMi | CLU_053536_0_0_1 |
InParanoidi | Q9NR56 |
OrthoDBi | 1543798at2759 |
PhylomeDBi | Q9NR56 |
TreeFami | TF321931 |
Enzyme and pathway databases
PathwayCommonsi | Q9NR56 |
Miscellaneous databases
BioGRID-ORCSi | 4154, 75 hits in 888 CRISPR screens |
ChiTaRSi | MBNL1, human |
EvolutionaryTracei | Q9NR56 |
GeneWikii | MBNL1 |
GenomeRNAii | 4154 |
Pharosi | Q9NR56, Tbio |
PROi | PR:Q9NR56 |
RNActi | Q9NR56, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000152601, Expressed in calcaneal tendon and 259 other tissues |
ExpressionAtlasi | Q9NR56, baseline and differential |
Genevisiblei | Q9NR56, HS |
Family and domain databases
InterProi | View protein in InterPro IPR000571, Znf_CCCH |
Pfami | View protein in Pfam PF00642, zf-CCCH, 1 hit |
SMARTi | View protein in SMART SM00356, ZnF_C3H1, 4 hits |
PROSITEi | View protein in PROSITE PS50103, ZF_C3H1, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MBNL1_HUMAN | |
Accessioni | Q9NR56Primary (citable) accession number: Q9NR56 Secondary accession number(s): E9PBW7 Q96RE3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 16, 2001 |
Last sequence update: | November 16, 2001 | |
Last modified: | February 10, 2021 | |
This is version 173 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants