MBNL2_HUMAN
ID MBNL2_HUMAN Reviewed; 373 AA.
AC Q5VZF2; Q3SXY5; Q58F19; Q8NEV3; Q8TD82;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Muscleblind-like protein 2;
DE AltName: Full=Muscleblind-like protein 1;
DE AltName: Full=Muscleblind-like protein-like;
DE AltName: Full=Muscleblind-like protein-like 39;
GN Name=MBNL2; Synonyms=MBLL, MBLL39, MLP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP INTERACTION WITH ITGA3, AND RNA-BINDING.
RX PubMed=16273094; DOI=10.1038/ncb1335;
RA Adereth Y., Dammai V., Kose N., Li R., Hsu T.;
RT "RNA-dependent integrin alpha3 protein localization regulated by the
RT muscleblind-like protein MLP1.";
RL Nat. Cell Biol. 7:1240-1247(2005).
RN [2]
RP ERRATUM OF PUBMED:16273094.
RA Adereth Y., Dammai V., Kose N., Li R., Hsu T.;
RL Nat. Cell Biol. 8:100-100(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Cervix carcinoma;
RA Teng-umnuay P., Urbinati C.R., Swanson M.S.;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Colon carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11929853; DOI=10.1093/hmg/11.7.805;
RA Fardaei M., Rogers M.T., Thorpe H.M., Larkin K., Hamshere M.G.,
RA Harper P.S., Brook J.D.;
RT "Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci
RT of expanded-repeat transcripts in DM1 and DM2 cells.";
RL Hum. Mol. Genet. 11:805-814(2002).
RN [8]
RP FUNCTION.
RX PubMed=15257297; DOI=10.1038/sj.emboj.7600300;
RA Ho T.H., Charlet-B N., Poulos M.G., Singh G., Swanson M.S., Cooper T.A.;
RT "Muscleblind proteins regulate alternative splicing.";
RL EMBO J. 23:3103-3112(2004).
RN [9]
RP FUNCTION.
RX PubMed=16946708; DOI=10.1038/sj.emboj.7601296;
RA Paul S., Dansithong W., Kim D., Rossi J., Webster N.J., Comai L., Reddy S.;
RT "Interaction of muscleblind, CUG-BP1 and hnRNP H proteins in DM1-associated
RT aberrant IR splicing.";
RL EMBO J. 25:4271-4283(2006).
RN [10]
RP STRUCTURE BY NMR OF 166-257.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ZF-CCCHx2 domain of muscleblind-like 2, isoform
RT 1 [Homo sapiens].";
RL Submitted (JUN-2007) to the PDB data bank.
RN [11]
RP STRUCTURE BY NMR OF 7-82 AND 166-257 IN COMPLEX WITH ZINC IONS.
RX PubMed=19177353; DOI=10.1002/pro.17;
RA He F., Dang W., Abe C., Tsuda K., Inoue M., Watanabe S., Kobayashi N.,
RA Kigawa T., Matsuda T., Yabuki T., Aoki M., Seki E., Harada T.,
RA Tomabechi Y., Terada T., Shirouzu M., Tanaka A., Guntert P., Muto Y.,
RA Yokoyama S.;
RT "Solution structure of the RNA binding domain in the human muscleblind-like
RT protein 2.";
RL Protein Sci. 18:80-91(2009).
CC -!- FUNCTION: Mediates pre-mRNA alternative splicing regulation. Acts
CC either as activator or repressor of splicing on specific pre-mRNA
CC targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion
CC but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle.
CC Antagonizes the alternative splicing activity pattern of CELF proteins.
CC RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed
CC zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat
CC expansion in myotonic dystrophy muscle cells by sequestering the target
CC RNAs. Seems to regulate expression and localization of ITGA3 by
CC transporting it from the nucleus to cytoplasm at adhesion plaques. May
CC play a role in myotonic dystrophy pathophysiology (DM).
CC {ECO:0000269|PubMed:15257297, ECO:0000269|PubMed:16273094,
CC ECO:0000269|PubMed:16946708}.
CC -!- SUBUNIT: Interacts with ITGA3. {ECO:0000269|PubMed:16273094,
CC ECO:0000269|PubMed:19177353}.
CC -!- INTERACTION:
CC Q5VZF2-2; P09012: SNRPA; NbExp=3; IntAct=EBI-13307411, EBI-607085;
CC Q5VZF2-2; Q01085-2: TIAL1; NbExp=3; IntAct=EBI-13307411, EBI-11064654;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11929853}. Cytoplasm
CC {ECO:0000269|PubMed:16273094}. Note=Greater concentration in the
CC nucleus. Expressed in or near large cytoplasmic adhesion plaques
CC (PubMed:16273094). Location in the cytoplasm is microtubule-dependent
CC (PubMed:16273094). In both DM1 and DM2 patients, colocalizes with
CC nuclear foci of retained expanded-repeat transcripts (PubMed:11929853).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5VZF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5VZF2-2; Sequence=VSP_022887;
CC Name=3;
CC IsoId=Q5VZF2-3; Sequence=VSP_022888;
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver,
CC skeletal muscle, kidney and pancreas. {ECO:0000269|PubMed:11929853}.
CC -!- SIMILARITY: Belongs to the muscleblind family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF491866; AAM09798.1; -; mRNA.
DR EMBL; AY101770; AAM50085.1; -; mRNA.
DR EMBL; CR749802; CAH18662.1; -; mRNA.
DR EMBL; AL161430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL442067; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020418; AAH20418.1; -; mRNA.
DR EMBL; BC104038; AAI04039.1; -; mRNA.
DR EMBL; BC104039; AAI04040.1; -; mRNA.
DR EMBL; BC104040; AAI04041.1; -; mRNA.
DR CCDS; CCDS76644.1; -. [Q5VZF2-1]
DR CCDS; CCDS9483.1; -. [Q5VZF2-3]
DR CCDS; CCDS9484.1; -. [Q5VZF2-2]
DR RefSeq; NP_001292999.1; NM_001306070.1. [Q5VZF2-1]
DR RefSeq; NP_659002.1; NM_144778.3. [Q5VZF2-2]
DR RefSeq; NP_997187.1; NM_207304.2. [Q5VZF2-3]
DR RefSeq; XP_016875798.1; XM_017020309.1.
DR RefSeq; XP_016875799.1; XM_017020310.1.
DR RefSeq; XP_016875800.1; XM_017020311.1.
DR PDB; 2E5S; NMR; -; A=167-257.
DR PDB; 2RPP; NMR; -; A=7-82.
DR PDBsum; 2E5S; -.
DR PDBsum; 2RPP; -.
DR AlphaFoldDB; Q5VZF2; -.
DR SMR; Q5VZF2; -.
DR BioGRID; 115452; 25.
DR IntAct; Q5VZF2; 6.
DR STRING; 9606.ENSP00000267287; -.
DR iPTMnet; Q5VZF2; -.
DR PhosphoSitePlus; Q5VZF2; -.
DR BioMuta; MBNL2; -.
DR DMDM; 125952110; -.
DR EPD; Q5VZF2; -.
DR jPOST; Q5VZF2; -.
DR MassIVE; Q5VZF2; -.
DR MaxQB; Q5VZF2; -.
DR PaxDb; Q5VZF2; -.
DR PeptideAtlas; Q5VZF2; -.
DR PRIDE; Q5VZF2; -.
DR ProteomicsDB; 65695; -. [Q5VZF2-1]
DR ProteomicsDB; 65696; -. [Q5VZF2-2]
DR ProteomicsDB; 65697; -. [Q5VZF2-3]
DR Antibodypedia; 24898; 128 antibodies from 20 providers.
DR DNASU; 10150; -.
DR Ensembl; ENST00000343600.9; ENSP00000344214.4; ENSG00000139793.20. [Q5VZF2-3]
DR Ensembl; ENST00000345429.10; ENSP00000267287.7; ENSG00000139793.20. [Q5VZF2-2]
DR Ensembl; ENST00000376673.8; ENSP00000365861.3; ENSG00000139793.20. [Q5VZF2-1]
DR Ensembl; ENST00000397601.5; ENSP00000380726.1; ENSG00000139793.20. [Q5VZF2-3]
DR GeneID; 10150; -.
DR KEGG; hsa:10150; -.
DR UCSC; uc001vmz.5; human. [Q5VZF2-1]
DR CTD; 10150; -.
DR DisGeNET; 10150; -.
DR GeneCards; MBNL2; -.
DR HGNC; HGNC:16746; MBNL2.
DR HPA; ENSG00000139793; Low tissue specificity.
DR MIM; 607327; gene.
DR neXtProt; NX_Q5VZF2; -.
DR OpenTargets; ENSG00000139793; -.
DR PharmGKB; PA134901420; -.
DR VEuPathDB; HostDB:ENSG00000139793; -.
DR eggNOG; KOG2494; Eukaryota.
DR GeneTree; ENSGT00950000182897; -.
DR InParanoid; Q5VZF2; -.
DR OMA; PTXNSEI; -.
DR PhylomeDB; Q5VZF2; -.
DR TreeFam; TF321931; -.
DR PathwayCommons; Q5VZF2; -.
DR SignaLink; Q5VZF2; -.
DR BioGRID-ORCS; 10150; 9 hits in 1080 CRISPR screens.
DR ChiTaRS; MBNL2; human.
DR EvolutionaryTrace; Q5VZF2; -.
DR GeneWiki; MBNL2; -.
DR GenomeRNAi; 10150; -.
DR Pharos; Q5VZF2; Tbio.
DR PRO; PR:Q5VZF2; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q5VZF2; protein.
DR Bgee; ENSG00000139793; Expressed in endothelial cell and 218 other tissues.
DR ExpressionAtlas; Q5VZF2; baseline and differential.
DR Genevisible; Q5VZF2; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IBA:GO_Central.
DR GO; GO:0043484; P:regulation of RNA splicing; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR InterPro; IPR000571; Znf_CCCH.
DR Pfam; PF00642; zf-CCCH; 2.
DR SMART; SM00356; ZnF_C3H1; 4.
DR PROSITE; PS50103; ZF_C3H1; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Metal-binding;
KW mRNA processing; mRNA splicing; Nucleus; Reference proteome; Repeat;
KW RNA-binding; Zinc; Zinc-finger.
FT CHAIN 1..373
FT /note="Muscleblind-like protein 2"
FT /id="PRO_0000274872"
FT ZN_FING 13..41
FT /note="C3H1-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 47..73
FT /note="C3H1-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 176..204
FT /note="C3H1-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT ZN_FING 212..238
FT /note="C3H1-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00723"
FT VAR_SEQ 320..331
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3"
FT /id="VSP_022888"
FT VAR_SEQ 332..373
FT /note="DNSEIISRNGMECQESALRITKHCYCTYYPVSSSIELPQTAC -> VPMMHS
FT ATSATVSAATTPATSVPFAATATANQIILK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16273094"
FT /id="VSP_022887"
FT CONFLICT 254
FT /note="A -> G (in Ref. 1; AAM09798)"
FT /evidence="ECO:0000305"
FT STRAND 12..16
FT /evidence="ECO:0007829|PDB:2RPP"
FT HELIX 20..24
FT /evidence="ECO:0007829|PDB:2RPP"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:2RPP"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2RPP"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:2RPP"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:2RPP"
FT HELIX 54..58
FT /evidence="ECO:0007829|PDB:2RPP"
FT HELIX 73..81
FT /evidence="ECO:0007829|PDB:2RPP"
FT STRAND 176..181
FT /evidence="ECO:0007829|PDB:2E5S"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:2E5S"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:2E5S"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:2E5S"
FT TURN 210..212
FT /evidence="ECO:0007829|PDB:2E5S"
FT STRAND 214..217
FT /evidence="ECO:0007829|PDB:2E5S"
FT HELIX 219..223
FT /evidence="ECO:0007829|PDB:2E5S"
FT HELIX 238..248
FT /evidence="ECO:0007829|PDB:2E5S"
SQ SEQUENCE 373 AA; 40518 MW; 8FC6D5C150781277 CRC64;
MALNVAPVRD TKWLTLEVCR QFQRGTCSRS DEECKFAHPP KSCQVENGRV IACFDSLKGR
CSRENCKYLH PPTHLKTQLE INGRNNLIQQ KTAAAMLAQQ MQFMFPGTPL HPVPTFPVGP
AIGTNTAISF APYLAPVTPG VGLVPTEILP TTPVIVPGSP PVTVPGSTAT QKLLRTDKLE
VCREFQRGNC ARGETDCRFA HPADSTMIDT SDNTVTVCMD YIKGRCMREK CKYFHPPAHL
QAKIKAAQHQ ANQAAVAAQA AAAAATVMAF PPGALHPLPK RQALEKSNGT SAVFNPSVLH
YQQALTSAQL QQHAAFIPTG SVLCMTPATS IDNSEIISRN GMECQESALR ITKHCYCTYY
PVSSSIELPQ TAC
