MDFI_MOUSE
ID MDFI_MOUSE Reviewed; 251 AA.
AC P70331; P70330; P70332; Q5XK64; Q99JM9;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=MyoD family inhibitor;
DE AltName: Full=Myogenic repressor I-mf;
GN Name=Mdfi;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS I-MFA; I-MFB AND I-MFC), FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=NIH Swiss; TISSUE=Embryo;
RX PubMed=8797820; DOI=10.1016/s0092-8674(00)80148-8;
RA Chen C.-M.A., Kraut N., Groudine M., Weintraub H.;
RT "I-mf, a novel myogenic repressor, interacts with members of the MyoD
RT family.";
RL Cell 86:731-741(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM I-MFA).
RC STRAIN=129, and FVB/N; TISSUE=Mammary gland;
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 [3]
RP FUNCTION.
RX PubMed=9799236; DOI=10.1093/emboj/17.21.6276;
RA Kraut N., Snider L., Chen C.-M.A., Tapscott S.J., Groudine M.;
RT "Requirement of the mouse I-mfa gene for placental development and skeletal
RT patterning.";
RL EMBO J. 17:6276-6288(1998).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11238923; DOI=10.1128/mcb.21.5.1866-1873.2001;
RA Snider L., Thirlwell H., Miller J.R., Moon R.T., Groudine M.,
RA Tapscott S.J.;
RT "Inhibition of Tcf3 binding by I-mfa domain proteins.";
RL Mol. Cell. Biol. 21:1866-1873(2001).
RN [5]
RP FUNCTION, AND INTERACTION WITH AXIN1 AND LEF1.
RX PubMed=12192039; DOI=10.1128/mcb.22.18.6393-6405.2002;
RA Kusano S., Raab-Traub N.;
RT "I-mfa domain proteins interact with Axin and affect its regulation of the
RT Wnt and c-Jun N-terminal kinase signaling pathways.";
RL Mol. Cell. Biol. 22:6393-6405(2002).
CC -!- FUNCTION: Inhibits the transactivation activity of the Myod family of
CC myogenic factors and represses myogenesis. Acts by associating with
CC Myod family members and retaining them in the cytoplasm by masking
CC their nuclear localization signals. Can also interfere with the DNA-
CC binding activity of Myod family members. Plays an important role in
CC trophoblast and chondrogenic differentiation. Regulates the
CC transcriptional activity of TCF7L1/TCF3 by interacting directly with
CC TCF7L1/TCF3 and preventing it from binding DNA. Binds to the axin
CC complex, resulting in an increase in the level of free beta-catenin.
CC Affects axin regulation of the WNT and JNK signaling pathways.
CC {ECO:0000269|PubMed:11238923, ECO:0000269|PubMed:12192039,
CC ECO:0000269|PubMed:8797820, ECO:0000269|PubMed:9799236}.
CC -!- SUBUNIT: The C-terminus interacts with AXIN1 and LEF1
CC (PubMed:12192039). Interacts with CCNT2 (By similarity).
CC {ECO:0000250|UniProtKB:Q99750, ECO:0000269|PubMed:12192039}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=I-mfB;
CC IsoId=P70331-1; Sequence=Displayed;
CC Name=I-mfA;
CC IsoId=P70331-2; Sequence=VSP_004056;
CC Name=I-mfC;
CC IsoId=P70331-3; Sequence=VSP_004055, VSP_004057;
CC -!- TISSUE SPECIFICITY: In the embryo, highly expressed in the sclerotome.
CC Also expressed in the notochord, neural tube, limb buds, heart,
CC branchial arches and head mesenchyme. In the adult, highly expressed in
CC skeletal muscle. Expressed at lower levels in most other tissues.
CC {ECO:0000269|PubMed:8797820}.
CC -!- SIMILARITY: Belongs to the MDFI family. {ECO:0000305}.
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DR EMBL; U57820; AAC52791.1; -; mRNA.
DR EMBL; U57821; AAC52792.1; -; mRNA.
DR EMBL; U57822; AAC52793.1; -; mRNA.
DR EMBL; BC006018; AAH06018.1; -; mRNA.
DR EMBL; BC010259; AAH10259.1; -; mRNA.
DR EMBL; BC083058; AAH83058.1; -; mRNA.
DR EMBL; BC085233; AAH85233.1; -; mRNA.
DR CCDS; CCDS50134.1; -. [P70331-2]
DR RefSeq; NP_001103443.1; NM_001109973.2. [P70331-2]
DR RefSeq; NP_001263319.1; NM_001276390.1. [P70331-2]
DR RefSeq; NP_034913.2; NM_010783.3. [P70331-2]
DR RefSeq; XP_006523806.1; XM_006523743.3. [P70331-1]
DR RefSeq; XP_006523807.1; XM_006523744.3. [P70331-1]
DR RefSeq; XP_006523808.1; XM_006523745.3. [P70331-1]
DR AlphaFoldDB; P70331; -.
DR BioGRID; 201368; 2.
DR STRING; 10090.ENSMUSP00000069915; -.
DR iPTMnet; P70331; -.
DR PhosphoSitePlus; P70331; -.
DR PaxDb; P70331; -.
DR PRIDE; P70331; -.
DR Antibodypedia; 30051; 168 antibodies from 30 providers.
DR DNASU; 17240; -.
DR Ensembl; ENSMUST00000035375; ENSMUSP00000037888; ENSMUSG00000032717. [P70331-2]
DR Ensembl; ENSMUST00000066368; ENSMUSP00000069915; ENSMUSG00000032717. [P70331-2]
DR GeneID; 17240; -.
DR KEGG; mmu:17240; -.
DR UCSC; uc008cwh.3; mouse. [P70331-2]
DR UCSC; uc008cwj.3; mouse. [P70331-1]
DR CTD; 4188; -.
DR MGI; MGI:107687; Mdfi.
DR VEuPathDB; HostDB:ENSMUSG00000032717; -.
DR eggNOG; ENOG502RZMC; Eukaryota.
DR GeneTree; ENSGT00940000160187; -.
DR HOGENOM; CLU_067479_1_0_1; -.
DR InParanoid; P70331; -.
DR OMA; CAECDLP; -.
DR OrthoDB; 1487193at2759; -.
DR PhylomeDB; P70331; -.
DR TreeFam; TF332113; -.
DR BioGRID-ORCS; 17240; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Mdfi; mouse.
DR PRO; PR:P70331; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P70331; protein.
DR Bgee; ENSMUSG00000032717; Expressed in ectoplacental cone and 143 other tissues.
DR ExpressionAtlas; P70331; baseline and differential.
DR Genevisible; P70331; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:UniProtKB.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IGI:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0060707; P:trophoblast giant cell differentiation; IMP:MGI.
DR InterPro; IPR026134; MDFI/MDFIC.
DR PANTHER; PTHR15304; PTHR15304; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; Differentiation;
KW Nucleus; Reference proteome.
FT CHAIN 1..251
FT /note="MyoD family inhibitor"
FT /id="PRO_0000096325"
FT REGION 1..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 132..158
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 136..163
FT /note="SLGSQAGRKSRGSARSASQVPLQAQEGK -> PQPPNRSAFRRVAWSPPRVT
FT RNTASRAW (in isoform I-mfC)"
FT /evidence="ECO:0000303|PubMed:8797820"
FT /id="VSP_004055"
FT VAR_SEQ 162..251
FT /note="GKAPAVRIHRQTASPTCCLRNAQLSGTALRSLRLESQGHRELNNKTLSQSNN
FT KKPGVAAHAAIIPALTRPKQNCHDPSLLPGTHGVGKEF -> DCCVHCILSCLFCEFLT
FT LCNILLDCATCGSCSSEDSCLCCCCCGSGECADCDLPCDLDCGIVDACCESADCLEICM
FT ECCGLCFSS (in isoform I-mfA)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8797820"
FT /id="VSP_004056"
FT VAR_SEQ 164..251
FT /note="Missing (in isoform I-mfC)"
FT /evidence="ECO:0000303|PubMed:8797820"
FT /id="VSP_004057"
SQ SEQUENCE 251 AA; 26013 MW; E77D693D935F1B83 CRC64;
MSQVSGQCPS RCDAPHGVPS AALDPAQTMS LLPGLEVARS THPVEASSEE GFPEEAAPSM
PHDSGLRAQQ ALNSIDLDVP TEAVTCQPQG NPQGCTPLLP NGSSHDHLSE PGSAGHAGNG
ALGGSKAHRK LQTHPSLGSQ AGRKSRGSAR SASQVPLQAQ EGKAPAVRIH RQTASPTCCL
RNAQLSGTAL RSLRLESQGH RELNNKTLSQ SNNKKPGVAA HAAIIPALTR PKQNCHDPSL
LPGTHGVGKE F
