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   24-JAN-2024, entry version 144.
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; 10090-ENSMUSP00000069915; -.
DR   Antibodypedia; 30051; 196 antibodies from 30 providers.
DR   DNASU; 17240; -.
DR   Ensembl; ENSMUST00000035375.14; ENSMUSP00000037888.8; ENSMUSG00000032717.15. [P70331-2]
DR   Ensembl; ENSMUST00000066368.13; ENSMUSP00000069915.7; ENSMUSG00000032717.15. [P70331-2]
DR   GeneID; 17240; -.
DR   KEGG; mmu:17240; -.
DR   UCSC; uc008cwh.3; mouse. [P70331-2]
DR   UCSC; uc008cwj.3; mouse. [P70331-1]
DR   AGR; MGI:107687; -.
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; CTPLLQN; -.
DR   OrthoDB; 5359989at2759; -.
DR   PhylomeDB; P70331; -.
DR   TreeFam; TF332113; -.
DR   BioGRID-ORCS; 17240; 2 hits in 80 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 146 other cell types or tissues.
DR   ExpressionAtlas; P70331; baseline and differential.
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; MYOD FAMILY INHIBITOR; 1.
DR   PANTHER; PTHR15304:SF1; MYOD FAMILY INHIBITOR; 1.
DR   Genevisible; P70331; MM.
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
//