MLX_MOUSE
ID MLX_MOUSE Reviewed; 298 AA.
AC O08609; Q9EQJ7; Q9EQJ8;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 167.
DE RecName: Full=Max-like protein X;
DE AltName: Full=Max-like bHLHZip protein;
DE AltName: Full=Protein BigMax;
DE AltName: Full=Transcription factor-like protein 4;
GN Name=Mlx; Synonyms=Tcfl4;
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] (ISOFORM GAMMA), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Intestine;
RX PubMed=8973301; DOI=10.1016/s0378-1119(96)00376-9;
RA Bjerknes M., Cheng H.;
RT "TCFL4: a gene at 17q21.1 encoding a putative basic helix-loop-helix
RT leucine-zipper transcription factor.";
RL Gene 181:7-11(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=10918583; DOI=10.1038/sj.onc.1203634;
RA Meroni G., Cairo S., Merla G., Messali S., Brent R., Ballabio A.,
RA Reymond A.;
RT "Mlx, a new Max-like bHLHZip family member: the center stage of a novel
RT transcription factors regulatory pathway?";
RL Oncogene 19:3266-3277(2000).
RN [3]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryonic stem cell;
RX PubMed=10593926; DOI=10.1074/jbc.274.51.36344;
RA Billin A.N., Eilers A.L., Queva C., Ayer D.E.;
RT "Mlx, a novel Max-like bHLHZip protein that interacts with the Max network
RT of transcription factors.";
RL J. Biol. Chem. 274:36344-36350(1999).
RN [4]
RP FUNCTION, AND INTERACTION WITH MLXIP.
RX PubMed=11073985; DOI=10.1128/mcb.20.23.8845-8854.2000;
RA Billin A.N., Eilers A.L., Coulter K.L., Logan J.S., Ayer D.E.;
RT "MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional
RT activator that constitutes a positive branch of a max-like network.";
RL Mol. Cell. Biol. 20:8845-8854(2000).
RN [5]
RP FUNCTION.
RX PubMed=16644671; DOI=10.2337/db05-0822;
RA Li M.V., Chang B., Imamura M., Poungvarin N., Chan L.;
RT "Glucose-dependent transcriptional regulation by an evolutionarily
RT conserved glucose-sensing module.";
RL Diabetes 55:1179-1189(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND SER-48, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45 AND SER-48, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Pancreas, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Transcription regulator. Forms a sequence-specific DNA-
CC binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which
CC recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4,
CC TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in
CC transcriptional activation of glycolytic target genes. Involved in
CC glucose-responsive gene regulation. {ECO:0000269|PubMed:10593926,
CC ECO:0000269|PubMed:11073985, ECO:0000269|PubMed:16644671}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Binds DNA as a heterodimer with MAD1, MAD4, MNT, WBSCR14 and
CC MLXIP. Can also bind DNA as a homodimer.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UH92}. Note=Found predominantly in the
CC cytoplasm. {ECO:0000250|UniProtKB:Q9UH92}.
CC -!- SUBCELLULAR LOCATION: [Isoform Beta]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UH92}. Note=Found predominantly in the
CC cytoplasm. {ECO:0000250|UniProtKB:Q9UH92}.
CC -!- SUBCELLULAR LOCATION: [Isoform Gamma]: Nucleus
CC {ECO:0000250|UniProtKB:Q9UH92}. Note=Found predominantly in the
CC nucleus. {ECO:0000250|UniProtKB:Q9UH92}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Gamma;
CC IsoId=O08609-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=O08609-2; Sequence=VSP_002139, VSP_002140;
CC Name=Beta;
CC IsoId=O08609-3; Sequence=VSP_002139;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined: stomach,
CC duodenum, jejunum, ileum, colon, liver, pancreas, salivary gland,
CC kidney, spleen, lung, heart, skeletal muscle, brain, ovary and testis.
CC {ECO:0000269|PubMed:8973301}.
CC -!- DEVELOPMENTAL STAGE: Expression peaks between dpc 9.5 to 11.5, then
CC decreases during later stages of organogenesis.
CC {ECO:0000269|PubMed:10593926}.
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DR EMBL; U43607; AAB51368.1; -; mRNA.
DR EMBL; U43548; AAB51367.1; -; mRNA.
DR EMBL; AF213670; AAG40149.1; -; mRNA.
DR EMBL; AF213671; AAG40150.1; -; mRNA.
DR EMBL; AF213672; AAG40151.1; -; mRNA.
DR CCDS; CCDS25447.1; -. [O08609-1]
DR CCDS; CCDS48935.1; -. [O08609-3]
DR CCDS; CCDS48936.1; -. [O08609-2]
DR RefSeq; NP_001152856.1; NM_001159384.1.
DR RefSeq; NP_001152857.1; NM_001159385.1.
DR RefSeq; NP_035680.3; NM_011550.3.
DR AlphaFoldDB; O08609; -.
DR BioGRID; 204019; 1.
DR CORUM; O08609; -.
DR STRING; 10090.ENSMUSP00000017945; -.
DR iPTMnet; O08609; -.
DR PhosphoSitePlus; O08609; -.
DR EPD; O08609; -.
DR MaxQB; O08609; -.
DR PaxDb; O08609; -.
DR PRIDE; O08609; -.
DR ProteomicsDB; 290261; -. [O08609-1]
DR ProteomicsDB; 290262; -. [O08609-2]
DR ProteomicsDB; 290263; -. [O08609-3]
DR DNASU; 21428; -.
DR GeneID; 21428; -.
DR KEGG; mmu:21428; -.
DR CTD; 6945; -.
DR MGI; MGI:108398; Mlx.
DR eggNOG; KOG1319; Eukaryota.
DR InParanoid; O08609; -.
DR OrthoDB; 1234389at2759; -.
DR PhylomeDB; O08609; -.
DR Reactome; R-MMU-163765; ChREBP activates metabolic gene expression.
DR BioGRID-ORCS; 21428; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Mlx; mouse.
DR PRO; PR:O08609; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O08609; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR032647; Mlx.
DR PANTHER; PTHR15741:SF25; PTHR15741:SF25; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..298
FT /note="Max-like protein X"
FT /id="PRO_0000127280"
FT DOMAIN 129..187
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 98..119
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 194..214
FT /note="Leucine-zipper"
FT COMPBIAS 98..112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UH92"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UH92"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UH92"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UH92"
FT VAR_SEQ 15..68
FT /note="Missing (in isoform Alpha and isoform Beta)"
FT /evidence="ECO:0000305"
FT /id="VSP_002139"
FT VAR_SEQ 81..110
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000305"
FT /id="VSP_002140"
SQ SEQUENCE 298 AA; 33339 MW; A494D5A86292B71C CRC64;
MTEPGASPED PWVKASFADA HAGEGRAGRA RARRGSGRRG APQLSPESPL LSGARGCRED
SSHPACAKVE YAYSDNSLDP GLFVESTHKG SVVSRANSIG STSASSVPNT DDEDSDYQQE
AYKESYKDRR RRAHTQAEQK RRDAIKRGYD DLQTIVPTCQ QQDFSIGSQK LSKAIVLQKT
IDYIQFLHKE KKKQEEEVST LRKDVTALKI MKVNYEQIVK AHQDNPHEGE DQVSDQVKFN
VFQGIMDSLF QSFNASISVA SFQELSACVF SWIEEHCEPQ TLREIVIGVL HQLKNQLY