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Transcription factor 12 (TCF-12) (Class A helix-loop-helix transcription factor ME1) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4)

 HTF4_MOUSE              Reviewed;         706 AA.
Q61286; E9QPN4;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 2.
28-MAR-2018, entry version 156.
RecName: Full=Transcription factor 12;
Short=TCF-12;
AltName: Full=Class A helix-loop-helix transcription factor ME1;
AltName: Full=DNA-binding protein HTF4;
AltName: Full=E-box-binding protein;
AltName: Full=Transcription factor HTF-4;
Name=Tcf12; Synonyms=Alf1, Meb;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALF1A AND ALF1B).
PubMed=1321336; DOI=10.1128/MCB.12.8.3449;
Nielsen A.L., Pallisgaard N., Pedersen F.S., Joergensen P.;
"Murine helix-loop-helix transcriptional activator proteins binding to
the E-box motif of the Akv murine leukemia virus enhancer identified
by cDNA cloning.";
Mol. Cell. Biol. 12:3449-3459(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=BALB/cJ; TISSUE=Cerebellum;
PubMed=8261111; DOI=10.1111/j.1460-9568.1993.tb00498.x;
Neuman T., Keen A., Knapik E., Shain D., Ross M., Nornes H.O.,
Zuber M.X.;
"ME1 and GE1: basic helix-loop-helix transcription factors expressed
at high levels in the developing nervous system and in
morphogenetically active regions.";
Eur. J. Neurosci. 5:311-318(1993).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[4]
INTERACTION WITH PTF1A.
PubMed=11562365; DOI=10.1074/jbc.M106264200;
Rose S.D., Swift G.H., Peyton M.J., Hammer R.E., MacDonald R.J.;
"The role of PTF1-P48 in pancreatic acinar gene expression.";
J. Biol. Chem. 276:44018-44026(2001).
[5]
FUNCTION, INTERACTION WITH NEUROD2, DNA-BINDING, DISRUPTION PHENOTYPE,
AND DEVELOPMENTAL STAGE.
PubMed=18214987; DOI=10.1002/jnr.21615;
Ravanpay A.C., Olson J.M.;
"E protein dosage influences brain development more than family member
identity.";
J. Neurosci. Res. 86:1472-1481(2008).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-124,
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-392 (ISOFORM ALF1A), AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, Brown adipose tissue, Lung, Pancreas, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: Transcriptional regulator. Involved in the initiation of
neuronal differentiation. Activates transcription by binding to
the E box (5'-CANNTG-3'). {ECO:0000269|PubMed:18214987}.
-!- SUBUNIT: Efficient DNA binding requires dimerization with another
bHLH protein. Forms homo- or heterooligomers with myogenin, E12
and ITF2 proteins and RUNX1T1 (By similarity). Interacts with
PTF1A. Interacts with NEUROD2. Interacts with BHLHA9.
{ECO:0000250|UniProtKB:Q99081, ECO:0000269|PubMed:11562365,
ECO:0000269|PubMed:18214987}.
-!- INTERACTION:
P22091:Tal1; NbExp=2; IntAct=EBI-8006499, EBI-8006437;
-!- SUBCELLULAR LOCATION: Nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=ALF1B; Synonyms=ME1A;
IsoId=Q61286-1; Sequence=Displayed;
Name=ALF1A; Synonyms=ME1B;
IsoId=Q61286-2; Sequence=VSP_002105;
Note=Contains a phosphoserine at position 392.
{ECO:0000244|PubMed:21183079};
-!- TISSUE SPECIFICITY: Widely expressed.
-!- DEVELOPMENTAL STAGE: Abundantly expressed during development of
the central nervous system, in particular in proliferating
neuroblasts and in cells at the initial stages of differentiation.
Also expressed at high levels in morphogenetically active regions
such as limb buds, somites and mesonephric tubules. Expression
decreases once cellular differentiation is over.
{ECO:0000269|PubMed:18214987}.
-!- DISRUPTION PHENOTYPE: Mice are smaller than their wild-type
littermates and fail to thrive 14 days after birth.
{ECO:0000269|PubMed:18214987}.
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EMBL; X64840; CAA46052.1; -; mRNA.
EMBL; M97635; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; M97636; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AC093483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC157575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC159001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
CCDS; CCDS23329.1; -. [Q61286-1]
CCDS; CCDS72272.1; -. [Q61286-2]
PIR; C45020; C45020.
PIR; S19958; S19958.
RefSeq; NP_001240794.1; NM_001253865.1.
RefSeq; NP_035674.2; NM_011544.3. [Q61286-1]
RefSeq; XP_006511057.1; XM_006510994.3. [Q61286-1]
RefSeq; XP_006511060.1; XM_006510997.2. [Q61286-2]
UniGene; Mm.171615; -.
UniGene; Mm.480117; -.
ProteinModelPortal; Q61286; -.
SMR; Q61286; -.
BioGrid; 204000; 17.
CORUM; Q61286; -.
DIP; DIP-42840N; -.
IntAct; Q61286; 4.
MINT; Q61286; -.
STRING; 10090.ENSMUSP00000034755; -.
iPTMnet; Q61286; -.
PhosphoSitePlus; Q61286; -.
PaxDb; Q61286; -.
PeptideAtlas; Q61286; -.
PRIDE; Q61286; -.
Ensembl; ENSMUST00000034755; ENSMUSP00000034755; ENSMUSG00000032228. [Q61286-2]
Ensembl; ENSMUST00000183404; ENSMUSP00000139365; ENSMUSG00000032228. [Q61286-1]
Ensembl; ENSMUST00000184783; ENSMUSP00000139364; ENSMUSG00000032228. [Q61286-1]
Ensembl; ENSMUST00000185117; ENSMUSP00000138925; ENSMUSG00000032228. [Q61286-2]
GeneID; 21406; -.
KEGG; mmu:21406; -.
UCSC; uc009qpf.2; mouse. [Q61286-1]
UCSC; uc009qpg.2; mouse. [Q61286-2]
CTD; 6938; -.
MGI; MGI:101877; Tcf12.
eggNOG; KOG3910; Eukaryota.
eggNOG; ENOG410XYUA; LUCA.
GeneTree; ENSGT00510000046438; -.
HOGENOM; HOG000234180; -.
HOVERGEN; HBG003854; -.
InParanoid; Q61286; -.
KO; K15603; -.
OMA; YYSFSAT; -.
OrthoDB; EOG091G07E2; -.
TreeFam; TF321672; -.
Reactome; R-MMU-375170; CDO in myogenesis.
Reactome; R-MMU-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
ChiTaRS; Tcf12; mouse.
PRO; PR:Q61286; -.
Proteomes; UP000000589; Chromosome 9.
Bgee; ENSMUSG00000032228; -.
CleanEx; MM_TCF12; -.
ExpressionAtlas; Q61286; baseline and differential.
Genevisible; Q61286; MM.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
GO; GO:0000790; C:nuclear chromatin; ISO:MGI.
GO; GO:0016607; C:nuclear speck; ISO:MGI.
GO; GO:0005654; C:nucleoplasm; ISO:MGI.
GO; GO:0005634; C:nucleus; ISO:MGI.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; ISO:MGI.
GO; GO:0005667; C:transcription factor complex; IDA:MGI.
GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
GO; GO:0035497; F:cAMP response element binding; IEA:Ensembl.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0003700; F:DNA binding transcription factor activity; ISO:MGI.
GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
GO; GO:0071837; F:HMG box domain binding; IEA:Ensembl.
GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0046332; F:SMAD binding; ISO:MGI.
GO; GO:0008134; F:transcription factor binding; ISO:MGI.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
CDD; cd00083; HLH; 1.
Gene3D; 4.10.280.10; -; 1.
InterPro; IPR011598; bHLH_dom.
InterPro; IPR036638; HLH_DNA-bd_sf.
Pfam; PF00010; HLH; 1.
SMART; SM00353; HLH; 1.
SUPFAM; SSF47459; SSF47459; 1.
PROSITE; PS50888; BHLH; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Developmental protein;
Differentiation; DNA-binding; Isopeptide bond; Neurogenesis; Nucleus;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation; Ubl conjugation.
CHAIN 1 706 Transcription factor 12.
/FTId=PRO_0000127230.
DOMAIN 601 654 bHLH. {ECO:0000255|PROSITE-
ProRule:PRU00981}.
REGION 119 140 Leucine-zipper.
REGION 656 679 Class A specific domain.
MOTIF 181 188 Nuclear localization signal.
{ECO:0000255}.
MOD_RES 47 47 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 67 67 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 79 79 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 98 98 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 116 116 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 124 124 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 313 313 Phosphothreonine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 333 333 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 564 564 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 581 581 Phosphothreonine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 582 582 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
MOD_RES 583 583 Phosphoserine.
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 110 110 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 181 181 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 543 543 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 574 574 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 633 633 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
CROSSLNK 677 677 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:Q99081}.
VAR_SEQ 397 420 Missing (in isoform ALF1A).
{ECO:0000303|PubMed:1321336}.
/FTId=VSP_002105.
CONFLICT 416 416 K -> E (in Ref. 2; M97635).
{ECO:0000305}.
CONFLICT 537 537 V -> F (in Ref. 2; M97635/M97636).
{ECO:0000305}.
CONFLICT 687 687 N -> S (in Ref. 1; CAA46052).
{ECO:0000305}.
SEQUENCE 706 AA; 75811 MW; 4394FE95A297F68C CRC64;
MNPQQQRMAA IGTDKELSDL LDFSAMFSPP VNSGKTRPTT LGSSQFSGSG MDERGGTTSW
GTSGQPSPSY DSSRGFTDSP HYSDHLNDSR LGTHEGLSPT PFMNSNLIGK TSERGSFSLY
SRDSGLSGCQ SSLLRQDLGL GSPAQLSSSG KPGTPYYSFS ATSSRRRPLH DSVALDPLQA
KKVRKVPPGL PSSVYAPSPN SDDFNRESPS YPSPKPPTSM FASTFFMQDG THSSSDLWSS
SNGMSQPGFG GILGTSTSHM SQSSSYGSLH SHDRLSYPPH SVSPTDINTS LPPMSSFHRG
STSSSPYVAA SHTPPINGSD SILGTRGNAA GSSQTGDALG KALASIYSPD HTSSSFPSNP
STPVGSPSPL TGTSQWPRAG GQAPSSPSYE NSLHSLKNRV EQQLHEHLQD AMSFLKDVCE
QSRMEDRLDR LDDAIHVLRN HAVGPSTSLP TSHSDIHSLL GPSHNASIGN LNSNYGGSSL
VTNSRSASMV GTHREDSVSL NGNHSVLSST VAASNTELNH KTPENFRGGV QNQSGSVVPT
EIKTENKEKD ENLHEPPSSD DMKSDDESSQ KDIKVSSRGR TSSTNEDEDL NPEQKIEREK
ERRMANNARE RLRVRDINEA FKELGRMCQL HLKSEKPQTK LLILHQAVAV ILSLEQQVRE
RNLNPKAACL KRREEEKVSA ASAEPPNTLP GAHPGLSEST NPMGHL


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