HTF4_MOUSE
ID HTF4_MOUSE Reviewed; 706 AA.
AC Q61286; E9QPN4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Transcription factor 12;
DE Short=TCF-12;
DE AltName: Full=Class A helix-loop-helix transcription factor ME1;
DE AltName: Full=DNA-binding protein HTF4;
DE AltName: Full=E-box-binding protein;
DE AltName: Full=Transcription factor HTF-4;
GN Name=Tcf12; Synonyms=Alf1, Meb;
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 ALF1A AND ALF1B).
RX PubMed=1321336; DOI=10.1128/mcb.12.8.3449-3459.1992;
RA Nielsen A.L., Pallisgaard N., Pedersen F.S., Joergensen P.;
RT "Murine helix-loop-helix transcriptional activator proteins binding to the
RT E-box motif of the Akv murine leukemia virus enhancer identified by cDNA
RT cloning.";
RL Mol. Cell. Biol. 12:3449-3459(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Cerebellum;
RX PubMed=8261111; DOI=10.1111/j.1460-9568.1993.tb00498.x;
RA Neuman T., Keen A., Knapik E., Shain D., Ross M., Nornes H.O., Zuber M.X.;
RT "ME1 and GE1: basic helix-loop-helix transcription factors expressed at
RT high levels in the developing nervous system and in morphogenetically
RT active regions.";
RL Eur. J. Neurosci. 5:311-318(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP INTERACTION WITH PTF1A.
RX PubMed=11562365; DOI=10.1074/jbc.m106264200;
RA Rose S.D., Swift G.H., Peyton M.J., Hammer R.E., MacDonald R.J.;
RT "The role of PTF1-P48 in pancreatic acinar gene expression.";
RL J. Biol. Chem. 276:44018-44026(2001).
RN [5]
RP FUNCTION, INTERACTION WITH NEUROD2, DNA-BINDING, DISRUPTION PHENOTYPE, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=18214987; DOI=10.1002/jnr.21615;
RA Ravanpay A.C., Olson J.M.;
RT "E protein dosage influences brain development more than family member
RT identity.";
RL J. Neurosci. Res. 86:1472-1481(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-98 AND SER-124,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-392 (ISOFORM ALF1A), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Lung, Pancreas, and Spleen;
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: Transcriptional regulator. Involved in the initiation of
CC neuronal differentiation. Activates transcription by binding to the E
CC box (5'-CANNTG-3'). {ECO:0000269|PubMed:18214987}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Forms homo- or heterooligomers with myogenin, E12 and ITF2
CC proteins and RUNX1T1 (By similarity). Interacts with PTF1A. Interacts
CC with NEUROD2. Interacts with BHLHA9. {ECO:0000250|UniProtKB:Q99081,
CC ECO:0000269|PubMed:11562365, ECO:0000269|PubMed:18214987}.
CC -!- INTERACTION:
CC Q61286; P22091: Tal1; NbExp=2; IntAct=EBI-8006499, EBI-8006437;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=ALF1B; Synonyms=ME1A;
CC IsoId=Q61286-1; Sequence=Displayed;
CC Name=ALF1A; Synonyms=ME1B;
CC IsoId=Q61286-2; Sequence=VSP_002105;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DEVELOPMENTAL STAGE: Abundantly expressed during development of the
CC central nervous system, in particular in proliferating neuroblasts and
CC in cells at the initial stages of differentiation. Also expressed at
CC high levels in morphogenetically active regions such as limb buds,
CC somites and mesonephric tubules. Expression decreases once cellular
CC differentiation is over. {ECO:0000269|PubMed:18214987}.
CC -!- DISRUPTION PHENOTYPE: Mice are smaller than their wild-type littermates
CC and fail to thrive 14 days after birth. {ECO:0000269|PubMed:18214987}.
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DR EMBL; X64840; CAA46052.1; -; mRNA.
DR EMBL; M97635; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M97636; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC093483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC157575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC159001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS23329.1; -. [Q61286-1]
DR CCDS; CCDS72272.1; -. [Q61286-2]
DR PIR; C45020; C45020.
DR PIR; S19958; S19958.
DR RefSeq; NP_001240794.1; NM_001253865.1.
DR RefSeq; NP_035674.2; NM_011544.3. [Q61286-1]
DR RefSeq; XP_006511057.1; XM_006510994.3. [Q61286-1]
DR RefSeq; XP_006511060.1; XM_006510997.2. [Q61286-2]
DR AlphaFoldDB; Q61286; -.
DR BMRB; Q61286; -.
DR SMR; Q61286; -.
DR BioGRID; 204000; 34.
DR CORUM; Q61286; -.
DR DIP; DIP-42840N; -.
DR IntAct; Q61286; 4.
DR MINT; Q61286; -.
DR STRING; 10090.ENSMUSP00000139365; -.
DR iPTMnet; Q61286; -.
DR PhosphoSitePlus; Q61286; -.
DR jPOST; Q61286; -.
DR MaxQB; Q61286; -.
DR PaxDb; Q61286; -.
DR PeptideAtlas; Q61286; -.
DR PRIDE; Q61286; -.
DR ProteomicsDB; 267070; -. [Q61286-1]
DR ProteomicsDB; 267071; -. [Q61286-2]
DR Antibodypedia; 913; 413 antibodies from 35 providers.
DR DNASU; 21406; -.
DR Ensembl; ENSMUST00000034755; ENSMUSP00000034755; ENSMUSG00000032228. [Q61286-2]
DR Ensembl; ENSMUST00000183404; ENSMUSP00000139365; ENSMUSG00000032228. [Q61286-1]
DR Ensembl; ENSMUST00000184783; ENSMUSP00000139364; ENSMUSG00000032228. [Q61286-1]
DR Ensembl; ENSMUST00000185117; ENSMUSP00000138925; ENSMUSG00000032228. [Q61286-2]
DR GeneID; 21406; -.
DR KEGG; mmu:21406; -.
DR UCSC; uc009qpf.2; mouse. [Q61286-1]
DR UCSC; uc009qpg.2; mouse. [Q61286-2]
DR CTD; 6938; -.
DR MGI; MGI:101877; Tcf12.
DR VEuPathDB; HostDB:ENSMUSG00000032228; -.
DR eggNOG; KOG3910; Eukaryota.
DR GeneTree; ENSGT00940000155047; -.
DR HOGENOM; CLU_021099_2_0_1; -.
DR InParanoid; Q61286; -.
DR OMA; XKTSERG; -.
DR PhylomeDB; Q61286; -.
DR TreeFam; TF321672; -.
DR Reactome; R-MMU-525793; Myogenesis.
DR Reactome; R-MMU-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR BioGRID-ORCS; 21406; 6 hits in 75 CRISPR screens.
DR ChiTaRS; Tcf12; mouse.
DR PRO; PR:Q61286; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q61286; protein.
DR Bgee; ENSMUSG00000032228; Expressed in ureter smooth muscle and 290 other tissues.
DR ExpressionAtlas; Q61286; baseline and differential.
DR Genevisible; Q61286; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0035497; F:cAMP response element binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0071837; F:HMG box domain binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA: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 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 Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW Isopeptide bond; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..706
FT /note="Transcription factor 12"
FT /id="PRO_0000127230"
FT DOMAIN 601..654
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 25..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 119..140
FT /note="Leucine-zipper"
FT REGION 140..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 520..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 656..679
FT /note="Class A specific domain"
FT REGION 674..706
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 181..188
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 29..80
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 520..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..604
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 67
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 313
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 564
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 581
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 110
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 181
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 543
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 574
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 633
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT CROSSLNK 677
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99081"
FT VAR_SEQ 397..420
FT /note="Missing (in isoform ALF1A)"
FT /evidence="ECO:0000303|PubMed:1321336"
FT /id="VSP_002105"
FT CONFLICT 416
FT /note="K -> E (in Ref. 2; M97635)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="V -> F (in Ref. 2; M97635/M97636)"
FT /evidence="ECO:0000305"
FT CONFLICT 687
FT /note="N -> S (in Ref. 1; CAA46052)"
FT /evidence="ECO:0000305"
FT MOD_RES Q61286-2:392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ 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
