ITF2_MOUSE
ID ITF2_MOUSE Reviewed; 670 AA.
AC Q60722; Q60721; Q62211; Q64072; Q80UE8;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Transcription factor 4;
DE Short=TCF-4;
DE AltName: Full=Class A helix-loop-helix transcription factor ME2;
DE AltName: Full=Immunoglobulin transcription factor 2;
DE Short=ITF-2;
DE Short=MITF-2;
DE AltName: Full=SL3-3 enhancer factor 2;
DE Short=SEF-2;
GN Name=Tcf4; Synonyms=Itf2, Sef2;
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 2).
RC TISSUE=Brain;
RX PubMed=7984047; DOI=10.1016/0169-328x(94)90297-6;
RA Soosaar A., Chiaramello A., Zuber M.X., Neuman T.;
RT "Expression of basic-helix-loop-helix transcription factor ME2 during brain
RT development and in the regions of neuronal plasticity in the adult brain.";
RL Brain Res. Mol. Brain Res. 25:176-180(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=8631961; DOI=10.1074/jbc.271.7.3555;
RA Skerjanc I.S., Truong J., Filion P., McBurney M.W.;
RT "A splice variant of the ITF-2 transcript encodes a transcription factor
RT that inhibits MyoD activity.";
RL J. Biol. Chem. 271:3555-3561(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8978694; DOI=10.1002/j.1460-2075.1996.tb01058.x;
RA Pscherer A., Doerflinger U., Kirfel J., Gawlas K., Rueschoff J.,
RA Buettner R., Schuele R.;
RT "The helix-loop-helix transcription factor SEF-2 regulates the activity of
RT a novel initiator element in the promoter of the human somatostatin
RT receptor II gene.";
RL EMBO J. 15:6680-6690(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [6]
RP INTERACTION WITH HIVEP2.
RC TISSUE=Brain;
RX PubMed=10207097; DOI=10.1128/mcb.19.5.3736;
RA Doerflinger U., Pscherer A., Moser M., Ruemmele P., Schuele R.,
RA Buettner R.;
RT "Activation of somatostatin receptor II expression by transcription factors
RT MIBP1 and SEF-2 in the murine brain.";
RL Mol. Cell. Biol. 19:3736-3747(1999).
RN [7]
RP FUNCTION, INTERACTION WITH NEUROD2, AND DNA-BINDING.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, 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: Transcription factor that binds to the immunoglobulin
CC enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal
CC differentiation. Activates transcription by binding to the E box (5'-
CC CANNTG-3'). Isoform 2 inhibits MYOD1 activation of the cardiac alpha-
CC actin promoter. Binds to the E-box present in the somatostatin receptor
CC 2 initiator element (SSTR2-INR) to activate transcription. May have a
CC regulatory function in developmental processes as well as during
CC neuronal plasticity. {ECO:0000269|PubMed:18214987}.
CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another bHLH
CC protein. Isoform 2 seems to form inactive heterodimers with MYOD1.
CC Interacts with HIVEP2. Interacts with NEUROD2. Interacts with AGBL1 (By
CC similarity). Interacts with BHLHA9. {ECO:0000250|UniProtKB:P15884,
CC ECO:0000269|PubMed:10207097, ECO:0000269|PubMed:18214987}.
CC -!- INTERACTION:
CC Q60722; O54972: Cbfa2t3; NbExp=2; IntAct=EBI-310070, EBI-8006703;
CC Q60722; P70662: Ldb1; NbExp=2; IntAct=EBI-310070, EBI-6272082;
CC Q60722; O54826: Mllt10; NbExp=3; IntAct=EBI-310070, EBI-8459555;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2; Synonyms=MITF-2B;
CC IsoId=Q60722-1; Sequence=Displayed;
CC Name=1; Synonyms=MITF-2A;
CC IsoId=Q60722-2; Sequence=VSP_002113, VSP_002114;
CC Name=3; Synonyms=MITF-2B-delta;
CC IsoId=Q60722-3; Sequence=VSP_002115;
CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex, Purkinje and
CC granule cell layers of the cerebellum, olfactory neuroepithelium,
CC pyramidal cells of hippocampal layers CA1-CA4, and in the granular
CC cells of the dentate gyrus.
CC -!- DEVELOPMENTAL STAGE: Expressed in proliferative zones during
CC development and in the adult in areas of neuronal plasticity. At 12
CC dpc, expression is localized in the cortex, cerebellum, pons, medulla
CC and spinal cord. From 18 dpc to adulthood, high levels of expression
CC are found in the pyramidal cells of hippocampal layers CA1-CA4, and in
CC the granular cells of the dentate gyrus. At postnatal day 7, expression
CC is high in the visual cortex and in the subependymal region extending
CC from the anterior lateral ventricle into the olfactory bulb.
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DR EMBL; S75870; AAB32662.1; -; mRNA.
DR EMBL; U16321; AAC52414.1; -; mRNA.
DR EMBL; U16322; AAC52415.1; -; mRNA.
DR EMBL; X91753; CAA62868.1; -; mRNA.
DR EMBL; AK081012; BAC38116.1; -; mRNA.
DR EMBL; BC043050; AAH43050.1; -; mRNA.
DR CCDS; CCDS29329.1; -. [Q60722-1]
DR CCDS; CCDS50315.1; -. [Q60722-3]
DR PIR; I52648; I52648.
DR RefSeq; NP_001077436.1; NM_001083967.1. [Q60722-3]
DR RefSeq; NP_038713.1; NM_013685.2. [Q60722-1]
DR RefSeq; XP_006525809.1; XM_006525746.3. [Q60722-1]
DR RefSeq; XP_006525810.1; XM_006525747.3.
DR RefSeq; XP_006525813.1; XM_006525750.3.
DR RefSeq; XP_006525825.1; XM_006525762.3.
DR RefSeq; XP_017173346.1; XM_017317857.1. [Q60722-3]
DR AlphaFoldDB; Q60722; -.
DR BMRB; Q60722; -.
DR BioGRID; 204006; 16.
DR DIP; DIP-42841N; -.
DR IntAct; Q60722; 31.
DR MINT; Q60722; -.
DR STRING; 10090.ENSMUSP00000110636; -.
DR iPTMnet; Q60722; -.
DR PhosphoSitePlus; Q60722; -.
DR jPOST; Q60722; -.
DR MaxQB; Q60722; -.
DR PaxDb; Q60722; -.
DR PeptideAtlas; Q60722; -.
DR PRIDE; Q60722; -.
DR ProteomicsDB; 268903; -. [Q60722-1]
DR ProteomicsDB; 268904; -. [Q60722-2]
DR ProteomicsDB; 268905; -. [Q60722-3]
DR Antibodypedia; 9596; 425 antibodies from 36 providers.
DR DNASU; 21413; -.
DR Ensembl; ENSMUST00000078486; ENSMUSP00000077577; ENSMUSG00000053477. [Q60722-1]
DR Ensembl; ENSMUST00000114978; ENSMUSP00000110629; ENSMUSG00000053477. [Q60722-2]
DR Ensembl; ENSMUST00000114980; ENSMUSP00000110631; ENSMUSG00000053477. [Q60722-1]
DR Ensembl; ENSMUST00000114982; ENSMUSP00000110633; ENSMUSG00000053477. [Q60722-3]
DR Ensembl; ENSMUST00000114985; ENSMUSP00000110636; ENSMUSG00000053477. [Q60722-1]
DR Ensembl; ENSMUST00000202116; ENSMUSP00000144512; ENSMUSG00000053477. [Q60722-3]
DR GeneID; 21413; -.
DR KEGG; mmu:21413; -.
DR UCSC; uc008fnq.1; mouse. [Q60722-1]
DR UCSC; uc008fns.1; mouse. [Q60722-3]
DR CTD; 6925; -.
DR MGI; MGI:98506; Tcf4.
DR VEuPathDB; HostDB:ENSMUSG00000053477; -.
DR eggNOG; KOG3910; Eukaryota.
DR GeneTree; ENSGT00940000159129; -.
DR InParanoid; Q60722; -.
DR OrthoDB; 571132at2759; -.
DR PhylomeDB; Q60722; -.
DR TreeFam; TF321672; -.
DR Reactome; R-MMU-525793; Myogenesis.
DR BioGRID-ORCS; 21413; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Tcf4; mouse.
DR PRO; PR:Q60722; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q60722; protein.
DR Bgee; ENSMUSG00000053477; Expressed in rostral migratory stream and 289 other tissues.
DR ExpressionAtlas; Q60722; baseline and differential.
DR Genevisible; Q60722; MM.
DR GO; GO:1990907; C:beta-catenin-TCF complex; ISO:MGI.
DR GO; GO:0070369; C:beta-catenin-TCF7L2 complex; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0043621; F:protein self-association; IMP:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001093; F:TFIIB-class transcription factor binding; IDA:BHF-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042118; P:endothelial cell activation; IDA:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
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; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0065004; P:protein-DNA complex assembly; IDA:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IDA:MGI.
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 Activator; Alternative splicing; Developmental protein; Differentiation;
KW DNA-binding; Neurogenesis; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..670
FT /note="Transcription factor 4"
FT /id="PRO_0000127257"
FT DOMAIN 567..620
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 1..83
FT /note="Essential for MYOD1 inhibition"
FT REGION 24..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 262..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 378..399
FT /note="Leucine-zipper"
FT REGION 406..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 465..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..645
FT /note="Class A specific domain"
FT REGION 637..670
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..123
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 266..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..487
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 512..573
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15884"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15884"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15884"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62655"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..159
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:8631961"
FT /id="VSP_002113"
FT VAR_SEQ 160..182
FT /note="LHSSAMEVQTKKVRKVPPGLPSS -> MYCAYTIPGMGGNSLMYYYNGKA
FT (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:8631961"
FT /id="VSP_002114"
FT VAR_SEQ 545..548
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:8631961"
FT /id="VSP_002115"
FT CONFLICT 159
FT /note="P -> S (in Ref. 3; CAA62868)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="P -> A (in Ref. 3; CAA62868)"
FT /evidence="ECO:0000305"
FT CONFLICT 238
FT /note="G -> A (in Ref. 1; AAB32662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 670 AA; 71625 MW; F21CF79FDC0BF09E CRC64;
MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG
TGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRENVQGC
HQQSLLGGDM DMGNPGTLSP TKPGSQYYQY SSNNARRRPL HSSAMEVQTK KVRKVPPGLP
SSVYAPSAST ADYNRDSPGY PSSKPAASTF PSSFFMQDGH HSSDPWSSSS GMNQPGYGGM
LGNSSHIPQS SSYCSLHPHE RLSYPSHSSA DINSSLPPMS TFHRSGTNHY STSSCTPPAN
GTDSIMANRG TGAAGSSQTG DALGKALASI YSPDHTNNSF SSNPSTPVGS PPSLSAGTAV
WSRNGGQASS SPNYEGPLHS LQSRIEDRLE RLDDAIHVLR NHAVGPSTAV PGGHGDMHGI
MGPSHNGAMG SLGSGYGTSL LSANRHSLMV GAHREDGVAL RGSHSLLPNQ VPVPQLPVQS
ATSPDLNPPQ DPYRGMPPGL QGQSVSSGSS EIKSDDEGDE NLQDTKSSED KKLDDDKKDI
KSITRSRSSN NDDEDLTPEQ KAEREKERRM ANNARERLRV RDINEAFKEL GRMVQLHLKS
DKPQTKLLIL HQAVAVILSL EQQVRERNLN PKAACLKRRE EEKVSSEPPP LSLAGPHPGM
GDAANHMGQM
