Q60722 (ITF2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor 4
Short name=TCF-4

Alternative name(s):
Class A helix-loop-helix transcription factor ME2
Immunoglobulin transcription factor 2
Short name=ITF-2
Short name=MITF-2
SL3-3 enhancer factor 2
Short name=SEF-2

Gene names

Name:	Tcf4
Synonyms:	Itf2, Sef2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	670 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor that binds to the immunoglobulin enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Isoform 2 inhibits MYOD1 activation of the cardiac alpha-actin promoter. Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription. May have a regulatory function in developmental processes as well as during neuronal plasticity. Ref.7
Subunit structure	Efficient DNA binding requires dimerization with another bHLH protein. Isoform 2 seems to form inactive heterodimers with MYOD1. The CTNNB1 and TCF4 complex interacts with PML. Identified in a complex with CTNNB1 and FERMT2 By similarity. Interacts with HIVEP2. Interacts with NEUROD2. Ref.6 Ref.7
Subcellular location	Nucleus Probable.
Tissue specificity	Expressed in the cerebral cortex, Purkinje and granule cell layers of the cerebellum, olfactory neuroepithelium, pyramidal cells of hippocampal layers CA1-CA4, and in the granular cells of the dentate gyrus.
Developmental stage	Expressed in proliferative zones during development and in the adult in areas of neuronal plasticity. At embryonic day 12 (E12), expression is localized in the cortex, cerebellum, pons, medulla and spinal cord. From E18 to adulthood, high levels of expression are found in the pyramidal cells of hippocampal layers CA1-CA4, and in the granular cells of the dentate gyrus. At postnatal day 7, expression is high in the visual cortex and in the subependymal region extending from the anterior lateral ventricle into the olfactory bulb.
Sequence similarities	Contains 1 bHLH (basic helix-loop-helix) domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator Developmental protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16950124. Source: MGI positive regulation of neuron differentiation Inferred from direct assay Ref.7. Source: UniProtKB protein-DNA complex assembly Inferred from direct assay Ref.3. Source: BHF-UCL transcription initiation from RNA polymerase II promoter Inferred from direct assay Ref.3. Source: BHF-UCL
Cellular_component	transcription factor complex Inferred from direct assay Ref.3. Source: BHF-UCL
Molecular_function	E-box binding Inferred from direct assay Ref.7. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from direct assay Ref.3. Source: BHF-UCL RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay Ref.3. Source: BHF-UCL TFIIB-class binding transcription factor activity Inferred from direct assay Ref.3. Source: BHF-UCL TFIIB-class transcription factor binding Inferred from direct assay Ref.3. Source: BHF-UCL protein heterodimerization activity Inferred from direct assay Ref.7. Source: UniProtKB sequence-specific DNA binding RNA polymerase recruiting transcription factor activity Inferred from direct assay Ref.3. Source: BHF-UCL transcription corepressor activity Inferred from direct assay PubMed 8999959. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: Q60722-1)

Also known as: MITF-2B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: Q60722-2)

Also known as: MITF-2A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: Missing.
     160-182: LHSSAMEVQTKKVRKVPPGLPSS → MYCAYTIPGMGGNSLMYYYNGKA

Isoform 3 (identifier: Q60722-3)

Also known as: MITF-2B-delta;

The sequence of this isoform differs from the canonical sequence as follows:
     545-548: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 670	670	Transcription factor 4		PRO_0000127257
Regions
	Domain	567 – 620	54	bHLH
	Region	1 – 83	83	Essential for MYOD1 inhibition
	Region	378 – 399	22	Leucine-zipper
	Region	622 – 645	24	Class A specific domain
	Compositional bias	227 – 230	4	Poly-Ser
Amino acid modifications
	Modified residue	514	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	1 – 159	159	Missing in isoform 1.		VSP_002113
	Alternative sequence	160 – 182	23	LHSSA…GLPSS → MYCAYTIPGMGGNSLMYYYN GKA in isoform 1.		VSP_002114
	Alternative sequence	545 – 548	4	Missing in isoform 3.		VSP_002115
Experimental info
	Sequence conflict	159	1	P → S in CAA62868. Ref.3
	Sequence conflict	180	1	P → A in CAA62868. Ref.3
	Sequence conflict	238	1	G → A in AAB32662. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 (MITF-2B) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: F21CF79FDC0BF09E	FASTA	670	71,625
	10 20 30 40 50 60 MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG 70 80 90 100 110 120 TGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRENVQGC 130 140 150 160 170 180 HQQSLLGGDM DMGNPGTLSP TKPGSQYYQY SSNNARRRPL HSSAMEVQTK KVRKVPPGLP 190 200 210 220 230 240 SSVYAPSAST ADYNRDSPGY PSSKPAASTF PSSFFMQDGH HSSDPWSSSS GMNQPGYGGM 250 260 270 280 290 300 LGNSSHIPQS SSYCSLHPHE RLSYPSHSSA DINSSLPPMS TFHRSGTNHY STSSCTPPAN 310 320 330 340 350 360 GTDSIMANRG TGAAGSSQTG DALGKALASI YSPDHTNNSF SSNPSTPVGS PPSLSAGTAV 370 380 390 400 410 420 WSRNGGQASS SPNYEGPLHS LQSRIEDRLE RLDDAIHVLR NHAVGPSTAV PGGHGDMHGI 430 440 450 460 470 480 MGPSHNGAMG SLGSGYGTSL LSANRHSLMV GAHREDGVAL RGSHSLLPNQ VPVPQLPVQS 490 500 510 520 530 540 ATSPDLNPPQ DPYRGMPPGL QGQSVSSGSS EIKSDDEGDE NLQDTKSSED KKLDDDKKDI 550 560 570 580 590 600 KSITRSRSSN NDDEDLTPEQ KAEREKERRM ANNARERLRV RDINEAFKEL GRMVQLHLKS 610 620 630 640 650 660 DKPQTKLLIL HQAVAVILSL EQQVRERNLN PKAACLKRRE EEKVSSEPPP LSLAGPHPGM 670 GDAANHMGQM
	Isoform 1 (MITF-2A) [UniParc]. Checksum: 44BA079B0A6CCE48	FASTA	511	54,591
	10 20 30 40 50 60 MYCAYTIPGM GGNSLMYYYN GKAVYAPSAS TADYNRDSPG YPSSKPAAST FPSSFFMQDG 70 80 90 100 110 120 HHSSDPWSSS SGMNQPGYGG MLGNSSHIPQ SSSYCSLHPH ERLSYPSHSS ADINSSLPPM 130 140 150 160 170 180 STFHRSGTNH YSTSSCTPPA NGTDSIMANR GTGAAGSSQT GDALGKALAS IYSPDHTNNS 190 200 210 220 230 240 FSSNPSTPVG SPPSLSAGTA VWSRNGGQAS SSPNYEGPLH SLQSRIEDRL ERLDDAIHVL 250 260 270 280 290 300 RNHAVGPSTA VPGGHGDMHG IMGPSHNGAM GSLGSGYGTS LLSANRHSLM VGAHREDGVA 310 320 330 340 350 360 LRGSHSLLPN QVPVPQLPVQ SATSPDLNPP QDPYRGMPPG LQGQSVSSGS SEIKSDDEGD 370 380 390 400 410 420 ENLQDTKSSE DKKLDDDKKD IKSITRSRSS NNDDEDLTPE QKAEREKERR MANNARERLR 430 440 450 460 470 480 VRDINEAFKE LGRMVQLHLK SDKPQTKLLI LHQAVAVILS LEQQVRERNL NPKAACLKRR 490 500 510 EEEKVSSEPP PLSLAGPHPG MGDAANHMGQ M
	Isoform 3 (MITF-2B-delta) [UniParc]. Checksum: E735F6DD18A1E37F	FASTA	666	71,138
	10 20 30 40 50 60 MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG 70 80 90 100 110 120 TGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRENVQGC 130 140 150 160 170 180 HQQSLLGGDM DMGNPGTLSP TKPGSQYYQY SSNNARRRPL HSSAMEVQTK KVRKVPPGLP 190 200 210 220 230 240 SSVYAPSAST ADYNRDSPGY PSSKPAASTF PSSFFMQDGH HSSDPWSSSS GMNQPGYGGM 250 260 270 280 290 300 LGNSSHIPQS SSYCSLHPHE RLSYPSHSSA DINSSLPPMS TFHRSGTNHY STSSCTPPAN 310 320 330 340 350 360 GTDSIMANRG TGAAGSSQTG DALGKALASI YSPDHTNNSF SSNPSTPVGS PPSLSAGTAV 370 380 390 400 410 420 WSRNGGQASS SPNYEGPLHS LQSRIEDRLE RLDDAIHVLR NHAVGPSTAV PGGHGDMHGI 430 440 450 460 470 480 MGPSHNGAMG SLGSGYGTSL LSANRHSLMV GAHREDGVAL RGSHSLLPNQ VPVPQLPVQS 490 500 510 520 530 540 ATSPDLNPPQ DPYRGMPPGL QGQSVSSGSS EIKSDDEGDE NLQDTKSSED KKLDDDKKDI 550 560 570 580 590 600 KSITSNNDDE DLTPEQKAER EKERRMANNA RERLRVRDIN EAFKELGRMV QLHLKSDKPQ 610 620 630 640 650 660 TKLLILHQAV AVILSLEQQV RERNLNPKAA CLKRREEEKV SSEPPPLSLA GPHPGMGDAA NHMGQM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of basic-helix-loop-helix transcription factor ME2 during brain development and in the regions of neuronal plasticity in the adult brain." Soosaar A., Chiaramello A., Zuber M.X., Neuman T. Brain Res. Mol. Brain Res. 25:176-180(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[2]	"A splice variant of the ITF-2 transcript encodes a transcription factor that inhibits MyoD activity." Skerjanc I.S., Truong J., Filion P., McBurney M.W. J. Biol. Chem. 271:3555-3561(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[3]	"The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene." Pscherer A., Doerflinger U., Kirfel J., Gawlas K., Rueschoff J., Buettner R., Schuele R. EMBO J. 15:6680-6690(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: BALB/c. Tissue: Brain.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Strain: C57BL/6J. Tissue: Head.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6. Tissue: Brain.
[6]	"Activation of somatostatin receptor II expression by transcription factors MIBP1 and SEF-2 in the murine brain." Doerflinger U., Pscherer A., Moser M., Ruemmele P., Schuele R., Buettner R. Mol. Cell. Biol. 19:3736-3747(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HIVEP2. Tissue: Brain.
[7]	"E protein dosage influences brain development more than family member identity." Ravanpay A.C., Olson J.M. J. Neurosci. Res. 86:1472-1481(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH NEUROD2, DNA-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S75870 mRNA. Translation: AAB32662.1. U16321 mRNA. Translation: AAC52414.1. U16322 mRNA. Translation: AAC52415.1. X91753 mRNA. Translation: CAA62868.1. AK081012 mRNA. Translation: BAC38116.1. BC043050 mRNA. Translation: AAH43050.1.
IPI	IPI00120128. IPI00400417. IPI00400418.
PIR	I52648.
RefSeq	NP_001077436.1. NM_001083967.1. NP_038713.1. NM_013685.2.
UniGene	Mm.4269.
3D structure databases
ProteinModelPortal	Q60722.
SMR	Q60722. Positions 568-627.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-42841N.
IntAct	Q60722. 2 interactions.
MINT	MINT-2567893.
PTM databases
PhosphoSite	Q60722.
Proteomic databases
PaxDb	Q60722.
PRIDE	Q60722.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000078486; ENSMUSP00000077577; ENSMUSG00000053477. ENSMUST00000114978; ENSMUSP00000110629; ENSMUSG00000053477. ENSMUST00000114980; ENSMUSP00000110631; ENSMUSG00000053477. ENSMUST00000114982; ENSMUSP00000110633; ENSMUSG00000053477. ENSMUST00000114985; ENSMUSP00000110636; ENSMUSG00000053477.
GeneID	21413.
KEGG	mmu:21413.
UCSC	uc008fnq.1. mouse. uc008fns.1. mouse.
Organism-specific databases
CTD	6925.
MGI	MGI:98506. Tcf4.
Phylogenomic databases
eggNOG	NOG282899.
GeneTree	ENSGT00510000046438.
HOGENOM	HOG000234180.
HOVERGEN	HBG003854.
KO	K15603.
OrthoDB	EOG4Z62N3.
Gene expression databases
ArrayExpress	Q60722.
Bgee	Q60722.
CleanEx	MM_TCF4.
Genevestigator	Q60722.
GermOnline	ENSMUSG00000053477. Mus musculus.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	TCF4. mouse.
NextBio	300700.
SOURCE	Search...

Entry information

Entry name

ITF2_MOUSE

Accession

Primary (citable) accession number: Q60722
Secondary accession number(s): Q60721 , Q62211, Q64072, Q80UE8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program