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Protein

Transcription factor 4

Gene

Tcf4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  • bHLH transcription factor binding Source: GO_Central
  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • E-box binding Source: UniProtKB
  • protein C-terminus binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: GO_Central
  • protein self-association Source: MGI
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  • TFIIB-class transcription factor binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcription corepressor activity Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding, RNA polymerase recruiting Source: BHF-UCL
  • transcription factor activity, TFIIB-class binding Source: BHF-UCL

GO - Biological processi

  • DNA-templated transcription, initiation Source: BHF-UCL
  • endothelial cell activation Source: MGI
  • negative regulation of angiogenesis Source: MGI
  • negative regulation of gene expression Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of neuron differentiation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • protein-DNA complex assembly Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: MGI
  • regulation of vascular endothelial growth factor signaling pathway Source: MGI
  • transcription initiation from RNA polymerase II promoter Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
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 namesi
Name:Tcf4
Synonyms:Itf2, Sef2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:98506. Tcf4.

Subcellular locationi

GO - Cellular componenti

  • nuclear chromatin Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001272571 – 670Transcription factor 4Add BLAST670

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei66PhosphoserineBy similarity1
Modified residuei87PhosphoserineBy similarity1
Modified residuei92PhosphoserineBy similarity1
Modified residuei371PhosphoserineBy similarity1
Modified residuei514PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ60722.
PeptideAtlasiQ60722.
PRIDEiQ60722.

PTM databases

iPTMnetiQ60722.
PhosphoSitePlusiQ60722.

Expressioni

Tissue specificityi

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 stagei

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.

Gene expression databases

BgeeiENSMUSG00000053477.
CleanExiMM_TCF4.
ExpressionAtlasiQ60722. baseline and differential.
GenevisibleiQ60722. MM.

Interactioni

Subunit structurei

Efficient DNA binding requires dimerization with another bHLH protein. Isoform 2 seems to form inactive heterodimers with MYOD1. Interacts with HIVEP2. Interacts with NEUROD2. Interacts with AGBL1 (By similarity). Interacts with BHLHA9.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cbfa2t3O549722EBI-310070,EBI-8006703
Ldb1P706622EBI-310070,EBI-6272082

GO - Molecular functioni

  • bHLH transcription factor binding Source: GO_Central
  • protein C-terminus binding Source: MGI
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: GO_Central
  • protein self-association Source: MGI
  • TFIIB-class transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi204006. 15 interactors.
DIPiDIP-42841N.
IntActiQ60722. 5 interactors.
MINTiMINT-2567893.
STRINGi10090.ENSMUSP00000077577.

Structurei

3D structure databases

ProteinModelPortaliQ60722.
SMRiQ60722.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini567 – 620bHLHPROSITE-ProRule annotationAdd BLAST54

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 83Essential for MYOD1 inhibitionAdd BLAST83
Regioni378 – 399Leucine-zipperAdd BLAST22
Regioni622 – 645Class A specific domainAdd BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi227 – 230Poly-Ser4

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3910. Eukaryota.
ENOG410XYUA. LUCA.
GeneTreeiENSGT00510000046438.
HOGENOMiHOG000234180.
HOVERGENiHBG003854.
InParanoidiQ60722.
KOiK15603.
PhylomeDBiQ60722.
TreeFamiTF321672.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q60722-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV
60 70 80 90 100
EDRSSSGSWG TGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI
110 120 130 140 150
QSKTERGSYS SYGRENVQGC HQQSLLGGDM DMGNPGTLSP TKPGSQYYQY
160 170 180 190 200
SSNNARRRPL HSSAMEVQTK KVRKVPPGLP SSVYAPSAST ADYNRDSPGY
210 220 230 240 250
PSSKPAASTF PSSFFMQDGH HSSDPWSSSS GMNQPGYGGM LGNSSHIPQS
260 270 280 290 300
SSYCSLHPHE RLSYPSHSSA DINSSLPPMS TFHRSGTNHY STSSCTPPAN
310 320 330 340 350
GTDSIMANRG TGAAGSSQTG DALGKALASI YSPDHTNNSF SSNPSTPVGS
360 370 380 390 400
PPSLSAGTAV WSRNGGQASS SPNYEGPLHS LQSRIEDRLE RLDDAIHVLR
410 420 430 440 450
NHAVGPSTAV PGGHGDMHGI MGPSHNGAMG SLGSGYGTSL LSANRHSLMV
460 470 480 490 500
GAHREDGVAL RGSHSLLPNQ VPVPQLPVQS ATSPDLNPPQ DPYRGMPPGL
510 520 530 540 550
QGQSVSSGSS EIKSDDEGDE NLQDTKSSED KKLDDDKKDI KSITRSRSSN
560 570 580 590 600
NDDEDLTPEQ KAEREKERRM ANNARERLRV RDINEAFKEL GRMVQLHLKS
610 620 630 640 650
DKPQTKLLIL HQAVAVILSL EQQVRERNLN PKAACLKRRE EEKVSSEPPP
660 670
LSLAGPHPGM GDAANHMGQM
Length:670
Mass (Da):71,625
Last modified:November 1, 1996 - v1
Checksum:iF21CF79FDC0BF09E
GO
Isoform 1 (identifier: Q60722-2) [UniParc]FASTAAdd to basket
Also known as: MITF-2A

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

Show »
Length:511
Mass (Da):54,591
Checksum:i44BA079B0A6CCE48
GO
Isoform 3 (identifier: Q60722-3) [UniParc]FASTAAdd to basket
Also known as: MITF-2B-delta

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

Show »
Length:666
Mass (Da):71,138
Checksum:iE735F6DD18A1E37F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti159P → S in CAA62868 (PubMed:8978694).Curated1
Sequence conflicti180P → A in CAA62868 (PubMed:8978694).Curated1
Sequence conflicti238G → A in AAB32662 (PubMed:7984047).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0021131 – 159Missing in isoform 1. 1 PublicationAdd BLAST159
Alternative sequenceiVSP_002114160 – 182LHSSA…GLPSS → MYCAYTIPGMGGNSLMYYYN GKA in isoform 1. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_002115545 – 548Missing in isoform 3. 2 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29329.1. [Q60722-1]
CCDS50315.1. [Q60722-3]
PIRiI52648.
RefSeqiNP_001077436.1. NM_001083967.1. [Q60722-3]
NP_038713.1. NM_013685.2. [Q60722-1]
XP_006525809.1. XM_006525746.3. [Q60722-1]
XP_006525810.1. XM_006525747.3. [Q60722-1]
XP_006525813.1. XM_006525750.3. [Q60722-3]
XP_006525825.1. XM_006525762.3.
XP_017173346.1. XM_017317857.1. [Q60722-3]
UniGeneiMm.4269.

Genome annotation databases

EnsembliENSMUST00000078486; ENSMUSP00000077577; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000114978; ENSMUSP00000110629; ENSMUSG00000053477. [Q60722-2]
ENSMUST00000114980; ENSMUSP00000110631; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000114982; ENSMUSP00000110633; ENSMUSG00000053477. [Q60722-3]
ENSMUST00000114985; ENSMUSP00000110636; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000202116; ENSMUSP00000144512; ENSMUSG00000053477. [Q60722-3]
GeneIDi21413.
KEGGimmu:21413.
UCSCiuc008fnq.1. mouse. [Q60722-1]
uc008fns.1. mouse. [Q60722-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS29329.1. [Q60722-1]
CCDS50315.1. [Q60722-3]
PIRiI52648.
RefSeqiNP_001077436.1. NM_001083967.1. [Q60722-3]
NP_038713.1. NM_013685.2. [Q60722-1]
XP_006525809.1. XM_006525746.3. [Q60722-1]
XP_006525810.1. XM_006525747.3. [Q60722-1]
XP_006525813.1. XM_006525750.3. [Q60722-3]
XP_006525825.1. XM_006525762.3.
XP_017173346.1. XM_017317857.1. [Q60722-3]
UniGeneiMm.4269.

3D structure databases

ProteinModelPortaliQ60722.
SMRiQ60722.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204006. 15 interactors.
DIPiDIP-42841N.
IntActiQ60722. 5 interactors.
MINTiMINT-2567893.
STRINGi10090.ENSMUSP00000077577.

PTM databases

iPTMnetiQ60722.
PhosphoSitePlusiQ60722.

Proteomic databases

PaxDbiQ60722.
PeptideAtlasiQ60722.
PRIDEiQ60722.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078486; ENSMUSP00000077577; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000114978; ENSMUSP00000110629; ENSMUSG00000053477. [Q60722-2]
ENSMUST00000114980; ENSMUSP00000110631; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000114982; ENSMUSP00000110633; ENSMUSG00000053477. [Q60722-3]
ENSMUST00000114985; ENSMUSP00000110636; ENSMUSG00000053477. [Q60722-1]
ENSMUST00000202116; ENSMUSP00000144512; ENSMUSG00000053477. [Q60722-3]
GeneIDi21413.
KEGGimmu:21413.
UCSCiuc008fnq.1. mouse. [Q60722-1]
uc008fns.1. mouse. [Q60722-3]

Organism-specific databases

CTDi6925.
MGIiMGI:98506. Tcf4.

Phylogenomic databases

eggNOGiKOG3910. Eukaryota.
ENOG410XYUA. LUCA.
GeneTreeiENSGT00510000046438.
HOGENOMiHOG000234180.
HOVERGENiHBG003854.
InParanoidiQ60722.
KOiK15603.
PhylomeDBiQ60722.
TreeFamiTF321672.

Miscellaneous databases

ChiTaRSiTcf4. mouse.
PROiQ60722.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000053477.
CleanExiMM_TCF4.
ExpressionAtlasiQ60722. baseline and differential.
GenevisibleiQ60722. MM.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiITF2_MOUSE
AccessioniPrimary (citable) accession number: Q60722
Secondary accession number(s): Q60721
, Q62211, Q64072, Q80UE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.