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Protein

POU domain, class 4, transcription factor 2

Gene

Pou4f2

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

Functioni

DNA-binding transcriptional regulator and coregulator that recognizes and binds to the consensus octamer binding site 5'-AT[A/T]A[T/A]T[A/T]A-3' in promoter of target genes (PubMed:7904822, PubMed:8290353, PubMed:7935408, PubMed:9111308, PubMed:10414983, PubMed:16152597, PubMed:17145718, PubMed:17668438, PubMed:21875655, PubMed:24643061). Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation (PubMed:8632990, PubMed:24643061, PubMed:25775587). Cooperates with the transcription factor ISL1 to achieve RGC fate specification in the developing retina (PubMed:25775587). Plays also a role in RGC axon formation and guidance by regulating gene expression of specific target genes (PubMed:8995448, PubMed:9261145, PubMed:8972215, PubMed:10357904, PubMed:11163266). Plays a role in TNFSF11-mediated terminal osteoclast differentiation (PubMed:17668438). Binds chromatin at promoter region of target genes (PubMed:17145718, PubMed:24643061).17 Publications
Isoform 1: Acts either as a transcriptional activator or repressor (PubMed:7904822, PubMed:8662774, PubMed:10526314, PubMed:10414983, PubMed:14726699, PubMed:15733064, PubMed:16152597, PubMed:18368538, PubMed:21875655, PubMed:24643061). Negatively regulates transcriptional activity of homeobox domain transcriptional factors DLX1 and DLX2, and hence prevents DLX1- and DLX2-mediated ability to promote amacrine cells specification (PubMed:21875655). Involved in the positive regulation of the transcriptional factor PAX6 expression through its binding to the neuroretina-specific enhancer in neuroretina cells (PubMed:10526314). Mediates positive transcriptional regulation of heat shock protein HSPB1 expression in cardiac myocytes (PubMed:18368538). Positively regulates POU4F1 expression by interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site of the POU4F1 gene promoter (PubMed:10414983). Plays a role in the regulation of breast cancer cell growth by promoting transcription activation as well as repression of specific target genes (PubMed:14726699, PubMed:16152597). Involved in tumor breast progression and invasion (PubMed:16152597). Plays also a role either as a transcriptional coactivator or corepressor (PubMed:8662774, PubMed:24643061). Transcriptional coactivator cooperating with transcription factors ISL1 and ISL2 to potentiate transcriptional activation of retinal ganglion cell (RGC) target genes (PubMed:24643061). Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to the octamer motif (PubMed:8662774). Binds to the octamer binding site to form a ternary complex with ISL1 in promoter of target genes (PubMed:24643061).10 Publications
Isoform 2: Acts either as a transcriptional activator or repressor (PubMed:8065921, PubMed:7935408, PubMed:7797498, PubMed:9694219, PubMed:14726699, PubMed:16152597, PubMed:17145718). Stimulates the promoter activity of the neuronal nicotinic acetylcholine receptor alpha CHRNA2 (PubMed:7797498). Negatively regulates the apoptosis regulator BAX promoter activity (PubMed:17145718). Inhibits promoter activity of the neuronal intermediate filament protein alpha-internexin INA gene (PubMed:7852360). Plays a role in the regulation of breast cancer cell growth by promoting transcription activation as well as repression of specific target genes (PubMed:14726699, PubMed:16152597). Involved in tumor breast progression and invasion (PubMed:11526481, PubMed:16152597). Plays also a role either as a transcriptional coactivator or corepressor (PubMed:8537352, PubMed:7935408, PubMed:7852360, PubMed:9448000, PubMed:17145718). Transcriptional coactivator cooperating with transcription factors TP53 to potentiate transcriptional activation of BAX promoter activity, and hence increases neuronal cell apoptosis (PubMed:17145718). Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to the octamer motif (PubMed:8537352, PubMed:7935408, PubMed:7852360). Acts also as a transcriptional coactivator via its interaction with the transcription factor ESR1 (PubMed:9448000).11 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi347 – 406HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • chromatin binding Source: MGI
  • promoter-specific chromatin binding Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: MGI

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • axon extension Source: MGI
  • axon guidance Source: MGI
  • axonogenesis Source: MGI
  • cellular response to cytokine stimulus Source: UniProtKB
  • cellular response to estradiol stimulus Source: UniProtKB
  • dorsal root ganglion development Source: UniProtKB
  • intracellular estrogen receptor signaling pathway Source: UniProtKB
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
  • MAPK cascade Source: UniProtKB
  • negative regulation of amacrine cell differentiation Source: UniProtKB
  • negative regulation of cell differentiation Source: UniProtKB
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • neuromuscular process controlling balance Source: MGI
  • neuron differentiation Source: MGI
  • positive regulation of axon extension Source: UniProtKB
  • positive regulation of cell differentiation Source: UniProtKB
  • positive regulation of osteoclast differentiation Source: UniProtKB
  • positive regulation of programmed cell death Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription regulatory region DNA binding Source: UniProtKB
  • regulation of retinal ganglion cell axon guidance Source: UniProtKB
  • regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • retina development in camera-type eye Source: MGI
  • retinal ganglion cell axon guidance Source: MGI
  • sensory perception of sound Source: MGI
  • spermatogenesis Source: Ensembl

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding, Repressor
Biological processApoptosis, Differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-6804759. Regulation of TP53 Activity through Association with Co-factors.

Names & Taxonomyi

Protein namesi
Recommended name:
POU domain, class 4, transcription factor 2Imported
Alternative name(s):
Brain-specific homeobox/POU domain protein 3B
Short name:
Brain-3B
Short name:
Brn-3B
Brn-3.21 Publication
Gene namesi
Name:Pou4f2Imported
Synonyms:Brn-3.21 Publication, Brn3b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:102524. Pou4f2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • intracellular Source: GOC
  • nuclear speck Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop to adulthood and are fertile (PubMed:8637595). Display a thinner optic nerve (PubMed:8632990, PubMed:10357904). Display a reduction in the number of retinal ganglion cells (RGC) (PubMed:8637595, PubMed:8632990). Mice show RGC axon guidance errors along the central visual pathways (PubMed:10357904, PubMed:11163266). Dorsal root ganglion projections in the spinal cord are normal (PubMed:22326227). Mice show a decrease in expression levels for several genes involved in the differentiation of RGCs (PubMed:24643061, PubMed:25775587). Show an increase in DLX1 and DLX2 mRNA expression in the embryonic retina, especially in the ganglion cell layer (PubMed:21875655).8 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi368I → V: Stimulates induction of neurite outgrowth and expression of synaptic genes. Abolishes the inhibitory effect on basal transcription and on gene activation by POU4F1. 5 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001007411 – 411POU domain, class 4, transcription factor 2Add BLAST411

Proteomic databases

PaxDbiQ63934.
PRIDEiQ63934.

PTM databases

iPTMnetiQ63934.
PhosphoSitePlusiQ63934.

Expressioni

Tissue specificityi

Expressed in retinal ganglion cells (RGCs) (PubMed:21875655, PubMed:23805044). Expressed in mature osteoclasts (PubMed:17668438). Expressed in cardiomyocytes (PubMed:18368538). Expressed in cells of layers of the superior colliculus and the adjacent periaqueductal gray (PubMed:7691107). Expressed in breast carcinoma (at protein level) (PubMed:16152597). Expressed in the brain, peripheral sensory nervous system and retina. Expressed in the optical, intermediate, and deep gray areas of the superior colliculus, the dorsal column of the mesencephalic and pontine central gray, and the lateral interpeduncular nucleus of the brain. Expressed predominantly in postmitotic, terminally differentiated neurons (PubMed:7904822). Expressed in ganglion cell layer (GCL) of the retina (PubMed:7691107, PubMed:23805044).7 Publications

Developmental stagei

Weakly expressed in the dorsal root ganglion neurons at 10.5 dpc, the expression increases at least to 15.5 dpc (PubMed:22326227). Expressed in the developing ganglion cell layer of the retina at 12.5, 13.5 and 16.5 dpc (PubMed:8632990). Expressed in the outer margin of the retina at 15.5 dpc (PubMed:10414983). Isoform 1 and isoform 2 are expressed in embryonic heart from 13.5 dpc until birth (at protein level) (PubMed:18368538). Expressed in embryonic heart from 9.5 dpc until birth (PubMed:18368538). Expressed in the developing spinal cord from 13 dpc to postnatal day 1, not expressed in adults (PubMed:8290353, PubMed:8537352). Expressed in retinal ganglion cells at 13.5 dpc and peaks at 15.5 dpc to decline late in development (PubMed:8637595). In the central nervous system, selectively expressed in postmitotic, terminally differentiated neurons (PubMed:7904822).8 Publications

Inductioni

Up-regulated by the osteoclast differentiation factor TNFSF11 (PubMed:17668438). Up-regulated by the steroid dexamethasone (PubMed:8995448). Down-regulated upon neuronal differentiation (PubMed:8995448). Down-regulated by serum starvation (PubMed:8995448). Down-regulated in presence of retinoic acid (PubMed:7904822). Down-regulated by dibutyryl cyclic AMP (PubMed:8065921).4 Publications

Gene expression databases

BgeeiENSMUSG00000031688.
CleanExiMM_POU4F2.
GenevisibleiQ63934. MM.

Interactioni

Subunit structurei

Isoform 1: Interacts with DLX1 (via homeobox DNA-binding domain); this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina and enhances retinal ganglion cell (RGC) differentiation (PubMed:21875655). Isoform 1: Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation (PubMed:21875655). Isoform 1: Interacts (via C-terminus) with ISL1 (via C-terminus) (PubMed:24643061). Isoform 1 interacts with ISL2 (PubMed:24643061). Isoform 1: Interacts with LHX2 (PubMed:24643061). Isoform 2: Interacts (via C-terminus) with TP53 (via C-terminus) (PubMed:17145718). Isoform 2: Interacts with POU4F1 isoform 1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities (PubMed:8537352). Isoform 2 interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000).5 Publications

Protein-protein interaction databases

BioGridi202311. 4 interactors.
STRINGi10090.ENSMUSP00000034115.

Structurei

3D structure databases

ProteinModelPortaliQ63934.
SMRiQ63934.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini252 – 329POU-specificPROSITE-ProRule annotationAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni93 – 239Transcriptional activation domain1 PublicationAdd BLAST147
Regioni240 – 411Transcriptional repression domain1 PublicationAdd BLAST172

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi112 – 121POU-IV box10
Motifi173 – 187Nuclear speckle targeting signalBy similarityAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 4Poly-Met4
Compositional biasi43 – 51Poly-Ser9
Compositional biasi54 – 67Poly-GlyAdd BLAST14
Compositional biasi69 – 75Poly-Ser7
Compositional biasi76 – 85Poly-Gly10
Compositional biasi128 – 131Poly-His4
Compositional biasi157 – 160Poly-Ser4
Compositional biasi173 – 184Poly-HisAdd BLAST12

Domaini

The transcriptional activation domain within the N-terminal region is sufficient to induce transcriptional activity (PubMed:8995448, PubMed:15733064). The transcriptional repression domain containing the POU-specific domain and POU homeodomain is necessary for DNA-binding activity and also sufficient to induce transcriptional repression in a DNA-binding independent manner (PubMed:8995448, PubMed:15733064). The polyhistidine repeat acts as a targeting signal to nuclear speckles (By similarity).By similarity2 Publications

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG1168. Eukaryota.
ENOG410XPNX. LUCA.
GeneTreeiENSGT00760000118935.
HOGENOMiHOG000116305.
HOVERGENiHBG031829.
InParanoidiQ63934.
KOiK09366.
OMAiQYHAAMN.
OrthoDBiEOG091G0WBK.
PhylomeDBiQ63934.
TreeFamiTF316413.

Family and domain databases

InterProiView protein in InterPro
IPR009057. Homeobox-like.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR010982. Lambda_DNA-bd_dom.
IPR013847. POU.
IPR000327. POU_dom.
PfamiView protein in Pfam
PF00046. Homeobox. 1 hit.
PF00157. Pou. 1 hit.
PRINTSiPR00028. POUDOMAIN.
SMARTiView protein in SMART
SM00389. HOX. 1 hit.
SM00352. POU. 1 hit.
SUPFAMiSSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEiView protein in PROSITE
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00035. POU_1. 1 hit.
PS00465. POU_2. 1 hit.
PS51179. POU_3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q63934-1) [UniParc]FASTAAdd to basket
Also known as: Brn-3b-long1 Publication, Brn-3b-l1 Publication

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
MMMMSLNSKQ AFSMPHAGSL HVEPKYSALH SASPGSSAPA APSASSPSSS
60 70 80 90 100
SNAGGGGGGG GGGGGGGRSS SSSSSGSGGS GGGGGSEAMR RACLPTPPSN
110 120 130 140 150
IFGGLDESLL ARAEALAAVD IVSQSKSHHH HPPHHSPFKP DATYHTMNTI
160 170 180 190 200
PCTSAASSSS VPISHPSALA GTHHHHHHHH HHHHQPHQAL EGELLEHLSP
210 220 230 240 250
GLALGAMAGP DGTVVSTPAH APHMATMNPM HQAALSMAHA HGLPSHMGCM
260 270 280 290 300
SDVDADPRDL EAFAERFKQR RIKLGVTQAD VGSALANLKI PGVGSLSQST
310 320 330 340 350
ICRFESLTLS HNNMIALKPI LQAWLEEAEK SHREKLTKPE LFNGAEKKRK
360 370 380 390 400
RTSIAAPEKR SLEAYFAIQP RPSSEKIAAI AEKLDLKKNV VRVWFCNQRQ
410
KQKRMKYSAG I
Length:411
Mass (Da):43,173
Last modified:November 1, 1996 - v1
Checksum:i97EA816F7DEC07C9
GO
Isoform 2 (identifier: Q63934-2) [UniParc]FASTAAdd to basket
Also known as: Brn-3b3 Publications1 Publication, Brn-3b-short1 Publication, Brn-3b-s1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MMMMSLNSKQ...MRRACLPTPP → MCAFYLQLQ

Show »
Length:322
Mass (Da):35,377
Checksum:i9183AC2FA7870F83
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti404 – 405RM → KV in AAB30578 (PubMed:8162704).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0588381 – 98MMMMS…LPTPP → MCAFYLQLQ in isoform 2. Add BLAST98

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68377 mRNA. Translation: AAC60672.1.
AK087546 mRNA. Translation: BAC39921.1.
S69351 Genomic DNA. Translation: AAB30578.1.
CCDSiCCDS22429.1. [Q63934-1]
RefSeqiNP_620394.2. NM_138944.2. [Q63934-1]
UniGeneiMm.234261.

Genome annotation databases

EnsembliENSMUST00000034115; ENSMUSP00000034115; ENSMUSG00000031688. [Q63934-1]
GeneIDi18997.
KEGGimmu:18997.
UCSCiuc009mhy.1. mouse. [Q63934-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68377 mRNA. Translation: AAC60672.1.
AK087546 mRNA. Translation: BAC39921.1.
S69351 Genomic DNA. Translation: AAB30578.1.
CCDSiCCDS22429.1. [Q63934-1]
RefSeqiNP_620394.2. NM_138944.2. [Q63934-1]
UniGeneiMm.234261.

3D structure databases

ProteinModelPortaliQ63934.
SMRiQ63934.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202311. 4 interactors.
STRINGi10090.ENSMUSP00000034115.

PTM databases

iPTMnetiQ63934.
PhosphoSitePlusiQ63934.

Proteomic databases

PaxDbiQ63934.
PRIDEiQ63934.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034115; ENSMUSP00000034115; ENSMUSG00000031688. [Q63934-1]
GeneIDi18997.
KEGGimmu:18997.
UCSCiuc009mhy.1. mouse. [Q63934-1]

Organism-specific databases

CTDi5458.
MGIiMGI:102524. Pou4f2.

Phylogenomic databases

eggNOGiKOG1168. Eukaryota.
ENOG410XPNX. LUCA.
GeneTreeiENSGT00760000118935.
HOGENOMiHOG000116305.
HOVERGENiHBG031829.
InParanoidiQ63934.
KOiK09366.
OMAiQYHAAMN.
OrthoDBiEOG091G0WBK.
PhylomeDBiQ63934.
TreeFamiTF316413.

Enzyme and pathway databases

ReactomeiR-MMU-6804759. Regulation of TP53 Activity through Association with Co-factors.

Miscellaneous databases

PROiPR:Q63934.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031688.
CleanExiMM_POU4F2.
GenevisibleiQ63934. MM.

Family and domain databases

InterProiView protein in InterPro
IPR009057. Homeobox-like.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR010982. Lambda_DNA-bd_dom.
IPR013847. POU.
IPR000327. POU_dom.
PfamiView protein in Pfam
PF00046. Homeobox. 1 hit.
PF00157. Pou. 1 hit.
PRINTSiPR00028. POUDOMAIN.
SMARTiView protein in SMART
SM00389. HOX. 1 hit.
SM00352. POU. 1 hit.
SUPFAMiSSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEiView protein in PROSITE
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00035. POU_1. 1 hit.
PS00465. POU_2. 1 hit.
PS51179. POU_3. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPO4F2_MOUSE
AccessioniPrimary (citable) accession number: Q63934
Secondary accession number(s): Q63954
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: June 7, 2017
This is version 138 of the entry and version 1 of the sequence. See 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.