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Protein

POU domain, class 4, transcription factor 2

Gene

POU4F2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:19266028, PubMed:23805044). Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner (PubMed:19266028, PubMed:23805044). Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Binds to an octamer site to form a ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to potentiate transcriptional activation of RGC target genes being involved in RGC fate commitment in the developing retina and RGC axon formation and pathfinding. Inhibits DLX1 and DLX2 transcriptional activities preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate specification. In cooperation with TP53 potentiates transcriptional activation of BAX promoter activity increasing neuronal cell apoptosis. Negatively regulates BAX promoter activity in the absence of TP53. Acts as a transcriptional coactivator via its interaction with the transcription factor ESR1 by enhancing its effect on estrogen response element (ERE)-containing promoter. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to an octamer motif. Involved in TNFSF11-mediated terminal osteoclast differentiation (By similarity).By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi345 – 404HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors
SignaLinkiQ12837
SIGNORiQ12837

Names & Taxonomyi

Protein namesi
Recommended name:
POU domain, class 4, transcription factor 2Curated
Alternative name(s):
Brain-specific homeobox/POU domain protein 3B
Short name:
Brain-3B
Short name:
Brn-3B
Gene namesi
Name:POU4F2Imported
Synonyms:BRN3B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000151615.3
HGNCiHGNC:9219 POU4F2
MIMi113725 gene
neXtProtiNX_Q12837

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi171 – 185Missing : Absent from nuclear speckle; no change in transcriptional activity. 1 PublicationAdd BLAST15

Organism-specific databases

DisGeNETi5458
OpenTargetsiENSG00000151615
PharmGKBiPA33543

Polymorphism and mutation databases

BioMutaiPOU4F2
DMDMi290457652

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001007401 – 409POU domain, class 4, transcription factor 2Add BLAST409

Proteomic databases

PaxDbiQ12837
PeptideAtlasiQ12837
PRIDEiQ12837
ProteomicsDBi58978

PTM databases

iPTMnetiQ12837
PhosphoSitePlusiQ12837

Expressioni

Tissue specificityi

Expressed in the brain (PubMed:7691107). Expressed in the ganglion cell layer of the retina (PubMed:7691107).1 Publication

Gene expression databases

BgeeiENSG00000151615 Expressed in 27 organ(s), highest expression level in secondary oocyte
CleanExiHS_POU4F2
GenevisibleiQ12837 HS

Interactioni

Subunit structurei

Interacts with POU4F1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities. 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. Interacts (via C-terminus) with TP53 (via N-terminus). Interacts with DLX1 (via homeobox DNA-binding domain); this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina enhancing retinal ganglion cell (RGC) differentiation. Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation. Interacts (via C-terminus) with ISL1 (via C-terminus). Interacts with ISL2. Interacts with LHX2.By similarity

Binary interactionsi

Protein-protein interaction databases

BioGridi111454, 1 interactor
IntActiQ12837, 74 interactors
STRINGi9606.ENSP00000281321

Structurei

3D structure databases

ProteinModelPortaliQ12837
SMRiQ12837
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini250 – 327POU-specificPROSITE-ProRule annotationAdd BLAST78

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni91 – 237Required for transcriptional activationBy similarityAdd BLAST147
Regioni238 – 409Required for DNA-binding and transcriptional repressionBy similarityAdd BLAST172

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi110 – 119POU-IV box10
Motifi171 – 185Nuclear speckle targeting signal1 PublicationAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi27 – 79Ser-richPROSITE-ProRule annotationAdd BLAST53
Compositional biasi54 – 83Gly-richPROSITE-ProRule annotationAdd BLAST30
Compositional biasi126 – 185His-richPROSITE-ProRule annotationAdd BLAST60

Domaini

The N-terminal transcriptional activation region is sufficient to induce transcriptional activity.By similarity
The POU-specific domain and POU homeodomain regions are necessary for DNA-binding activity and transcriptional repression.By similarity
The polyhistidine motif acts as a targeting signal to nuclear speckles.1 Publication

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG1168 Eukaryota
ENOG410XPNX LUCA
GeneTreeiENSGT00760000118935
HOGENOMiHOG000116305
HOVERGENiHBG031829
InParanoidiQ12837
KOiK09366
OMAiTHAPHMA
OrthoDBiEOG091G0WBK
PhylomeDBiQ12837
TreeFamiTF316413

Family and domain databases

CDDicd00086 homeodomain, 1 hit
cd00093 HTH_XRE, 1 hit
InterProiView protein in InterPro
IPR001387 Cro/C1-type_HTH
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR010982 Lambda_DNA-bd_dom_sf
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: Q12837-1) [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 AFSMPHGGSL HVEPKYSALH STSPGSSAPI APSASSPSSS
60 70 80 90 100
SNAGGGGGGG GGGGGGGGRS SSSSSSGSSG GGGSEAMRRA CLPTPPSNIF
110 120 130 140 150
GGLDESLLAR AEALAAVDIV SQSKSHHHHP PHHSPFKPDA TYHTMNTIPC
160 170 180 190 200
TSAASSSSVP ISHPSALAGT HHHHHHHHHH HHQPHQALEG ELLEHLSPGL
210 220 230 240 250
ALGAMAGPDG AVVSTPAHAP HMATMNPMHQ AALSMAHAHG LPSHMGCMSD
260 270 280 290 300
VDADPRDLEA FAERFKQRRI KLGVTQADVG SALANLKIPG VGSLSQSTIC
310 320 330 340 350
RFESLTLSHN NMIALKPILQ AWLEEAEKSH REKLTKPELF NGAEKKRKRT
360 370 380 390 400
SIAAPEKRSL EAYFAIQPRP SSEKIAAIAE KLDLKKNVVR VWFCNQRQKQ

KRMKYSAGI
Length:409
Mass (Da):43,087
Last modified:March 2, 2010 - v2
Checksum:i42E2C174674E8DFC
GO
Isoform 2 (identifier: Q12837-2) [UniParc]FASTAAdd to basket
Also known as: Brn-3b short1 Publication, Brn-3b-s1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.

Show »
Length:265
Mass (Da):29,042
Checksum:iA31096BF6445757A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54G → GG in AAA16509 (PubMed:7691107).Curated1
Sequence conflicti54G → GG in BAG37481 (PubMed:14702039).Curated1
Sequence conflicti54G → GG in AAI36345 (PubMed:14702039).Curated1
Sequence conflicti54G → GG in AAI36346 (PubMed:14702039).Curated1
Sequence conflicti165S → C in AAA16509 (PubMed:7691107).Curated1
Sequence conflicti182Missing in CAA50589 (PubMed:8332509).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05932140I → T. Corresponds to variant dbSNP:rs13152799Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0588371 – 144Missing in isoform 2. Add BLAST144

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06233 mRNA Translation: AAA16509.1
AK314982 mRNA Translation: BAG37481.1
AC093887 Genomic DNA No translation available.
BC136344 mRNA Translation: AAI36345.1
BC136345 mRNA Translation: AAI36346.1
EU439706 mRNA Translation: ACA49233.1
X71488 mRNA Translation: CAA50589.1
L20434 mRNA Translation: AAA36393.1
CCDSiCCDS34074.1 [Q12837-1]
PIRiI38502
RefSeqiNP_004566.2, NM_004575.2 [Q12837-1]
UniGeneiHs.266

Genome annotation databases

EnsembliENST00000281321; ENSP00000281321; ENSG00000151615 [Q12837-1]
GeneIDi5458
KEGGihsa:5458
UCSCiuc003ikv.4 human [Q12837-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06233 mRNA Translation: AAA16509.1
AK314982 mRNA Translation: BAG37481.1
AC093887 Genomic DNA No translation available.
BC136344 mRNA Translation: AAI36345.1
BC136345 mRNA Translation: AAI36346.1
EU439706 mRNA Translation: ACA49233.1
X71488 mRNA Translation: CAA50589.1
L20434 mRNA Translation: AAA36393.1
CCDSiCCDS34074.1 [Q12837-1]
PIRiI38502
RefSeqiNP_004566.2, NM_004575.2 [Q12837-1]
UniGeneiHs.266

3D structure databases

ProteinModelPortaliQ12837
SMRiQ12837
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111454, 1 interactor
IntActiQ12837, 74 interactors
STRINGi9606.ENSP00000281321

PTM databases

iPTMnetiQ12837
PhosphoSitePlusiQ12837

Polymorphism and mutation databases

BioMutaiPOU4F2
DMDMi290457652

Proteomic databases

PaxDbiQ12837
PeptideAtlasiQ12837
PRIDEiQ12837
ProteomicsDBi58978

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000281321; ENSP00000281321; ENSG00000151615 [Q12837-1]
GeneIDi5458
KEGGihsa:5458
UCSCiuc003ikv.4 human [Q12837-1]

Organism-specific databases

CTDi5458
DisGeNETi5458
EuPathDBiHostDB:ENSG00000151615.3
GeneCardsiPOU4F2
H-InvDBiHIX0031516
HGNCiHGNC:9219 POU4F2
MIMi113725 gene
neXtProtiNX_Q12837
OpenTargetsiENSG00000151615
PharmGKBiPA33543
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1168 Eukaryota
ENOG410XPNX LUCA
GeneTreeiENSGT00760000118935
HOGENOMiHOG000116305
HOVERGENiHBG031829
InParanoidiQ12837
KOiK09366
OMAiTHAPHMA
OrthoDBiEOG091G0WBK
PhylomeDBiQ12837
TreeFamiTF316413

Enzyme and pathway databases

ReactomeiR-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors
SignaLinkiQ12837
SIGNORiQ12837

Miscellaneous databases

GeneWikiiPOU4F2
GenomeRNAii5458
PROiPR:Q12837
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151615 Expressed in 27 organ(s), highest expression level in secondary oocyte
CleanExiHS_POU4F2
GenevisibleiQ12837 HS

Family and domain databases

CDDicd00086 homeodomain, 1 hit
cd00093 HTH_XRE, 1 hit
InterProiView protein in InterPro
IPR001387 Cro/C1-type_HTH
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR010982 Lambda_DNA-bd_dom_sf
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_HUMAN
AccessioniPrimary (citable) accession number: Q12837
Secondary accession number(s): B1PJR6
, B2RC84, Q13883, Q14987
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 2, 2010
Last modified: November 7, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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