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Protein

POU domain, class 4, transcription factor 2

Gene

POU4F2

Organism
Homo sapiens (Human)
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:19266028, PubMed:23805044). Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor ISL1 to achieve RGC fate specification in the developing retina. Plays also a role in RGC axon formation and guidance by regulating gene expression of specific target genes. Plays a role in TNFSF11-mediated terminal osteoclast differentiation. Binds chromatin at promoter region of target genes (By similarity).By similarity2 Publications
Isoform 1: Acts either as a transcriptional activator or repressor (PubMed:19266028, PubMed:23805044). 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. Involved in the positive regulation of the transcriptional factor PAX6 expression through its binding to the neuroretina-specific enhancer in neuroretina cells. Mediates positive transcriptional regulation of heat shock protein HSPB1 expression in cardiac myocytes. Positively regulates POU4F1 expression by interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site of the POU4F1 gene promoter. Plays a role in the regulation of breast cancer cell growth by promoting transcription activation as well as repression of specific target genes. Involved in tumor breast progression and invasion (By similarity). Stimulates the promoter activity of the GTP-binding protein RIT2 gene containing the octamer binding site in retinal ganglion cells (PubMed:23805044). Plays also a role either as a transcriptional coactivator or corepressor. Transcriptional coactivator cooperating with transcription factors ISL1 and ISL2 to potentiate transcriptional activation of retinal ganglion cell (RGC) target genes. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to the octamer motif. Binds to the octamer binding site to form a ternary complex with ISL1 in promoter of target genes (By similarity).By similarity1 Publication
Isoform 2: Acts either as a transcriptional activator or repressor (PubMed:23805044). Stimulates the promoter activity of the neuronal nicotinic acetylcholine receptor alpha CHRNA2. Negatively regulates the apoptosis regulator BAX promoter activity. Inhibits promoter activity of the neuronal intermediate filament protein alpha-internexin INA gene. Plays a role in the regulation of breast cancer cell growth by promoting transcription activation as well as repression of specific target genes. Involved in tumor breast progression and invasion (By similarity). Inhibits the promoter activity of the GTP-binding protein RIT2 gene containing the octamer binding site in retinal ganglion cells (PubMed:23805044). Plays also a role either as transcriptional coactivator or corepressor. Transcriptional coactivator cooperating with transcription factors TP53 to potentiate transcriptional activation of BAX promoter activity, and hence increases neuronal cell apoptosis. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to the octamer motif. Acts also as a transcriptional coactivator via its interaction with the transcription factor ESR1 (By similarity).By similarity1 Publication

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 2Imported
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

HGNCiHGNC:9219. POU4F2.

Subcellular locationi

  • Nucleus 1 Publication
  • Nucleus speckle 1 Publication
  • Cytoplasm By similarity
  • Cell membrane By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nuclear speck Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, 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.

PTM databases

iPTMnetiQ12837.
PhosphoSitePlusiQ12837.

Expressioni

Tissue specificityi

Expressed in the ganglion cell layer of the retina (PubMed:7691107). Expressed in breast cancer cell lines (at protein level) (PubMed:11526481). Expressed in the brain (PubMed:7691107). Expressed in breast cancer cell lines (PubMed:11526481).2 Publications

Gene expression databases

BgeeiENSG00000151615.
CleanExiHS_POU4F2.
GenevisibleiQ12837. HS.

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. Isoform 1: Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation. Isoform 1: Interacts (via C-terminus) with ISL1 (via C-terminus). Isoform 1: Interacts with ISL2. Isoform 1 interacts with LHX2. Isoform 2: Interacts (via C-terminus) with TP53 (via C-terminus). Isoform 2: Interacts with POU4F1 isoform 1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities. 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.By similarity

Protein-protein interaction databases

BioGridi111454. 1 interactor.
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 – 237Transcriptional activation domainBy similarityAdd BLAST147
Regioni238 – 409Transcriptional repression domainBy 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 biasi1 – 4Poly-Met4
Compositional biasi43 – 51Poly-Ser9
Compositional biasi54 – 68Poly-GlyAdd BLAST15
Compositional biasi70 – 79Poly-Ser10
Compositional biasi80 – 83Poly-Gly4
Compositional biasi126 – 129Poly-His4
Compositional biasi155 – 158Poly-Ser4
Compositional biasi171 – 182Poly-HisAdd BLAST12

Domaini

The transcriptional activation domain within the N-terminal region is sufficient to induce transcriptional activity. 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 (By similarity). The polyhistidine repeat acts as a targeting signal to nuclear speckles (PubMed:19266028).By similarity1 Publication

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG1168. Eukaryota.
ENOG410XPNX. LUCA.
GeneTreeiENSGT00760000118935.
HOGENOMiHOG000116305.
HOVERGENiHBG031829.
InParanoidiQ12837.
KOiK09366.
OMAiQYHAAMN.
OrthoDBiEOG091G0WBK.
PhylomeDBiQ12837.
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: 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

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.

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: June 7, 2017
This is version 158 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. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families