Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

POU domain, class 4, transcription factor 1

Gene

Pou4f1

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

Functioni

Multifunctional transcription factor with different regions mediating its different effects (PubMed:10640682, PubMed:8621561, PubMed:9694219, PubMed:9722627). Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes (PubMed:8621561, PubMed:17668438). Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor (PubMed:12934100). Ativates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain) (PubMed:9722627). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins (PubMed:8972215). Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity (PubMed:9448000). May positively regulate POU4F2 and POU4F3 (PubMed:8876243). Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord (PubMed:22326227). Plays a role in TNFSF11-mediated terminal osteoclast differentiation (PubMed:17668438). Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site (PubMed:12441296).11 Publications
Isoform 2: Able to act as transcription factor, cannot regulate the expression of the same subset of genes than isoform 1 (PubMed:12934100). Does not have antiapoptotic effect on neuronal cells (PubMed:9722627).2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi357 – 416HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • chromatin binding Source: ParkinsonsUK-UCL
  • DNA binding Source: MGI
  • GTPase binding Source: ParkinsonsUK-UCL
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • single-stranded DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: NTNU_SB
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: MGI

GO - Biological processi

  • cell migration in hindbrain Source: MGI
  • cellular response to cytokine stimulus Source: UniProtKB
  • cellular response to estradiol stimulus Source: UniProtKB
  • central nervous system neuron differentiation Source: MGI
  • habenula development Source: MGI
  • innervation Source: MGI
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
  • mesoderm development Source: MGI
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of neuron apoptotic process Source: BHF-UCL
  • negative regulation of programmed cell death Source: UniProtKB
  • negative regulation of transcription elongation from RNA polymerase I promoter Source: ParkinsonsUK-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • nervous system development Source: MGI
  • neuron differentiation Source: MGI
  • neuron fate specification Source: BHF-UCL
  • neuron projection development Source: UniProtKB
  • peripheral nervous system neuron development Source: BHF-UCL
  • peripheral nervous system neuron differentiation Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of cell cycle arrest Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of osteoclast differentiation Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription regulatory region DNA binding Source: UniProtKB
  • proprioception involved in equilibrioception Source: MGI
  • regulation of neurogenesis Source: MGI
  • regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • regulation of transcription, DNA-templated Source: MGI
  • sensory system development Source: BHF-UCL
  • suckling behavior Source: MGI
  • trigeminal nerve development Source: BHF-UCL
  • ventricular compact myocardium morphogenesis Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, DNA-binding
Biological processTranscription, 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 1
Alternative name(s):
Brain-specific homeobox/POU domain protein 3A
Short name:
Brain-3A
Short name:
Brn-3A
Brn-3.0
Gene namesi
Name:Pou4f1
Synonyms:Brn-3, Brn3, Brn3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:102525. Pou4f1.

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

Disruption phenotypei

Mutants have defective suckling and uncoordinated limb and trunk movements, leading to early postnatal death. They show a loss of neurons in the trigerminal ganglia, the medial habenula, the red nucleus and the caudal region of the inferior olivary nucleus (PubMed:8876243). Mutant dorsal root ganglions are defective in sensory neuron specification, and sensory afferent axons fail to form normal trajectories in the spinal cord (PubMed:22326227).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi378V → I: Abolishes transcriptional activity. Increases transcriptional repression. Disrupts induction of neurite outgrowth and expression of synaptic genes. No effect on transactivation of BCL2 expression. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001007371 – 421POU domain, class 4, transcription factor 1Add BLAST421

Proteomic databases

PaxDbiP17208.
PRIDEiP17208.

PTM databases

PhosphoSitePlusiP17208.

Expressioni

Tissue specificityi

Expressed in mature osteoclasts (at protein level) (PubMed:17668438). Brain, peripheral sensory nervous system and retina (PubMed:8162704). In the adult nervous system, predominates in the medial habenula, superficial gray of the superior colliculus, red nucleus, mesencephalic nucleus of the trigeminal ganglion, nucleus ambiguus, inferior olivary nucleus, and peripheral sensory ganglia (PubMed:8290353).3 Publications

Developmental stagei

Expressed in the spinal cord from E11 to the adult stage (PubMed:8290353). As early as E10.5 to E15.5, strongly expressed in all dorsal root ganglion neurons (PubMed:22326227). In retinal ganglion cells, expression starts at E15.5 and exhibits a slow decrease with moderate levels detectable at P8 (PubMed:8637595).3 Publications

Inductioni

Up-regulated by the osteoclast differentiation factor TNFSF11 (PubMed:17668438).1 Publication

Gene expression databases

BgeeiENSMUSG00000048349.
CleanExiMM_POU4F1.
GenevisibleiP17208. MM.

Interactioni

Subunit structurei

Interacts (via N-terminus) with RIT2; the interaction controls POU4F1 transactivation activity on some neuronal target genes (PubMed:12934100). Isoform 1 interacts with POU4F2 isoform 2; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities (PubMed:8537352). Isoform 1 interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction decreases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000).3 Publications

GO - Molecular functioni

  • GTPase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi202310. 2 interactors.
STRINGi10090.ENSMUSP00000060798.

Structurei

3D structure databases

ProteinModelPortaliP17208.
SMRiP17208.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini262 – 339POU-specificPROSITE-ProRule annotationAdd BLAST78

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi57 – 66POU-IV box10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi100 – 108Poly-His9
Compositional biasi130 – 187Gly-richAdd BLAST58
Compositional biasi205 – 258Ala-richAdd BLAST54

Domaini

The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain (PubMed:8621561, PubMed:9722627). Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction (PubMed:8972215).3 Publications

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG1168. Eukaryota.
ENOG410XPNX. LUCA.
GeneTreeiENSGT00760000118935.
HOGENOMiHOG000116305.
HOVERGENiHBG031829.
InParanoidiP17208.
KOiK09366.
OMAiKYTTLHS.
OrthoDBiEOG091G0WBK.
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.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR010982. Lambda_DNA-bd_dom.
IPR013847. POU.
IPR015584. POU4-TF1.
IPR000327. POU_dom.
PANTHERiPTHR11636:SF42. PTHR11636:SF42. 1 hit.
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: P17208-1) [UniParc]FASTAAdd to basket
Also known as: Brn-3A-Long1 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
MMSMNSKQPH FAMHPTLPEH KYPSLHSSSE AIRRACLPTP PLQSNLFASL
60 70 80 90 100
DETLLARAEA LAAVDIAVSQ GKSHPFKPDA TYHTMNSVPC TSTSTVPLAH
110 120 130 140 150
HHHHHHHHQA LEPGDLLDHI SSPSLALMAG AGGAGAAGGG GGAHDGPGGG
160 170 180 190 200
GGPGGGGGPG GGGPGGGGGG GGPGGGGGGP GGGLLGGSAH PHPHMHGLGH
210 220 230 240 250
LSHPAAAAAM NMPSGLPHPG LVAAAAHHGA AAAAAAAAAG QVAAASAAAA
260 270 280 290 300
VVGAAGLASI CDSDTDPREL EAFAERFKQR RIKLGVTQAD VGSALANLKI
310 320 330 340 350
PGVGSLSQST ICRFESLTLS HNNMIALKPI LQAWLEEAEG AQREKMNKPE
360 370 380 390 400
LFNGGEKKRK RTSIAAPEKR SLEAYFAVQP RPSSEKIAAI AEKLDLKKNV
410 420
VRVWFCNQRQ KQKRMKFSAT Y
Length:421
Mass (Da):42,767
Last modified:July 27, 2011 - v3
Checksum:i64EC98E5C0CF79E2
GO
Isoform 21 Publication (identifier: P17208-2) [UniParc]FASTAAdd to basket
Also known as: Brn-3A-Short1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-84: Missing.

Show »
Length:337
Mass (Da):33,561
Checksum:i3BEF938636EE1E65
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti179G → A in AAB30577 (PubMed:8162704).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0586371 – 84Missing in isoform 2. CuratedAdd BLAST84

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S69350 Genomic DNA. Translation: AAB30577.2.
AC121997 Genomic DNA. No translation available.
X51959 mRNA. Translation: CAA36218.1.
CCDSiCCDS27319.1. [P17208-1]
RefSeqiNP_035273.3. NM_011143.4. [P17208-1]
XP_006518768.1. XM_006518705.3. [P17208-1]
XP_006518769.1. XM_006518706.3. [P17208-1]
UniGeneiMm.246550.

Genome annotation databases

EnsembliENSMUST00000053016; ENSMUSP00000060798; ENSMUSG00000048349. [P17208-1]
GeneIDi18996.
KEGGimmu:18996.
UCSCiuc007uxb.2. mouse. [P17208-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPO4F1_MOUSE
AccessioniPrimary (citable) accession number: P17208
Secondary accession number(s): E9QPT6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: October 25, 2017
This is version 151 of the entry and version 3 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