PO4F1_RAT
ID PO4F1_RAT Reviewed; 420 AA.
AC P20266; Q91XM4;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 3.
DT 25-MAY-2022, entry version 169.
DE RecName: Full=POU domain, class 4, transcription factor 1;
DE AltName: Full=Brain-specific homeobox/POU domain protein 3A;
DE Short=Brain-3A;
DE Short=Brn-3A;
GN Name=Pou4f1; Synonyms=Brn-3, Brn3, Brn3a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 279-406, AND TISSUE SPECIFICITY.
RX PubMed=2739723; DOI=10.1038/340035a0;
RA He X., Treacy M.N., Simmons D.M., Ingraham H.A., Swanson L.W.,
RA Rosenfeld M.G.;
RT "Expression of a large family of POU-domain regulatory genes in mammalian
RT brain development.";
RL Nature 340:35-42(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 285-400.
RX PubMed=1383937; DOI=10.1093/nar/20.19.5093;
RA Lillycrop K.A., Budrahan V.S., Lakin N.D., Terrenghi G., Wood J.N.,
RA Polak J.M., Latchman D.S.;
RT "A novel POU family transcription factor is closely related to Brn-3 but
RT has a distinct expression pattern in neuronal cells.";
RL Nucleic Acids Res. 20:5093-5096(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 329-401.
RA Vogelaar C.F., Smits S.M., Brakkee J.H., Gispen W.H., Smidt M.P.,
RA Schrama L.H., Hoekman M.F.M., Burbach J.P.H.;
RT "Homeobox gene repertoire in adult rat dorsal root ganglia.";
RL Neurosci. Res. Commun. 32:49-59(2003).
RN [4]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=8835784; DOI=10.1007/bf02736850;
RA Liu Y.Z., Dawson S.J., Latchman D.S.;
RT "Alternative splicing of the Brn-3a and Brn-3b transcription factor RNAs is
RT regulated in neuronal cells.";
RL J. Mol. Neurosci. 7:77-85(1996).
RN [5]
RP FUNCTION.
RX PubMed=10640682; DOI=10.1016/s0169-328x(99)00271-5;
RA Smith M.D., Ensor E.A., Stohl L., Wagner J.A., Latchman D.S.;
RT "Regulation of NGFI-A (Egr-1) gene expression by the POU domain
RT transcription factor Brn-3a.";
RL Brain Res. Mol. Brain Res. 74:117-125(1999).
RN [6]
RP FUNCTION.
RX PubMed=11053412; DOI=10.1074/jbc.m007068200;
RA Ensor E., Smith M.D., Latchman D.S.;
RT "The BRN-3A transcription factor protects sensory but not sympathetic
RT neurons from programmed cell death/apoptosis.";
RL J. Biol. Chem. 276:5204-5212(2001).
CC -!- FUNCTION: Multifunctional transcription factor with different regions
CC mediating its different effects (PubMed:10640682). Acts by binding (via
CC its C-terminal domain) to sequences related to the consensus octamer
CC motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes.
CC Regulates the expression of specific genes involved in differentiation
CC and survival within a subset of neuronal lineages (PubMed:11053412). It
CC has been shown that activation of some of these genes requires its N-
CC terminal domain, maybe through a neuronal-specific cofactor. Ativates
CC BCL2 expression and protects neuronal cells from apoptosis (via the N-
CC terminal domain). Induces neuronal process outgrowth and the coordinate
CC expression of genes encoding synaptic proteins. Exerts its major
CC developmental effects in somatosensory neurons and in brainstem nuclei
CC involved in motor control. Stimulates the binding affinity of the
CC nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE),
CC and hence modulates ESR1-induced transcriptional activity. May
CC positively regulate POU4F2 and POU4F3. Regulates dorsal root ganglion
CC sensory neuron specification and axonal projection into the spinal
CC cord. Plays a role in TNFSF11-mediated terminal osteoclast
CC differentiation. Negatively regulates its own expression interacting
CC directly with a highly conserved autoregulatory domain surrounding the
CC transcription initiation site (By similarity).
CC {ECO:0000250|UniProtKB:P17208, ECO:0000269|PubMed:10640682,
CC ECO:0000269|PubMed:11053412}.
CC -!- FUNCTION: [Isoform 2]: Able to act as transcription factor, cannot
CC regulate the expression of the same subset of genes than isoform 1.
CC Does not have anitapoptotic effect on neuronal cells.
CC {ECO:0000250|UniProtKB:P17208}.
CC -!- SUBUNIT: Interacts (via N-terminus) with RIT2; the interaction controls
CC POU4F1 transactivation activity on some neuronal target genes. Isoform
CC 1 interacts with POU4F2; this interaction inhibits both POU4F1 DNA-
CC binding and transcriptional activities. Isoform 1 interacts (C-
CC terminus) with ESR1 (via DNA-binding domain); this interaction
CC decreases the estrogen receptor ESR1 transcriptional activity in a
CC DNA- and ligand 17-beta-estradiol-independent manner.
CC {ECO:0000250|UniProtKB:P17208}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P17208}. Cytoplasm
CC {ECO:0000250|UniProtKB:P17208}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000303|PubMed:8835784}; Synonyms=Brn-3A-Long
CC {ECO:0000303|PubMed:8835784};
CC IsoId=P20266-1; Sequence=Displayed;
CC Name=2 {ECO:0000303|PubMed:8835784}; Synonyms=Brn-3A-Short
CC {ECO:0000303|PubMed:8835784};
CC IsoId=P20266-2; Sequence=VSP_058638;
CC -!- TISSUE SPECIFICITY: Detected in brain, spinal cord and dorsal root
CC ganglion (PubMed:2739723, PubMed:8835784). Isoform 2 is detected in
CC brain, spinal cord, dorsal root ganglion and spleen (PubMed:8835784).
CC {ECO:0000269|PubMed:2739723, ECO:0000269|PubMed:8835784}.
CC -!- DOMAIN: The C-terminal domain is able to act as both DNA-binding domain
CC and a transcriptional activator. The N-terminal domain is also required
CC for transactivation activity on some target genes acting as a discrete
CC activation domain. Neurite outgrowth and expression of genes required
CC for synapse formation are primarily dependent on the C-terminal domain,
CC however the N-terminal domain is required for maximal induction.
CC {ECO:0000250|UniProtKB:P17208}.
CC -!- SIMILARITY: Belongs to the POU transcription factor family. Class-4
CC subfamily. {ECO:0000305}.
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DR EMBL; AF390075; AAK70502.1; -; mRNA.
DR PIR; S05045; S05045.
DR RefSeq; XP_008769153.1; XM_008770931.2. [P20266-1]
DR MINT; P20266; -.
DR PaxDb; P20266; -.
DR GeneID; 114503; -.
DR KEGG; rno:114503; -.
DR UCSC; RGD:620074; rat. [P20266-1]
DR CTD; 5457; -.
DR RGD; 620074; Pou4f1.
DR eggNOG; KOG1168; Eukaryota.
DR InParanoid; P20266; -.
DR OrthoDB; 929123at2759; -.
DR Reactome; R-RNO-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR PRO; PR:P20266; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0051020; F:GTPase binding; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0021535; P:cell migration in hindbrain; ISO:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
DR GO; GO:0021953; P:central nervous system neuron differentiation; ISO:RGD.
DR GO; GO:0021986; P:habenula development; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0007498; P:mesoderm development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0043069; P:negative regulation of programmed cell death; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0048665; P:neuron fate specification; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0048935; P:peripheral nervous system neuron development; ISO:RGD.
DR GO; GO:0048934; P:peripheral nervous system neuron differentiation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; ISS:UniProtKB.
DR GO; GO:0051355; P:proprioception involved in equilibrioception; ISO:RGD.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0048880; P:sensory system development; ISO:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0001967; P:suckling behavior; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:RGD.
DR GO; GO:0021559; P:trigeminal nerve development; ISO:RGD.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISO:RGD.
DR CDD; cd00086; homeodomain; 1.
DR CDD; cd00093; HTH_XRE; 1.
DR Gene3D; 1.10.260.40; -; 1.
DR InterPro; IPR001387; Cro/C1-type_HTH.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR010982; Lambda_DNA-bd_dom_sf.
DR InterPro; IPR013847; POU.
DR InterPro; IPR015584; POU4-TF1.
DR InterPro; IPR000327; POU_dom.
DR PANTHER; PTHR11636:SF42; PTHR11636:SF42; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00157; Pou; 1.
DR PRINTS; PR00028; POUDOMAIN.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00352; POU; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF47413; SSF47413; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00035; POU_1; 1.
DR PROSITE; PS00465; POU_2; 1.
DR PROSITE; PS51179; POU_3; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; Developmental protein; DNA-binding;
KW Homeobox; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..420
FT /note="POU domain, class 4, transcription factor 1"
FT /id="PRO_0000100738"
FT DOMAIN 261..338
FT /note="POU-specific"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00530"
FT DNA_BIND 356..415
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 72..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 57..66
FT /note="POU-IV box"
FT VAR_SEQ 1..84
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8835784"
FT /id="VSP_058638"
FT CONFLICT 340
FT /note="A -> P (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 420 AA; 43275 MW; 64B4FAE98FE27011 CRC64;
MMSMNSKQPH FAMHPTLPEH KYPSLHSSSE AIRRACLPTP PLQSNLFASL DETLLARAEA
LAAVDIAVSQ GKSHPFKPDA TYHTMNSVPC TSTSTVPLAH HHHHHHHHQA LEPGDLLDHI
SSPSLALMAG AGGAGAAGGG GAPTRPRGAG GPGGGGGPGG GGPGVAGRRR GPGGGGGGPG
GGLLGXSAHP HPHMHGXGHL SHPAAAAAMN MPSGLPHPGL VAAAAHHGAA AAAAAAAAGQ
VAAASAAAAV VGAAGLASIC DSDTDPRELE AFAERFKQRR IKLGVTQADV GSALANLKIP
GVGSLSQSTI CRFESLTLSH NNMIALKPIL QAWLEEAEGA QREKMNKPEL FNGGEKKRKR
TSIAAPEKRS LEAYFAVQPR PSSEKIAAIA EKLDLKKNVV RVWFCNQRQK QKRMKFSATY
