PO4F2_MOUSE
ID PO4F2_MOUSE Reviewed; 411 AA.
AC Q63934; Q63954;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=POU domain, class 4, transcription factor 2 {ECO:0000305};
DE AltName: Full=Brain-specific homeobox/POU domain protein 3B;
DE Short=Brain-3B;
DE Short=Brn-3B;
DE AltName: Full=Brn-3.2 {ECO:0000303|PubMed:7904822};
GN Name=Pou4f2 {ECO:0000312|MGI:MGI:102524};
GN Synonyms=Brn-3.2 {ECO:0000303|PubMed:7904822}, Brn3b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, DNA-BINDING, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=7904822; DOI=10.1016/0896-6273(94)90164-3;
RA Turner E.E., Jenne K.J., Rosenfeld M.G.;
RT "Brn-3.2: a Brn-3-related transcription factor with distinctive central
RT nervous system expression and regulation by retinoic acid.";
RL Neuron 12:205-218(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2).
RC STRAIN=CD;
RX PubMed=8162704; DOI=10.1159/000133709;
RA Theil T., Zechner U., Klett C., Adolph S., Moeroey T.;
RT "Chromosomal localization and sequences of the murine Brn-3 family of
RT developmental control genes.";
RL Cytogenet. Cell Genet. 66:267-271(1994).
RN [4]
RP TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=7691107; DOI=10.1016/0896-6273(93)90079-7;
RA Xiang M., Zhou L.-J., Peng Y., Eddy R.L., Shows T.B., Nathans J.;
RT "Brn-3b: a POU domain gene expressed in a subset of retinal ganglion
RT cells.";
RL Neuron 11:689-701(1993).
RN [5]
RP DNA-BINDING, ALTERNATIVE SPLICING (ISOFORM 2), AND DEVELOPMENTAL STAGE.
RX PubMed=8290353; DOI=10.1093/nar/21.25.5921;
RA Theil T., McLean-Hunter S., Zoernig M., Moeroey T.;
RT "Mouse Brn-3 family of POU transcription factors: a new aminoterminal
RT domain is crucial for the oncogenic activity of Brn-3a.";
RL Nucleic Acids Res. 21:5921-5929(1993).
RN [6]
RP FUNCTION.
RX PubMed=7935408; DOI=10.1128/mcb.14.10.6907-6914.1994;
RA Morris P.J., Theil T., Ring C.J., Lillycrop K.A., Moroy T., Latchman D.S.;
RT "The opposite and antagonistic effects of the closely related POU family
RT transcription factors Brn-3a and Brn-3b on the activity of a target
RT promoter are dependent on differences in the POU domain.";
RL Mol. Cell. Biol. 14:6907-6914(1994).
RN [7]
RP FUNCTION, ALTERNATIVE SPLICING (ISOFORM 2), AND INDUCTION.
RX PubMed=8065921; DOI=10.1093/nar/22.15.3092;
RA Budhram-Mahadeo V., Theil T., Morris P.J., Lillycrop K.A., Moroy T.,
RA Latchman D.S.;
RT "The DNA target site for the Brn-3 POU family transcription factors can
RT confer responsiveness to cyclic AMP and removal of serum in neuronal
RT cells.";
RL Nucleic Acids Res. 22:3092-3098(1994).
RN [8]
RP FUNCTION, INTERACTION WITH POU4F1 (ISOFORM 2), AND DEVELOPMENTAL STAGE.
RX PubMed=8537352; DOI=10.1074/jbc.270.52.30958;
RA Theil T., Roedel B., Spiegelhalter F., Moeroey T.;
RT "Short isoform of POU factor Brn-3b can form a heterodimer with Brn-3a that
RT is inactive for octamer motif binding.";
RL J. Biol. Chem. 270:30958-30964(1995).
RN [9]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=8637595; DOI=10.1038/381603a0;
RA Erkman L., McEvilly R.J., Luo L., Ryan A.K., Hooshmand F., O'Connell S.M.,
RA Keithley E.M., Rapaport D.H., Ryan A.F., Rosenfeld M.G.;
RT "Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual
RT system development.";
RL Nature 381:603-606(1996).
RN [10]
RP FUNCTION, AND REGION.
RX PubMed=7852360; DOI=10.1074/jbc.270.6.2853;
RA Budhram-Mahadeo V., Morris P.J., Lakin N.D., Theil T., Ching G.Y.,
RA Lillycrop K.A., Moeroey T., Liem R.K., Latchman D.S.;
RT "Activation of the alpha-internexin promoter by the Brn-3a transcription
RT factor is dependent on the N-terminal region of the protein.";
RL J. Biol. Chem. 270:2853-2858(1995).
RN [11]
RP FUNCTION.
RX PubMed=7797498; DOI=10.1074/jbc.270.25.15143;
RA Milton N.G., Bessis A., Changeux J.P., Latchman D.S.;
RT "The neuronal nicotinic acetylcholine receptor alpha 2 subunit gene
RT promoter is activated by the Brn-3b POU family transcription factor and not
RT by Brn-3a or Brn-3c.";
RL J. Biol. Chem. 270:15143-15147(1995).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ILE-368.
RX PubMed=8662774; DOI=10.1074/jbc.271.20.11897;
RA Dawson S.J., Morris P.J., Latchman D.S.;
RT "A single amino acid change converts an inhibitory transcription factor
RT into an activator.";
RL J. Biol. Chem. 271:11631-11633(1996).
RN [13]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=8632990; DOI=10.1073/pnas.93.9.3920;
RA Gan L., Xiang M., Zhou L., Wagner D.S., Klein W.H., Nathans J.;
RT "POU domain factor Brn-3b is required for the development of a large set of
RT retinal ganglion cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:3920-3925(1996).
RN [14]
RP FUNCTION, INDUCTION, MUTAGENESIS OF ILE-368, AND REGION.
RX PubMed=8995448; DOI=10.1074/jbc.272.2.1382;
RA Smith M.D., Dawson S.J., Latchman D.S.;
RT "Inhibition of neuronal process outgrowth and neuronal specific gene
RT activation by the Brn-3b transcription factor.";
RL J. Biol. Chem. 272:1382-1388(1997).
RN [15]
RP FUNCTION, AND MUTAGENESIS OF ILE-368.
RX PubMed=9261145; DOI=10.1074/jbc.272.34.21325;
RA Smith M.D., Morris P.J., Dawson S.J., Schwartz M.L., Schlaepfer W.W.,
RA Latchman D.S.;
RT "Coordinate induction of the three neurofilament genes by the Brn-3a
RT transcription factor.";
RL J. Biol. Chem. 272:21325-21333(1997).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF ILE-368.
RX PubMed=8972215; DOI=10.1128/mcb.17.1.345;
RA Smith M.D., Dawson S.J., Latchman D.S.;
RT "The Brn-3a transcription factor induces neuronal process outgrowth and the
RT coordinate expression of genes encoding synaptic proteins.";
RL Mol. Cell. Biol. 17:345-354(1997).
RN [17]
RP DNA-BINDING.
RX PubMed=9111308; DOI=10.1128/mcb.17.5.2391;
RA Gruber C.A., Rhee J.M., Gleiberman A., Turner E.E.;
RT "POU domain factors of the Brn-3 class recognize functional DNA elements
RT which are distinctive, symmetrical, and highly conserved in evolution.";
RL Mol. Cell. Biol. 17:2391-2400(1997).
RN [18]
RP FUNCTION, AND INTERACTION WITH ESR1 (ISOFORM 2).
RX PubMed=9448000; DOI=10.1128/mcb.18.2.1029;
RA Budhram-Mahadeo V., Parker M., Latchman D.S.;
RT "POU transcription factors Brn-3a and Brn-3b interact with the estrogen
RT receptor and differentially regulate transcriptional activity via an
RT estrogen response element.";
RL Mol. Cell. Biol. 18:1029-1041(1998).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF ILE-368.
RX PubMed=9694219; DOI=10.1097/00001756-199807130-00029;
RA Dawson S.J., Palmer R.D., Morris P.J., Latchman D.S.;
RT "Functional role of position 22 in the homeodomain of Brn-3 transcription
RT factors.";
RL NeuroReport 9:2305-2309(1998).
RN [20]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10357904; DOI=10.1006/dbio.1999.9280;
RA Gan L., Wang S.W., Huang Z., Klein W.H.;
RT "POU domain factor Brn-3b is essential for retinal ganglion cell
RT differentiation and survival but not for initial cell fate specification.";
RL Dev. Biol. 210:469-480(1999).
RN [21]
RP FUNCTION.
RX PubMed=10526314;
RX DOI=10.1002/(sici)1097-4695(19991115)41:3<349::aid-neu4>3.0.co;2-f;
RA Plaza S., Hennemann H., Moeroey T., Saule S., Dozier C.;
RT "Evidence that POU factor Brn-3B regulates expression of Pax-6 in
RT neuroretina cells.";
RL J. Neurobiol. 41:349-358(1999).
RN [22]
RP FUNCTION, DNA-BINDING, AND DEVELOPMENTAL STAGE.
RX PubMed=10414983; DOI=10.1523/jneurosci.19-15-06549.1999;
RA Trieu M., Rhee J.M., Fedtsova N., Turner E.E.;
RT "Autoregulatory sequences are revealed by complex stability screening of
RT the mouse brn-3.0 locus.";
RL J. Neurosci. 19:6549-6558(1999).
RN [23]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11163266; DOI=10.1016/s0896-6273(00)00153-7;
RA Erkman L., Yates P.A., McLaughlin T., McEvilly R.J., Whisenhunt T.,
RA O'Connell S.M., Krones A.I., Kirby M.A., Rapaport D.H.,
RA Bermingham J.R. Jr., O'Leary D.D.M., Rosenfeld M.G.;
RT "A POU domain transcription factor-dependent program regulates axon
RT pathfinding in the vertebrate visual system.";
RL Neuron 28:779-792(2000).
RN [24]
RP FUNCTION.
RX PubMed=14726699; DOI=10.4161/cbt.3.3.698;
RA Samady L., Dennis J., Budhram-Mahadeo V., Latchman D.S.;
RT "Activation of CDK4 gene expression in human breast cancer cells by the
RT Brn-3b POU family transcription factor.";
RL Cancer Biol. Ther. 3:317-323(2004).
RN [25]
RP FUNCTION, AND REGION.
RX PubMed=15733064; DOI=10.1111/j.1432-0436.2005.07301004.x;
RA Martin S.E., Mu X., Klein W.H.;
RT "Identification of an N-terminal transcriptional activation domain within
RT Brn3b/POU4f2.";
RL Differentiation 73:18-27(2005).
RN [26]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=16152597; DOI=10.1002/ijc.21435;
RA Samady L., Faulkes D.J., Budhram-Mahadeo V., Ndisang D., Potter E.,
RA Brabant G., Latchman D.S.;
RT "The Brn-3b POU family transcription factor represses plakoglobin gene
RT expression in human breast cancer cells.";
RL Int. J. Cancer 118:869-878(2006).
RN [27]
RP FUNCTION, INTERACTION WITH TP53 (ISOFORM 2), AND CHROMATIN BINDING.
RX PubMed=17145718; DOI=10.1093/nar/gkl878;
RA Budhram-Mahadeo V.S., Bowen S., Lee S., Perez-Sanchez C., Ensor E.,
RA Morris P.J., Latchman D.S.;
RT "Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of
RT cell cycle arrest by cooperating in trans-activation of bax expression.";
RL Nucleic Acids Res. 34:6640-6652(2006).
RN [28]
RP FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RX PubMed=17668438; DOI=10.1002/jcb.21257;
RA Schulze-Spaete U., Battaglino R., Fu J., Sharma A., Vokes M., Stashenko P.;
RT "Brn3 transcription factors control terminal osteoclastogenesis.";
RL J. Cell. Biochem. 102:1-12(2007).
RN [29]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18368538; DOI=10.1007/s12192-008-0028-2;
RA Farooqui-Kabir S.R., Diss J.K., Henderson D., Marber M.S., Latchman D.S.,
RA Budhram-Mahadeo V., Heads R.J.;
RT "Cardiac expression of Brn-3a and Brn-3b POU transcription factors and
RT regulation of Hsp27 gene expression.";
RL Cell Stress Chaperones 13:297-312(2008).
RN [30]
RP FUNCTION, INTERACTION WITH DLX1 AND DLX2, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=21875655; DOI=10.1016/j.neuroscience.2011.08.015;
RA Feng L., Eisenstat D.D., Chiba S., Ishizaki Y., Gan L., Shibasaki K.;
RT "Brn-3b inhibits generation of amacrine cells by binding to and negatively
RT regulating DLX1/2 in developing retina.";
RL Neuroscience 195:9-20(2011).
RN [31]
RP DEVELOPMENTAL STAGE.
RX PubMed=22326227; DOI=10.1016/j.ydbio.2012.01.021;
RA Zou M., Li S., Klein W.H., Xiang M.;
RT "Brn3a/Pou4f1 regulates dorsal root ganglion sensory neuron specification
RT and axonal projection into the spinal cord.";
RL Dev. Biol. 364:114-127(2012).
RN [32]
RP TISSUE SPECIFICITY.
RX PubMed=23805044;
RA Zhang L., Wahlin K., Li Y., Masuda T., Yang Z., Zack D.J., Esumi N.;
RT "RIT2, a neuron-specific small guanosine triphosphatase, is expressed in
RT retinal neuronal cells and its promoter is modulated by the POU4
RT transcription factors.";
RL Mol. Vis. 19:1371-1386(2013).
RN [33]
RP FUNCTION, INTERACTION WITH ISL1; ISL2 AND LHX2 (ISOFORM 1), DNA-BINDING,
RP CHROMATIN BINDING, AND DISRUPTION PHENOTYPE.
RX PubMed=24643061; DOI=10.1371/journal.pone.0092105;
RA Li R., Wu F., Ruonala R., Sapkota D., Hu Z., Mu X.;
RT "Isl1 and Pou4f2 form a complex to regulate target genes in developing
RT retinal ganglion cells.";
RL PLoS ONE 9:E92105-E92105(2014).
RN [34]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25775587; DOI=10.1073/pnas.1421535112;
RA Wu F., Kaczynski T.J., Sethuramanujam S., Li R., Jain V., Slaughter M.,
RA Mu X.;
RT "Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the
RT retinal ganglion cell fate.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1559-E1568(2015).
CC -!- FUNCTION: Tissue-specific DNA-binding transcription factor involved in
CC the development and differentiation of target cells (PubMed:7904822,
CC PubMed:8995448, PubMed:8972215, PubMed:10357904, PubMed:10414983,
CC PubMed:11163266, PubMed:17668438, PubMed:25775587). Functions either as
CC activator or repressor by modulating the rate of target gene
CC transcription through RNA polymerase II enzyme in a promoter-dependent
CC manner (PubMed:7904822, PubMed:7935408, PubMed:8065921, PubMed:7852360,
CC PubMed:7797498, PubMed:8662774, PubMed:9694219, PubMed:10526314,
CC PubMed:15733064, PubMed:17145718, PubMed:18368538). Binds to the
CC consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of
CC target genes (PubMed:7904822, PubMed:8290353, PubMed:9111308,
CC PubMed:10414983, PubMed:16152597, PubMed:17668438, PubMed:24643061).
CC Plays a fundamental role in the gene regulatory network essential for
CC retinal ganglion cell (RGC) differentiation (PubMed:8632990,
CC PubMed:10357904, PubMed:25775587). Binds to an octamer site to form a
CC ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to
CC potentiate transcriptional activation of RGC target genes being
CC involved in RGC fate commitment in the developing retina and RGC axon
CC formation and pathfinding (PubMed:8995448, PubMed:9261145,
CC PubMed:8972215, PubMed:10357904, PubMed:11163266, PubMed:24643061,
CC PubMed:25775587). Inhibits DLX1 and DLX2 transcriptional activities
CC preventing DLX1- and DLX2-mediated ability to promote amacrine cell
CC fate specification (PubMed:21875655). In cooperation with TP53
CC potentiates transcriptional activation of BAX promoter activity
CC increasing neuronal cell apoptosis (PubMed:17145718). Negatively
CC regulates BAX promoter activity in the absence of TP53
CC (PubMed:17145718). Acts as a transcriptional coactivator via its
CC interaction with the transcription factor ESR1 by enhancing its effect
CC on estrogen response element (ERE)-containing promoter
CC (PubMed:9448000). Antagonizes the transcriptional stimulatory activity
CC of POU4F1 by preventing its binding to an octamer motif
CC (PubMed:7935408, PubMed:8065921, PubMed:8537352, PubMed:7852360,
CC PubMed:8662774). Involved in TNFSF11-mediated terminal osteoclast
CC differentiation (PubMed:17668438). {ECO:0000269|PubMed:10357904,
CC ECO:0000269|PubMed:10414983, ECO:0000269|PubMed:10526314,
CC ECO:0000269|PubMed:11163266, ECO:0000269|PubMed:15733064,
CC ECO:0000269|PubMed:16152597, ECO:0000269|PubMed:17145718,
CC ECO:0000269|PubMed:17668438, ECO:0000269|PubMed:18368538,
CC ECO:0000269|PubMed:21875655, ECO:0000269|PubMed:24643061,
CC ECO:0000269|PubMed:25775587, ECO:0000269|PubMed:7797498,
CC ECO:0000269|PubMed:7852360, ECO:0000269|PubMed:7904822,
CC ECO:0000269|PubMed:7935408, ECO:0000269|PubMed:8065921,
CC ECO:0000269|PubMed:8290353, ECO:0000269|PubMed:8537352,
CC ECO:0000269|PubMed:8632990, ECO:0000269|PubMed:8662774,
CC ECO:0000269|PubMed:8972215, ECO:0000269|PubMed:8995448,
CC ECO:0000269|PubMed:9111308, ECO:0000269|PubMed:9261145,
CC ECO:0000269|PubMed:9448000, ECO:0000269|PubMed:9694219}.
CC -!- SUBUNIT: Isoform 2: Interacts with POU4F1 isoform 1; this interaction
CC inhibits both POU4F1 DNA-binding and transcriptional activities
CC (PubMed:8537352). Isoform 2: Interacts (C-terminus) with ESR1 (via DNA-
CC binding domain); this interaction increases the estrogen receptor ESR1
CC transcriptional activity in a DNA- and ligand 17-beta-estradiol-
CC independent manner (PubMed:9448000). Isoform 2: Interacts (via C-
CC terminus) with TP53 (via N-terminus) (PubMed:17145718). Interacts with
CC DLX1 (via homeobox DNA-binding domain); this interaction suppresses
CC DLX1-mediated transcriptional activity in postnatal retina enhancing
CC retinal ganglion cell (RGC) differentiation (PubMed:21875655).
CC Interacts with DLX2 (via homeobox DNA-binding domain); this interaction
CC enhances RGC differentiation (PubMed:21875655). Isoform 1: Interacts
CC (via C-terminus) with ISL1 (via C-terminus) (PubMed:24643061). Isoform
CC 1: Interacts with ISL2 (PubMed:24643061). Isoform 1: Interacts with
CC LHX2 (PubMed:24643061). {ECO:0000269|PubMed:17145718,
CC ECO:0000269|PubMed:21875655, ECO:0000269|PubMed:24643061,
CC ECO:0000269|PubMed:8537352, ECO:0000269|PubMed:9448000}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17668438}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q12837}. Cytoplasm
CC {ECO:0000269|PubMed:17668438}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Brn-3b-long {ECO:0000303|PubMed:8537352}, Brn-3b-l
CC {ECO:0000303|PubMed:8537352};
CC IsoId=Q63934-1; Sequence=Displayed;
CC Name=2; Synonyms=Brn-3b {ECO:0000269|PubMed:8065921,
CC ECO:0000303|PubMed:7935408, ECO:0000303|PubMed:8162704,
CC ECO:0000303|PubMed:8290353}, Brn-3b-short {ECO:0000303|PubMed:8537352},
CC Brn-3b-s {ECO:0000303|PubMed:8537352};
CC IsoId=Q63934-2; Sequence=VSP_058838;
CC -!- TISSUE SPECIFICITY: Expressed in retinal ganglion cells (RGCs)
CC (PubMed:21875655, PubMed:23805044). Expressed in mature osteoclasts
CC (PubMed:17668438). Expressed in cells of layers of the superior
CC colliculus and the adjacent periaqueductal gray (at protein level)
CC (PubMed:7691107). Expressed in the brain, peripheral sensory nervous
CC system and retina (PubMed:7904822). Expressed in the optical,
CC intermediate, and deep gray areas of the superior colliculus, the
CC dorsal column of the mesencephalic and pontine central gray, and the
CC lateral interpeduncular nucleus of the brain (PubMed:7904822).
CC Expressed predominantly in postmitotic, terminally differentiated
CC neurons (PubMed:7904822). Expressed in ganglion cell layer (GCL) of the
CC retina (PubMed:7691107, PubMed:23805044). {ECO:0000269|PubMed:17668438,
CC ECO:0000269|PubMed:21875655, ECO:0000269|PubMed:23805044,
CC ECO:0000269|PubMed:7691107, ECO:0000269|PubMed:7904822}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in the dorsal root ganglion
CC neurons at 10.5 dpc, the expression increases at least until 15.5 dpc
CC (PubMed:22326227). Expressed in the developing ganglion cell layer of
CC the retina at 12.5, 13.5 and 16.5 dpc (PubMed:8632990). Expressed in
CC the outer margin of the retina at 15.5 dpc (PubMed:10414983). Expressed
CC in embryonic heart from 13.5 dpc until birth (at protein level)
CC (PubMed:18368538). Expressed in the developing spinal cord from 13 dpc
CC until postnatal day 1 (PubMed:8290353, PubMed:8537352). Expressed in
CC retinal ganglion cells (RGC) at 13.5 dpc, peaks at 15.5 dpc, declining
CC later in development (PubMed:8637595). {ECO:0000269|PubMed:10414983,
CC ECO:0000269|PubMed:18368538, ECO:0000269|PubMed:22326227,
CC ECO:0000269|PubMed:8290353, ECO:0000269|PubMed:8537352,
CC ECO:0000269|PubMed:8632990, ECO:0000269|PubMed:8637595}.
CC -!- INDUCTION: Up-regulated by the osteoclast differentiation factor
CC TNFSF11 (PubMed:17668438). Down-regulated upon neuronal differentiation
CC (PubMed:8995448). Down-regulated in presence of retinoic acid
CC (PubMed:7904822). Down-regulated by dibutyryl cyclic AMP
CC (PubMed:8065921). {ECO:0000269|PubMed:17668438,
CC ECO:0000269|PubMed:7904822, ECO:0000269|PubMed:8065921,
CC ECO:0000269|PubMed:8995448}.
CC -!- DOMAIN: The N-terminal transcriptional activation region is sufficient
CC to induce transcriptional activity. {ECO:0000269|PubMed:15733064,
CC ECO:0000269|PubMed:8995448}.
CC -!- DOMAIN: The POU-specific domain and POU homeodomain regions are
CC necessary for DNA-binding activity and transcriptional repression.
CC {ECO:0000269|PubMed:15733064, ECO:0000269|PubMed:8995448}.
CC -!- DOMAIN: The polyhistidine motif acts as a targeting signal to nuclear
CC speckles. {ECO:0000250|UniProtKB:Q12837}.
CC -!- DISRUPTION PHENOTYPE: Mice develop to adulthood and are fertile
CC (PubMed:8637595). Show a reduction in the number of retinal ganglion
CC cells (RGC) and a thinner optic nerve compared to wild-type mice
CC (PubMed:8637595, PubMed:8632990, PubMed:10357904). Show RGC axon
CC pathfinding alterations along the central visual pathways
CC (PubMed:10357904, PubMed:11163266). Show an alteration in the
CC expression levels for several genes involved in the differentiation of
CC RGCs (PubMed:24643061, PubMed:25775587). Display an increase in DLX1
CC and DLX2 mRNA expression in the embryonic retina, especially in the
CC ganglion cell layer (PubMed:21875655). {ECO:0000269|PubMed:10357904,
CC ECO:0000269|PubMed:11163266, ECO:0000269|PubMed:21875655,
CC ECO:0000269|PubMed:24643061, ECO:0000269|PubMed:25775587,
CC ECO:0000269|PubMed:8632990, ECO:0000269|PubMed:8637595}.
CC -!- SIMILARITY: Belongs to the POU transcription factor family. Class-4
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; S68377; AAC60672.1; -; mRNA.
DR EMBL; AK087546; BAC39921.1; -; mRNA.
DR EMBL; S69351; AAB30578.1; -; Genomic_DNA.
DR CCDS; CCDS22429.1; -. [Q63934-1]
DR RefSeq; NP_620394.2; NM_138944.2. [Q63934-1]
DR AlphaFoldDB; Q63934; -.
DR SMR; Q63934; -.
DR BioGRID; 202311; 4.
DR IntAct; Q63934; 3.
DR STRING; 10090.ENSMUSP00000034115; -.
DR iPTMnet; Q63934; -.
DR PhosphoSitePlus; Q63934; -.
DR PaxDb; Q63934; -.
DR PRIDE; Q63934; -.
DR ProteomicsDB; 289859; -. [Q63934-1]
DR ProteomicsDB; 289860; -. [Q63934-2]
DR Antibodypedia; 16443; 168 antibodies from 24 providers.
DR DNASU; 18997; -.
DR Ensembl; ENSMUST00000034115; ENSMUSP00000034115; ENSMUSG00000031688. [Q63934-1]
DR GeneID; 18997; -.
DR KEGG; mmu:18997; -.
DR UCSC; uc009mhy.1; mouse. [Q63934-1]
DR CTD; 5458; -.
DR MGI; MGI:102524; Pou4f2.
DR VEuPathDB; HostDB:ENSMUSG00000031688; -.
DR eggNOG; KOG1168; Eukaryota.
DR GeneTree; ENSGT00940000160339; -.
DR HOGENOM; CLU_013065_0_0_1; -.
DR InParanoid; Q63934; -.
DR OMA; THAPHMA; -.
DR OrthoDB; 929123at2759; -.
DR PhylomeDB; Q63934; -.
DR TreeFam; TF316413; -.
DR Reactome; R-MMU-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR BioGRID-ORCS; 18997; 6 hits in 72 CRISPR screens.
DR PRO; PR:Q63934; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q63934; protein.
DR Bgee; ENSMUSG00000031688; Expressed in lumbar dorsal root ganglion and 24 other tissues.
DR Genevisible; Q63934; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0000791; C:euchromatin; IDA:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:ARUK-UCL.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0048675; P:axon extension; IGI:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
DR GO; GO:0071453; P:cellular response to oxygen levels; ISO:MGI.
DR GO; GO:1990791; P:dorsal root ganglion development; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IGI:ARUK-UCL.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; ISS:UniProtKB.
DR GO; GO:1904178; P:negative regulation of adipose tissue development; IMP:BHF-UCL.
DR GO; GO:1902870; P:negative regulation of amacrine cell differentiation; IMP:UniProtKB.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IGI:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP:UniProtKB.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IMP:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:UniProtKB.
DR GO; GO:0043068; P:positive regulation of programmed cell death; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0090259; P:regulation of retinal ganglion cell axon guidance; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IMP:MGI.
DR GO; GO:0007605; P:sensory perception of sound; IGI:MGI.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
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; IPR000327; POU_dom.
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 1: Evidence at protein level;
KW Activator; Alternative splicing; Apoptosis; Cytoplasm;
KW Developmental protein; Differentiation; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..411
FT /note="POU domain, class 4, transcription factor 2"
FT /id="PRO_0000100741"
FT DOMAIN 252..329
FT /note="POU-specific"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00530"
FT DNA_BIND 347..406
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 29..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 93..239
FT /note="Required for transcriptional activation"
FT /evidence="ECO:0000269|PubMed:15733064"
FT REGION 154..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..411
FT /note="Required for DNA-binding and transcriptional
FT repression"
FT /evidence="ECO:0000269|PubMed:15733064,
FT ECO:0000269|PubMed:7852360"
FT MOTIF 112..121
FT /note="POU-IV box"
FT MOTIF 173..187
FT /note="Nuclear speckle targeting signal"
FT /evidence="ECO:0000250|UniProtKB:Q12837"
FT COMPBIAS 30..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..81
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..185
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..98
FT /note="MMMMSLNSKQAFSMPHAGSLHVEPKYSALHSASPGSSAPAAPSASSPSSSSN
FT AGGGGGGGGGGGGGGRSSSSSSSGSGGSGGGGGSEAMRRACLPTPP -> MCAFYLQLQ
FT (in isoform 2)"
FT /id="VSP_058838"
FT MUTAGEN 368
FT /note="I->V: Stimulates induction of neurite outgrowth and
FT expression of synaptic genes. Abolishes the inhibitory
FT effect on basal transcription and on gene activation by
FT POU4F1."
FT /evidence="ECO:0000269|PubMed:8662774,
FT ECO:0000269|PubMed:8972215, ECO:0000269|PubMed:8995448,
FT ECO:0000269|PubMed:9261145, ECO:0000269|PubMed:9694219"
FT CONFLICT 404..405
FT /note="RM -> KV (in Ref. 3; AAB30578)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 411 AA; 43173 MW; 97EA816F7DEC07C9 CRC64;
MMMMSLNSKQ AFSMPHAGSL HVEPKYSALH SASPGSSAPA APSASSPSSS SNAGGGGGGG
GGGGGGGRSS SSSSSGSGGS GGGGGSEAMR RACLPTPPSN IFGGLDESLL ARAEALAAVD
IVSQSKSHHH HPPHHSPFKP DATYHTMNTI PCTSAASSSS VPISHPSALA GTHHHHHHHH
HHHHQPHQAL EGELLEHLSP GLALGAMAGP DGTVVSTPAH APHMATMNPM HQAALSMAHA
HGLPSHMGCM SDVDADPRDL EAFAERFKQR RIKLGVTQAD VGSALANLKI PGVGSLSQST
ICRFESLTLS HNNMIALKPI LQAWLEEAEK SHREKLTKPE LFNGAEKKRK RTSIAAPEKR
SLEAYFAIQP RPSSEKIAAI AEKLDLKKNV VRVWFCNQRQ KQKRMKYSAG I
