PO4F3_HUMAN
ID PO4F3_HUMAN Reviewed; 338 AA.
AC Q15319; O60557; Q2M3F8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=POU domain, class 4, transcription factor 3;
DE AltName: Full=Brain-specific homeobox/POU domain protein 3C;
DE Short=Brain-3C;
DE Short=Brn-3C;
GN Name=POU4F3; Synonyms=BRN3C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=7623109; DOI=10.1523/jneurosci.15-07-04762.1995;
RA Xiang M., Zhou L.-J., Macke J.P., Yoshioka T., Hendry S.H., Eddy R.L.,
RA Shows T.B., Nathans J.;
RT "The Brn-3 family of POU-domain factors: primary structure, binding
RT specificity, and expression in subsets of retinal ganglion cells and
RT somatosensory neurons.";
RL J. Neurosci. 15:4762-4785(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INVOLVEMENT IN
RP DFNA15.
RX PubMed=9506947; DOI=10.1126/science.279.5358.1950;
RA Vahava O., Morell R., Lynch E.D., Weiss S., Kagan M.E., Ahituv N.,
RA Morrow J.E., Lee M.K., Skvorak A.B., Morton C.C., Blumenfeld A.,
RA Frydman M., Friedman T.B., King M.-C., Avraham K.B.;
RT "Mutation in transcription factor POU4F3 associated with inherited
RT progressive hearing loss in humans.";
RL Science 279:1950-1954(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP VARIANT DFNA15 PHE-289.
RX PubMed=18347256; DOI=10.1001/archotol.134.3.294;
RA Pauw R.J., van Drunen F.J., Collin R.W., Huygen P.L., Kremer H.,
RA Cremers C.W.;
RT "Audiometric characteristics of a Dutch family linked to DFNA15 with a
RT novel mutation (p.L289F) in POU4F3.";
RL Arch. Otolaryngol. Head Neck Surg. 134:294-300(2008).
RN [5]
RP VARIANTS DFNA15 PRO-223 AND PHE-289, CHARACTERIZATION OF VARIANTS DFNA15
RP PRO-223 AND PHE-289, FUNCTION, DNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=18228599; DOI=10.1002/humu.20693;
RA Collin R.W.J., Chellappa R., Pauw R.-J., Vriend G., Oostrik J.,
RA van Drunen W., Huygen P.L., Admiraal R., Hoefsloot L.H., Cremers F.P.M.,
RA Xiang M., Cremers C.W.R.J., Kremer H.;
RT "Missense mutations in POU4F3 cause autosomal dominant hearing impairment
RT DFNA15 and affect subcellular localization and DNA binding.";
RL Hum. Mutat. 29:545-554(2008).
RN [6]
RP VARIANT DFNA15 LYS-232.
RX PubMed=22938506; DOI=10.1186/1750-1172-7-60;
RA Baek J.I., Oh S.K., Kim D.B., Choi S.Y., Kim U.K., Lee K.Y., Lee S.H.;
RT "Targeted massive parallel sequencing: the effective detection of novel
RT causative mutations associated with hearing loss in small families.";
RL Orphanet J. Rare Dis. 7:60-60(2012).
RN [7]
RP VARIANT DFNA15 LYS-326.
RX PubMed=24260153; DOI=10.1371/journal.pone.0079063;
RA Kim H.J., Won H.H., Park K.J., Hong S.H., Ki C.S., Cho S.S., Venselaar H.,
RA Vriend G., Kim J.W.;
RT "SNP linkage analysis and whole exome sequencing identify a novel POU4F3
RT mutation in autosomal dominant late-onset nonsyndromic hearing loss
RT (DFNA15).";
RL PLoS ONE 8:E79063-E79063(2013).
RN [8]
RP VARIANT DFNA15 ARG-164.
RX PubMed=25388789; DOI=10.1186/s12967-014-0311-1;
RA Wei Q., Zhu H., Qian X., Chen Z., Yao J., Lu Y., Cao X., Xing G.;
RT "Targeted genomic capture and massively parallel sequencing to identify
RT novel variants causing Chinese hereditary hearing loss.";
RL J. Transl. Med. 12:311-311(2014).
RN [9]
RP VARIANTS DFNA15 VAL-64; 143-GLN--HIS-338 DEL; 192-GLU--HIS-338 DEL;
RP TYR-194; LEU-222; TYR-240; VAL-281; LEU-299 AND 326-ARG--HIS-338 DEL.
RX PubMed=28545070; DOI=10.1371/journal.pone.0177636;
RA Kitano T., Miyagawa M., Nishio S.Y., Moteki H., Oda K., Ohyama K.,
RA Miyazaki H., Hidaka H., Nakamura K.I., Murata T., Matsuoka R., Ohta Y.,
RA Nishiyama N., Kumakawa K., Furutate S., Iwasaki S., Yamada T., Ohta Y.,
RA Uehara N., Noguchi Y., Usami S.I.;
RT "POU4F3 mutation screening in Japanese hearing loss patients: Massively
RT parallel DNA sequencing-based analysis identified novel variants associated
RT with autosomal dominant hearing loss.";
RL PLoS ONE 12:E0177636-E0177636(2017).
RN [10]
RP VARIANT DFNA15 GLU-328, CHARACTERIZATION OF VARIANT DFNA15 GLU-328, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28790396; DOI=10.1038/s41598-017-08236-y;
RA Lin Y.H., Lin Y.H., Lu Y.C., Liu T.C., Chen C.Y., Hsu C.J., Chen P.L.,
RA Wu C.C.;
RT "A novel missense variant in the nuclear localization signal of POU4F3
RT causes autosomal dominant non-syndromic hearing loss.";
RL Sci. Rep. 7:7551-7551(2017).
CC -!- FUNCTION: Acts as a transcriptional activator (PubMed:18228599). Acts
CC by binding to sequences related to the consensus octamer motif 5'-
CC ATGCAAAT-3' in the regulatory regions of its target genes
CC (PubMed:18228599). Involved in the auditory system development,
CC required for terminal differentiation of hair cells in the inner ear
CC (By similarity). {ECO:0000250|UniProtKB:Q63955,
CC ECO:0000269|PubMed:18228599}.
CC -!- SUBUNIT: Interacts with ISL1. {ECO:0000250|UniProtKB:Q63955}.
CC -!- INTERACTION:
CC Q15319; Q9H596: DUSP21; NbExp=3; IntAct=EBI-12033574, EBI-7357329;
CC Q15319; Q08379: GOLGA2; NbExp=3; IntAct=EBI-12033574, EBI-618309;
CC Q15319; Q15323: KRT31; NbExp=3; IntAct=EBI-12033574, EBI-948001;
CC Q15319; P0CG21: NHLRC4; NbExp=3; IntAct=EBI-12033574, EBI-12868744;
CC Q15319; O15496: PLA2G10; NbExp=3; IntAct=EBI-12033574, EBI-726466;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18228599,
CC ECO:0000269|PubMed:28790396}. Cytoplasm {ECO:0000269|PubMed:28790396}.
CC Note=Preferentially localized in the nucleus.
CC {ECO:0000269|PubMed:28790396}.
CC -!- TISSUE SPECIFICITY: Brain. Seems to be specific to the retina.
CC {ECO:0000269|PubMed:7623109, ECO:0000269|PubMed:9506947}.
CC -!- DISEASE: Deafness, autosomal dominant, 15 (DFNA15) [MIM:602459]: A form
CC of non-syndromic hearing loss with variable phenotype in terms of age
CC at onset, levels of progression, and shape of audiograms.
CC {ECO:0000269|PubMed:18228599, ECO:0000269|PubMed:18347256,
CC ECO:0000269|PubMed:22938506, ECO:0000269|PubMed:24260153,
CC ECO:0000269|PubMed:25388789, ECO:0000269|PubMed:28545070,
CC ECO:0000269|PubMed:28790396, ECO:0000269|PubMed:9506947}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the POU transcription factor family. Class-4
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page;
CC URL="https://hereditaryhearingloss.org/dominant-genes";
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DR EMBL; U10061; AAA57160.1; -; Genomic_DNA.
DR EMBL; U10060; AAA57160.1; JOINED; Genomic_DNA.
DR EMBL; AF044575; AAC06203.1; -; Genomic_DNA.
DR EMBL; BC104923; AAI04924.1; -; mRNA.
DR EMBL; BC112207; AAI12208.1; -; mRNA.
DR CCDS; CCDS4281.1; -.
DR RefSeq; NP_002691.1; NM_002700.2.
DR AlphaFoldDB; Q15319; -.
DR SMR; Q15319; -.
DR BioGRID; 111455; 10.
DR IntAct; Q15319; 5.
DR STRING; 9606.ENSP00000230732; -.
DR iPTMnet; Q15319; -.
DR PhosphoSitePlus; Q15319; -.
DR BioMuta; POU4F3; -.
DR DMDM; 2495302; -.
DR MassIVE; Q15319; -.
DR PaxDb; Q15319; -.
DR PeptideAtlas; Q15319; -.
DR PRIDE; Q15319; -.
DR Antibodypedia; 15803; 293 antibodies from 31 providers.
DR DNASU; 5459; -.
DR Ensembl; ENST00000646991.2; ENSP00000495718.1; ENSG00000091010.6.
DR GeneID; 5459; -.
DR KEGG; hsa:5459; -.
DR MANE-Select; ENST00000646991.2; ENSP00000495718.1; NM_002700.3; NP_002691.1.
DR UCSC; uc003loa.2; human.
DR CTD; 5459; -.
DR DisGeNET; 5459; -.
DR GeneCards; POU4F3; -.
DR GeneReviews; POU4F3; -.
DR HGNC; HGNC:9220; POU4F3.
DR HPA; ENSG00000091010; Not detected.
DR MalaCards; POU4F3; -.
DR MIM; 602459; phenotype.
DR MIM; 602460; gene.
DR neXtProt; NX_Q15319; -.
DR OpenTargets; ENSG00000091010; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA33544; -.
DR VEuPathDB; HostDB:ENSG00000091010; -.
DR eggNOG; KOG1168; Eukaryota.
DR GeneTree; ENSGT00940000160880; -.
DR HOGENOM; CLU_013065_0_0_1; -.
DR InParanoid; Q15319; -.
DR OMA; MKYSAAH; -.
DR OrthoDB; 929123at2759; -.
DR PhylomeDB; Q15319; -.
DR TreeFam; TF316413; -.
DR PathwayCommons; Q15319; -.
DR SignaLink; Q15319; -.
DR SIGNOR; Q15319; -.
DR BioGRID-ORCS; 5459; 10 hits in 1083 CRISPR screens.
DR GeneWiki; POU4F3; -.
DR GenomeRNAi; 5459; -.
DR Pharos; Q15319; Tbio.
DR PRO; PR:Q15319; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q15319; protein.
DR Bgee; ENSG00000091010; Expressed in smooth muscle tissue and 3 other tissues.
DR Genevisible; Q15319; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR GO; GO:0021562; P:vestibulocochlear nerve development; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
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; IPR032961; POU4F3.
DR InterPro; IPR000327; POU_dom.
DR PANTHER; PTHR11636:SF43; PTHR11636:SF43; 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 1: Evidence at protein level;
KW Activator; Cytoplasm; Deafness; Differentiation; Disease variant;
KW DNA-binding; Homeobox; Non-syndromic deafness; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..338
FT /note="POU domain, class 4, transcription factor 3"
FT /id="PRO_0000100742"
FT DOMAIN 179..256
FT /note="POU-specific"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00530"
FT DNA_BIND 274..333
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT MOTIF 56..65
FT /note="POU-IV box"
FT VARIANT 64
FT /note="D -> V (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079859"
FT VARIANT 143..338
FT /note="Missing (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079860"
FT VARIANT 164
FT /note="P -> R (in DFNA15; unknown pathological
FT significance; dbSNP:rs367737951)"
FT /evidence="ECO:0000269|PubMed:25388789"
FT /id="VAR_079861"
FT VARIANT 192..338
FT /note="Missing (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079862"
FT VARIANT 194
FT /note="F -> Y (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079863"
FT VARIANT 222
FT /note="S -> L (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079864"
FT VARIANT 223
FT /note="L -> P (in DFNA15; decreases subcellular
FT localization in the nucleus; decreases DNA-binding
FT activity; decreases transcriptional activity;
FT dbSNP:rs121909057)"
FT /evidence="ECO:0000269|PubMed:18228599"
FT /id="VAR_045682"
FT VARIANT 232
FT /note="E -> K (in DFNA15; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:22938506"
FT /id="VAR_079865"
FT VARIANT 240
FT /note="N -> Y (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079866"
FT VARIANT 281
FT /note="I -> V (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079867"
FT VARIANT 289
FT /note="L -> F (in DFNA15; decreases subcellular
FT localization in the nucleus; decreases DNA-binding
FT activity; decreases transcriptional activity;
FT dbSNP:rs121909056)"
FT /evidence="ECO:0000269|PubMed:18228599,
FT ECO:0000269|PubMed:18347256"
FT /id="VAR_045683"
FT VARIANT 299
FT /note="P -> L (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079868"
FT VARIANT 326..338
FT /note="Missing (in DFNA15)"
FT /evidence="ECO:0000269|PubMed:28545070"
FT /id="VAR_079869"
FT VARIANT 326
FT /note="R -> K (in DFNA15; dbSNP:rs398123070)"
FT /evidence="ECO:0000269|PubMed:24260153"
FT /id="VAR_079870"
FT VARIANT 328
FT /note="K -> E (in DFNA15; decreases subcellular
FT localization in the nucleus; dbSNP:rs1339291105)"
FT /evidence="ECO:0000269|PubMed:28790396"
FT /id="VAR_079871"
FT CONFLICT 67
FT /note="S -> F (in Ref. 2; AAC06203)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 338 AA; 37052 MW; E2D2EEB25B299A5C CRC64;
MMAMNSKQPF GMHPVLQEPK FSSLHSGSEA MRRVCLPAPQ LQGNIFGSFD ESLLARAEAL
AAVDIVSHGK NHPFKPDATY HTMSSVPCTS TSSTVPISHP AALTSHPHHA VHQGLEGDLL
EHISPTLSVS GLGAPEHSVM PAQIHPHHLG AMGHLHQAMG MSHPHTVAPH SAMPACLSDV
ESDPRELEAF AERFKQRRIK LGVTQADVGA ALANLKIPGV GSLSQSTICR FESLTLSHNN
MIALKPVLQA WLEEAEAAYR EKNSKPELFN GSERKRKRTS IAAPEKRSLE AYFAIQPRPS
SEKIAAIAEK LDLKKNVVRV WFCNQRQKQK RMKYSAVH
