ID   PO3F4_HUMAN             Reviewed;         361 AA.
AC   P49335; B2RC71; Q5H9G9; Q99410;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   24-JAN-2024, entry version 203.
DE   RecName: Full=POU domain, class 3, transcription factor 4;
DE   AltName: Full=Brain-specific homeobox/POU domain protein 4;
DE            Short=Brain-4;
DE            Short=Brn-4;
DE   AltName: Full=Octamer-binding protein 9;
DE            Short=Oct-9;
DE   AltName: Full=Octamer-binding transcription factor 9;
DE            Short=OTF-9;
GN   Name=POU3F4; Synonyms=BRN4, OTF9;
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 [MRNA], VARIANT ALA-237, AND VARIANTS DFNX2 TRP-317 AND
RP   GLU-334.
RC   TISSUE=Brain;
RX   PubMed=7839145; DOI=10.1126/science.7839145;
RA   de Kok Y.J.M., van der Maarel S.M., Bitner-Glindzicz M., Huber I.,
RA   Monaco A.P., Malcolm S., Pembrey M.E., Ropers H.-H., Cremers F.P.M.;
RT   "Association between X-linked mixed deafness and mutations in the POU
RT   domain gene POU3F4.";
RL   Science 267:685-688(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-237.
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   INTERACTION WITH HNRNPU.
RX   PubMed=9105675; DOI=10.1016/s0169-328x(96)00238-0;
RA   Malik K.F., Jaffe H., Brady J., Young W.S. III;
RT   "The class III POU factor Brn-4 interacts with other class III POU factors
RT   and the heterogeneous nuclear ribonucleoprotein U.";
RL   Brain Res. Mol. Brain Res. 45:99-107(1997).
RN   [6]
RP   VARIANT DFNX2 VAL-312.
RX   PubMed=7581392; DOI=10.1093/hmg/4.8.1467;
RA   Bitner-Glindzicz M., Turnpenny P., Hoeglund P., Keaearieainen H.,
RA   Sankila E.-M., van der Maarel S.M., de Kok Y.J.M., Ropers H.-H.,
RA   Cremers F.P.M., Pembrey M., Malcolm S.;
RT   "Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-
RT   linked deafness, DFN3.";
RL   Hum. Mol. Genet. 4:1467-1469(1995).
RN   [7]
RP   VARIANTS DFNX2 GLY-323 AND SER-330.
RX   PubMed=9298820;
RX   DOI=10.1002/(sici)1098-1004(1997)10:3<207::aid-humu5>3.0.co;2-f;
RA   de Kok Y.J.M., Cremers C.W.R.J., Ropers H.-H., Cremers F.P.M.;
RT   "The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic
RT   cases: identification of a somatic mosaicism for a POU3F4 missense
RT   mutation.";
RL   Hum. Mutat. 10:207-211(1997).
RN   [8]
RP   VARIANT DFNX2 201-PHE-LYS-202 DEL.
RX   PubMed=9778298; DOI=10.1097/00005537-199810000-00022;
RA   Hagiwara H., Tamagawa Y., Kitamura K., Kodera K.;
RT   "A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed
RT   deafness (DFN3).";
RL   Laryngoscope 108:1544-1547(1998).
CC   -!- FUNCTION: Probable transcription factor which exert its primary action
CC       widely during early neural development and in a very limited set of
CC       neurons in the mature brain.
CC   -!- SUBUNIT: Interacts with HNRNPU. {ECO:0000269|PubMed:9105675}.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Brain specific.
CC   -!- DISEASE: Deafness, X-linked, 2 (DFNX2) [MIM:304400]: A form of deafness
CC       characterized by both conductive hearing loss resulting from stapes
CC       (perilymphatic gusher) fixation, and progressive sensorineural
CC       deafness. {ECO:0000269|PubMed:7581392, ECO:0000269|PubMed:7839145,
CC       ECO:0000269|PubMed:9298820, ECO:0000269|PubMed:9778298}. 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-3
CC       subfamily. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page;
CC       URL="https://hereditaryhearingloss.org/xlinked-genes";
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DR   EMBL; X82324; CAA57767.1; -; mRNA.
DR   EMBL; AK314967; BAG37468.1; -; mRNA.
DR   EMBL; Z82170; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471104; EAW98577.1; -; Genomic_DNA.
DR   CCDS; CCDS14450.1; -.
DR   PIR; A55557; A55557.
DR   RefSeq; NP_000298.3; NM_000307.4.
DR   AlphaFoldDB; P49335; -.
DR   SMR; P49335; -.
DR   BioGRID; 111452; 11.
DR   STRING; 9606.ENSP00000495996; -.
DR   iPTMnet; P49335; -.
DR   PhosphoSitePlus; P49335; -.
DR   BioMuta; POU3F4; -.
DR   DMDM; 77416874; -.
DR   jPOST; P49335; -.
DR   MassIVE; P49335; -.
DR   MaxQB; P49335; -.
DR   PaxDb; 9606-ENSP00000362296; -.
DR   PeptideAtlas; P49335; -.
DR   ProteomicsDB; 55990; -.
DR   DNASU; 5456; -.
DR   GeneID; 5456; -.
DR   KEGG; hsa:5456; -.
DR   UCSC; uc004eeg.3; human.
DR   AGR; HGNC:9217; -.
DR   CTD; 5456; -.
DR   DisGeNET; 5456; -.
DR   GeneCards; POU3F4; -.
DR   GeneReviews; POU3F4; -.
DR   HGNC; HGNC:9217; POU3F4.
DR   MalaCards; POU3F4; -.
DR   MIM; 300039; gene.
DR   MIM; 304400; phenotype.
DR   neXtProt; NX_P49335; -.
DR   Orphanet; 90641; Rare mitochondrial non-syndromic sensorineural deafness.
DR   Orphanet; 1435; Xq21 microdeletion syndrome.
DR   PharmGKB; PA33541; -.
DR   eggNOG; KOG3802; Eukaryota.
DR   HOGENOM; CLU_013065_1_2_1; -.
DR   InParanoid; P49335; -.
DR   OrthoDB; 4250502at2759; -.
DR   PhylomeDB; P49335; -.
DR   TreeFam; TF316413; -.
DR   PathwayCommons; P49335; -.
DR   SignaLink; P49335; -.
DR   SIGNOR; P49335; -.
DR   BioGRID-ORCS; 5456; 13 hits in 790 CRISPR screens.
DR   ChiTaRS; POU3F4; human.
DR   GeneWiki; POU3F4; -.
DR   GenomeRNAi; 5456; -.
DR   Pharos; P49335; Tbio.
DR   PRO; PR:P49335; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; P49335; Protein.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR   GO; GO:0007420; P:brain development; IEA:InterPro.
DR   GO; GO:0090103; P:cochlea morphogenesis; ISS:UniProtKB.
DR   GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; ISS:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   Gene3D; 1.10.260.40; lambda repressor-like DNA-binding domains; 1.
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   InterPro; IPR016362; TF_POU_3.
DR   PANTHER; PTHR11636; POU DOMAIN; 1.
DR   PANTHER; PTHR11636:SF83; POU DOMAIN, CLASS 3, TRANSCRIPTION FACTOR 4; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF00157; Pou; 1.
DR   PIRSF; PIRSF002629; Transcription_factor_POU; 1.
DR   PRINTS; PR00028; POUDOMAIN.
DR   SMART; SM00389; HOX; 1.
DR   SMART; SM00352; POU; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   SUPFAM; SSF47413; lambda repressor-like DNA-binding domains; 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.
DR   Genevisible; P49335; HS.
PE   1: Evidence at protein level;
KW   Deafness; Disease variant; DNA-binding; Homeobox; Non-syndromic deafness;
KW   Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..361
FT                   /note="POU domain, class 3, transcription factor 4"
FT                   /id="PRO_0000100732"
FT   DOMAIN          186..260
FT                   /note="POU-specific"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00530"
FT   DNA_BIND        278..337
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          99..131
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          144..192
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        110..131
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        167..192
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         265
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P20265"
FT   VARIANT         201..202
FT                   /note="Missing (in DFNX2)"
FT                   /evidence="ECO:0000269|PubMed:9778298"
FT                   /id="VAR_015261"
FT   VARIANT         237
FT                   /note="G -> A (in dbSNP:rs5921979)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:7839145"
FT                   /id="VAR_067431"
FT   VARIANT         312
FT                   /note="A -> V (in DFNX2; dbSNP:rs387906502)"
FT                   /evidence="ECO:0000269|PubMed:7581392"
FT                   /id="VAR_003782"
FT   VARIANT         317
FT                   /note="L -> W (in DFNX2; dbSNP:rs104894921)"
FT                   /evidence="ECO:0000269|PubMed:7839145"
FT                   /id="VAR_003783"
FT   VARIANT         323
FT                   /note="R -> G (in DFNX2; somatic mosaicism in 50% of the
FT                   peripheral blood lymphocytes; dbSNP:rs104894924)"
FT                   /evidence="ECO:0000269|PubMed:9298820"
FT                   /id="VAR_003784"
FT   VARIANT         330
FT                   /note="R -> S (in DFNX2; dbSNP:rs104894923)"
FT                   /evidence="ECO:0000269|PubMed:9298820"
FT                   /id="VAR_003785"
FT   VARIANT         334
FT                   /note="K -> E (in DFNX2; dbSNP:rs104894922)"
FT                   /evidence="ECO:0000269|PubMed:7839145"
FT                   /id="VAR_003786"
SQ   SEQUENCE   361 AA;  39427 MW;  DE30602CFAC4683A CRC64;
     MATAASNPYS ILSSTSLVHA DSAGMQQGSP FRNPQKLLQS DYLQGVPSNG HPLGHHWVTS
     LSDGGPWSST LATSPLDQQD VKPGREDLQL GAIIHHRSPH VAHHSPHTNH PNAWGASPAP
     NPSITSSGQP LNVYSQPGFT VSGMLEHGGL TPPPAAASAQ SLHPVLREPP DHGELGSHHC
     QDHSDEETPT SDELEQFAKQ FKQRRIKLGF TQADVGLALG TLYGNVFSQT TICRFEGLQL
     SFKNMCKLKP LLNKWLEEAD SSTGSPTSID KIAAQGRKRK KRTSIEVSVK GVLETHFLKC
     PKPAAQEISS LADSLQLEKE VVRVWFCNRR QKEKRMTPPG DQQPHEVYSH TVKTDTSCHD
     L
//