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";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 Genevisible; P49335; HS.
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.
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
//
