P49335 (PO3F4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
POU domain, class 3, transcription factor 4

Alternative name(s):
Brain-specific homeobox/POU domain protein 4
Short name=Brain-4
Short name=Brn-4
Octamer-binding protein 9
Short name=Oct-9
Octamer-binding transcription factor 9
Short name=OTF-9

Gene names

Name:	POU3F4
Synonyms:	BRN4, OTF9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	361 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain.
Subcellular location	Nucleus.
Tissue specificity	Brain specific.
Involvement in disease	Deafness, X-linked, 2 (DFNX2) [MIM:304400]: A form of deafness characterized by both conductive hearing loss resulting from stapes (perilymphatic gusher) fixation, and progressive sensorineural deafness. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the POU transcription factor family. Class-3 subfamily. Contains 1 homeobox DNA-binding domain. Contains 1 POU-specific domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Homeobox
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cochlea morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB forebrain neuron differentiation Inferred from electronic annotation. Source: Compara negative regulation of mesenchymal cell apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB sensory perception of sound Traceable author statement Ref.1. Source: ProtInc transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	AT DNA binding Inferred from electronic annotation. Source: Compara double-stranded DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 361	361	POU domain, class 3, transcription factor 4		PRO_0000100732
Regions
	Domain	186 – 260	75	POU-specific
	DNA binding	278 – 337	60	Homeobox
Natural variations
	Natural variant	201 – 202	2	Missing in DFNX2.		VAR_015261
	Natural variant	237	1	G → A. Ref.1 Ref.2 Corresponds to variant rs5921979 [ dbSNP | Ensembl ].		VAR_067431
	Natural variant	312	1	A → V in DFNX2. Ref.5		VAR_003782
	Natural variant	317	1	L → W in DFNX2. Ref.1		VAR_003783
	Natural variant	323	1	R → G in DFNX2; somatic mosaicism in 50% of the peripheral blood lymphocytes. Ref.6		VAR_003784
	Natural variant	330	1	R → S in DFNX2. Ref.6		VAR_003785
	Natural variant	334	1	K → E in DFNX2. Ref.1		VAR_003786

Sequences

	Sequence		Length	Mass (Da)
	P49335 [UniParc]. Last modified October 11, 2005. Version 2. Checksum: DE30602CFAC4683A	FASTA	361	39,427
	10 20 30 40 50 60 MATAASNPYS ILSSTSLVHA DSAGMQQGSP FRNPQKLLQS DYLQGVPSNG HPLGHHWVTS 70 80 90 100 110 120 LSDGGPWSST LATSPLDQQD VKPGREDLQL GAIIHHRSPH VAHHSPHTNH PNAWGASPAP 130 140 150 160 170 180 NPSITSSGQP LNVYSQPGFT VSGMLEHGGL TPPPAAASAQ SLHPVLREPP DHGELGSHHC 190 200 210 220 230 240 QDHSDEETPT SDELEQFAKQ FKQRRIKLGF TQADVGLALG TLYGNVFSQT TICRFEGLQL 250 260 270 280 290 300 SFKNMCKLKP LLNKWLEEAD SSTGSPTSID KIAAQGRKRK KRTSIEVSVK GVLETHFLKC 310 320 330 340 350 360 PKPAAQEISS LADSLQLEKE VVRVWFCNRR QKEKRMTPPG DQQPHEVYSH TVKTDTSCHD L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4." de Kok Y.J.M., van der Maarel S.M., Bitner-Glindzicz M., Huber I., Monaco A.P., Malcolm S., Pembrey M.E., Ropers H.-H., Cremers F.P.M. Science 267:685-688(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-237; DFNX2 TRP-317 AND GLU-334. Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-237. Tissue: Brain.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3." Bitner-Glindzicz M., Turnpenny P., Hoeglund P., Keaearieainen H., Sankila E.-M., van der Maarel S.M., de Kok Y.J.M., Ropers H.-H., Cremers F.P.M., Pembrey M., Malcolm S. Hum. Mol. Genet. 4:1467-1469(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNX2 VAL-312.
[6]	"The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases: identification of a somatic mosaicism for a POU3F4 missense mutation." de Kok Y.J.M., Cremers C.W.R.J., Ropers H.-H., Cremers F.P.M. Hum. Mutat. 10:207-211(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS DFNX2 GLY-323 AND SER-330.
[7]	"A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3)." Hagiwara H., Tamagawa Y., Kitamura K., Kodera K. Laryngoscope 108:1544-1547(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT DFNX2 201-PHE-LYS-202 DEL.
+	Additional computationally mapped references.

Web resources

Hereditary hearing loss homepage

Gene page

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X82324 mRNA. Translation: CAA57767.1. AK314967 mRNA. Translation: BAG37468.1. Z82170 Genomic DNA. Translation: CAI42602.1. CH471104 Genomic DNA. Translation: EAW98577.1.
IPI	IPI00026790.
PIR	A55557.
RefSeq	NP_000298.3. NM_000307.4.
UniGene	Hs.2229.
3D structure databases
ProteinModelPortal	P49335.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000362296.
PTM databases
PhosphoSite	P49335.
Polymorphism databases
DMDM	77416874.
Proteomic databases
PaxDb	P49335.
PRIDE	P49335.
Protocols and materials databases
DNASU	5456.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373200; ENSP00000362296; ENSG00000196767.
GeneID	5456.
KEGG	hsa:5456.
UCSC	uc004eeg.2. human.
Organism-specific databases
CTD	5456.
GeneCards	GC0XP082763.
H-InvDB	HIX0028415.
HGNC	HGNC:9217. POU3F4.
HPA	HPA031984.
MIM	300039. gene. 304400. phenotype.
neXtProt	NX_P49335.
Orphanet	163988. Developmental delay - deafness, Hildebrand type. 383. Gusher syndrome.
PharmGKB	PA33541.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG261729.
HOGENOM	HOG000116303.
HOVERGEN	HBG053120.
InParanoid	P49335.
KO	K09365.
OMA	VAHHSPH.
OrthoDB	EOG4HDSTS.
PhylomeDB	P49335.
Gene expression databases
Bgee	P49335.
CleanEx	HS_POU3F4.
Genevestigator	P49335.
GermOnline	ENSG00000196767. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit. 1.10.260.40. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR010982. Lambda_DNA-bd_dom. IPR013847. POU. IPR000327. POU_specific. IPR016362. Transcription_factor_POU. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. PF00157. Pou. 1 hit. [Graphical view]
PIRSF	PIRSF002629. Transcription_factor_POU. 1 hit.
PRINTS	PR00028. POUDOMAIN.
SMART	SM00389. HOX. 1 hit. SM00352. POU. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit. SSF47413. Lambda_like_DNA. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. PS00035. POU_1. 1 hit. PS00465. POU_2. 1 hit. PS51179. POU_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5456.
NextBio	21117.
SOURCE	Search...

Entry information

Entry name

PO3F4_HUMAN

Accession

Primary (citable) accession number: P49335
Secondary accession number(s): B2RC71, Q5H9G9, Q99410

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	October 11, 2005
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.