PO3F3_HUMAN
ID PO3F3_HUMAN Reviewed; 500 AA.
AC P20264; P78379; Q4ZG25;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=POU domain, class 3, transcription factor 3 {ECO:0000305};
DE AltName: Full=Brain-specific homeobox/POU domain protein 1;
DE Short=Brain-1;
DE Short=Brn-1;
DE AltName: Full=Octamer-binding protein 8;
DE Short=Oct-8;
DE AltName: Full=Octamer-binding transcription factor 8;
DE Short=OTF-8;
GN Name=POU3F3 {ECO:0000312|HGNC:HGNC:9216}; Synonyms=BRN1, OTF8;
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].
RX PubMed=8703082; DOI=10.1007/bf02338824;
RA Sumiyama K., Washio-Watanabe K., Saitou N., Hayakawa T., Ueda S.;
RT "Class III POU genes: generation of homopolymeric amino acid repeats under
RT GC pressure in mammals.";
RL J. Mol. Evol. 43:170-178(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 332-456.
RC TISSUE=Brain;
RX PubMed=2739723; DOI=10.1038/340035a0;
RA He X., Treacy M.N., Simmons D.M., Ingraham H.A., Swanson L.W.,
RA Rosenfeld M.G.;
RT "Expression of a large family of POU-domain regulatory genes in mammalian
RT brain development.";
RL Nature 340:35-42(1989).
RN [4]
RP INVOLVEMENT IN SNIBFIS, VARIANTS SNIBFIS 63-TYR--GLN-500 DEL;
RP 223-SER--GLN-500 DEL; 331-GLN--LYS-335 DEL; LEU-362; GLY-407; LEU-407;
RP 414-GLU--GLN-500 DEL; 428-CYS--GLN-500 DEL AND SER-456, CHARACTERIZATION OF
RP VARIANTS SNIBFIS 223-SER--GLN-500 DEL; 331-GLN--LYS-335 DEL; LEU-362;
RP GLY-407; LEU-407; 428-CYS--GLN-500 DEL AND SER-456, FUNCTION, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RX PubMed=31303265; DOI=10.1016/j.ajhg.2019.06.007;
RG DDD Study;
RA Snijders Blok L., Kleefstra T., Venselaar H., Maas S., Kroes H.Y.,
RA Lachmeijer A.M.A., van Gassen K.L.I., Firth H.V., Tomkins S., Bodek S.,
RA Ounap K., Wojcik M.H., Cunniff C., Bergstrom K., Powis Z., Tang S.,
RA Shinde D.N., Au C., Iglesias A.D., Izumi K., Leonard J., Abou Tayoun A.,
RA Baker S.W., Tartaglia M., Niceta M., Dentici M.L., Okamoto N., Miyake N.,
RA Matsumoto N., Vitobello A., Faivre L., Philippe C., Gilissen C., Wiel L.,
RA Pfundt R., Deriziotis P., Brunner H.G., Fisher S.E.;
RT "De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause a
RT Characteristic Neurodevelopmental Disorder.";
RL Am. J. Hum. Genet. 105:403-412(2019).
CC -!- FUNCTION: Transcription factor that acts synergistically with SOX11 and
CC SOX4. Plays a role in neuronal development (PubMed:31303265). Is
CC implicated in an enhancer activity at the embryonic met-mesencephalic
CC junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-
CC 3') (By similarity). {ECO:0000250|UniProtKB:P31361,
CC ECO:0000250|UniProtKB:Q63262, ECO:0000269|PubMed:31303265}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:31303265}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31303265}.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000305|PubMed:31303265}.
CC -!- DISEASE: Snijders Blok-Fisher syndrome (SNIBFIS) [MIM:618604]: An
CC autosomal dominant neurodevelopmental disorder characterized by global
CC developmental delay, hypotonia, intellectual disability, autistic
CC features, impairments in speech and language skills, and dysmorphic
CC features including abnormal, cupped, or prominent ears and ocular
CC anomalies. {ECO:0000269|PubMed:31303265}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the POU transcription factor family. Class-3
CC subfamily. {ECO:0000305}.
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DR EMBL; AB001835; BAA19459.1; -; Genomic_DNA.
DR EMBL; AC018730; AAX88973.1; -; Genomic_DNA.
DR CCDS; CCDS33265.1; -.
DR RefSeq; NP_006227.1; NM_006236.2.
DR AlphaFoldDB; P20264; -.
DR SMR; P20264; -.
DR BioGRID; 111451; 23.
DR IntAct; P20264; 4.
DR MINT; P20264; -.
DR STRING; 9606.ENSP00000355001; -.
DR BindingDB; P20264; -.
DR ChEMBL; CHEMBL5243; -.
DR iPTMnet; P20264; -.
DR PhosphoSitePlus; P20264; -.
DR BioMuta; POU3F3; -.
DR DMDM; 2506534; -.
DR jPOST; P20264; -.
DR MassIVE; P20264; -.
DR MaxQB; P20264; -.
DR PaxDb; P20264; -.
DR PeptideAtlas; P20264; -.
DR PRIDE; P20264; -.
DR ProteomicsDB; 53736; -.
DR Antibodypedia; 32979; 161 antibodies from 33 providers.
DR DNASU; 5455; -.
DR Ensembl; ENST00000361360.4; ENSP00000355001.2; ENSG00000198914.5.
DR Ensembl; ENST00000674056.1; ENSP00000501036.1; ENSG00000198914.5.
DR GeneID; 5455; -.
DR KEGG; hsa:5455; -.
DR MANE-Select; ENST00000361360.4; ENSP00000355001.2; NM_006236.3; NP_006227.1.
DR UCSC; uc010ywg.3; human.
DR CTD; 5455; -.
DR DisGeNET; 5455; -.
DR GeneCards; POU3F3; -.
DR HGNC; HGNC:9216; POU3F3.
DR HPA; ENSG00000198914; Group enriched (brain, epididymis, kidney, seminal vesicle).
DR MalaCards; POU3F3; -.
DR MIM; 602480; gene.
DR MIM; 618604; phenotype.
DR neXtProt; NX_P20264; -.
DR OpenTargets; ENSG00000198914; -.
DR PharmGKB; PA33540; -.
DR VEuPathDB; HostDB:ENSG00000198914; -.
DR eggNOG; KOG3802; Eukaryota.
DR GeneTree; ENSGT00940000163665; -.
DR HOGENOM; CLU_013065_1_2_1; -.
DR InParanoid; P20264; -.
DR OMA; CKRMFSE; -.
DR OrthoDB; 752252at2759; -.
DR PhylomeDB; P20264; -.
DR TreeFam; TF316413; -.
DR PathwayCommons; P20264; -.
DR SignaLink; P20264; -.
DR SIGNOR; P20264; -.
DR BioGRID-ORCS; 5455; 11 hits in 1042 CRISPR screens.
DR ChiTaRS; POU3F3; human.
DR GenomeRNAi; 5455; -.
DR Pharos; P20264; Tbio.
DR PRO; PR:P20264; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P20264; protein.
DR Bgee; ENSG00000198914; Expressed in ventricular zone and 100 other tissues.
DR Genevisible; P20264; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
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:0071837; F:HMG box domain binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IEA:Ensembl.
DR GO; GO:0048878; P:chemical homeostasis; IEA:Ensembl.
DR GO; GO:0021869; P:forebrain ventricular zone progenitor cell division; IEA:Ensembl.
DR GO; GO:0072218; P:metanephric ascending thin limb development; ISS:UniProtKB.
DR GO; GO:0072240; P:metanephric DCT cell differentiation; ISS:UniProtKB.
DR GO; GO:0072236; P:metanephric loop of Henle development; ISS:UniProtKB.
DR GO; GO:0072227; P:metanephric macula densa development; ISS:UniProtKB.
DR GO; GO:0072233; P:metanephric thick ascending limb development; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0071918; P:urea transmembrane transport; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR Gene3D; 1.10.260.40; -; 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 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; 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 Developmental protein; Disease variant; DNA-binding; Homeobox;
KW Intellectual disability; Neurogenesis; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..500
FT /note="POU domain, class 3, transcription factor 3"
FT /id="PRO_0000100727"
FT DOMAIN 314..388
FT /note="POU-specific"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00530"
FT DNA_BIND 406..465
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 32..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 122..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..500
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..148
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..183
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..288
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 465..500
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 63..500
FT /note="Missing (in SNIBFIS)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083083"
FT VARIANT 223..500
FT /note="Missing (in SNIBFIS; mislocation in cytoplasm in
FT addition to nuclear location; decreased transcriptional
FT activation function; abolished homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083084"
FT VARIANT 331..335
FT /note="Missing (in SNIBFIS; mislocation within the nucleus;
FT decreased transcriptional activation function; decreased
FT homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083085"
FT VARIANT 362
FT /note="R -> L (in SNIBFIS; no effect on nuclear location;
FT decreased transcriptional activation function; no effect on
FT homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083086"
FT VARIANT 407
FT /note="R -> G (in SNIBFIS; no effect on nuclear location;
FT no effect on transcriptional activation function; no effect
FT on homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083087"
FT VARIANT 407
FT /note="R -> L (in SNIBFIS; no effect on nuclear location;
FT increased transcriptional activation function; no effect on
FT homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083088"
FT VARIANT 414..500
FT /note="Missing (in SNIBFIS)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083089"
FT VARIANT 428..500
FT /note="Missing (in SNIBFIS; mislocation within the nucleus;
FT decreased transcriptional activation function; decreased
FT homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083090"
FT VARIANT 456
FT /note="N -> S (in SNIBFIS; no effect on nuclear location;
FT decreased transcriptional activation function; slightly
FT decreased homodimerization)"
FT /evidence="ECO:0000269|PubMed:31303265"
FT /id="VAR_083091"
FT CONFLICT 433
FT /note="A -> S (in Ref. 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 50327 MW; E536EFFFA5212319 CRC64;
MATAASNPYL PGNSLLAAGS IVHSDAAGAG GGGGGGGGGG GGGAGGGGGG MQPGSAAVTS
GAYRGDPSSV KMVQSDFMQG AMAASNGGHM LSHAHQWVTA LPHAAAAAAA AAAAAVEASS
PWSGSAVGMA GSPQQPPQPP PPPPQGPDVK GGAGRDDLHA GTALHHRGPP HLGPPPPPPH
QGHPGGWGAA AAAAAAAAAA AAAAHLPSMA GGQQPPPQSL LYSQPGGFTV NGMLSAPPGP
GGGGGGAGGG AQSLVHPGLV RGDTPELAEH HHHHHHHAHP HPPHPHHAQG PPHHGGGGGG
AGPGLNSHDP HSDEDTPTSD DLEQFAKQFK QRRIKLGFTQ ADVGLALGTL YGNVFSQTTI
CRFEALQLSF KNMCKLKPLL NKWLEEADSS TGSPTSIDKI AAQGRKRKKR TSIEVSVKGA
LESHFLKCPK PSAQEITNLA DSLQLEKEVV RVWFCNRRQK EKRMTPPGIQ QQTPDDVYSQ
VGTVSADTPP PHHGLQTSVQ
