ID RFX3_HUMAN Reviewed; 749 AA. AC P48380; A8K0H5; D3DRH8; D3DRH9; Q5JTL7; Q5JTL8; Q6NW13; Q8WTU4; Q95HL5; AC Q95HL6; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2003, sequence version 2. DT 27-MAR-2024, entry version 190. DE RecName: Full=Transcription factor RFX3; DE AltName: Full=Regulatory factor X 3; GN Name=RFX3; 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] (ISOFORM 2). RX PubMed=8289803; DOI=10.1128/mcb.14.2.1230-1244.1994; RA Reith W., Ucla C., Barras E., Gaud A., Durand B., Herrero-Sanchez C., RA Kobr M., Mach B.; RT "RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel RT family of homodimeric and heterodimeric DNA-binding proteins."; RL Mol. Cell. Biol. 14:1230-1244(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum; 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=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Muscle, and Testis; 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 [6] RP SUBUNIT. RX PubMed=10330134; DOI=10.1128/mcb.19.6.3940; RA Iwama A., Pan J., Zhang P., Reith W., Mach B., Tenen D.G., Sun Z.; RT "Dimeric RFX proteins contribute to the activity and lineage specificity of RT the interleukin-5 receptor alpha promoter through activation and repression RT domains."; RL Mol. Cell. Biol. 19:3940-3950(1999). RN [7] RP FUNCTION. RX PubMed=12411430; DOI=10.1074/jbc.m209574200; RA Nakayama A., Murakami H., Maeyama N., Yamashiro N., Sakakibara A., Mori N., RA Takahashi M.; RT "Role for RFX transcription factors in non-neuronal cell-specific RT inactivation of the microtubule-associated protein MAP1A promoter."; RL J. Biol. Chem. 278:233-240(2003). RN [8] RP FUNCTION, DNA-BINDING, AND INTERACTION WITH RFX6. RX PubMed=20148032; DOI=10.1038/nature08748; RA Smith S.B., Qu H.Q., Taleb N., Kishimoto N.Y., Scheel D.W., Lu Y., RA Patch A.M., Grabs R., Wang J., Lynn F.C., Miyatsuka T., Mitchell J., RA Seerke R., Desir J., Eijnden S.V., Abramowicz M., Kacet N., Weill J., RA Renard M.E., Gentile M., Hansen I., Dewar K., Hattersley A.T., Wang R., RA Wilson M.E., Johnson J.D., Polychronakos C., German M.S.; RT "Rfx6 directs islet formation and insulin production in mice and humans."; RL Nature 463:775-780(2010). CC -!- FUNCTION: Transcription factor required for ciliogenesis and islet cell CC differentiation during endocrine pancreas development. Essential for CC the differentiation of nodal monocilia and left-right asymmetry CC specification during embryogenesis. Required for the biogenesis of CC motile cilia by governing growth and beating efficiency of motile CC cells. Also required for ciliated ependymal cell differentiation. CC Regulates the expression of genes involved in ciliary assembly CC (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility CC (DNAH11, DNAH9 and DNAH5) (By similarity). Together with RFX6, CC participates in the differentiation of 4 of the 5 islet cell types CC during endocrine pancreas development, with the exception of pancreatic CC PP (polypeptide-producing) cells. Regulates transcription by forming a CC heterodimer with another RFX protein and binding to the X-box in the CC promoter of target genes (PubMed:20148032). Represses transcription of CC MAP1A in non-neuronal cells but not in neuronal cells CC (PubMed:12411430). {ECO:0000250|UniProtKB:P48381, CC ECO:0000269|PubMed:12411430, ECO:0000269|PubMed:20148032}. CC -!- SUBUNIT: Heterodimer; heterodimerizes with RFX1 and RFX2, and RFX6. CC {ECO:0000269|PubMed:10330134, ECO:0000269|PubMed:20148032}. CC -!- INTERACTION: CC P48380; Q14192: FHL2; NbExp=10; IntAct=EBI-742557, EBI-701903; CC P48380; Q13643: FHL3; NbExp=4; IntAct=EBI-742557, EBI-741101; CC P48380; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-742557, EBI-16439278; CC P48380; Q12933: TRAF2; NbExp=5; IntAct=EBI-742557, EBI-355744; CC P48380; Q15654: TRIP6; NbExp=3; IntAct=EBI-742557, EBI-742327; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P48380-1; Sequence=Displayed; CC Name=2; CC IsoId=P48380-2; Sequence=VSP_007626, VSP_007627; CC Name=3; CC IsoId=P48380-3; Sequence=VSP_015162, VSP_015163; CC -!- SIMILARITY: Belongs to the RFX family. {ECO:0000255|PROSITE- CC ProRule:PRU00858}. 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; X76092; CAA53706.1; -; mRNA. DR EMBL; AK289540; BAF82229.1; -; mRNA. DR EMBL; AL365202; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL133549; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL354941; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58795.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58796.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58798.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58799.1; -; Genomic_DNA. DR EMBL; BC022191; AAH22191.1; -; mRNA. DR EMBL; BC067778; AAH67778.1; -; mRNA. DR CCDS; CCDS6449.1; -. [P48380-1] DR CCDS; CCDS6450.1; -. [P48380-2] DR CCDS; CCDS75809.1; -. [P48380-3] DR PIR; D55926; D55926. DR RefSeq; NP_001269045.1; NM_001282116.1. [P48380-1] DR RefSeq; NP_001269046.1; NM_001282117.1. [P48380-3] DR RefSeq; NP_002910.1; NM_002919.3. [P48380-2] DR RefSeq; NP_602304.1; NM_134428.2. [P48380-1] DR AlphaFoldDB; P48380; -. DR SMR; P48380; -. DR BioGRID; 111923; 45. DR IntAct; P48380; 21. DR MINT; P48380; -. DR STRING; 9606.ENSP00000371434; -. DR iPTMnet; P48380; -. DR PhosphoSitePlus; P48380; -. DR SwissPalm; P48380; -. DR BioMuta; RFX3; -. DR DMDM; 32172437; -. DR EPD; P48380; -. DR jPOST; P48380; -. DR MassIVE; P48380; -. DR MaxQB; P48380; -. DR PaxDb; 9606-ENSP00000371434; -. DR PeptideAtlas; P48380; -. DR ProteomicsDB; 55883; -. [P48380-1] DR ProteomicsDB; 55884; -. [P48380-2] DR ProteomicsDB; 55885; -. [P48380-3] DR Pumba; P48380; -. DR Antibodypedia; 23939; 269 antibodies from 31 providers. DR DNASU; 5991; -. DR Ensembl; ENST00000302303.5; ENSP00000303847.2; ENSG00000080298.16. [P48380-3] DR Ensembl; ENST00000358730.6; ENSP00000351574.2; ENSG00000080298.16. [P48380-2] DR Ensembl; ENST00000382004.7; ENSP00000371434.3; ENSG00000080298.16. [P48380-1] DR Ensembl; ENST00000617270.5; ENSP00000482598.1; ENSG00000080298.16. [P48380-1] DR GeneID; 5991; -. DR KEGG; hsa:5991; -. DR MANE-Select; ENST00000617270.5; ENSP00000482598.1; NM_001282116.2; NP_001269045.1. DR UCSC; uc003zhr.5; human. [P48380-1] DR AGR; HGNC:9984; -. DR CTD; 5991; -. DR DisGeNET; 5991; -. DR GeneCards; RFX3; -. DR HGNC; HGNC:9984; RFX3. DR HPA; ENSG00000080298; Tissue enhanced (testis). DR MIM; 601337; gene. DR neXtProt; NX_P48380; -. DR OpenTargets; ENSG00000080298; -. DR PharmGKB; PA34354; -. DR VEuPathDB; HostDB:ENSG00000080298; -. DR eggNOG; KOG3712; Eukaryota. DR GeneTree; ENSGT01050000244879; -. DR HOGENOM; CLU_010393_1_1_1; -. DR InParanoid; P48380; -. DR OMA; ADCPEEM; -. DR OrthoDB; 2915941at2759; -. DR PhylomeDB; P48380; -. DR TreeFam; TF321340; -. DR PathwayCommons; P48380; -. DR SignaLink; P48380; -. DR SIGNOR; P48380; -. DR BioGRID-ORCS; 5991; 15 hits in 1179 CRISPR screens. DR ChiTaRS; RFX3; human. DR GeneWiki; RFX3; -. DR GenomeRNAi; 5991; -. DR Pharos; P48380; Tbio. DR PRO; PR:P48380; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P48380; Protein. DR Bgee; ENSG00000080298; Expressed in bronchial epithelial cell and 178 other cell types or tissues. DR ExpressionAtlas; P48380; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; IEA:GOC. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005667; C:transcription regulator complex; ISS:BHF-UCL. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:ARUK-UCL. 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:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0048469; P:cell maturation; ISS:BHF-UCL. DR GO; GO:0060271; P:cilium assembly; ISS:BHF-UCL. DR GO; GO:0060285; P:cilium-dependent cell motility; ISS:UniProtKB. DR GO; GO:0006351; P:DNA-templated transcription; IEA:Ensembl. DR GO; GO:0031018; P:endocrine pancreas development; ISS:UniProtKB. DR GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; ISS:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0072560; P:type B pancreatic cell maturation; IEA:Ensembl. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR InterPro; IPR003150; DNA-bd_RFX. DR InterPro; IPR039779; RFX-like. DR InterPro; IPR007668; RFX1_trans_act. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR12619; RFX TRANSCRIPTION FACTOR FAMILY; 1. DR PANTHER; PTHR12619:SF20; TRANSCRIPTION FACTOR RFX3; 1. DR Pfam; PF04589; RFX1_trans_act; 1. DR Pfam; PF02257; RFX_DNA_binding; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS51526; RFX_DBD; 1. DR Genevisible; P48380; HS. PE 1: Evidence at protein level; KW Alternative splicing; Developmental protein; Differentiation; DNA-binding; KW Nucleus; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1..749 FT /note="Transcription factor RFX3" FT /id="PRO_0000215290" FT DNA_BIND 183..258 FT /note="RFX-type winged-helix" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00858" FT REGION 663..699 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 401..413 FT /note="SNLSEIESRLPKA -> RSESTSFPIHFHG (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_015162" FT VAR_SEQ 414..749 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_015163" FT VAR_SEQ 657..707 FT /note="FGDLNAVSPGNLDKDEGSEVESEMDEELDDSSEPQAKREKTELSQAFPVGC FT -> VREAERAVTHWVIKNKPELHFSLNTLLIKTMVPNQVSLRARRDCGVIARVP (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:8289803" FT /id="VSP_007626" FT VAR_SEQ 708..749 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8289803" FT /id="VSP_007627" FT CONFLICT 150 FT /note="H -> P (in Ref. 2; BAF82229)" FT /evidence="ECO:0000305" FT CONFLICT 310 FT /note="E -> G (in Ref. 5; AAH67778)" FT /evidence="ECO:0000305" SQ SEQUENCE 749 AA; 83530 MW; 531F5CFCA7A707C7 CRC64; MQTSETGSDT GSTVTLQTSV ASQAAVPTQV VQQVPVQQQV QQVQTVQQVQ HVYPAQVQYV EGSDTVYTNG AIRTTTYPYT ETQMYSQNTG GNYFDTQGSS AQVTTVVSSH SMVGTGGIQM GVTGGQLISS SGGTYLIGNS MENSGHSVTH TTRASPATIE MAIETLQKSD GLSTHRSSLL NSHLQWLLDN YETAEGVSLP RSTLYNHYLR HCQEHKLDPV NAASFGKLIR SIFMGLRTRR LGTRGNSKYH YYGIRVKPDS PLNRLQEDMQ YMAMRQQPMQ QKQRYKPMQK VDGVADGFTG SGQQTGTSVE QTVIAQSQHH QQFLDASRAL PEFGEVEISS LPDGTTFEDI KSLQSLYREH CEAILDVVVN LQFSLIEKLW QTFWRYSPST PTDGTTITES SNLSEIESRL PKAKLITLCK HESILKWMCN CDHGMYQALV EILIPDVLRP IPSALTQAIR NFAKSLEGWL SNAMNNIPQR MIQTKVAAVS AFAQTLRRYT SLNHLAQAAR AVLQNTSQIN QMLSDLNRVD FANVQEQASW VCQCDDNMVQ RLETDFKMTL QQQSTLEQWA AWLDNVMMQA LKPYEGRPSF PKAARQFLLK WSFYSSMVIR DLTLRSAASF GSFHLIRLLY DEYMFYLVEH RVAQATGETP IAVMGEFGDL NAVSPGNLDK DEGSEVESEM DEELDDSSEP QAKREKTELS QAFPVGCMQP VLETGVQPSL LNPIHSEHIV TSTQTIRQCS ATGNTYTAV //