ID   RFX3_MOUSE              Reviewed;         749 AA.
AC   P48381; Q8BLW2; Q8C0R3; Q8VBY6;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   20-JUN-2003, sequence version 2.
DT   27-MAR-2024, entry version 172.
DE   RecName: Full=Transcription factor RFX3;
DE   AltName: Full=Regulatory factor X 3;
GN   Name=Rfx3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J; TISSUE=Aorta, and Vein;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Mammary gland;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 137-325 (ISOFORM 1).
RC   STRAIN=BALB/cJ; TISSUE=Spleen;
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   [4]
RP   SUBUNIT.
RX   PubMed=15229132; DOI=10.1095/biolreprod.104.032268;
RA   Horvath G.C., Kistler W.S., Kistler M.K.;
RT   "RFX2 is a potential transcriptional regulatory factor for histone H1t and
RT   other genes expressed during the meiotic phase of spermatogenesis.";
RL   Biol. Reprod. 71:1551-1559(2004).
RN   [5]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=15121860; DOI=10.1128/mcb.24.10.4417-4427.2004;
RA   Bonnafe E., Touka M., Ait-Lounis A., Baas D., Barras E., Ucla C.,
RA   Moreau A., Flamant F., Dubruille R., Couble P., Collignon J., Durand B.,
RA   Reith W.;
RT   "The transcription factor RFX3 directs nodal cilium development and left-
RT   right asymmetry specification.";
RL   Mol. Cell. Biol. 24:4417-4427(2004).
RN   [6]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=16930429; DOI=10.1111/j.1460-9568.2006.05002.x;
RA   Baas D., Meiniel A., Benadiba C., Bonnafe E., Meiniel O., Reith W.,
RA   Durand B.;
RT   "A deficiency in RFX3 causes hydrocephalus associated with abnormal
RT   differentiation of ependymal cells.";
RL   Eur. J. Neurosci. 24:1020-1030(2006).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=17229940; DOI=10.2337/db06-1187;
RA   Ait-Lounis A., Baas D., Barras E., Benadiba C., Charollais A.,
RA   Nlend Nlend R., Liegeois D., Meda P., Durand B., Reith W.;
RT   "Novel function of the ciliogenic transcription factor RFX3 in development
RT   of the endocrine pancreas.";
RL   Diabetes 56:950-959(2007).
RN   [8]
RP   FUNCTION, DNA-BINDING, AND SUBCELLULAR LOCATION.
RX   PubMed=19671664; DOI=10.1242/jcs.048348;
RA   El Zein L., Ait-Lounis A., Morle L., Thomas J., Chhin B., Spassky N.,
RA   Reith W., Durand B.;
RT   "RFX3 governs growth and beating efficiency of motile cilia in mouse and
RT   controls the expression of genes involved in human ciliopathies.";
RL   J. Cell Sci. 122:3180-3189(2009).
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 cells
CC       (PubMed:15121860, PubMed:19671664). Also required for ciliated
CC       ependymal cell differentiation (PubMed:16930429). 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 (PubMed:17229940). Regulates
CC       transcription by forming a heterodimer with another RFX protein and
CC       binding to the X-box in the promoter of target genes (By similarity).
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). Represses transcription of MAP1A in non-
CC       neuronal cells but not in neuronal cells.
CC       {ECO:0000250|UniProtKB:P48380, ECO:0000269|PubMed:15121860,
CC       ECO:0000269|PubMed:16930429, ECO:0000269|PubMed:17229940,
CC       ECO:0000269|PubMed:19671664}.
CC   -!- SUBUNIT: Heterodimer; heterodimerizes with RFX1 and RFX2, and RFX6.
CC       {ECO:0000250|UniProtKB:P48380, ECO:0000269|PubMed:15229132}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00858,
CC       ECO:0000269|PubMed:19671664}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P48381-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P48381-2; Sequence=VSP_007628, VSP_007629, VSP_007630;
CC   -!- TISSUE SPECIFICITY: Expressed in ciliated cells of the node and in the
CC       ciliated ependymal cells of the subcommissural organ (SCO), choroid
CC       plexuses (CP) and ventricular walls during embryonic and postnatal
CC       development. Expressed in developing and mature pancreatic endocrine
CC       cells during embryogenesis and in adults (at protein level).
CC       {ECO:0000269|PubMed:15121860, ECO:0000269|PubMed:16930429,
CC       ECO:0000269|PubMed:17229940}.
CC   -!- DISRUPTION PHENOTYPE: High rate of embryonic lethality. 2 peaks of
CC       death are observed: approximately half of the embryos die around days
CC       11 or 12 of embryonic development. Of the embryos that survive past
CC       this stage, approximately two-thirds die at birth. Surviving mice are
CC       systematically smaller. Their body weights at birth are approximately
CC       one-third lower. This growth retardation increases with age, and the
CC       body weights that adult male or female mice attain are less than half
CC       those of wild-type mice. Mice exhibit a pronounced defect in nodal
CC       cilia: cilia are present but remain markedly stunted. Mice also suffer
CC       from hydrocephalus without stenosis of the aqueduct of Sylvius. In
CC       pancreatic endocrine cells, primary cilia are reduced in number and
CC       severely stunted: this ciliary abnormality is associated with a
CC       developmental defect leading to an altered cellular composition of the
CC       islets of Langerhans. Just before birth, islets contain considerably
CC       less insulin-, glucagon-, and ghrelin-producing cells, whereas
CC       pancreatic PP (polypeptide-producing) cells are markedly increased in
CC       number. In adult mice, the defect leads to small and disorganized
CC       islets, reduced insulin production, and impaired glucose tolerance.
CC       {ECO:0000269|PubMed:15121860, ECO:0000269|PubMed:16930429,
CC       ECO:0000269|PubMed:17229940}.
CC   -!- SIMILARITY: Belongs to the RFX family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00858}.
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DR   EMBL; AK030008; BAC26730.1; -; mRNA.
DR   EMBL; AK041120; BAC30829.1; -; mRNA.
DR   EMBL; BC017598; AAH17598.1; -; mRNA.
DR   EMBL; X76090; CAA53704.1; -; mRNA.
DR   CCDS; CCDS29725.1; -. [P48381-1]
DR   PIR; E55926; E55926.
DR   RefSeq; NP_001159886.1; NM_001166414.1. [P48381-1]
DR   RefSeq; NP_035395.2; NM_011265.3. [P48381-1]
DR   RefSeq; XP_006526845.1; XM_006526782.3.
DR   RefSeq; XP_011245471.1; XM_011247169.2. [P48381-1]
DR   AlphaFoldDB; P48381; -.
DR   SMR; P48381; -.
DR   BioGRID; 202874; 1.
DR   IntAct; P48381; 2.
DR   MINT; P48381; -.
DR   STRING; 10090.ENSMUSP00000126313; -.
DR   iPTMnet; P48381; -.
DR   PhosphoSitePlus; P48381; -.
DR   SwissPalm; P48381; -.
DR   EPD; P48381; -.
DR   MaxQB; P48381; -.
DR   PaxDb; 10090-ENSMUSP00000133461; -.
DR   PeptideAtlas; P48381; -.
DR   ProteomicsDB; 253232; -. [P48381-1]
DR   ProteomicsDB; 253233; -. [P48381-2]
DR   Antibodypedia; 23939; 269 antibodies from 31 providers.
DR   DNASU; 19726; -.
DR   Ensembl; ENSMUST00000165566.8; ENSMUSP00000126313.2; ENSMUSG00000040929.18. [P48381-1]
DR   Ensembl; ENSMUST00000172907.8; ENSMUSP00000134141.2; ENSMUSG00000040929.18. [P48381-1]
DR   Ensembl; ENSMUST00000174850.8; ENSMUSP00000133461.2; ENSMUSG00000040929.18. [P48381-1]
DR   GeneID; 19726; -.
DR   KEGG; mmu:19726; -.
DR   UCSC; uc008hcb.2; mouse. [P48381-1]
DR   UCSC; uc008hcd.3; mouse. [P48381-2]
DR   AGR; MGI:106582; -.
DR   CTD; 5991; -.
DR   MGI; MGI:106582; Rfx3.
DR   VEuPathDB; HostDB:ENSMUSG00000040929; -.
DR   eggNOG; KOG3712; Eukaryota.
DR   GeneTree; ENSGT01050000244879; -.
DR   InParanoid; P48381; -.
DR   OMA; ADCPEEM; -.
DR   OrthoDB; 2915941at2759; -.
DR   PhylomeDB; P48381; -.
DR   TreeFam; TF321340; -.
DR   BioGRID-ORCS; 19726; 2 hits in 76 CRISPR screens.
DR   ChiTaRS; Rfx3; mouse.
DR   PRO; PR:P48381; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; P48381; Protein.
DR   Bgee; ENSMUSG00000040929; Expressed in olfactory epithelium and 225 other cell types or tissues.
DR   ExpressionAtlas; P48381; 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; IEA:UniProtKB-SubCell.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:BHF-UCL.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; IDA:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR   GO; GO:0048469; P:cell maturation; IMP:BHF-UCL.
DR   GO; GO:0060271; P:cilium assembly; IMP:BHF-UCL.
DR   GO; GO:0060285; P:cilium-dependent cell motility; IMP:UniProtKB.
DR   GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR   GO; GO:0006351; P:DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:0031018; P:endocrine pancreas development; IMP:UniProtKB.
DR   GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; IMP:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:2000078; P:positive regulation of type B pancreatic cell development; IMP:BHF-UCL.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB.
DR   GO; GO:0050796; P:regulation of insulin secretion; IMP: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; IMP:BHF-UCL.
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; P48381; MM.
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_0000215291"
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         159..183
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_007628"
FT   VAR_SEQ         401..413
FT                   /note="SNLSEIESRLPKA -> RSESIGLSDLFSR (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_007629"
FT   VAR_SEQ         414..749
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_007630"
FT   CONFLICT        372
FT                   /note="Q -> K (in Ref. 1; BAC26730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        459
FT                   /note="I -> V (in Ref. 1; BAC26730)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        494
FT                   /note="Q -> H (in Ref. 1; BAC26730)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   749 AA;  83512 MW;  5527A5F3826D32AA 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 PADGTTITES SNLSEIESRL PKAKLITLCK
     HESILKWMCN CDHGMYQALV EILIPDVLRP IPSALTQAIR NFAKSLEGWL SNAMNNIPQR
     MIQTKVAAVS AFAQTLRRYT SLNHLAQAAR AVLQNTSQIN QMLSDLNRVD FANVQEQASW
     VCQCDDNMVQ RLETDFKMTL QQQSTLEQWA AWLDNVMMQA LKPYEGRPSF PKAARQFLLK
     WSFYSSMVIR DLTLRSAASF GSFHLIRLLY DEYMFYLVEH RVAQVTGETP IAVMGEFGDL
     NAVSPGNLDK DEGSEVESET DEDLDDSSEP RAKREKTELS QAFPVGCMQP VLESAVQPSL
     LNPLHSEHIV TSTQTIRQCS ATGNTYTAV
//