RFX3_MOUSE
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 03-AUG-2022, entry version 164.
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.ENSMUSP00000133461; -.
DR iPTMnet; P48381; -.
DR PhosphoSitePlus; P48381; -.
DR SwissPalm; P48381; -.
DR EPD; P48381; -.
DR MaxQB; P48381; -.
DR PaxDb; P48381; -.
DR PeptideAtlas; P48381; -.
DR PRIDE; P48381; -.
DR ProteomicsDB; 253232; -. [P48381-1]
DR ProteomicsDB; 253233; -. [P48381-2]
DR Antibodypedia; 23939; 251 antibodies from 31 providers.
DR DNASU; 19726; -.
DR Ensembl; ENSMUST00000165566; ENSMUSP00000126313; ENSMUSG00000040929. [P48381-1]
DR Ensembl; ENSMUST00000172907; ENSMUSP00000134141; ENSMUSG00000040929. [P48381-1]
DR Ensembl; ENSMUST00000174850; ENSMUSP00000133461; ENSMUSG00000040929. [P48381-1]
DR GeneID; 19726; -.
DR KEGG; mmu:19726; -.
DR UCSC; uc008hcb.2; mouse. [P48381-1]
DR UCSC; uc008hcd.3; mouse. [P48381-2]
DR CTD; 5991; -.
DR MGI; MGI:106582; Rfx3.
DR VEuPathDB; HostDB:ENSMUSG00000040929; -.
DR eggNOG; KOG3712; Eukaryota.
DR GeneTree; ENSGT01050000244879; -.
DR InParanoid; P48381; -.
DR OMA; HATRVSQ; -.
DR OrthoDB; 346630at2759; -.
DR PhylomeDB; P48381; -.
DR TreeFam; TF321340; -.
DR BioGRID-ORCS; 19726; 2 hits in 71 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 223 other tissues.
DR ExpressionAtlas; P48381; baseline and differential.
DR Genevisible; P48381; MM.
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: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 transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:2000078; P:positive regulation of type B pancreatic cell development; IMP:BHF-UCL.
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:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0072560; P:type B pancreatic cell maturation; IMP:BHF-UCL.
DR Gene3D; 1.10.10.10; -; 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; PTHR12619; 1.
DR Pfam; PF04589; RFX1_trans_act; 1.
DR Pfam; PF02257; RFX_DNA_binding; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS51526; RFX_DBD; 1.
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
