P48381 (RFX3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor RFX3

Alternative name(s):
Regulatory factor X 3

Gene names

Name:

Rfx3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	749 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development. Essential for the differentiation of nodal monocilia and left-right asymmetry specification during embryogenesis. Required for the biogenesis of motile cilia by governing growth and beating efficiency of motile cells. Also required for ciliated ependymal cell differentiation. Together with RFX6, participates in the differentiation of 4 of the 5 islet cell types during endocrine pancreas development, with the exception of pancreatic PP (polypeptide-producing) cells. Regulates transcription by forming a heterodimer with another RFX protein and binding to the X-box in the promoter of target genes. Regulates the expression of genes involved in ciliary assembly (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility (DNAH11, DNAH9 and DNAH5). Represses transcription of MAP1A in non-neuronal cells but not in neuronal cells. Ref.4 Ref.5 Ref.6 Ref.7
Subunit structure	Interacts with RFX6 By similarity.
Subcellular location	Nucleus Ref.7.
Tissue specificity	Expressed in ciliated cells of the node and in the ciliated ependymal cells of the subcommissural organ (SCO), choroid plexuses (CP) and ventricular walls during embryonic and postnatal development. Expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults (at protein level). Ref.4 Ref.5 Ref.6
Disruption phenotype	High rate of embryonic lethality. 2 peaks of death are observed: approximately half of the embryos die around days 11 or 12 of embryonic development. Of the embryos that survive past this stage, approximately two-thirds die at birth. Surviving mice are systematically smaller. Their body weights at birth are approximately one-third lower. This growth retardation increases with age, and the body weights that adult male or female mice attain are less than half those of wild-type mice. Mice exhibit a pronounced defect in nodal cilia: cilia are present but remain markedly stunted. Mice also suffer from hydrocephalus without stenosis of the aqueduct of Sylvius. In pancreatic endocrine cells, primary cilia are reduced in number and severely stunted: this ciliary abnormality is associated with a developmental defect leading to an altered cellular composition of the islets of Langerhans. Just before birth, islets contain considerably less insulin-, glucagon-, and ghrelin-producing cells, whereas pancreatic PP (polypeptide-producing) cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance. Ref.4 Ref.5 Ref.6
Sequence similarities	Belongs to the RFX family. Contains 1 RFX-type winged-helix DNA-binding domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ciliary cell motility Inferred from mutant phenotype Ref.7. Source: UniProtKB cilium assembly Inferred from mutant phenotype PubMed 20413507. Source: BHF-UCL epithelial cilium movement involved in determination of left/right asymmetry Inferred from mutant phenotype Ref.4. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20413507. Source: BHF-UCL positive regulation of type B pancreatic cell development Inferred from mutant phenotype PubMed 20413507. Source: BHF-UCL regulation of insulin secretion Inferred from mutant phenotype Ref.6. Source: UniProtKB transcription, DNA-dependent Inferred from mutant phenotype Ref.7. Source: UniProtKB type B pancreatic cell maturation Inferred from mutant phenotype PubMed 20413507. Source: BHF-UCL
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 20413507. Source: BHF-UCL transcription factor complex Inferred by curator PubMed 20413507. Source: BHF-UCL
Molecular_function	sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 20413507. Source: BHF-UCL transcription regulatory region DNA binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48381-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P48381-2)

The sequence of this isoform differs from the canonical sequence as follows:
     159-183: Missing.
     401-413: SNLSEIESRLPKA → RSESIGLSDLFSR
     414-749: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 749	749	Transcription factor RFX3		PRO_0000215291
Regions
	DNA binding	183 – 258	76	RFX-type winged-helix Ref.7
Natural variations
	Alternative sequence	159 – 183	25	Missing in isoform 2.		VSP_007628
	Alternative sequence	401 – 413	13	SNLSE…RLPKA → RSESIGLSDLFSR in isoform 2.		VSP_007629
	Alternative sequence	414 – 749	336	Missing in isoform 2.		VSP_007630
Experimental info
	Sequence conflict	372	1	Q → K in BAC26730. Ref.1
	Sequence conflict	459	1	I → V in BAC26730. Ref.1
	Sequence conflict	494	1	Q → H in BAC26730. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 20, 2003. Version 2. Checksum: 5527A5F3826D32AA	FASTA	749	83,512
	10 20 30 40 50 60 MQTSETGSDT GSTVTLQTSV ASQAAVPTQV VQQVPVQQQV QQVQTVQQVQ HVYPAQVQYV 70 80 90 100 110 120 EGSDTVYTNG AIRTTTYPYT ETQMYSQNTG GNYFDTQGSS AQVTTVVSSH SMVGTGGIQM 130 140 150 160 170 180 GVTGGQLISS SGGTYLIGNS MENSGHSVTH TTRASPATIE MAIETLQKSD GLSTHRSSLL 190 200 210 220 230 240 NSHLQWLLDN YETAEGVSLP RSTLYNHYLR HCQEHKLDPV NAASFGKLIR SIFMGLRTRR 250 260 270 280 290 300 LGTRGNSKYH YYGIRVKPDS PLNRLQEDMQ YMAMRQQPMQ QKQRYKPMQK VDGVADGFTG 310 320 330 340 350 360 SGQQTGTSVE QTVIAQSQHH QQFLDASRAL PEFGEVEISS LPDGTTFEDI KSLQSLYREH 370 380 390 400 410 420 CEAILDVVVN LQFSLIEKLW QTFWRYSPST PADGTTITES SNLSEIESRL PKAKLITLCK 430 440 450 460 470 480 HESILKWMCN CDHGMYQALV EILIPDVLRP IPSALTQAIR NFAKSLEGWL SNAMNNIPQR 490 500 510 520 530 540 MIQTKVAAVS AFAQTLRRYT SLNHLAQAAR AVLQNTSQIN QMLSDLNRVD FANVQEQASW 550 560 570 580 590 600 VCQCDDNMVQ RLETDFKMTL QQQSTLEQWA AWLDNVMMQA LKPYEGRPSF PKAARQFLLK 610 620 630 640 650 660 WSFYSSMVIR DLTLRSAASF GSFHLIRLLY DEYMFYLVEH RVAQVTGETP IAVMGEFGDL 670 680 690 700 710 720 NAVSPGNLDK DEGSEVESET DEDLDDSSEP RAKREKTELS QAFPVGCMQP VLESAVQPSL 730 740 LNPLHSEHIV TSTQTIRQCS ATGNTYTAV
	Isoform 2 [UniParc]. Checksum: CDA2971DA0E4DE79	FASTA	388	42,900
	10 20 30 40 50 60 MQTSETGSDT GSTVTLQTSV ASQAAVPTQV VQQVPVQQQV QQVQTVQQVQ HVYPAQVQYV 70 80 90 100 110 120 EGSDTVYTNG AIRTTTYPYT ETQMYSQNTG GNYFDTQGSS AQVTTVVSSH SMVGTGGIQM 130 140 150 160 170 180 GVTGGQLISS SGGTYLIGNS MENSGHSVTH TTRASPATLQ WLLDNYETAE GVSLPRSTLY 190 200 210 220 230 240 NHYLRHCQEH KLDPVNAASF GKLIRSIFMG LRTRRLGTRG NSKYHYYGIR VKPDSPLNRL 250 260 270 280 290 300 QEDMQYMAMR QQPMQQKQRY KPMQKVDGVA DGFTGSGQQT GTSVEQTVIA QSQHHQQFLD 310 320 330 340 350 360 ASRALPEFGE VEISSLPDGT TFEDIKSLQS LYREHCEAIL DVVVNLQFSL IEKLWQTFWR 370 380 YSPSTPADGT TITESRSESI GLSDLFSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Aorta and Vein.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Mammary gland.
[3]	"RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family of homodimeric and heterodimeric DNA-binding proteins." Reith W., Ucla C., Barras E., Gaud A., Durand B., Herrero-Sanchez C., Kobr M., Mach B. Mol. Cell. Biol. 14:1230-1244(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 137-325 (ISOFORM 1). Strain: BALB/c. Tissue: Spleen.
[4]	"The transcription factor RFX3 directs nodal cilium development and left-right asymmetry specification." Bonnafe E., Touka M., Ait-Lounis A., Baas D., Barras E., Ucla C., Moreau A., Flamant F., Dubruille R., Couble P., Collignon J., Durand B., Reith W. Mol. Cell. Biol. 24:4417-4427(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[5]	"A deficiency in RFX3 causes hydrocephalus associated with abnormal differentiation of ependymal cells." Baas D., Meiniel A., Benadiba C., Bonnafe E., Meiniel O., Reith W., Durand B. Eur. J. Neurosci. 24:1020-1030(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[6]	"Novel function of the ciliogenic transcription factor RFX3 in development of the endocrine pancreas." Ait-Lounis A., Baas D., Barras E., Benadiba C., Charollais A., Nlend Nlend R., Liegeois D., Meda P., Durand B., Reith W. Diabetes 56:950-959(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]	"RFX3 governs growth and beating efficiency of motile cilia in mouse and controls the expression of genes involved in human ciliopathies." El Zein L., Ait-Lounis A., Morle L., Thomas J., Chhin B., Spassky N., Reith W., Durand B. J. Cell Sci. 122:3180-3189(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK030008 mRNA. Translation: BAC26730.1. AK041120 mRNA. Translation: BAC30829.1. BC017598 mRNA. Translation: AAH17598.1. X76090 mRNA. Translation: CAA53704.1.
IPI	IPI00121582. IPI00855166.
PIR	E55926.
RefSeq	NP_001159886.1. NM_001166414.1. NP_035395.2. NM_011265.3.
UniGene	Mm.313321.
3D structure databases
ProteinModelPortal	P48381.
SMR	P48381. Positions 184-257.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48381. 1 interaction.
PTM databases
PhosphoSite	P48381.
Proteomic databases
PaxDb	P48381.
PRIDE	P48381.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000165566; ENSMUSP00000126313; ENSMUSG00000040929. ENSMUST00000172907; ENSMUSP00000134141; ENSMUSG00000040929. ENSMUST00000174850; ENSMUSP00000133461; ENSMUSG00000040929.
GeneID	19726.
KEGG	mmu:19726.
UCSC	uc008hcb.2. mouse. uc008hcd.2. mouse.
Organism-specific databases
CTD	5991.
MGI	MGI:106582. Rfx3.
Phylogenomic databases
eggNOG	NOG264634.
GeneTree	ENSGT00550000074532.
HOGENOM	HOG000294091.
HOVERGEN	HBG002753.
InParanoid	P48381.
KO	K09173.
OMA	MQTPEAG.
Gene expression databases
ArrayExpress	P48381.
Bgee	P48381.
Genevestigator	P48381.
GermOnline	ENSMUSG00000040929. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR003150. DNA-bd_RFX. IPR007668. RFX1_trans_act. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF04589. RFX1_trans_act. 1 hit. PF02257. RFX_DNA_binding. 1 hit. [Graphical view]
PROSITE	PS51526. RFX_DBD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	297136.
SOURCE	Search...

Entry information

Entry name

RFX3_MOUSE

Accession

Primary (citable) accession number: P48381
Secondary accession number(s): Q8BLW2, Q8C0R3, Q8VBY6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	June 20, 2003
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program