RFX6_MOUSE
ID RFX6_MOUSE Reviewed; 927 AA.
AC Q8C7R7; Q8CDN5;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=DNA-binding protein RFX6;
DE AltName: Full=Regulatory factor X 6;
DE AltName: Full=Regulatory factor X domain-containing protein 1;
GN Name=Rfx6; Synonyms=Rfxdc1;
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 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 213-927 (ISOFORM 1).
RC TISSUE=Brain;
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 [4]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=20040487; DOI=10.1242/dev.041673;
RA Soyer J., Flasse L., Raffelsberger W., Beucher A., Orvain C., Peers B.,
RA Ravassard P., Vermot J., Voz M.L., Mellitzer G., Gradwohl G.;
RT "Rfx6 is an Ngn3-dependent winged helix transcription factor required for
RT pancreatic islet cell development.";
RL Development 137:203-212(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND INTERACTION WITH RFX3.
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 to direct islet cell
CC differentiation during endocrine pancreas development. Specifically
CC required for the differentiation of 4 of the 5 islet cell types and for
CC the production of insulin. Not required for pancreatic PP (polypeptide-
CC producing) cells differentiation. Acts downstream of NEUROG3 and
CC regulates the transcription factors involved in beta-cell maturation
CC and function, thereby restricting the expression of the beta-cell
CC differentiation and specification genes, and thus the beta-cell fate
CC choice. Activates transcription by forming a heterodimer with RFX3 and
CC binding to the X-box in the promoter of target genes (PubMed:20148032).
CC Involved in glucose-stimulated insulin secretion by promoting insulin
CC and L-type calcium channel gene transcription (By similarity).
CC {ECO:0000250|UniProtKB:Q8HWS3, ECO:0000269|PubMed:20148032}.
CC -!- SUBUNIT: Interacts with RFX3 (PubMed:20148032).
CC {ECO:0000269|PubMed:20148032}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20148032}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8C7R7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C7R7-2; Sequence=VSP_030122, VSP_030123;
CC Name=3;
CC IsoId=Q8C7R7-3; Sequence=VSP_030121;
CC -!- TISSUE SPECIFICITY: In the adult pancreas, expression is restricted to
CC the islets where it could be detected in all endocrine lineages.
CC {ECO:0000269|PubMed:20040487, ECO:0000269|PubMed:20148032}.
CC -!- DEVELOPMENTAL STAGE: Expressed initially broadly in the definitive
CC endoderm after gastrulation, becomes restricted to the gut and
CC pancreatic bud at mid gestation, and is reactivated by Neurog3 in islet
CC progenitor cells and is ultimately restricted to pancreatic islets in
CC the mature pancreas (at protein level). {ECO:0000269|PubMed:20040487,
CC ECO:0000269|PubMed:20148032}.
CC -!- INDUCTION: By Neurog3. {ECO:0000269|PubMed:20040487}.
CC -!- DISRUPTION PHENOTYPE: Mice were born at the expected Mendelian ratio,
CC but fail to feed normally, exhibit gross bowel distension due to small
CC bowel obstruction and die within 2 days post partum. Some, but not all,
CC of the animals also have reduced pancreas size. pancreata had almost no
CC expression of the islet hormones genes, except for PP (polypeptide-
CC producing). {ECO:0000269|PubMed:20148032}.
CC -!- SIMILARITY: Belongs to the RFX family. {ECO:0000255|PROSITE-
CC ProRule:PRU00858}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI32105.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAI32295.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK029809; BAC26627.1; -; mRNA.
DR EMBL; AK049380; BAC33722.1; -; mRNA.
DR EMBL; AC153527; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132104; AAI32105.1; ALT_INIT; mRNA.
DR EMBL; BC132294; AAI32295.1; ALT_INIT; mRNA.
DR CCDS; CCDS23835.1; -. [Q8C7R7-3]
DR CCDS; CCDS48558.1; -. [Q8C7R7-1]
DR RefSeq; NP_001152861.1; NM_001159389.1. [Q8C7R7-1]
DR RefSeq; NP_796280.1; NM_177306.3. [Q8C7R7-3]
DR AlphaFoldDB; Q8C7R7; -.
DR SMR; Q8C7R7; -.
DR BioGRID; 236448; 1.
DR STRING; 10090.ENSMUSP00000116057; -.
DR iPTMnet; Q8C7R7; -.
DR PhosphoSitePlus; Q8C7R7; -.
DR PaxDb; Q8C7R7; -.
DR PRIDE; Q8C7R7; -.
DR ProteomicsDB; 254926; -. [Q8C7R7-1]
DR ProteomicsDB; 254928; -. [Q8C7R7-3]
DR Antibodypedia; 32535; 75 antibodies from 19 providers.
DR DNASU; 320995; -.
DR Ensembl; ENSMUST00000050455; ENSMUSP00000057384; ENSMUSG00000019900. [Q8C7R7-3]
DR Ensembl; ENSMUST00000122922; ENSMUSP00000116057; ENSMUSG00000019900. [Q8C7R7-1]
DR GeneID; 320995; -.
DR KEGG; mmu:320995; -.
DR UCSC; uc007fax.2; mouse. [Q8C7R7-2]
DR UCSC; uc007fay.1; mouse. [Q8C7R7-1]
DR UCSC; uc011xdt.1; mouse. [Q8C7R7-3]
DR CTD; 222546; -.
DR MGI; MGI:2445208; Rfx6.
DR VEuPathDB; HostDB:ENSMUSG00000019900; -.
DR eggNOG; KOG3712; Eukaryota.
DR GeneTree; ENSGT01050000244879; -.
DR HOGENOM; CLU_013981_0_0_1; -.
DR InParanoid; Q8C7R7; -.
DR OMA; GSAPCMF; -.
DR OrthoDB; 346630at2759; -.
DR PhylomeDB; Q8C7R7; -.
DR TreeFam; TF321340; -.
DR BioGRID-ORCS; 320995; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q8C7R7; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8C7R7; protein.
DR Bgee; ENSMUSG00000019900; Expressed in islet of Langerhans and 31 other tissues.
DR ExpressionAtlas; Q8C7R7; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0031018; P:endocrine pancreas development; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IMP:UniProtKB.
DR GO; GO:0003311; P:pancreatic D cell differentiation; IMP:UniProtKB.
DR GO; GO:0090104; P:pancreatic epsilon cell differentiation; IMP:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS: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:0003309; P:type B pancreatic cell differentiation; IMP:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR003150; DNA-bd_RFX.
DR InterPro; IPR039779; RFX-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR12619; PTHR12619; 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; Diabetes mellitus;
KW Differentiation; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..927
FT /note="DNA-binding protein RFX6"
FT /id="PRO_0000313722"
FT DNA_BIND 123..198
FT /note="RFX-type winged-helix"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00858"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..264
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030121"
FT VAR_SEQ 519..524
FT /note="SFHLIR -> IQCVLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030122"
FT VAR_SEQ 525..927
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030123"
SQ SEQUENCE 927 AA; 102566 MW; 787F0837902D3E21 CRC64;
MAKVRELEEA FVQEQPSPQL PSEIAEECCA QLLGKGLLVY PEDSAYLLAE TAAGARSSGE
KGGDPGLQVG VKSEMQLNNG NFSSEEEDAD TQESKTKAAD PQLSQKKSIT QMMKDKKKQT
QLTLQWLEDN YIVCEGVCLP RCILYAHYLD FCRKEKLEPA CAATFGKTIR QKFPLLTTRR
LGTRGHSKYH YYGIGIKESS AYYHSVYSGK GLTRFSGSKL KNEGGFTRKY SLSSKTGTLL
PEFPSAQHLV YQGCISKDKV DTLIMMYKTH CQCILDNAIN GNFEEIQHFL LHFWQGMPDH
LLPLLENPVI IDIFCVCDSI LYKVLTDVLI PATMQEMPES LLADIRNFAK NWEQWVVSSL
ENLPEALIDK KIPILRRFVS SLKRQTSFLH LAQIARPALF DQHVVNAMVS DIEKVDLNSI
GSQALLTISN STDTESDIYS EHDSITVFQE LKDLLKKNAT VEAFIEWLDT VVEQRVIKMS
KQNGRSLKKR AQDFLLKWSF FGARVMHNLT LNNASSFGSF HLIRMLLDEY ILLAMETQFN
NDKEQELQNL LDKYMKNSDA SKAAFTASPS SCFLANRNKA SSLASDTVKN ESHVETSYVP
LPSSQPGAIP PALHPFSTED TDNMPLPGQI ELSQSTGHLM TPPISPAIAS RGSVINQGPM
ASRPPSVGTV LSAPTHCSTY AEPIYPTLSP ANHDFYGTNS NYQTMFRTQS HPASSLYAHR
AEHGRCMAWT EQQLSRDFFG GSCAGSPYNC RPPSSYGPST HTQESHSMQV LNTGSFNFLS
NAGAGSCQGS TLPSNSPNGY YGNNINYSEA HRLGSMVNQH VSVISSVRSL PPYSDIHDPL
NILDDSSRKQ NNSFYADTLS PVACRTTVVA SNLQTQIPSS SSQCMYGTSN QYPVQDSLDS
NAASNREMVS SLPPINTVFM GTAAGDT
