RFX4_MOUSE
ID RFX4_MOUSE Reviewed; 735 AA.
AC Q7TNK1; B2RS52; Q3V158; Q76KT2; Q8HWA6; Q9D453;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Transcription factor RFX4;
DE AltName: Full=Regulatory factor X 4;
GN Name=Rfx4;
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 [MRNA] (ISOFORM 1).
RA Belaoussoff M., Dohrmann C.E., Armsen W., Gruss P.;
RT "Mouse Rfx4, a gene expressed in the proliferative zones of the central
RT nervous system.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=12925582; DOI=10.1242/dev.00661;
RA Blackshear P.J., Graves J.P., Stumpo D.J., Cobos I., Rubenstein J.L.R.,
RA Zeldin D.C.;
RT "Graded phenotypic response to partial and complete deficiency of a brain-
RT specific transcript variant of the winged helix transcription factor
RT RFX4.";
RL Development 130:4539-4552(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION,
RP INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Suprachiasmatic nucleus, and Testis;
RX PubMed=14701801; DOI=10.1074/jbc.m312761200;
RA Araki R., Takahashi H., Fukumura R., Sun F., Umeda N., Sujino M.,
RA Inouye S.T., Saito T., Abe M.;
RT "Restricted expression and photic induction of a novel mouse regulatory
RT factor X4 transcript in the suprachiasmatic nucleus.";
RL J. Biol. Chem. 279:10237-10242(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, and 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16893423; DOI=10.1111/j.1471-4159.2006.03930.x;
RA Zhang D., Stumpo D.J., Graves J.P., DeGraff L.M., Grissom S.F.,
RA Collins J.B., Li L., Zeldin D.C., Blackshear P.J.;
RT "Identification of potential target genes for RFX4_v3, a transcription
RT factor critical for brain development.";
RL J. Neurochem. 98:860-875(2006).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GPS2.
RX PubMed=18218630; DOI=10.1074/jbc.m708209200;
RA Zhang D., Harry G.J., Blackshear P.J., Zeldin D.C.;
RT "G-protein pathway suppressor 2 (GPS2) interacts with the regulatory factor
RT X4 variant 3 (RFX4_v3) and functions as a transcriptional co-activator.";
RL J. Biol. Chem. 283:8580-8590(2008).
CC -!- FUNCTION: [Isoform 1]: Transcription factor that plays a role in early
CC brain development. May activate transcription by interacting directly
CC with the X-box. May activate transcription from CX3CL1 promoter through
CC the X-box during brain development. {ECO:0000269|PubMed:12925582,
CC ECO:0000269|PubMed:16893423, ECO:0000269|PubMed:18218630}.
CC -!- SUBUNIT: Homodimer. Heterodimer with RFX2 and RFX3. Binds DNA (By
CC similarity). Interacts with GPS2 (PubMed:18218630).
CC {ECO:0000250|UniProtKB:Q33E94, ECO:0000269|PubMed:18218630}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00858,
CC ECO:0000269|PubMed:14701801, ECO:0000269|PubMed:18218630}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=bRFX4, RFX4_v3;
CC IsoId=Q7TNK1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TNK1-2; Sequence=VSP_030248, VSP_030249;
CC Name=3;
CC IsoId=Q7TNK1-3; Sequence=VSP_030247;
CC Name=4;
CC IsoId=Q7TNK1-4; Sequence=VSP_030248, VSP_030249, VSP_030250,
CC VSP_030251;
CC -!- TISSUE SPECIFICITY: Isoform 1: Brain-specific. Isoform 2: Testis-
CC specific. Isoform 1: Highly expressed in the suprachiasmatic nucleus,
CC the central pacemaker site of the circadian clock (at protein level).
CC {ECO:0000269|PubMed:12925582, ECO:0000269|PubMed:14701801}.
CC -!- DEVELOPMENTAL STAGE: At 8.5 dpc, detected in most of the neural plate
CC but is excluded from the presumptive forebrain region. At 9.5 dpc, its
CC expression is mostly restricted to two large regions, the caudal
CC diencephalon/mesencephalon and the spinal cord. By 10.5 dpc, is present
CC throughout the neural tube, and it is also detected in the cerebral
CC cortex. It is also strongly expressed in the developing subcommissural
CC organ (SCO) from 14.5 dpc to birth. {ECO:0000269|PubMed:12925582}.
CC -!- INDUCTION: [Isoform 1]: Induced in a subjective night-specific manner.
CC {ECO:0000269|PubMed:14701801}.
CC -!- DISRUPTION PHENOTYPE: Mice with an insertion of a cardiac-specific
CC epoxygenase transgene into an intron in the Rfx4 locus develop head
CC swelling and rapid neurological decline in young adulthood, and have
CC marked hydrocephalus of the lateral and third ventricles. Interruption
CC of two alleles results in profound failure of dorsal midline brain
CC structure formation and perinatal death. Interruption of a single
CC allele prevents formation of the subcommissural organ, a structure
CC important for cerebrospinal fluid flow through the aqueduct of Sylvius
CC and results in congenital hydrocephalus. {ECO:0000269|PubMed:12925582,
CC ECO:0000269|PubMed:16893423}.
CC -!- SIMILARITY: Belongs to the RFX family. {ECO:0000255|PROSITE-
CC ProRule:PRU00858}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC28598.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY342003; AAQ17042.1; -; mRNA.
DR EMBL; AY102010; AAM52485.2; -; mRNA.
DR EMBL; AB086957; BAD07408.1; -; mRNA.
DR EMBL; AB089184; BAD07409.1; -; mRNA.
DR EMBL; AK016791; BAB30432.1; -; mRNA.
DR EMBL; AK034131; BAC28598.1; ALT_INIT; mRNA.
DR EMBL; AK132673; BAE21294.1; -; mRNA.
DR EMBL; BC138719; AAI38720.1; -; mRNA.
DR EMBL; BC138720; AAI38721.1; -; mRNA.
DR CCDS; CCDS24082.1; -. [Q7TNK1-1]
DR CCDS; CCDS24083.1; -. [Q7TNK1-2]
DR RefSeq; NP_001020089.1; NM_001024918.1. [Q7TNK1-1]
DR RefSeq; NP_081965.2; NM_027689.3. [Q7TNK1-2]
DR AlphaFoldDB; Q7TNK1; -.
DR SMR; Q7TNK1; -.
DR BioGRID; 214500; 4.
DR IntAct; Q7TNK1; 2.
DR STRING; 10090.ENSMUSP00000051107; -.
DR PhosphoSitePlus; Q7TNK1; -.
DR MaxQB; Q7TNK1; -.
DR PaxDb; Q7TNK1; -.
DR PeptideAtlas; Q7TNK1; -.
DR PRIDE; Q7TNK1; -.
DR ProteomicsDB; 255242; -. [Q7TNK1-1]
DR ProteomicsDB; 255243; -. [Q7TNK1-2]
DR ProteomicsDB; 255244; -. [Q7TNK1-3]
DR ProteomicsDB; 255245; -. [Q7TNK1-4]
DR Antibodypedia; 30672; 142 antibodies from 22 providers.
DR DNASU; 71137; -.
DR Ensembl; ENSMUST00000060397; ENSMUSP00000051107; ENSMUSG00000020037. [Q7TNK1-1]
DR Ensembl; ENSMUST00000095388; ENSMUSP00000093035; ENSMUSG00000020037. [Q7TNK1-2]
DR Ensembl; ENSMUST00000166696; ENSMUSP00000128690; ENSMUSG00000020037. [Q7TNK1-3]
DR GeneID; 71137; -.
DR KEGG; mmu:71137; -.
DR UCSC; uc007gkv.1; mouse. [Q7TNK1-1]
DR UCSC; uc007gkw.1; mouse. [Q7TNK1-2]
DR CTD; 5992; -.
DR MGI; MGI:1918387; Rfx4.
DR VEuPathDB; HostDB:ENSMUSG00000020037; -.
DR eggNOG; KOG3712; Eukaryota.
DR GeneTree; ENSGT01050000244879; -.
DR HOGENOM; CLU_377067_0_0_1; -.
DR InParanoid; Q7TNK1; -.
DR OMA; YQLNSQM; -.
DR OrthoDB; 346630at2759; -.
DR PhylomeDB; Q7TNK1; -.
DR TreeFam; TF321340; -.
DR BioGRID-ORCS; 71137; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q7TNK1; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q7TNK1; protein.
DR Bgee; ENSMUSG00000020037; Expressed in lumbar subsegment of spinal cord and 108 other tissues.
DR Genevisible; Q7TNK1; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
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; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:MGI.
DR GO; GO:0021914; P:negative regulation of smoothened signaling pathway involved in ventral spinal cord patterning; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0070613; P:regulation of protein processing; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0021537; P:telencephalon development; IMP:MGI.
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 Activator; Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..735
FT /note="Transcription factor RFX4"
FT /id="PRO_0000314238"
FT DNA_BIND 44..126
FT DNA_BIND 61..136
FT /note="RFX-type winged-helix"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00858"
FT REGION 27..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..487
FT /note="Necessary for dimerization"
FT REGION 501..538
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..143
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030247"
FT VAR_SEQ 1..94
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14701801,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT /id="VSP_030248"
FT VAR_SEQ 95..126
FT /note="TQPVNAASFGKIIRQQFPQLTTRRLGTRGQSK -> MNWAAFGGPEFFIPGG
FT MKMEASCPLGRNFTEW (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14701801,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072"
FT /id="VSP_030249"
FT VAR_SEQ 452..476
FT /note="SFHLIHLMFDDYVLYLLESLHCQER -> LFYCPASKATLLGQGWEAPCDLS
FT GT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030250"
FT VAR_SEQ 477..735
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030251"
FT CONFLICT 227
FT /note="F -> L (in Ref. 4; BAB30432)"
FT /evidence="ECO:0000305"
FT CONFLICT 578
FT /note="T -> N (in Ref. 4; BAE21294)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 735 AA; 83371 MW; 5D51484CC26A8338 CRC64;
MHCGLLEEPD MDSTESWIER CLNESENKRY SSHTSLGNVS NDENEEKENN RASKPHSTPA
TLQWLEENYE IAEGVCIPRS ALYMHYLDFC EKNDTQPVNA ASFGKIIRQQ FPQLTTRRLG
TRGQSKYHYY GIAVKESSQY YDVMYSKKGA AWVSETGKRE VTKQTVAYSP RSKLGTLLPD
FPNVKDLNLP ASLPEEKVST FIMMYRTHCQ RILDTVIRAN FDEVQSFLLH FWQGMPPHML
PVLGSSTVVN IVGVCDSILY KAISGVLMPT VLQALPDSLT QVIRKFAKQL DEWLKVALHD
LPENLRNIKF ELSRRFSQIL RRQTSLNHLC QASRTVIHSA DITFQMLEDW RNVDLSSITK
QTLYTMEDSR DEHRRLIIQL YQEFDHLLEE QSPIESYIEW LDTMVDRCVV KVAAKRQGSL
KKVAQQFLLM WSCFGTRVIR DMTLHSAPSF GSFHLIHLMF DDYVLYLLES LHCQERANEL
MRAMKGEGST AEAQEEIILT EATPPTPSPG PSFSPAKSAT SVEVPPPSSP VSNPSPEYTG
LSTAGAMQSY TWSLTYTVTT AAGSPAENSQ QLPCMRSTHM PSSSVTHRIP VYSHREEHGY
TGSYNYGSYG NQHPHPLQNQ YPALPHDTAI SGPLHYSPYH RSSAQYPFNS PTSRMEPCLM
SSTPRLHPTP VTPRWPEVPT ANACYTSPSV HSTRYGNSSD MYTPLTTRRN SEYEHMQHFP
GFAYINGEAS TGWAK
