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Protein

DNA-binding protein RFX6

Gene

RFX6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor required to direct islet cell differentiation during endocrine pancreas development. Specifically required for the differentiation of 4 of the 5 islet cell types and for the production of insulin. Not required for pancreatic PP (polypeptide-producing) cells differentiation. Acts downstream of NEUROG3 and regulates the transcription factors involved in beta-cell maturation and function, thereby restricting the expression of the beta-cell differentiation and specification genes, and thus the beta-cell fate choice. Activates transcription by forming a heterodimer with RFX3 and binding to the X-box in the promoter of target genes.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi124 – 19976RFX-type winged-helixPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: GO_Central
  2. RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  3. RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  4. sequence-specific DNA binding transcription factor activity Source: GO_Central
  5. transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. endocrine pancreas development Source: UniProtKB
  2. glucose homeostasis Source: UniProtKB
  3. pancreatic A cell differentiation Source: UniProtKB
  4. pancreatic D cell differentiation Source: UniProtKB
  5. pancreatic epsilon cell differentiation Source: UniProtKB
  6. positive regulation of transcription, DNA-templated Source: UniProtKB
  7. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  8. regulation of insulin secretion Source: UniProtKB
  9. regulation of transcription from RNA polymerase II promoter Source: GO_Central
  10. type B pancreatic cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
DNA-binding protein RFX6
Alternative name(s):
Regulatory factor X 6
Regulatory factor X domain-containing protein 1
Gene namesi
Name:RFX6
Synonyms:RFXDC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:21478. RFX6.

Subcellular locationi

  1. Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Mitchell-Riley syndrome (MTCHRS)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder. There is no dysmorphic features.

See also OMIM:615710
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti181 – 1811R → Q in MTCHRS; abolishes DNA-binding. 1 Publication
VAR_062978
Natural varianti217 – 2171S → P in MTCHRS; induces a slight reduction in DNA-binding; in a patient still alive at age 4.5 years. 1 Publication
VAR_062979

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

MIMi615710. phenotype.
Orphaneti293864. Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome.
PharmGKBiPA162401254.

Polymorphism and mutation databases

BioMutaiRFX6.
DMDMi166225159.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 928928DNA-binding protein RFX6PRO_0000313721Add
BLAST

Proteomic databases

PaxDbiQ8HWS3.
PRIDEiQ8HWS3.

PTM databases

PhosphoSiteiQ8HWS3.

Expressioni

Tissue specificityi

Specifically expressed in pancreas, small intestine and colon.1 Publication

Gene expression databases

BgeeiQ8HWS3.
CleanExiHS_RFX6.
GenevestigatoriQ8HWS3.

Organism-specific databases

HPAiHPA037696.

Interactioni

Subunit structurei

Interacts with RFX3.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
AESQ081173EBI-746118,EBI-717810
CATSPER1Q8NEC53EBI-746118,EBI-744545
DTX2Q86UW94EBI-746118,EBI-740376
FRS3O435593EBI-746118,EBI-725515
NEDD9Q145113EBI-746118,EBI-2108053
PLEKHN1Q494U13EBI-746118,EBI-10241513
PRKAA1Q131313EBI-746118,EBI-1181405
PRKAA2P546463EBI-746118,EBI-1383852
SNRPBP14678-23EBI-746118,EBI-372475
SNRPCQ5TAL43EBI-746118,EBI-10246938
STK16O757163EBI-746118,EBI-749295
VPS37CA5D8V63EBI-746118,EBI-2559305

Protein-protein interaction databases

BioGridi128803. 25 interactions.
IntActiQ8HWS3. 20 interactions.
STRINGi9606.ENSP00000332208.

Structurei

3D structure databases

ProteinModelPortaliQ8HWS3.
SMRiQ8HWS3. Positions 124-198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the RFX family.PROSITE-ProRule annotation
Contains 1 RFX-type winged-helix DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG243313.
GeneTreeiENSGT00550000074532.
HOGENOMiHOG000154105.
HOVERGENiHBG108402.
InParanoidiQ8HWS3.
OMAiIHDPLNI.
OrthoDBiEOG79CXXT.
PhylomeDBiQ8HWS3.
TreeFamiTF321340.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR003150. DNA-bd_RFX.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF02257. RFX_DNA_binding. 1 hit.
[Graphical view]
PROSITEiPS51526. RFX_DBD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8HWS3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKVPELEDT FLQAQPAPQL SPGIQEDCCV QLLGKGLLVY PEETVYLAAE
60 70 80 90 100
GQPGGEQGGG EKGEDPELPG AVKSEMHLNN GNFSSEEEDA DNHDSKTKAA
110 120 130 140 150
DQYLSQKKTI TQIVKDKKKQ TQLTLQWLEE NYIVCEGVCL PRCILYAHYL
160 170 180 190 200
DFCRKEKLEP ACAATFGKTI RQKFPLLTTR RLGTRGHSKY HYYGIGIKES
210 220 230 240 250
SAYYHSVYSG KGLTRFSGSK LKNEGGFTRK YSLSSKTGTL LPEFPSAQHL
260 270 280 290 300
VYQGCISKDK VDTLIMMYKT HCQCILDNAI NGNFEEIQHF LLHFWQGMPD
310 320 330 340 350
HLLPLLENPV IIDIFCVCDS ILYKVLTDVL IPATMQEMPE SLLADIRNFA
360 370 380 390 400
KNWEQWVVSS LENLPEALTD KKIPIVRRFV SSLKRQTSFL HLAQIARPAL
410 420 430 440 450
FDQHVVNSMV SDIERVDLNS IGSQALLTIS GSTDTESGIY TEHDSITVFQ
460 470 480 490 500
ELKDLLKKNA TVEAFIEWLD TVVEQRVIKT SKQNGRSLKK RAQDFLLKWS
510 520 530 540 550
FFGARVMHNL TLNNASSFGS FHLIRMLLDE YILLAMETQF NNDKEQELQN
560 570 580 590 600
LLDKYMKNSD ASKAAFTASP SSCFLANRNK GSMVSSDAVK NESHVETTYL
610 620 630 640 650
PLPSSQPGGL GPALHQFPAG NTDNMPLTGQ MELSQIAGHL MTPPISPAMA
660 670 680 690 700
SRGSVINQGP MAGRPPSVGP VLSAPSHCST YPEPIYPTLP QANHDFYSTS
710 720 730 740 750
SNYQTVFRAQ PHSTSGLYPH HTEHGRCMAW TEQQLSRDFF SGSCAGSPYN
760 770 780 790 800
SRPPSSYGPS LQAQDSHNMQ FLNTGSFNFL SNTGAASCQG ATLPPNSPNG
810 820 830 840 850
YYGSNINYPE SHRLGSMVNQ HVSVISSIRS LPPYSDIHDP LNILDDSGRK
860 870 880 890 900
QTSSFYTDTS SPVACRTPVL ASSLQTPIPS SSSQCMYGTS NQYPAQETLD
910 920
SHGTSSREMV SSLPPINTVF MGTAAGGT
Length:928
Mass (Da):102,461
Last modified:January 15, 2008 - v2
Checksum:i9BB5340736CFC903
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti6 – 61E → K.1 Publication
Corresponds to variant rs17853900 [ dbSNP | Ensembl ].
VAR_037709
Natural varianti17 – 171A → E.
Corresponds to variant rs9489056 [ dbSNP | Ensembl ].
VAR_061768
Natural varianti181 – 1811R → Q in MTCHRS; abolishes DNA-binding. 1 Publication
VAR_062978
Natural varianti217 – 2171S → P in MTCHRS; induces a slight reduction in DNA-binding; in a patient still alive at age 4.5 years. 1 Publication
VAR_062979
Natural varianti688 – 6881T → A.1 Publication
Corresponds to variant rs17857184 [ dbSNP | Ensembl ].
VAR_037710
Natural varianti743 – 7431S → N.
Corresponds to variant rs582803 [ dbSNP | Ensembl ].
VAR_037711

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL355272 Genomic DNA. Translation: CAI23444.2.
CH471051 Genomic DNA. Translation: EAW48213.1.
BC039248 mRNA. Translation: AAH39248.1.
CCDSiCCDS5113.1.
RefSeqiNP_775831.2. NM_173560.3.
UniGeneiHs.352276.

Genome annotation databases

EnsembliENST00000332958; ENSP00000332208; ENSG00000185002.
GeneIDi222546.
KEGGihsa:222546.
UCSCiuc003pxm.3. human.

Polymorphism and mutation databases

BioMutaiRFX6.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL355272 Genomic DNA. Translation: CAI23444.2.
CH471051 Genomic DNA. Translation: EAW48213.1.
BC039248 mRNA. Translation: AAH39248.1.
CCDSiCCDS5113.1.
RefSeqiNP_775831.2. NM_173560.3.
UniGeneiHs.352276.

3D structure databases

ProteinModelPortaliQ8HWS3.
SMRiQ8HWS3. Positions 124-198.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128803. 25 interactions.
IntActiQ8HWS3. 20 interactions.
STRINGi9606.ENSP00000332208.

PTM databases

PhosphoSiteiQ8HWS3.

Polymorphism and mutation databases

BioMutaiRFX6.
DMDMi166225159.

Proteomic databases

PaxDbiQ8HWS3.
PRIDEiQ8HWS3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332958; ENSP00000332208; ENSG00000185002.
GeneIDi222546.
KEGGihsa:222546.
UCSCiuc003pxm.3. human.

Organism-specific databases

CTDi222546.
GeneCardsiGC06P117199.
H-InvDBHIX0025215.
HGNCiHGNC:21478. RFX6.
HPAiHPA037696.
MIMi612659. gene.
615710. phenotype.
neXtProtiNX_Q8HWS3.
Orphaneti293864. Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome.
PharmGKBiPA162401254.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG243313.
GeneTreeiENSGT00550000074532.
HOGENOMiHOG000154105.
HOVERGENiHBG108402.
InParanoidiQ8HWS3.
OMAiIHDPLNI.
OrthoDBiEOG79CXXT.
PhylomeDBiQ8HWS3.
TreeFamiTF321340.

Miscellaneous databases

GeneWikiiRFX6.
GenomeRNAii222546.
NextBioi91623.
PROiQ8HWS3.
SOURCEiSearch...

Gene expression databases

BgeeiQ8HWS3.
CleanExiHS_RFX6.
GenevestigatoriQ8HWS3.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR003150. DNA-bd_RFX.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF02257. RFX_DNA_binding. 1 hit.
[Graphical view]
PROSITEiPS51526. RFX_DBD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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], VARIANTS LYS-6 AND ALA-688.
    Tissue: Testis.
  4. "Identification and characterization of novel human tissue-specific RFX transcription factors."
    Aftab S., Semenec L., Chu J.S.-C., Chen N.
    BMC Evol. Biol. 8:226-226(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.
  5. Cited for: FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, VARIANTS MTCHRS GLN-181 AND PRO-217, CHARACTERIZATION OF VARIANTS MTCHRS GLN-181 AND PRO-217.

Entry informationi

Entry nameiRFX6_HUMAN
AccessioniPrimary (citable) accession number: Q8HWS3
Secondary accession number(s): Q5T6B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: April 29, 2015
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.