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Q8HWS3 (RFX6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA-binding protein RFX6
Alternative name(s):
Regulatory factor X 6
Regulatory factor X domain-containing protein 1
Gene names
Name:RFX6
Synonyms:RFXDC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length928 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Subunit structure

Interacts with RFX3 By similarity.

Subcellular location

Nucleus By similarity.

Tissue specificity

Specifically expressed in pancreas, small intestine and colon. Ref.5

Involvement in disease

Mitchell-Riley syndrome (MIRIS) [MIM:601346]: A disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder. There is no dysmorphic features.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the RFX family.

Contains 1 RFX-type winged-helix DNA-binding domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
Disease mutation
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processendocrine pancreas development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

glucose homeostasis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

pancreatic A cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

pancreatic D cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

pancreatic epsilon cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of insulin secretion

Inferred from mutant phenotype Ref.5. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

type B pancreatic cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentnucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

transcription regulatory region DNA binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 928928DNA-binding protein RFX6
PRO_0000313721

Regions

DNA binding124 – 19976RFX-type winged-helix Ref.5

Natural variations

Natural variant61E → K. Ref.3
Corresponds to variant rs17853900 [ dbSNP | Ensembl ].
VAR_037709
Natural variant171A → E.
Corresponds to variant rs9489056 [ dbSNP | Ensembl ].
VAR_061768
Natural variant1811R → Q in MIRIS; abolishes DNA-binding. Ref.5
VAR_062978
Natural variant2171S → P in MIRIS; induces a slight reduction in DNA-binding; in a patient still alive at age 4.5 years. Ref.5
VAR_062979
Natural variant6881T → A. Ref.3
Corresponds to variant rs17857184 [ dbSNP | Ensembl ].
VAR_037710
Natural variant7431S → N.
Corresponds to variant rs582803 [ dbSNP | Ensembl ].
VAR_037711

Sequences

Sequence LengthMass (Da)Tools
Q8HWS3 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 9BB5340736CFC903

FASTA928102,461
        10         20         30         40         50         60 
MAKVPELEDT FLQAQPAPQL SPGIQEDCCV QLLGKGLLVY PEETVYLAAE GQPGGEQGGG 

        70         80         90        100        110        120 
EKGEDPELPG AVKSEMHLNN GNFSSEEEDA DNHDSKTKAA DQYLSQKKTI TQIVKDKKKQ 

       130        140        150        160        170        180 
TQLTLQWLEE NYIVCEGVCL PRCILYAHYL DFCRKEKLEP ACAATFGKTI RQKFPLLTTR 

       190        200        210        220        230        240 
RLGTRGHSKY HYYGIGIKES SAYYHSVYSG KGLTRFSGSK LKNEGGFTRK YSLSSKTGTL 

       250        260        270        280        290        300 
LPEFPSAQHL VYQGCISKDK VDTLIMMYKT HCQCILDNAI NGNFEEIQHF LLHFWQGMPD 

       310        320        330        340        350        360 
HLLPLLENPV IIDIFCVCDS ILYKVLTDVL IPATMQEMPE SLLADIRNFA KNWEQWVVSS 

       370        380        390        400        410        420 
LENLPEALTD KKIPIVRRFV SSLKRQTSFL HLAQIARPAL FDQHVVNSMV SDIERVDLNS 

       430        440        450        460        470        480 
IGSQALLTIS GSTDTESGIY TEHDSITVFQ ELKDLLKKNA TVEAFIEWLD TVVEQRVIKT 

       490        500        510        520        530        540 
SKQNGRSLKK RAQDFLLKWS FFGARVMHNL TLNNASSFGS FHLIRMLLDE YILLAMETQF 

       550        560        570        580        590        600 
NNDKEQELQN LLDKYMKNSD ASKAAFTASP SSCFLANRNK GSMVSSDAVK NESHVETTYL 

       610        620        630        640        650        660 
PLPSSQPGGL GPALHQFPAG NTDNMPLTGQ MELSQIAGHL MTPPISPAMA SRGSVINQGP 

       670        680        690        700        710        720 
MAGRPPSVGP VLSAPSHCST YPEPIYPTLP QANHDFYSTS SNYQTVFRAQ PHSTSGLYPH 

       730        740        750        760        770        780 
HTEHGRCMAW TEQQLSRDFF SGSCAGSPYN SRPPSSYGPS LQAQDSHNMQ FLNTGSFNFL 

       790        800        810        820        830        840 
SNTGAASCQG ATLPPNSPNG YYGSNINYPE SHRLGSMVNQ HVSVISSIRS LPPYSDIHDP 

       850        860        870        880        890        900 
LNILDDSGRK QTSSFYTDTS SPVACRTPVL ASSLQTPIPS SSSQCMYGTS NQYPAQETLD 

       910        920 
SHGTSSREMV SSLPPINTVF MGTAAGGT 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Rfx6 directs islet formation and insulin production in mice and humans."
Smith S.B., Qu H.Q., Taleb N., Kishimoto N.Y., Scheel D.W., Lu Y., Patch A.M., Grabs R., Wang J., Lynn F.C., Miyatsuka T., Mitchell J., Seerke R., Desir J., Eijnden S.V., Abramowicz M., Kacet N., Weill J. expand/collapse author list , Renard M.E., Gentile M., Hansen I., Dewar K., Hattersley A.T., Wang R., Wilson M.E., Johnson J.D., Polychronakos C., German M.S.
Nature 463:775-780(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, TISSUE SPECIFICITY, VARIANTS MIRIS GLN-181 AND PRO-217, CHARACTERIZATION OF VARIANTS MIRIS GLN-181 AND PRO-217.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL355272 Genomic DNA. Translation: CAI23444.2.
CH471051 Genomic DNA. Translation: EAW48213.1.
BC039248 mRNA. Translation: AAH39248.1.
CCDSCCDS5113.1.
RefSeqNP_775831.2. NM_173560.3.
UniGeneHs.352276.

3D structure databases

ProteinModelPortalQ8HWS3.
SMRQ8HWS3. Positions 124-198.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128803. 9 interactions.
IntActQ8HWS3. 10 interactions.
STRING9606.ENSP00000332208.

PTM databases

PhosphoSiteQ8HWS3.

Polymorphism databases

DMDM166225159.

Proteomic databases

PaxDbQ8HWS3.
PRIDEQ8HWS3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332958; ENSP00000332208; ENSG00000185002.
GeneID222546.
KEGGhsa:222546.
UCSCuc003pxm.3. human.

Organism-specific databases

CTD222546.
GeneCardsGC06P117199.
H-InvDBHIX0025215.
HGNCHGNC:21478. RFX6.
HPAHPA037696.
MIM601346. phenotype.
612659. gene.
neXtProtNX_Q8HWS3.
Orphanet293864. Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome.
PharmGKBPA162401254.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG243313.
HOGENOMHOG000154105.
HOVERGENHBG108402.
OMAIHDPLNI.
OrthoDBEOG79CXXT.
PhylomeDBQ8HWS3.
TreeFamTF321340.

Gene expression databases

BgeeQ8HWS3.
CleanExHS_RFX6.
GenevestigatorQ8HWS3.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR003150. DNA-bd_RFX.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF02257. RFX_DNA_binding. 1 hit.
[Graphical view]
PROSITEPS51526. RFX_DBD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRFX6.
GenomeRNAi222546.
NextBio91623.
PROQ8HWS3.
SOURCESearch...

Entry information

Entry nameRFX6_HUMAN
AccessionPrimary (citable) accession number: Q8HWS3
Secondary accession number(s): Q5T6B3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM