RFX6

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 (PubMed:20148032, PubMed:25497100). 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 (PubMed:20148032). Involved in glucose-stimulated insulin secretion by promoting insulin and L-type calcium channel gene transcription (PubMed:25497100).2 Publications

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
DNA bindingⁱ	124 – 199	RFX-type winged-helixPROSITE-ProRule annotationAdd BLAST		76

GO - Molecular functionⁱ

RNA polymerase II proximal promoter sequence-specific DNA binding Source: GO_Central
RNA polymerase II regulatory region sequence-specific DNA binding
Source: NTNU_SB
Inferred from direct assayⁱ
- 20148032
RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding
Source: NTNU_SB
Inferred from direct assayⁱ
- 20148032
transcription regulatory region DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 20148032

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

endocrine pancreas development
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20148032
glucose homeostasis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20148032
pancreatic A cell differentiation Source: UniProtKB
pancreatic D cell differentiation Source: UniProtKB
pancreatic epsilon cell differentiation Source: UniProtKB
positive regulation of insulin secretion involved in cellular response to glucose stimulus
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25497100
positive regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 20148032
positive regulation of transcription by RNA polymerase II
Source: NTNU_SB
Inferred from direct assayⁱ
- 20148032
regulation of insulin secretion
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20148032
type B pancreatic cell differentiation Source: UniProtKB

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding
Biological process	Differentiation, Transcription, Transcription regulation

Enzyme and pathway databases

Reactomeⁱ	R-HSA-210745 Regulation of gene expression in beta cells

Reactomeⁱ

R-HSA-210745 Regulation of gene expression in beta cells

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 6

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000185002.9
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:21478 RFX6
MIMⁱ	612659 gene
neXtProtⁱ	NX_Q8HWS3

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Mitchell-Riley syndrome (MTCHRS)2 Publications

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.

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_062978	181	R → Q in MTCHRS; abolishes DNA-binding. 1 PublicationCorresponds to variant dbSNP:rs267607013EnsemblClinVar.	1
Natural variantⁱVAR_062979	217	S → P in MTCHRS; induces a slight reduction in DNA-binding; in a patient still alive at age 4.5 years. 1 PublicationCorresponds to variant dbSNP:rs267607012EnsemblClinVar.	1
Natural variantⁱVAR_074215	506	V → G in MTCHRS; inhibits the transactivation of the insulin and beta-cell L-type calcium channel genes. 1 Publication	1

Keywords - Diseaseⁱ

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	222546
MalaCards human disease database More...MalaCardsⁱ	RFX6
MIMⁱ	615710 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000185002
Orphanetⁱ	293864 Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome
PharmGKBⁱ	PA162401254

Polymorphism and mutation databases

BioMutaⁱ	RFX6
DMDMⁱ	166225159

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000313721	1 – 928	DNA-binding protein RFX6Add BLAST		928

Proteomic databases

PaxDbⁱ	Q8HWS3
PeptideAtlas More...PeptideAtlasⁱ	Q8HWS3
PRIDEⁱ	Q8HWS3
ProteomicsDBⁱ	70500

PTM databases

iPTMnetⁱ	Q8HWS3
PhosphoSitePlusⁱ	Q8HWS3

Expressionⁱ

Tissue specificityⁱ

Expressed in pancreas (PubMed:25497100). Expressed in pancreatic beta-cells (insulin-positive cells) and alpha-cells (glucagon-positive cells) (at protein level). Specifically expressed in pancreas, small intestine and colon (PubMed:20148032). Expressed in endocrine cells in the islets (PubMed:25497100).2 Publications

Gene expression databases

Bgeeⁱ	ENSG00000185002 Expressed in 40 organ(s), highest expression level in adrenal tissue
CleanExⁱ	HS_RFX6
Genevisibleⁱ	Q8HWS3 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA037696 HPA037697

HPAⁱ

HPA037696
HPA037697

Interactionⁱ

Subunit structureⁱ

Interacts with RFX3.By similarity

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
AES	Q08117	3	EBI-746118,EBI-717810
CATSPER1	Q8NEC5	5	EBI-746118,EBI-744545
DTX2	Q86UW9	4	EBI-746118,EBI-740376
FRS3	O43559	5	EBI-746118,EBI-725515
HGS	A0A0S2Z4Q4	3	EBI-746118,EBI-16429135
HGS	O14964	3	EBI-746118,EBI-740220
NEDD9	Q14511	3	EBI-746118,EBI-2108053
PLEKHN1	Q494U1	3	EBI-746118,EBI-10241513
PRKAA1	Q13131	3	EBI-746118,EBI-1181405
PRKAA2	P54646	3	EBI-746118,EBI-1383852
RFX2	P48378	3	EBI-746118,EBI-746731
SNRPB	P14678-2	5	EBI-746118,EBI-372475
SNRPC	Q5TAL4	3	EBI-746118,EBI-10246938
STK16	O75716	3	EBI-746118,EBI-749295
VPS37C	A5D8V6	3	EBI-746118,EBI-2559305
ZNF688	A0A0S2Z5X4	3	EBI-746118,EBI-16429014

Protein-protein interaction databases

BioGridⁱ	128803, 26 interactors
IntActⁱ	Q8HWS3, 37 interactors
Molecular INTeraction database More...MINTⁱ	Q8HWS3
STRINGⁱ	9606.ENSP00000332208

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q8HWS3
SMRⁱ	Q8HWS3
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the RFX family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGⁱ	KOG3712 Eukaryota ENOG410XSKJ LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00550000074532
HOGENOMⁱ	HOG000154105
HOVERGENⁱ	HBG108402
InParanoidⁱ	Q8HWS3
KEGG Orthology (KO) More...KOⁱ	K19521
OMAⁱ	IDIFCVC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G01JI
PhylomeDBⁱ	Q8HWS3
TreeFamⁱ	TF321340

Family and domain databases

Gene3Dⁱ	1.10.10.10, 1 hit
InterProⁱ	View protein in InterPro IPR003150 DNA-bd_RFX IPR036388 WH-like_DNA-bd_sf IPR036390 WH_DNA-bd_sf
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF02257 RFX_DNA_binding, 1 hit
SUPFAMⁱ	SSF46785 SSF46785, 1 hit
PROSITEⁱ	View protein in PROSITE PS51526 RFX_DBD, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

Q8HWS3-1 [UniParc]FASTA Add 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 key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_037709	6	E → K1 PublicationCorresponds to variant dbSNP:rs17853900Ensembl.	1
Natural variantⁱVAR_061768	17	A → E. Corresponds to variant dbSNP:rs9489056EnsemblClinVar.	1
Natural variantⁱVAR_062978	181	R → Q in MTCHRS; abolishes DNA-binding. 1 PublicationCorresponds to variant dbSNP:rs267607013EnsemblClinVar.	1
Natural variantⁱVAR_062979	217	S → P in MTCHRS; induces a slight reduction in DNA-binding; in a patient still alive at age 4.5 years. 1 PublicationCorresponds to variant dbSNP:rs267607012EnsemblClinVar.	1
Natural variantⁱVAR_074215	506	V → G in MTCHRS; inhibits the transactivation of the insulin and beta-cell L-type calcium channel genes. 1 Publication	1
Natural variantⁱVAR_037710	688	T → A1 PublicationCorresponds to variant dbSNP:rs17857184Ensembl.	1
Natural variantⁱVAR_037711	743	S → N. Corresponds to variant dbSNP:rs582803Ensembl.	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AL355272 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48213.1 BC039248 mRNA Translation: AAH39248.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS5113.1
NCBI Reference Sequences More...RefSeqⁱ	NP_775831.2, NM_173560.3
UniGeneⁱ	Hs.352276

Genome annotation databases

Ensemblⁱ	ENST00000332958; ENSP00000332208; ENSG00000185002
GeneIDⁱ	222546
KEGGⁱ	hsa:222546
UCSC genome browser More...UCSCⁱ	uc003pxm.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Protein	Similar proteins		Species	Score	Length	Source
Q8HWS3	DNA-binding protein RFX6		AILME		928	UniRef90_Q8HWS3
Uncharacterized protein		MACFA		932
Uncharacterized protein		MACMU		932
Regulatory factor X6		LOXAF		931
DNA-binding protein RFX6		Florida manatee		929
+86

Protein	Similar proteins		Species	Score	Length	Source
Q8HWS3	DNA-binding protein RFX6		AILME		928	UniRef50_Q8HWS3
DNA-binding protein RFX6		MOUSE		927
DNA-binding protein RFX6		DANRE		848
Uncharacterized protein		MACFA		932
Uncharacterized protein		MACMU		932
+346

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AL355272 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48213.1 BC039248 mRNA Translation: AAH39248.1
CCDSⁱ	CCDS5113.1
RefSeqⁱ	NP_775831.2, NM_173560.3
UniGeneⁱ	Hs.352276

3D structure databases

ProteinModelPortalⁱ	Q8HWS3
SMRⁱ	Q8HWS3
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	128803, 26 interactors
IntActⁱ	Q8HWS3, 37 interactors
MINTⁱ	Q8HWS3
STRINGⁱ	9606.ENSP00000332208

PTM databases

iPTMnetⁱ	Q8HWS3
PhosphoSitePlusⁱ	Q8HWS3

Polymorphism and mutation databases

BioMutaⁱ	RFX6
DMDMⁱ	166225159

Proteomic databases

PaxDbⁱ	Q8HWS3
PeptideAtlasⁱ	Q8HWS3
PRIDEⁱ	Q8HWS3
ProteomicsDBⁱ	70500

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000332958; ENSP00000332208; ENSG00000185002
GeneIDⁱ	222546
KEGGⁱ	hsa:222546
UCSCⁱ	uc003pxm.4 human

Organism-specific databases

CTDⁱ	222546
DisGeNETⁱ	222546
EuPathDBⁱ	HostDB:ENSG00000185002.9
GeneCardsⁱ	RFX6
H-InvDBⁱ	HIX0025215
HGNCⁱ	HGNC:21478 RFX6
HPAⁱ	HPA037696 HPA037697
MalaCardsⁱ	RFX6
MIMⁱ	612659 gene 615710 phenotype
neXtProtⁱ	NX_Q8HWS3
OpenTargetsⁱ	ENSG00000185002
Orphanetⁱ	293864 Hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome
PharmGKBⁱ	PA162401254
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG3712 Eukaryota ENOG410XSKJ LUCA
GeneTreeⁱ	ENSGT00550000074532
HOGENOMⁱ	HOG000154105
HOVERGENⁱ	HBG108402
InParanoidⁱ	Q8HWS3
KOⁱ	K19521
OMAⁱ	IDIFCVC
OrthoDBⁱ	EOG091G01JI
PhylomeDBⁱ	Q8HWS3
TreeFamⁱ	TF321340

Enzyme and pathway databases

Reactomeⁱ	R-HSA-210745 Regulation of gene expression in beta cells

Reactomeⁱ

R-HSA-210745 Regulation of gene expression in beta cells

Miscellaneous databases

GeneWikiⁱ	RFX6
GenomeRNAiⁱ	222546
Protein Ontology More...PROⁱ	PR:Q8HWS3
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000185002 Expressed in 40 organ(s), highest expression level in adrenal tissue
CleanExⁱ	HS_RFX6
Genevisibleⁱ	Q8HWS3 HS

Family and domain databases

Gene3Dⁱ	1.10.10.10, 1 hit
InterProⁱ	View protein in InterPro IPR003150 DNA-bd_RFX IPR036388 WH-like_DNA-bd_sf IPR036390 WH_DNA-bd_sf
Pfamⁱ	View protein in Pfam PF02257 RFX_DNA_binding, 1 hit
SUPFAMⁱ	SSF46785 SSF46785, 1 hit
PROSITEⁱ	View protein in PROSITE PS51526 RFX_DBD, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	RFX6_HUMAN
Accessionⁱ	Q8HWS3Primary (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:	September 12, 2018
	This is version 135 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

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Annotation systems

Supporting data

UniProtKB - Q8HWS3 (RFX6_HUMAN)

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DNA-binding protein RFX6

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ