UniProtKB - Q8HWS3 (RFX6_HUMAN)
DNA-binding protein RFX6
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 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 124 – 199 | RFX-type winged-helixPROSITE-ProRule annotationAdd BLAST | 76 |
GO - Molecular functioni
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- endocrine pancreas development Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- 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
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: NTNU_SB
- regulation of insulin secretion Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- type B pancreatic cell differentiation Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, DNA-binding |
Biological process | Differentiation, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q8HWS3 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells |
SignaLinki | Q8HWS3 |
Names & Taxonomyi
Protein namesi | Recommended name: DNA-binding protein RFX6Alternative 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21478, RFX6 |
MIMi | 612659, gene |
neXtProti | NX_Q8HWS3 |
VEuPathDBi | HostDB:ENSG00000185002 |
Pathology & Biotechi
Involvement in diseasei
Mitchell-Riley syndrome (MTCHRS)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | 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 variantOrganism-specific databases
DisGeNETi | 222546 |
MalaCardsi | RFX6 |
MIMi | 615710, phenotype |
OpenTargetsi | ENSG00000185002 |
Orphaneti | 293864, Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome |
PharmGKBi | PA162401254 |
Miscellaneous databases
Pharosi | Q8HWS3, Tbio |
Genetic variation 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
MassIVEi | Q8HWS3 |
PaxDbi | Q8HWS3 |
PeptideAtlasi | Q8HWS3 |
PRIDEi | Q8HWS3 |
ProteomicsDBi | 70500 |
PTM databases
iPTMneti | Q8HWS3 |
PhosphoSitePlusi | Q8HWS3 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000185002, Expressed in islet of Langerhans and 51 other tissues |
Genevisiblei | Q8HWS3, HS |
Organism-specific databases
HPAi | ENSG00000185002, Group enriched (adrenal gland, intestine, pancreas, stomach) |
Interactioni
Subunit structurei
Interacts with RFX3.
By similarityBinary interactionsi
Q8HWS3
Protein-protein interaction databases
BioGRIDi | 128803, 42 interactors |
IntActi | Q8HWS3, 43 interactors |
MINTi | Q8HWS3 |
STRINGi | 9606.ENSP00000332208 |
Miscellaneous databases
RNActi | Q8HWS3, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 20 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 50 – 98 | DisorderedSequence analysisAdd BLAST | 49 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 82 – 98 | Basic and acidic residuesSequence analysisAdd BLAST | 17 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3712, Eukaryota |
GeneTreei | ENSGT00980000198574 |
HOGENOMi | CLU_013981_0_0_1 |
InParanoidi | Q8HWS3 |
OMAi | GSAPCMF |
OrthoDBi | 346630at2759 |
PhylomeDBi | Q8HWS3 |
TreeFami | TF321340 |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR003150, DNA-bd_RFX IPR039779, RFX-like IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR12619, PTHR12619, 1 hit |
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 |
i Sequence
Sequence statusi: Complete.
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | 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 |
CCDSi | CCDS5113.1 |
RefSeqi | NP_775831.2, NM_173560.3 |
Genome annotation databases
Ensembli | ENST00000332958.3; ENSP00000332208.2; ENSG00000185002.10 |
GeneIDi | 222546 |
KEGGi | hsa:222546 |
MANE-Selecti | ENST00000332958.3; ENSP00000332208.2; NM_173560.4; NP_775831.2 |
UCSCi | uc003pxm.4, human |
Similar proteinsi
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 |
3D structure databases
AlphaFoldDBi | Q8HWS3 |
SMRi | Q8HWS3 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 128803, 42 interactors |
IntActi | Q8HWS3, 43 interactors |
MINTi | Q8HWS3 |
STRINGi | 9606.ENSP00000332208 |
PTM databases
iPTMneti | Q8HWS3 |
PhosphoSitePlusi | Q8HWS3 |
Genetic variation databases
BioMutai | RFX6 |
DMDMi | 166225159 |
Proteomic databases
MassIVEi | Q8HWS3 |
PaxDbi | Q8HWS3 |
PeptideAtlasi | Q8HWS3 |
PRIDEi | Q8HWS3 |
ProteomicsDBi | 70500 |
Protocols and materials databases
Antibodypediai | 32535, 73 antibodies from 19 providers |
DNASUi | 222546 |
Genome annotation databases
Ensembli | ENST00000332958.3; ENSP00000332208.2; ENSG00000185002.10 |
GeneIDi | 222546 |
KEGGi | hsa:222546 |
MANE-Selecti | ENST00000332958.3; ENSP00000332208.2; NM_173560.4; NP_775831.2 |
UCSCi | uc003pxm.4, human |
Organism-specific databases
CTDi | 222546 |
DisGeNETi | 222546 |
GeneCardsi | RFX6 |
HGNCi | HGNC:21478, RFX6 |
HPAi | ENSG00000185002, Group enriched (adrenal gland, intestine, pancreas, stomach) |
MalaCardsi | RFX6 |
MIMi | 612659, gene 615710, phenotype |
neXtProti | NX_Q8HWS3 |
OpenTargetsi | ENSG00000185002 |
Orphaneti | 293864, Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome |
PharmGKBi | PA162401254 |
VEuPathDBi | HostDB:ENSG00000185002 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3712, Eukaryota |
GeneTreei | ENSGT00980000198574 |
HOGENOMi | CLU_013981_0_0_1 |
InParanoidi | Q8HWS3 |
OMAi | GSAPCMF |
OrthoDBi | 346630at2759 |
PhylomeDBi | Q8HWS3 |
TreeFami | TF321340 |
Enzyme and pathway databases
PathwayCommonsi | Q8HWS3 |
Reactomei | R-HSA-210745, Regulation of gene expression in beta cells |
SignaLinki | Q8HWS3 |
Miscellaneous databases
BioGRID-ORCSi | 222546, 13 hits in 1088 CRISPR screens |
GeneWikii | RFX6 |
GenomeRNAii | 222546 |
Pharosi | Q8HWS3, Tbio |
PROi | PR:Q8HWS3 |
RNActi | Q8HWS3, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000185002, Expressed in islet of Langerhans and 51 other tissues |
Genevisiblei | Q8HWS3, HS |
Family and domain databases
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR003150, DNA-bd_RFX IPR039779, RFX-like IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR12619, PTHR12619, 1 hit |
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 |
MobiDBi | 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: | May 25, 2022 | |
This is version 159 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
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families