P48381
SS
Gene name |
Rfx3 |
Protein name |
Transcription factor RFX3 |
Names |
Regulatory factor X 3 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:19726 |
EC number |
|
Protein Class |
|
Descriptions
RFX1 is a regulatory factor essential for MHC class II genes expression, and binds to the X boxes of MHC class II genes. This protein possesses intrinsically disordered regions (IDRs) with large negative charge, some of which involve a consecutive sequence of aspartate (D) or glutamate (E) residues, known as D/E repeats. These D/E repeats can cause autoinhibition through intramolecular electrostatic interaction with HMG boxes and modulate binding to DNA. This autoinhibited state can transition into the uninhibited complex with DNA through an electrostatically driven induced-fit process, which accelerates the target DNA search kinetics in the presence of non-functional high-affinity ligands ('decoys').
Autoinhibitory domains (AIDs)
Target domain |
113-272 (DNA binding domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Wang X et al. (2023) "Negatively charged, intrinsically disordered regions can accelerate target search by DNA-binding proteins", Nucleic acids research, 51, 4701-4712
- Katan-Khaykovich Y et al. (2001) "Nuclear import and DNA-binding activity of RFX1. Evidence for an autoinhibitory mechanism", European journal of biochemistry, 268, 3108-16
- Stott K et al. (2010) "Tail-mediated collapse of HMGB1 is dynamic and occurs via differential binding of the acidic tail to the A and B domains", Journal of molecular biology, 403, 706-22
- Watson M et al. (2007) "Mapping intramolecular interactions between domains in HMGB1 using a tail-truncation approach", Journal of molecular biology, 374, 1286-97
- Stott K et al. (2014) "Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain", The Journal of biological chemistry, 289, 29817-26
- Ueshima S et al. (2017) "Internal Associations of the Acidic Region of Upstream Binding Factor Control Its Nucleolar Localization", Molecular and cellular biology, 37,
- Wang X et al. (2021) "Dynamic Autoinhibition of the HMGB1 Protein via Electrostatic Fuzzy Interactions of Intrinsically Disordered Regions", Journal of molecular biology, 433, 167122
- Gajiwala KS et al. (2000) "Structure of the winged-helix protein hRFX1 reveals a new mode of DNA binding", Nature, 403, 916-21
Autoinhibited structure
Activated structure
1 structures for P48381
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P48381-F1 | Predicted | AlphaFoldDB |
23 variants for P48381
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs864270135 | 87 | Q>R | No | EVA | |
| rs3389545711 | 133 | G>R | No | EVA | |
| rs3389526186 | 167 | Q>* | No | EVA | |
| rs3389480963 | 171 | G>S | No | EVA | |
| rs3389532037 | 267 | E>K | No | EVA | |
| rs3389442470 | 324 | L>* | No | EVA | |
| rs3389526129 | 370 | N>Y | No | EVA | |
| rs3389442436 | 377 | E>* | No | EVA | |
| rs3389545718 | 408 | S>N | No | EVA | |
| rs3389526112 | 418 | L>R | No | EVA | |
| rs3389534090 | 491 | A>T | No | EVA | |
| rs864264656 | 561 | Q>L | No | EVA | |
| rs3409235101 | 607 | M>L | No | EVA | |
| rs3389543104 | 609 | I>V | No | EVA | |
| rs3389533211 | 634 | M>I | No | EVA | |
| rs3389499782 | 634 | M>L | No | EVA | |
| rs3389499782 | 634 | M>V | No | EVA | |
| rs3389528512 | 667 | N>S | No | EVA | |
| rs3389526156 | 670 | K>N | No | EVA | |
| rs222395018 | 680 | T>M | No | EVA | |
| rs240008741 | 691 | R>Q | No | EVA | |
| rs30366372 | 715 | A>G | No | EVA | |
| rs3389533225 | 737 | R>M | No | EVA |
No associated diseases with P48381
No regional properties for P48381
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for P48381 | |||
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| chromatin | The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. |
| extracellular region | The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| transcription regulator complex | A protein complex that is capable of associating with DNA by direct binding, or via other DNA-binding proteins or complexes, and regulating transcription. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| DNA-binding transcription factor activity | A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons. |
| DNA-binding transcription factor activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II. |
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II. |
| sequence-specific DNA binding | Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding. |
| transcription cis-regulatory region binding | Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon. |
15 GO annotations of biological process
| Name | Definition |
|---|---|
| cell maturation | The cellular developmental process, independent of morphogenetic (shape) change, that is required for a specific cell to attain its fully functional state. |
| cilium assembly | The assembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole. |
| cilium-dependent cell motility | Cell motility due to the motion of one or more eukaryotic cilia. A eukaryotic cilium is a specialized organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole. |
| determination of left/right symmetry | The establishment of an organism's body plan or part of an organism with respect to the left and right halves. The pattern can either be symmetric, such that the halves are mirror images, or asymmetric where the pattern deviates from this symmetry. |
| DNA-templated transcription | The synthesis of an RNA transcript from a DNA template. |
| endocrine pancreas development | The process whose specific outcome is the progression of the endocrine pancreas over time, from its formation to the mature structure. The endocrine pancreas is made up of islet cells that produce insulin, glucagon and somatostatin. |
| epithelial cilium movement involved in determination of left/right asymmetry | The movement of cilia of epithelial cells of the Left Right Organizer (LRO), also referred to as the node in mouse or the Kupffer's vesicle in zebrafish, resulting in the leftward fluid flow across the LRO and generation or transport of a signal which determines asymmetry in an organism's body plan with respect to the left and right halves. |
| negative regulation of DNA-templated transcription | Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription. |
| positive regulation of DNA-templated transcription | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| positive regulation of type B pancreatic cell development | Any process that activates or increases the frequency, rate or extent of pancreatic B cell development. |
| regulation of DNA-templated transcription | Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. |
| regulation of insulin secretion | Any process that modulates the frequency, rate or extent of the regulated release of insulin. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| type B pancreatic cell maturation | A developmental process, independent of morphogenetic (shape) change, that is required for a type B pancreatic cell to attain its fully functional state. A type B pancreatic cell is a cell located towards center of the islets of Langerhans that secretes insulin. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P22670 | RFX1 | MHC class II regulatory factor RFX1 | Homo sapiens (Human) | EV |
| P48378 | RFX2 | DNA-binding protein RFX2 | Homo sapiens (Human) | SS |
| P48380 | RFX3 | Transcription factor RFX3 | Homo sapiens (Human) | SS |
| P48377 | Rfx1 | MHC class II regulatory factor RFX1 | Mus musculus (Mouse) | SS |
| Q0V9K5 | rfx3 | Transcription factor RFX3 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MQTSETGSDT | GSTVTLQTSV | ASQAAVPTQV | VQQVPVQQQV | QQVQTVQQVQ | HVYPAQVQYV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EGSDTVYTNG | AIRTTTYPYT | ETQMYSQNTG | GNYFDTQGSS | AQVTTVVSSH | SMVGTGGIQM |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GVTGGQLISS | SGGTYLIGNS | MENSGHSVTH | TTRASPATIE | MAIETLQKSD | GLSTHRSSLL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| NSHLQWLLDN | YETAEGVSLP | RSTLYNHYLR | HCQEHKLDPV | NAASFGKLIR | SIFMGLRTRR |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LGTRGNSKYH | YYGIRVKPDS | PLNRLQEDMQ | YMAMRQQPMQ | QKQRYKPMQK | VDGVADGFTG |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SGQQTGTSVE | QTVIAQSQHH | QQFLDASRAL | PEFGEVEISS | LPDGTTFEDI | KSLQSLYREH |
| 370 | 380 | 390 | 400 | 410 | 420 |
| CEAILDVVVN | LQFSLIEKLW | QTFWRYSPST | PADGTTITES | SNLSEIESRL | PKAKLITLCK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| HESILKWMCN | CDHGMYQALV | EILIPDVLRP | IPSALTQAIR | NFAKSLEGWL | SNAMNNIPQR |
| 490 | 500 | 510 | 520 | 530 | 540 |
| MIQTKVAAVS | AFAQTLRRYT | SLNHLAQAAR | AVLQNTSQIN | QMLSDLNRVD | FANVQEQASW |
| 550 | 560 | 570 | 580 | 590 | 600 |
| VCQCDDNMVQ | RLETDFKMTL | QQQSTLEQWA | AWLDNVMMQA | LKPYEGRPSF | PKAARQFLLK |
| 610 | 620 | 630 | 640 | 650 | 660 |
| WSFYSSMVIR | DLTLRSAASF | GSFHLIRLLY | DEYMFYLVEH | RVAQVTGETP | IAVMGEFGDL |
| 670 | 680 | 690 | 700 | 710 | 720 |
| NAVSPGNLDK | DEGSEVESET | DEDLDDSSEP | RAKREKTELS | QAFPVGCMQP | VLESAVQPSL |
| 730 | 740 | ||||
| LNPLHSEHIV | TSTQTIRQCS | ATGNTYTAV |