P48377
SS
Gene name |
Rfx1 |
Protein name |
MHC class II regulatory factor RFX1 |
Names |
Regulatory factor X 1 , Transcription factor RFX1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:19724 |
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 |
342-512 (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 P48377
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P48377-F1 | Predicted | AlphaFoldDB |
38 variants for P48377
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs259255201 | 17 | S>P | No | EVA | |
| rs3399348277 | 29 | Q>P | No | EVA | |
| rs3388988355 | 84 | P>L | No | EVA | |
| rs3388981736 | 104 | R>W | No | EVA | |
| rs3388995275 | 121 | T>I | No | EVA | |
| rs3388992798 | 145 | Q>E | No | EVA | |
| rs3388995722 | 150 | H>Y | No | EVA | |
| rs3388966018 | 188 | T>R | No | EVA | |
| rs3388987443 | 197 | S>Y | No | EVA | |
| rs3507898442 | 218 | A>V | No | EVA | |
| rs3388995252 | 310 | E>G | No | EVA | |
| rs3388992665 | 313 | I>T | No | EVA | |
| rs3389000451 | 314 | Y>* | No | EVA | |
| rs3388992596 | 440 | P>S | No | EVA | |
| rs3388981717 | 442 | S>N | No | EVA | |
| rs3388976456 | 451 | H>D | No | EVA | |
| rs3388988313 | 475 | G>S | No | EVA | |
| rs3388996993 | 504 | R>W | No | EVA | |
| rs3399175622 | 513 | A>S | No | EVA | |
| rs1134878815 | 515 | R>Q | No | EVA | |
| rs3388972393 | 517 | Q>K | No | EVA | |
| rs3388992802 | 518 | P>S | No | EVA | |
| rs3388992788 | 597 | R>L | No | EVA | |
| rs3399414291 | 623 | W>C | No | EVA | |
| rs3399348268 | 638 | V>V*SHMQRSPPSEPWGLTRP | No | EVA | |
| rs3388994304 | 643 | E>K | No | EVA | |
| rs3388992826 | 647 | P>S | No | EVA | |
| rs3388992604 | 677 | E>G | No | EVA | |
| rs3388946855 | 677 | E>K | No | EVA | |
| rs3388994278 | 740 | H>Y | No | EVA | |
| rs3388999804 | 786 | Q>K | No | EVA | |
| rs3388946849 | 822 | G>D | No | EVA | |
| rs3388992803 | 832 | L>P | No | EVA | |
| rs3388992797 | 842 | S>Y | No | EVA | |
| rs3388988330 | 844 | V>E | No | EVA | |
| rs3388999872 | 918 | E>* | No | EVA | |
| rs3388966037 | 948 | A>T | No | EVA | |
| rs3546748591 | 953 | R>H | No | EVA |
No associated diseases with P48377
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| 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. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| DNA binding | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). |
| 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. |
1 GO annotations of biological process
| Name | Definition |
|---|---|
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P48378 | RFX2 | DNA-binding protein RFX2 | Homo sapiens (Human) | SS |
| P48380 | RFX3 | Transcription factor RFX3 | Homo sapiens (Human) | SS |
| P22670 | RFX1 | MHC class II regulatory factor RFX1 | Homo sapiens (Human) | EV |
| P48381 | Rfx3 | Transcription factor RFX3 | Mus musculus (Mouse) | SS |
| Q0V9K5 | rfx3 | Transcription factor RFX3 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MATQSYVTEL | QAAPQASQPP | QAPPQALPQP | PPPAAPQPPA | AATPQPQYVT | ELQSPQPQTQ |
| 70 | 80 | 90 | 100 | 110 | 120 |
| PPGSQKQYVA | ELPAAPAPSQ | PATPAPSPVA | QQYIVVTVSE | GAMRASETVS | EASPSSTASQ |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TGVPTQVVQQ | VQGTQQRLLV | QASVQAKPGH | VSPLQLTNIQ | VPQQAIPTQH | LVVQSPAPGT |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KSGQVSLTVH | SAQQVHSAPE | RSPVQANNST | SKTAGTPAAT | VQQLQVHSVQ | QSVPVTQERS |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VVQATPQTKA | GPVQQLTVQG | LQPVHVAQEV | QQLPQVPVPH | VYSSQVQYVE | GGDASYTASA |
| 310 | 320 | 330 | 340 | 350 | 360 |
| IRSSTYQYPE | TPIYTQTAGT | SYYEASGTAA | QVSTPATSQT | VASSGSVPMY | VSGSPIVASS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| SSSEAGASNS | SVGAGGNGGG | GSSGGGSGGS | SGSGAGTYVI | QGGYMLGNAS | QSYSHTTRAS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PATVQWLLDN | YETAEGVSLP | RSTLYCHYLL | HCQEQKLEPV | NAASFGKLIR | SVFMGLRTRR |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LGTRGNSKYH | YYGLRIKASS | PLLRLMEDQQ | HMAMRGQPFS | QKQRLKPIQK | MEGVANGVAV |
| 550 | 560 | 570 | 580 | 590 | 600 |
| GQQSTGLSDI | SAQVQQYQQF | LDASRSLPDF | AELDLQGKVL | PEGVGPGDIK | AFQVLYREHC |
| 610 | 620 | 630 | 640 | 650 | 660 |
| EAIVDVMVNL | QFTLVETLWK | TFWRYNLSQP | SEAPPLAVHD | EAEKRLPRAS | LVLLSKFQPV |
| 670 | 680 | 690 | 700 | 710 | 720 |
| LQWTKHCDNV | LYQGLVEILI | PDVLRPIPSA | LTQAIRNFAK | SLESWLTHAM | VNIPEEMLRV |
| 730 | 740 | 750 | 760 | 770 | 780 |
| KVAAAGAFAQ | TLRRYTSLNH | LAQAARAVLQ | NTAQINQMLS | DLNRVDFANV | QEQASWVCRC |
| 790 | 800 | 810 | 820 | 830 | 840 |
| EDRVVQRLEQ | DFKVTLQQQN | SLEQWAAWLD | GVVSQVLKPY | QGSSGFPKAA | KLFLLKWSFY |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SSMVIRDLTL | RSAASFGSFH | LIRLLYDEYM | YYLIEHRVAQ | AKGETPIAVM | GEFANLATSL |
| 910 | 920 | 930 | 940 | 950 | 960 |
| NPLDPDKDEE | EEEEEESEDE | LPQDISLAAG | SESPALGPEA | LEPPAKLART | DTRGLFVQAL |
| PSS |