Table 1 Examples of RNA binding proteins where a disordered, non-classical region is involved in direct RNA binding. Additional details for each protein are presented in Additional file 1: Figure S1. Disorder prediction was calculated using IUPred [172]
Protein | Properties of disorder involved in RNA binding | Â | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
ID | Name | Aliases | Species | Canonical domains | Function | Class | Sequence | Disorder assignment | Target RNA preference | Regulation at disordered region | Interaction with other biomolecules | Ref |
SRSF1 | Serine/arginine-rich splicing factor 1 | ASF, SF2, SF2P33, SFRS1 | Homo sapiens | 2xRRM | RNA splicing. Essential for heart development. | RS | 196−GPRSPSYGRSRSRSR SRSRSRSRSNSRSRS YS−227 | Experimental | - | Serine phosphorylated. Becomes more structured upon phosphorylation. Alternatively spliced. | Protein | |
U2AF2 | Splicing factor U2AF 65 kDa subunit | U2AF65 | Homo sapiens | 3xRRM | RNA splicing. | RS | 1−MSDFDEFERQLNENK QERDKENRHRKRSHS RSRSRDRKRRSRSRD RRNRDQRSASRDRRR RSKPLTRGAKEEHGG LIRSPRHEKKKKVRK YWDVPPPG−98 | Predicted | No specificity | Serine phosphorylation, lysine acetylation, lysine hydroxylation a | Protein | |
NKAP | NF-kappa-B-activating protein | - | Homo sapiens | None | RNA splicing, transcriptional repression. | RS | 1−MAPVSGSRSPDREAS GSGGRRRSSSKSPKP SKSARSPRGRRSRSH SCSRSGDRNGLTHQL GGLSQGSRNQSYRSR SRSRSRERPSAPRGI PFASASSSVYYGSYS RPYGSDKPWP−115 | Predicted | poly (U) | Lysine acetylation a | Protein | [43] |
Nucleo-capsid protein | - | Nucleoprotein, NC, N | Severe acute respiratory syndrome coronavirus (SARS-CoV) | None | Major structural component of virions that associates with genomic RNA to form a long, flexible, helical nucleo-capsid. | Other, RS, polyK/ other | 1−MSDNGPQSNQRSAPR ITFGGPTDSTDNNQN GGRNGARPKQRRPQ−44, 182−QASSRSSSRSRGNSR NSTPGSSRGNSPARM ASGGGETALALLLLDR LNQLESKVSGKGQQQ QGQTV−247, 366−PTEPKKDKKKKTDEA QPLPQRQKKQPTVTL LPAADMDDFSRQLQN SMSGASADSTQ−422 | Experimental | poly (U) ssRNA | - | - | |
ALYREF | Aly/REF export factor 2 | Alyref | Mus musculus | 1xRRM | RNA export. | RG | 22−VNRGGGPRRNRPAIA RGGRNRPAPYSR−48 | Experimental | - | TAP displaces RNA from ALYREF | Protein | |
Aven | Cell death regulator Aven | - | Homo sapiens | None | Positive translational regulator. | RG | 1−MQAERGARGGRGRRP GRGRPGGDRHSERPG AAAAVARGGGGGGGG DGGGRRGRGRGRGFR GARGGRGGGGAPR−73 | Predicted | RNA G-quadruplex | Methylated (no influence on RNA binding; influences protein interactions and polysome association). Alternative transcript (mouse) | Protein | |
Caprin-1 | - | GPIAP1, GPIP137, M11S1, RNG105 | Homo sapiens, Xenopus | None | Regulation of localised translation, synaptic plasticity, cell proliferation and migration. | RG | 612−RGGSRGARGLMNGYR GPANGFRGGYDGYRP SFSNTPNSGYTQSQF SAPRDYSGYQRDGYQ QNFKRGSGQSGPRGA PRGRGGPPRPNRGMP QMNTQQV−708 (human), 578−RGMARGGQRGNRGMM NGYRGQSNGFRGG−605 (Xenopus) | Predicted | - | The end of the human sequence (RGGPPRPNRGMPQMNTQQV) is in an alternative isoform a | - | |
DDX4 | Probable ATP-dependent RNA helicase DDX4 | Vasa | Homo sapiens | None | RNA helicase. | RG | 1−MGDEDWEAEINPHMS SYVPIFEKDRYSGEN GDNFNRTPASSSEMD DGPSRRDHFMKSGFA SGRNFGNRDAGECNK RDNTSTMGGFGVGKS FGNRGFSNSRFEDGD SSGFWRESSNDCEDN PTRNRGFSKRGGYRD GNNSEASGPYRRGGR GSFRGCRGGFGLGSP NNDLDPDECMQRTGG LFGSRRPVLSGTGNG DTSQSRSGSGSERGG YKGLNEEVITGSGKN SWKSEAEGGES−236 | Experimental | Single-stranded DNA. | Arginine methylation. Alternative isoforms a | - | [130] |
EWS | RNA-binding protein EWS | EWSR1 | Homo sapiens | 1xRRM | Transcription, splicing. | RG | 288−PGENRSMSGPDNRGR GRGGFDRGGMSRGGR GGGRGGMGSAGERGG FNKPGGPMDEGPDLD LGPPVDP−354, 450−PMNSMRGGLPPREGR GMPPPLRGGPGGPGG PGGPMGRMGGRGGDR GGFPPRG−501, 545−APKPEGFLPPPFPPP GGDRGRGGPGGMRGG RGGLMDRGGPGGMFR GGRGGDRGGFRGGRG MDRGGFGGGRRGGPG GPPGPLMEQMGGRRG GRGGPGKMDKGEHRQERRDRPY−656 | Predicted | G-quadruplex (RGG3, not RGG1 or RGG2) | Alternative splicing a. Arginine dimethylation at RGG repeats affects protein sub cellular localization | DNA (via RGG3). All three RGG repeats bind SMN protein. | |
FMRP | Fragile X mental retardation protein 1 | FMR1 | Homo sapiens, mouse | 2xKH | Regulation of translation (repressor). | RG | 527−RRGDGRRRGGGGRGQ GGRGRGGGFKG−552 | Experimental | G quartets, G-quadruplex | Arg methylation. Alternative splicing at regions flanking the RGG-box alters FMRP’s capacity to bind RNA, to be methylated, and associate with polysomes. | C-terminal part of this protein that also includes the RG region is involved in protein-protein interactions. | |
FUS | RNA-binding protein FUS | TLS | Homo sapiens, Drosophila melanogaster | 1xRRM | Splicing, poly-adenylation. | RG | 213−RGGRGRGG−220, 241−PRGRGGGRGGRGG−253, 377−RGGGNGRGGRGRGGP MGRGGYGGGGSGGGG RGG−409, 472−RRGGRGGYDRGGYRG RGGDRGGFRGGRGGG DRGG−505 | Predicted | G-quadruplex | Arginine methylation. | - | |
hnRNP U | Heterogeneous nuclear ribonucleoprotein U | HNRPU, SAFA, U21.1 | Homo sapiens | None | RNA stability, U2 snRNP maturation, DNA binding. | RG | 714−MRGGNFRGGAPGNRG GYNRRGNMPQR−739 | Predicted | Poly (U and poly (G) homopolymers, UGUGG | - | DNA | |
ICP27 | Infected cell protein 27, Immediate-early protein IE63 | - | Herpes simplex virus | None | RNA export. | RG | 138−RGGRRGRRRGRGRGG−152 | Predicted | poly (G) and poly (U) homopolymers, GC-rich sequences | Methylated | - | |
LAF1 | - | DDX3 | C. elegans | None | RNA helicase. | RG | 1−MESNQSNNGGSGNAA LNRGGRYVPPHLRGG DGGAAAAASAGGDDR RGGAGGGGYRRGGGN SGGGGGGGYDRGYND NRDDRDNRGGSGGYG RDRNYEDRGYNGGGG GGGNRGYNNNRGGGG GGYNRQDRGDGGSSN FSRGGYNNRDEGSDN RGSGRSYNNDRRDNG GDG−168 | Experimental | - | Region 43–106 containing RG-repeat is alternative. | - | [142] |
NXF1 | Nuclear RNA export factor 1 | TAP | Mus musculus, homo sapiens | None | Nuclear export. | RG | 2−ADEGKSYSEHDDERV NFPQRKKKGRGPFRW KYGEGNRRSGRGGSG IRSSRLEEDDGDVAM SDAQDGPRVRYNPYT TRPNRRGDTWHDRDR IHVTVRRDRAPPERG GAGTSQDGTSKN−118 | Predicted | Non-specific | - | Protein. Overlaps a nuclear localisation and export signals. | |
Nucle- olin | - | NCL, Protein C23 | Hamster | 4xRRM | Chromatin decondensation, pre-rRNA transcription, ribosome assembly. | RG | 630−MEDGEIDGNKVTLDW AKPKGEGGFGGRGGG RGGFGGRGGGRGGGR GGFGGRGRGGFGGRG GFRGGRGGGGGGGDF KPQGKKTKFE−714 | Experimental. Suggested to form a flexible β-spiral. | None | - | Protein (in human) | |
RBMX | RNA-binding motif protein, X chromosome | HNRPG, RBMXP1 | Homo sapiens, Xenopus laevis | 1xRRM | Regulation of transcription, splicing. | RG | 333−DLYSSGRDRVGRQER GLPPSMERGYPPPRD SYSSSSRGAPRGGGR GGSRSDRGGGRSR−390 | Predicted | C-terminal regions binds structured (hairpin) RNA | Identical C-terminal sequence is mouse RBMX is alternatively spliced. | - | |
Foamy virus Gag | - | - | Human foamy virus | None | Viral genome binding, capsid formation. | RG | 485−RPSRGRGRGQN−495 | Predicted | - | - | - | |
TERF2 | Telomeric repeat-binding factor 2 | TRBF2, TRF2 | Homo sapiens | None | Presynaptic plasticity, axonal mRNA transport, telomere maintenance | RG | 43−MAGGGGSSDGSGRAAGRRASRSSGRARRGRHEPGLGGPAERGAG- 86 | Predicted | G-rich, TERRA | Arginine methylation | Protein | |
XTUT7 | - | - | Xenopus laevis | Zinc finger | RNA polyuridylat-ion, translational repression. | Basic patch (poly R) | 453−MRRNRVRRRNNENAG NQRY−471 | Predicted | - | - | - | [215] |
Tat | Transactivating regulatory protein | - | Human immuno-deficiency virus (HIV) | None | transcriptional activator, transcription elongation. | Basic patch (poly R) | 49−RKKRRQRRR−57 | Experimental | Structured RNA (HIV-1 Trans-activation response element, TAR) | Arginine methylation (with impact on RNA binding). Lysine acetylation (impact on TAR binding, through an effect on Tat-TAR-CyclinT1 ternary complex formation). | Protein | |
Rev | Regulator of expression of viral proteins | - | Human immuno-deficiency virus (HIV) | None | RNA export. | Basic patch (poly R) | 34−TRQARRNRRRRWRER QR−50 | Experimental | Structured RNA (HIV-1 Rev response element, RRE) | Arginine methylation. | Protein | |
Tat | Transactivating regulatory protein | S ORF, bTat | Bovine immunodeficiency virus | None | Transcriptional activator | Basic patch (polyR) | 70−RGTRGKGRRIRR−81 | Experimental | Structured RNA (TAR) | - | Protein | [91] |
Coat protein | - | - | Alfalfa mosaic virus | None | Capsid protein, viral RNA. Translation initiation. | Basic patch (poly K) | 6−KKAGGKAGKPTKRSQ NYAALRK−27 | Experimental | - | - | - | |
PAPD5 | Non-canonical poly (A) RNA polymerase PAPD5 | - | Homo sapiens | None | RNA oligoadenylation, RNA stability | Basic patch (poly K) | 557−KKRKHKR−563 | Predicted | May have a preference for structured RNA | Alternative splicing a | - | [109] |
SDAD1 | Protein SDA1 homolog | - | Homo sapiens | None | Protein transport, ribosomal large subunit export from nucleus. | Basic patch (poly K) | 244−RDLLVQYATGKKSSK NKKKLEKAMKVLKKQ KKKKKPEVFNFS−285 | Predicted | - | - | - | [58] |
HMGA1 | High mobility group protein HMG-I/HMG-Y | - | Homo sapiens | None | - | (e) AT | 21−TEKRGRGRPRK−31 | Experimental | Binds structured RNA. | Arginine methylation. | DNA | |
Tip5 | Bromodomain adjacent to zinc finger domain protein 2A | BAZ2A | Homo sapiens | None | Epigenetic rRNA gene silencing. | (e) AT | 650−GKRGRPRNTEK−660, 670−KRGRGRPPKVKIT−682 | Experimental | Exhibits preferential binding towards dsRNA | - | DNA | |
PTOV1 | Prostate tumor-overexpressed gene 1 protein | ACID2, PP642 | Homo sapiens | None | Regulation of transcription. | (e) AT | 1−MVRPRRAPYRSGAGG PLGGRGRPPRPLVVR AVRSRSWPASPRG−43 | Predicted | Exhibits preferential binding towards dsRNA | Alternative splicing a | DNA | [127] |
GPBP1 | - | Vasculin, GPBP, SSH6 | Homo sapiens | None | Transcription factor, positive regulation of transcription | e (AT) | 38−NRYDVNRRRHNSSDG FDSAIGRPNGGNFGR KEKNGWRTHGRNG−80 | Predicted | Exhibits preferential binding towards dsRNA | Alternative splicing a | DNA | [127] |
SRSF2 | Serine/arginine-rich splicing factor 2 | SFRS2 | Homo sapiens | 1xRRM | RNA splicing. | Other (GRP) | 1−MSYGRPPP−8, 93−GRPPDSHHS−101 | Experimental | UCCA/UG, UGGA/UG | - |  | |
Tra2-β1 | Transformer-2 protein homolog beta | TRA2B, SFRS10 | Homo sapiens | 1xRRM | RNA splicing. | Other | 110−NRANPDPNCC−119, 194−SITKRPHT−201 | Experimental | GAAGAA (primary), AGAAG (primary), GACUUCAACA AGUC (structured) | - | - | |
hnRNPA1 | Heterogeneous nuclear ribonucleoprotein A1 | HNRPA1 | Human, Xenopus tropical | 2xRRM | hnRNP particle formation, nucleo-cytoplasmic transport, splicing. | Other/RG | 186−MASASSSQRGRSGSG NFGGGRGGGFGGNDN FGRGGNFSGRGGFGG SRGGGGYGGSGDGYN GFGNDGGYGGGGPGY SGGSRGYGSGGQGYG NQGSGYGGSGSYDSY NNGGGGGFGGGSGSN FGGGGSYNDFGNYNN QSSNFGPMKGGNFGG RSSGPYGGGGQYFAK PRNQGGYGGSSSSSS YGSGRRF−372 | Predicted | - | Region containing the RG- and FG-repeat peptides is alternatively spliced. RG-region may mediate RNA binding. The entire region is involved in hnRNPA1 aggregation and includes a nuclear targeting sequence. | - | |
LUZP4 | Leucine zipper protein 4 | CT-28, | Homo sapiens | None | Nuclear export. |  | 51−RQNHSKKESPSRQQSKAHRHRHRRGYSRCR−80, 238−LVDTQSDLIATQRDLIATQKDLIATQRDLIATQRDLIVTQRDLVATERDL−287 | Predicted | - | Alternative splicing affecting the first, R-rich region a | Protein | [197] |
ORF57 | 52 kDa immediate-early phosphoprotein, mRNA export factor ICP27 homolog | - | Herpes-virus saimiri | None | Viral RNA regulation. | Other | 64−RQRSPITWEHQSPLS RVYRSPSPMRFGKRP RISSNSTSRSCKTSW ADRVREAAAQRR−120 | Experimental | Viral RNA: GAAGAGG, CAGUCGCGAAGAGG | RNA binding region partially overlaps with ALYREF binding site. | Protein | [178] |
APC | Adenomatous polyposis coli protein | - | Mus musculus | None | Microtubule binding, negative regulator of Wnt signaling. | Other | 2223−SISRGRTMIHIPGLR NSSSSTSPVSKKGPP LKTPASKSPSEGPGA TTSPRGTKPAGKSEL SPITRQTSQISGSNK GSSRSGSRDSTPSRP TQQPLSRPMQSPGRN SISPGRNGISPPNKL SQLPRTSSPSTASTK SSGSGKMSYTSPGRQ LSQQNLTKQASLSKN ASSIPRSESASKGLN QMSNGNGSNKKVELS RMSSTKSSGSESDSS ERPALVRQSTFIKEA PSPTLRRKLEESASF ESLSPSSRPDSPTRS QAQTPVLSPSLPDMS LSTHPSVQAGGWRKL PPNLSPTIEYNDGRP TKRHDIARSHSESPS RLPINRAGTWKREHS KHSSSLPRVSTWRRT GSSSSILSASSE−2579 | Predicted | G-rich motif | - | - | [238] |
CTCF | Transcriptional repressor CTCF | - | Homo sapiens | 11x Zn finger (3 according to Pfam) | - | Other | 575−DNCAGPDGVEGENGG ETKKSKRGRKRKMRS KKEDSSDSENAEPDL DDNEDEEEPAVEIEP EPEPQPVTPAPPPAK KRRGRPPGRTNQPKQ NQPTAIIQVEDQNTG AIENIIVEVKKEPDA EPAEGEEEEAQPAAT DAPNGDLTPEMILSM MDR−727 | Predicted | - | Serine phosphorylation a | - | [239] |
Df31 | Decondensation factor 31 | Anon1A4 | D. melanogaster | None | Regulation of higher-order chromatin structure, maintenance of open chromatin. | Other | 1−MADVAEQKNETPVVE KVAAEEVDAVKKDAV AAEEVAAEKASITEN GGAEEESVAKENGAA DSSATEPTDAVDGEK ASEPTVSFAADKDEK KDEDKKEDSAADGED TKKESSEAVLPAVEN GSEEVTNGDSTDAPA IEAVKRKVDEAAAKA DEAVATPEKKAKLDE ASTKDEVQNGAEASE VAA−183 | Experimental | Non-specific but does not bind ssDNA or dsDNA. Preferentially binds snoRNA. | - | - | |
Ezh2 | Histone-lysine N-methyltransferase EZH2 | Enx1h | Mus musculus | None | Polycomb group protein. Involved in H3 methylation (H3K9me and H3K27me). | Other | 342−RIKTPPKRPGGRRRG RLPNNSSRPSTPTI−370 | Predicted | May have a preference for RNA stem loops. | 1st Thr is phosphorylated in a cell cycle dependent manner. Phosphorylation increases RNA binding. | This region overlaps a region involved in protein-protein interactions in human, however, RNA and protein binding regions may be distinct from one another. | |
Nrep | Neuronal regeneration-related protein | P311 | Mus musculus | None | Axonal regeneration, cell differentiation. | Other | 27−KGRLPVPKEVNRKKM EETGAASLTPPGSRE FTSP−60 | Experimental | - | - | Protein | [244] |
Gemin5 | Gem-associated protein 5 | - | Homo sapiens | None | snRNP assembly, splicing, IRES-mediated translation initiation. | Other | 1297−PNSSVWVRAGHRTLS VEPSQQLDTASTEET DPETSQPEPNRPSEL DLRLTEEGERMLSTF KELFSEKHASLQNSQ RTVAEVQETLAEMIR QHQKSQLCKSTANGP DKNEPEVEAEQ−1412, 1383−EMIRQHQKSQLCKSTANGPDKNEPEVEAEQPLCSSQSQCKEEKNEPLSLPELTKRLTEANQRMAKFPESIKAWPFPDVLECCLVLLLIRSHFPGCLAQEMQQQAQELLQKYGNTKTYRRHCQTFCM−1508 | Experimental | - | - | - | [245] |
Nup153 | - | - | Homo sapiens | None | Component of the nucleopore, RNA trafficking. | Other | 250−KTSQLGDSPFYPGKT TYGGAAAAVRQSKLR NTPYQAPVRRQMKAK QLSAQSYGVTSSTAR RILQSLEKMSSPLAD AKRIPSIVSSPLNSP LDRSGIDITDFQAKR EKVDSQYPPVQRLMT PKPVSIATNRSVYFK PSLTPSGEFRKTNQR I−400 | Predicted | Single-stranded RNA with little sequence preference | Serine and threonine phosphorylation a | - | |
SCML2 | Sex comb on midleg-like protein 2 | - | Homo sapiens | None | Binds Polycomb Repressive Complex 1 and histones. Involved in epigenetic silencing. | Other | 256−SPSEASQHSMQSPQK TTLILPTQQVRRSSR IKPPGPTAVPKRSSS VKNITPRKKGPNSGK KEKPLPVICSTSAAS−330 | Predicted | No specificity, but discriminates between RNA and DNA. | Alternative isoform a , Serine phosphorylation a | - | [248] |
KDM4D | Lysine-specific demethylase 4D | JMJD2D | Homo sapiens | None | Demethylates lysine 9 on histone H3. | Other | 348−MEPRVPASQELSTQK EVQLPRRAALGLRQL PSHWARHSPWPMAAR SGTRCHTLVCSSLPR RSAVSGTATQPRAAA VHSSKKPSSTPSSTP GPSAQIIHPSNGRRG RGRPPQKLRAQELTL QTPAKRPLLAGTTCT ASGPEPEPLPEDGAL MDKPVPLSPGLQHPV KASGCSWAPVP−523 | Experimental | - | - | - | [249] |
- | - | - | Synthetic | None | Bind HIV RNA (RRE) | Other/polyR | SRSSRRNRRRRRRR, NHRRRRRQRRRRRR, SPCRSRRSGSSRRRRRRR | Experimental | Structured RNA (HIV-1 Rev response element, RRE) | - | - | [105] |