LLPS-Hos-a172

▼ OVERVIEW


Status: Reviewed
Ensembl Gene: ENSG00000096063.15
Ensembl Protein: ENSP00000354674.3
Organism: Homo sapiens
Taxa ID: 9606
LLPS Type: Client
PDB: 1WBP (A, B) More


▼ PROPERTY



——— Disorder propensity (calculated by IUPred2A)

▼ Classification


Condensates:
CondensateDescriptionTissue/CellPMIDs
Nucleolus
"...The data set from all our nucleolar mass spectrometry analyses defines an updated group of 692 proteins that reproducibly copurify with human nucleoli."
HeLa cells15635413

▼ FUNCTION


Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.

▼ SEQUENCE


Protein Sequence (FASTA)
1     KGERWSGLRH  EGQWSPGRGP  VLALQARKKR  TKAKKDKAQR  KSETQHRGSA  PHSESDLPEQ  60
61    EEEILGSDDD  EQEDPNDYCK  GGYHLVKIGD  LFNGRYHVIR  KLGWGHFSTV  WLSWDIQGKK  120
121   FVAMKVVKSA  EHYTETALDE  IRLLKSVRNS  DPNDPNREMV  VQLLDDFKIS  GVNGTHICMV  180
181   FEVLGHHLLK  WIIKSNYQGL  PLPCVKKIIQ  QVLQGLDYLH  TKCRIIHTDI  KPENILLSVN  240
241   EQYIRRLAAE  ATEWQRSGAP  PPSGSAVSTA  PQPKPADKMS  KNKKKKLKKK  QKRQAELLEK  300
301   RMQEIEEMEK  ESGPGQKRPN  KQEESESPVE  RPLKENPPNK  MTQEKLEESS  TIGQDQTLME  360
361   RDTEGGAAEI  NCNGVIEVIN  YTQNSNNETL  RHKEDLHNAN  DCDVQNLNQE  SSFLSSQNGD  420
421   SSTSQETDSC  TPITSEVSDT  MVCQSSSTVG  QSFSEQHISQ  LQESIRAEIP  CEDEQEQEHN  480
481   GPLDNKGKST  AGNFLVNPLE  PKNAEKLKVK  IADLGNACWV  HKHFTEDIQT  RQYRSLEVLI  540
541   GSGYNTPADI  WSTACMAFEL  ATGDYLFEPH  SGEEYTRDED  HIALIIELLG  KVPRKLIVAG  600
601   KYSKEFFTKK  GDLKHITKLK  PWGLFEVLVE  KYEWSQEEAA  GFTDFLLPML  ELIPEKRATA  660
661   AECLRHPWLN  S  671
Nucleotide CDS Sequence (FASTA)
1     Sequence u  navailable  20

▼ KEYWORD


ID
Family
3D-structure
Alternative splicing
ATP-binding
Chromosome partition
Complete proteome
Cytoplasm
Differentiation
Direct protein sequencing
Endoplasmic reticulum
Host-virus interaction
Kinase
Microsome
mRNA processing
mRNA splicing
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase

▼ GENE ONTOLOGY


ID
Classification
Description
Cellular Component
Cytoplasm
Cellular Component
Cytosol
Cellular Component
Endoplasmic reticulum
Cellular Component
Nuclear matrix
Cellular Component
Nucleus
Cellular Component
Plasma membrane
Molecular Function
ATP binding
Molecular Function
Magnesium ion binding
Molecular Function
Protein kinase activity
Molecular Function
Protein serine/threonine kinase activity
Molecular Function
RNA binding
Biological Process
Chromosome segregation
Biological Process
Innate immune response
Biological Process
Intracellular signal transduction
Biological Process
Negative regulation of viral genome replication
Biological Process
Positive regulation of viral genome replication
Biological Process
Protein phosphorylation
Biological Process
Regulation of gene expression
Biological Process
Regulation of mRNA processing
Biological Process
Regulation of mRNA splicing, via spliceosome
Biological Process
RNA splicing
Biological Process
Sperm chromatin condensation
Biological Process
Spliceosomal complex assembly
Biological Process
Viral process

▼ KEGG



▼ ANNOTATION


Disorder
IUPred2A
Variation
dbSNPVarCards
Physicochemical
AAindex
Function
THANATOS
Proteomics
THPA
Structure
PDBMMDB
Localization
COMPARTMENTS
Methylation
TCGAMethyCancer

▼ ORTHOLOGY


DrLLPS IDOrganismIdentityE-valueScore
LLPS-Gog-a169Gorilla gorilla100.00.01363
LLPS-Poa-a169Pongo abelii99.850.01360
LLPS-Pap-a168Pan paniscus99.850.01351
LLPS-Pat-a168Pan troglodytes99.690.01360
LLPS-Chs-4484Chlorocebus sabaeus99.390.01344
LLPS-Maf-4027Macaca fascicularis99.390.01354
LLPS-Paa-a172Papio anubis99.390.01354
LLPS-Man-a170Macaca nemestrina99.240.01354
LLPS-Mam-3941Macaca mulatta99.230.01343
LLPS-Mal-a168Mandrillus leucophaeus98.920.01336
LLPS-Aon-a173Aotus nancymaae98.770.01337
LLPS-Caj-a168Callithrix jacchus98.470.01345
LLPS-Cea-4461Cercocebus atys97.240.01303
LLPS-Otg-a172Otolemur garnettii96.990.01281
LLPS-Aim-a165Ailuropoda melanoleuca96.770.01310
LLPS-Orc-a166Oryctolagus cuniculus96.660.01319
LLPS-Nol-a175Nomascus leucogenys96.650.01316
LLPS-Mup-a172Mustela putorius furo96.640.01320
LLPS-Fec-a171Felis catus96.620.01305
LLPS-Caf-2757Canis familiaris96.490.01310
LLPS-Sus-0795Sus scrofa96.490.01317
LLPS-Rhb-4750Rhinopithecus bieti96.490.01308
LLPS-Ict-a170Ictidomys tridecemlineatus96.340.01315
LLPS-Urm-0474Ursus maritimus96.170.01064
LLPS-Ova-1811Ovis aries95.850.01232
LLPS-Bot-a175Bos taurus95.710.01222
LLPS-Loa-a167Loxodonta africana95.420.01226
LLPS-Fud-a167Fukomys damarensis94.620.01216
LLPS-Myl-a165Myotis lucifugus93.850.01205
LLPS-Mea-a159Mesocricetus auratus92.670.01194
LLPS-Eqc-2171Equus caballus91.980.01239
LLPS-Mum-3489Mus musculus91.60.01176
LLPS-Ran-3375Rattus norvegicus90.380.01168
LLPS-Mod-a163Monodelphis domestica87.20.01101
LLPS-Cap-2189Cavia porcellus84.820.01043
LLPS-Pes-a153Pelodiscus sinensis81.50.01028
LLPS-Ora-a155Ornithorhynchus anatinus81.310.0834
LLPS-Anp-a153Anas platyrhynchos79.970.01021
LLPS-Gaga-3917Gallus gallus79.760.01025
LLPS-Fia-a157Ficedula albicollis79.730.01018
LLPS-Tag-a153Taeniopygia guttata78.160.0952
LLPS-Anc-a162Anolis carolinensis77.260.0984
LLPS-Cas-0583Carlito syrichta73.744e-137427
LLPS-Dio-3154Dipodomys ordii73.021e-121382
LLPS-Cii-1858Ciona intestinalis72.918e-119378
LLPS-Meg-1627Meleagris gallopavo71.640.0822
LLPS-Lac-a157Latimeria chalumnae69.250.0873
LLPS-Leo-a148Lepisosteus oculatus68.50.0826
LLPS-Xet-a153Xenopus tropicalis67.370.0822
LLPS-Orn-a151Oreochromis niloticus66.670.0790
LLPS-Scf-a148Scleropages formosus65.40.0738
LLPS-Icp-a156Ictalurus punctatus65.220.0801
LLPS-Dar-a150Danio rerio65.130.0785
LLPS-Ten-a148Tetraodon nigroviridis63.610.0776
LLPS-Pof-a152Poecilia formosa62.960.0795
LLPS-Xim-a157Xiphophorus maculatus62.810.0801
LLPS-Tar-3964Takifugu rubripes62.70.0778
LLPS-Asm-a145Astyanax mexicanus62.460.0774
LLPS-Scm-a142Scophthalmus maximus62.090.0783
LLPS-Sem-2287Selaginella moellendorffii61.827e-67234
LLPS-Orl-a149Oryzias latipes61.820.0769
LLPS-Hea-1872Helianthus annuus61.353e-67238
LLPS-Asn-0815Aspergillus nidulans60.958e-62224
LLPS-Bro-a040Brassica oleracea60.749e-67236
LLPS-Brn-a048Brassica napus60.749e-67236
LLPS-Glm-2038Glycine max60.713e-69243
LLPS-Chr-a061Chlamydomonas reinhardtii60.624e-62226
LLPS-Nia-a037Nicotiana attenuata60.611e-68241
LLPS-Amt-a029Amborella trichopoda60.615e-67238
LLPS-Vir-1460Vigna radiata60.612e-69243
LLPS-Dac-1523Daucus carota60.492e-66236
LLPS-Orr-a036Oryza rufipogon60.371e-65233
LLPS-Orni-a037Oryza nivara60.372e-65233
LLPS-Orb-a035Oryza barthii60.375e-67235
LLPS-Ori-a039Oryza indica60.371e-65233
LLPS-Org-a034Oryza glaberrima60.371e-65233
LLPS-Orgl-a035Oryza glumaepatula60.371e-65233
LLPS-Brr-a036Brassica rapa60.129e-67236
LLPS-Lep-a030Leersia perrieri60.01e-65234
LLPS-Phv-0585Phaseolus vulgaris60.04e-68240
LLPS-Sot-1508Solanum tuberosum60.01e-66236
LLPS-Prp-a031Prunus persica60.03e-68241
LLPS-Orm-a026Oryza meridionalis59.766e-65232
LLPS-Asc-0290Aspergillus clavatus59.769e-61221
LLPS-Gaa-2797Gasterosteus aculeatus59.610.0777
LLPS-Pot-1802Populus trichocarpa59.521e-68242
LLPS-Cym-1088Cyanidioschyzon merolae59.512e-59221
LLPS-Coc-2034Corchorus capsularis59.392e-67239
LLPS-Via-1553Vigna angularis59.392e-67238
LLPS-Orp-a030Oryza punctata59.393e-65233
LLPS-Mua-a037Musa acuminata59.393e-66233
LLPS-Viv-2103Vitis vinifera59.395e-67237
LLPS-Ast-1409Aspergillus terreus59.39e-62223
LLPS-Lem-1158Leptosphaeria maculans59.33e-61222
LLPS-Chc-0552Chondrus crispus59.262e-56209
LLPS-Asni-0788Aspergillus niger59.171e-59218
LLPS-Sob-a040Sorghum bicolor59.153e-65233
LLPS-Zem-a036Zea mays59.156e-65232
LLPS-Met-1848Medicago truncatula58.934e-68240
LLPS-Gas-a009Galdieria sulphuraria58.95e-60216
LLPS-Sol-0754Solanum lycopersicum58.91e-65233
LLPS-Orbr-a036Oryza brachyantha58.797e-65232
LLPS-Thc-2016Theobroma cacao58.793e-67238
LLPS-Sei-a033Setaria italica58.795e-65233
LLPS-Art-1522Arabidopsis thaliana58.793e-66234
LLPS-Sah-a162Sarcophilus harrisii58.590.0716
LLPS-Coo-a008Colletotrichum orbiculare58.563e-63226
LLPS-Pytr-0143Pyrenophora triticirepentis58.435e-62225
LLPS-Pyt-a011Pyrenophora teres58.434e-62225
LLPS-Osl-a028Ostreococcus lucimarinus58.185e-61217
LLPS-Gag-a007Gaeumannomyces graminis58.013e-62223
LLPS-Aso-0046Aspergillus oryzae57.923e-63226
LLPS-Asf-0259Aspergillus flavus57.923e-63228
LLPS-Trv-a008Trichoderma virens57.848e-64229
LLPS-Trr-1515Trichoderma reesei57.842e-63226
LLPS-Asfu-0019Aspergillus fumigatus57.787e-61221
LLPS-Nef-0764Neosartorya fischeri57.787e-61221
LLPS-Cus-a028Cucumis sativus57.743e-64230
LLPS-Abg-a015Absidia glauca57.322e-55207
LLPS-Scs-1073Sclerotinia sclerotiorum57.31e-63229
LLPS-Tra-a048Triticum aestivum57.236e-64229
LLPS-Phn-a009Phaeosphaeria nodorum56.972e-55204
LLPS-Hov-a031Hordeum vulgare56.895e-62224
LLPS-Drm-a049Drosophila melanogaster56.783e-70254
LLPS-Mel-0834Melampsora laricipopulina55.724e-62229
LLPS-Zyt-0421Zymoseptoria tritici55.686e-60218
LLPS-Crn-1464Cryptococcus neoformans54.234e-59217
LLPS-Blg-1448Blumeria graminis54.152e-61223
LLPS-Scj-a005Schizosaccharomyces japonicus53.993e-53198
LLPS-Brd-a035Brachypodium distachyon53.981e-60221
LLPS-Tru-a025Triticum urartu53.982e-61222
LLPS-Mae-1555Manihot esculenta53.921e-67238
LLPS-Yal-a010Yarrowia lipolytica53.772e-60218
LLPS-Nec-a011Neurospora crassa53.44e-63227
LLPS-Ved-0078Verticillium dahliae53.332e-64229
LLPS-Ors-a039Oryza sativa53.176e-58209
LLPS-Beb-a007Beauveria bassiana52.882e-63228
LLPS-Cogr-1601Colletotrichum graminicola52.862e-63227
LLPS-Cog-0792Colletotrichum gloeosporioides52.864e-64228
LLPS-Arl-2545Arabidopsis lyrata52.454e-67238
LLPS-Fuo-1531Fusarium oxysporum52.382e-63227
LLPS-Fuv-0382Fusarium verticillioides52.382e-63227
LLPS-Cae-1614Caenorhabditis elegans52.374e-83290
LLPS-Spr-0503Sporisorium reilianum51.96e-59219
LLPS-Usm-1548Ustilago maydis51.94e-59220
LLPS-Tum-0290Tuber melanosporum51.66e-60219
LLPS-Scc-a005Schizosaccharomyces cryophilus50.572e-52196
LLPS-Scp-a006Schizosaccharomyces pombe50.281e-51194