RNA-binding protein FUS

Function

DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response. Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3'. Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing. Also binds its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay. Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair. In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity).

Classification

Family (Pfam)

PF00076 RRM_1, PF00641 Zn_ribbon_RanBP

InterPro

Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom, TET_fam, Znf_RanBP2, Znf_RanBP2_sf

Functional cluster

RNA-Binding & Splicing Proteins

Experimental structures · PDB · 23

• 2LA6 NMR
• 2LCW NMR
• 4FDD X-ray 2.30A
• 4FQ3 X-ray 3.00A
• 5W3N NMR
• 5XRR X-ray 1.50A
• 5XSG EM 0.73A
• 5YVG X-ray 4.05A
• 5YVH X-ray 3.15A
• 5YVI X-ray 2.90A
• 6BWZ X-ray 1.10A
• 6BXV X-ray 1.10A
• … and 11 more

A predicted model is available from AlphaFold.

Gene Ontology · 24

• GO:0098982 GABA-ergic synapse
• GO:0098978 glutamatergic synapse
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0099524 postsynaptic cytosol
• GO:0099523 presynaptic cytosol
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0042802 identical protein binding
• GO:0140693 molecular condensate scaffold activity
• GO:0003730 mRNA 3'-UTR binding
• GO:0003723 RNA binding
• GO:0003713 transcription coactivator activity
• GO:0003712 transcription coregulator activity
• GO:0008270 zinc ion binding
• GO:1990000 amyloid fibril formation
• GO:0140694 membraneless organelle assembly
• GO:0048255 mRNA stabilization
• GO:1905168 positive regulation of double-strand break repair via homologous recombination
• GO:0051260 protein homooligomerization
• GO:0006355 regulation of DNA-templated transcription
• GO:0043484 regulation of RNA splicing
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0008380 RNA splicing

Disease associations

• amyotrophic lateral sclerosis type 6 MONDO:0011951
• histiocytoma, Angiomatoid fibrous MONDO:0012809
• tremor, hereditary essential, 4 MONDO:0013888

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• RNA-binding protein FUS 1.00
• RNA-binding protein FUS 1.00
• TATA-binding protein-associated factor 2N 0.93
• RNA-binding protein EWS 0.92
• RNA-binding protein EWS 0.92
• Transcription initiation factor TFIID subunit 15b 0.89
• RNA-binding protein cabeza 0.89
• Heterogeneous nuclear ribonucleoprotein 87F 0.86
• Heterogeneous nuclear ribonucleoprotein A1 0.85
• Heterogeneous nuclear ribonucleoprotein A3 homolog 2 0.84
• Heterogeneous nuclear ribonucleoprotein A1 0.84
• Heterogeneous nuclear ribonucleoprotein A3 homolog 1 0.84

Co-cited proteins · studied together in the literature

• TATA-binding protein-associated factor 2N 3 shared papers
• RNA-binding protein Raly 1 shared papers
• DNA damage-inducible transcript 3 protein 2 shared papers
• E3 ubiquitin-protein ligase LRSAM1 1 shared papers
• Transcriptional regulator ERG 1 shared papers
• Cyclic AMP-dependent transcription factor ATF-1 1 shared papers
• SAP domain-containing ribonucleoprotein 1 shared papers
• Superoxide dismutase [Cu-Zn] 1 shared papers
• Serine/arginine-rich splicing factor 10 1 shared papers
• Serine/arginine-rich splicing factor 2 1 shared papers
• RNA-binding protein EWS 3 shared papers
• ATP-dependent RNA helicase DDX39A 1 shared papers

Literature · 39 cited papers

• The hnRNP raly regulates PRMT1 expression and interacts with the ALS-linked protein FUS: implication for reciprocal cellular localization. Mol. Biol. Cell · 2018
• The prionlike domain of FUS is multiphosphorylated following DNA damage without altering nuclear localization. Mol. Biol. Cell · 2018
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription. Sci. Rep. · 2016
• A novel missense mutation of CMT2P alters transcription machinery. Ann. Neurol. · 2016
• Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China. Sci. Rep. · 2016
• FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP. Proc. Natl. Acad. Sci. U.S.A. · 2015
• N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
• Self-assembled FUS binds active chromatin and regulates gene transcription. Proc. Natl. Acad. Sci. U.S.A. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• ALS-associated FUS mutations result in compromised FUS alternative splicing and autoregulation. PLoS Genet. · 2013
• Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol. Cell. Proteomics · 2014
• … and 27 more in the literature graph