FUS geenistä erikseen tietoa , Suositeltu nimi: RNA-binding protein FUS (16p11.2)

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=FUS&keywords=FUS

Aliases for FUS Gene

• GeneCards Symbol: FUS ²
• FUS RNA Binding Protein ^{2 3 5}
• TLS ^{2 3 4 5}
• HNRNPP2 ^{2 3 5}
• FUS1 ^{2 3 5}
• Heterogeneous Nuclear Ribonucleoprotein P2 ^{2 3}
• Translocated In Liposarcoma Protein ^{3 4}
• 75 KDa DNA-Pairing Protein ^{3 4}
• RNA-Binding Protein FUS ^{3 4}
• Fused In Sarcoma ^{2 3}
• Oncogene FUS ^{3 4}
• Oncogene TLS ^{3 4}

• HnRNP-P2 ^{2 5}
• ALS6 ^{3 5}
• Fusion (Involved In T(12;16) In Malignant Liposarcoma) ²
• Fusion, Derived From T(12;16) Malignant Liposarcoma ²
• Fusion Gene In Myxoid Liposarcoma ³
• Amyotrophic Lateral Sclerosis 6 ²
• Translocated In Liposarcoma ²
• Fus-Like Protein ³
• POMP75 ³
• AltFUS ³
• POMp75 ⁴
• ETM4 ³

NCBI Gene Summary for FUS Gene

• This gene encodes a multifunctional protein component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. The hnRNP complex is involved in pre-mRNA splicing and the export of fully processed mRNA to the cytoplasm. This protein belongs to the FET family of RNA-binding proteins which have been implicated in cellular processes that include regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. Alternative splicing results in multiple transcript variants. Defects in this gene result in amyotrophic lateral sclerosis type 6. [provided by RefSeq, Sep 2009]

GeneCards Summary for FUS Gene

FUS (FUS RNA Binding Protein) is a Protein Coding gene. Diseases associated with FUS include Amyotrophic Lateral Sclerosis 6 With Or Without Frontotemporal Dementia and Tremor, Hereditary Essential, 4. Among its related pathways are Processing of Capped Intron-Containing Pre-mRNA and Translational Control. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and identical protein binding. An important paralog of this gene is EWSR1.

UniProtKB/Swiss-Prot Summary for FUS Gene

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 (PubMed:27731383). 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 (PubMed:26124092). Binds also its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay (PubMed:24204307). Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (PubMed:10567410). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (By similarity). ( FUS_HUMAN,P35637 

Recommended name:RNA-binding protein FUS

Size:526 amino acids, Molecular mass: 53426 Da

Quaternary structure: (Ainutlaatuinen rakenne!)

• Self-oligomerizes (via N-terminal region) (PubMed:25453086).
  Oligomerization is essential for chromatin binding (PubMed:25453086).
  Component of nuclear riboprotein complexes.
  Interacts with ILF3, TDRD3 and SF1 (PubMed:9660765).
  Interacts through its C-terminus with SFRS13A (PubMed:9774382).
  Interacts with OTUB1 and SARNP.
  Interacts with LRSAM1 (PubMed:27615052).
  Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin (PubMed:27731383).
  Interacts with MATR3 (PubMed:27731383).
  Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing (PubMed:26124092).
  Interacts (through its RNA-binding domain) with RALY (through its RNA-binding domain); both are components of the same RNPs (PubMed:30354839).

Post-translational modifications for FUS Gene

• Arg-216 and Arg-218 are dimethylated, probably to asymmetric dimethylarginine. ( P35637-FUS_HUMAN )
• Phosphorylated in its N-terminal serine residues upon induced DNA damage.
  ATM and DNA-PK are able to phosphorylate FUS N-terminal region.
  ( P35637-FUS_HUMAN )
• Ubiquitination at Lys316 and Lys365 ( NX_P35637 [NX_P35637-1] )
• Modification sites at PhosphoSitePlus ( P35637 )
• Glycosylation from GlyGen (P35637) 13 sites, 1 N-linked glycan (1 site), 3 O-linked glycans (12 sites)

Gene Families for FUS Gene

HGNC:

• Heterogeneous nuclear ribonucleoproteins
• RNA binding motif containing
• Zinc fingers RANBP2-type

The Human Protein Atlas (HPA):

• Cancer-related genes
• Disease related genes
• Human disease related genes
• Plasma proteins
• Predicted intracellular proteins

Protein Domains for FUS Gene

InterPro:

• Nucleotide-bd_a/b_plait_sf
• RBD_domain_sf ( 
  Many eukaryotic proteins containing one or more copies of a putative RNA-binding domain of about 90 amino acids are known to bind single-stranded RNAs ^{[10, 1, 2]} . The largest group of single strand RNA-binding proteins is the eukaryotic RNA recognition motif (RRM) family that contains an eight amino acid RNP-1 consensus sequence

  ^{[8, 5]} . RRM proteins have a variety of RNA binding preferences and functions, and include heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing (SR, U2AF, Sxl), protein components of small nuclear ribonucleoproteins (U1 and U2 snRNPs), and proteins that regulate RNA stability and translation (PABP, La, Hu) ^{[1, 2, 5]}

  . The RRM in heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) appears to have two RRM-like domains with specialised features for protein recognition ^[9]. The motif also appears in a few single stranded DNA binding proteins.
  The typical RRM consists of four anti-parallel β-strands and two α-helices arranged in a β-α-β-β-α-β fold with side chains that stack with RNA bases. Specificity of RNA binding is determined by multiple contacts with surrounding amino acids. A third helix is present during RNA binding in some cases^[7]. The RRM is reviewed in a number of publications
  ^{[6, 3, 4]}  )
• RRM_dom
• Znf_RanBP2 (This entry represents the zinc finger domain found in RanBP2 proteins. Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran binding protein 2 (RanBP2) is a 358kDa nucleoporin located on the cytoplasmic side of the nuclear pore complex which plays a role in nuclear protein import
  ^[7]. RanBP2 contains multiple zinc fingers which mediate binding to RanGDP ^[6]

  .Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates

  ^{[1, 2, 3, 4, 8]}

  . Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies (sf)  of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few

  ^[5]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.  ).
• Znf_RanBP2_sf
• TET_fam (TAF15/EWS/TLS family members include human FUS (Fused in liposarcoma), EWS (Ewing Sarcoma) and TAF15 (TATA binding associated factor 15), and the Drosophila orthologue Cabeza. They are RNA binding proteins that contain a transcriptional-activation domain (EAD), 3 glycine-arginine (RGG) rich regions, an RNA-binding domain (RBD), and a zinc finger domain
  ^{[1, 2]}. They are involved in transcription and alternative splicing. They are subjected to different environmental signals that induce post-translational modifications in their RBD and in the RGG domains, thus modulating their activity ^[2]. TAF15/EWS/TLS play important roles in oncogenesis and neuronal disease ^[3].)
• See less «

Blocks:

• RNA-binding region RNP-1 (RNA recognition motif)
• Zn-finger, Ran-binding

Suggested Antigen Peptide Sequences for FUS Gene

GenScript: Design optimal peptide antigens:

• cDNA FLJ58049, highly similar to RNA-binding protein FUS (B4DR70_HUMAN)
• Translocated in liposarcoma protein (FUS_HUMAN)
• Fusion, derived from t(12 (Q6IBQ5_HUMAN)
• Fusion (Involved in t(12 (Q8TBR3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P35637

UniProtKB/Swiss-Prot:

FUS_HUMAN :

• Belongs to the RRM TET family.

Family:

• Belongs to the RRM TET family.