NONO
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3SDE
Identifiers
Aliases	NONO, NMT55, NRB54, P54, P54NRB, PPP1R114, MRXS34, non-POU domain containing, octamer-binding, non-POU domain containing octamer binding
External IDs	OMIM: 300084; MGI: 1855692; HomoloGene: 7212; GeneCards: NONO; OMA:NONO - orthologs
Gene location (Human) Chr. X chromosome (human)[1] Band Xq13.1 Start 71,254,814 bp[1] End 71,301,522 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X|X D Start 100,472,924 bp[2] End 100,492,197 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone thymus trachea cerebellar vermis epithelium of bronchus paraflocculus of cerebellum stromal cell of endometrium ovary left ovary Top expressed in genital tubercle ventricular zone tail of embryo yolk sac neural layer of retina zygote embryo embryo dentate gyrus of hippocampal formation granule cell lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA binding chromatin binding transcription cis-regulatory region binding protein binding identical protein binding nucleic acid binding RNA binding Cellular component paraspeckles nuclear speck membrane nuclear matrix nucleoplasm RNA polymerase II transcription regulator complex nucleolus nucleus Biological process mRNA splicing, via spliceosome DNA recombination regulation of transcription, DNA-templated rhythmic process mRNA processing transcription, DNA-templated cellular response to DNA damage stimulus regulation of circadian rhythm circadian rhythm RNA splicing negative regulation of transcription, DNA-templated negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway DNA repair activation of innate immune response immune system process innate immune response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4841 53610 Ensembl ENSG00000147140 ENSMUSG00000031311 UniProt Q15233 Q99K48 RefSeq (mRNA) NM_007363 NM_001145408 NM_001145409 NM_001145410 NM_001252518 NM_023144 RefSeq (protein) NP_001138880 NP_001138881 NP_001138882 NP_031389 NP_001239447 NP_075633 Location (UCSC) Chr X: 71.25 – 71.3 Mb Chr X: 100.47 – 100.49 Mb PubMed search [3] [4]
Wikidata
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Non-POU domain-containing octamer-binding protein (NonO) is a protein that in humans is encoded by the NONO gene.^[5][6][7]

The NonO protein belongs to the Drosophila behaviour/human splicing (DBHS) family of proteins.^[8] Proteins in the DHBS family include mammalian SFPQ (splicing factor, proline- and glutamine-rich; a.k.a. PSF), NONO (Non-POU domain-containing octamer-binding protein; a.k.a. p54nrb) and PSPC1 (paraspeckle component 1; a.k.a. PSP1) and invertebrate NONA (Protein no-on-transient A) and Hrp65.^[9]

NONO has been shown to interact with SFPQ,^[10] SPI1^[11] and Androgen receptor.^[12]

NONO is involved with many nuclear processes and binds to both DNA and RNA.^[13]

As with all proteins of the DBHS familprotein is described as a multifunctional nuclear protein.^[14] The NONO protein has been shown to be implicated in many biological functions including, pre-mRNA splicing; activation of transcription; termination of transcription; DNA unwinding and pairing and maintaining correct circadian clock function.^{[13][15][16][17][18][19]}

NONO has been identified to bind with Rasd1 protein, resulting dimer Rasd1 may act to modulate the function of NONO to down regulate the expression of the CREB genes, NR4A1 and Nr4A2.^[20]

NONO binds to SFPQ to form a heterodimer that interacts with the MATR3 protein.^[21] The interaction of these three proteins may be part of the process in the nucleus that is responsible for the retention of RNAs that are defective, not yet mature enough to be exported or are designed to be retained in nucleus.^[21]

NONO protein (Human) is encoded by the NONO gene which is located on the plus strand of the X chromosome.^[22]

NONO has been shown to be more strongly expressed in melanoma cell lines and melanoma tissue samples compared to normal human cell lines and normal skin tissue.^[23] Studies have found that the knockout of NONO protein from melanoma cell lines results in both reduced proliferation rates of the cancer cells and a significant decrease in the potential migration of the cancer cells.^[23]

Studies into breast cancers have found that the loss or alteration of NONO in conjunction with the loss of the estrogen receptor hERα results in more aggressive breast cancers which show an increase in both tumor size and metastases.^[24]

Studies in humans and mice have identified that NONO null mutations likely lead to the development of a clinically recognizable intellectual disability with cognitive and affective deficits.^[25] It was later found that these pathogenic variants were also strongly associated with cardiomyopathy with left ventricular noncompaction and sometimes Ebstein's anomaly.^[26][27]

As with other proteins of the DBHS family, NONO protein functions rarely functions alone and primarily forms homo- and heterodimers with other DBHS proteins to perform its various functions.^[28] It is theorised that these dimers may have different functions that are specific to the type of cell that they are found in.^[29]

It is speculated that it is the phosphorylation state on NONO that acts to direct the proteins many disparate functions within the nucleus.^[13]

NONO is found in the nucleus of most mammalian cells and is primarily distributed within the nucleoplasm, it can also be found concentrated within sub-nuclear domains known as paraspeckles.^[30]

NONO has also been observed within the brain, localised in the cytoplasm of hippocampal neurons that are associated with RNA transport granules.^[31] It is also highly expressed within heart tissue. ^[27]

NONO protein was first discovered in 1993 by researchers at Cold Springs Harbor Laboratory. Due to the protein being originally identified as a RNA-binding protein it was named p54nrb for Nuclear RNA-binding protein, 54 kDa.^[8]