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Gene

PROSER3
Identifiers
Aliases	PROSER3, C19orf55, proline and serine rich 3
External IDs	MGI: 2681861; HomoloGene: 134643; GeneCards: PROSER3; OMA:PROSER3 - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.12 Start 35,758,143 bp End 35,771,028 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 B1 Start 30,238,559 bp End 30,251,724 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell right uterine tube left testis right testis sural nerve stromal cell of endometrium body of uterus right ovary left ovary left uterine tube Top expressed in genital tubercle tail of embryo ventricular zone thymus zygote bone marrow testicle ganglionic eminence secondary oocyte yolk sac More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 148137 333193 Ensembl ENSG00000167595 ENSMUSG00000036864 UniProt Q2NL68 Q7TSA6 RefSeq (mRNA) NM_001039887 NM_144692 NM_001367856 NM_183321 NM_001374643 NM_001382459 RefSeq (protein) NP_001034976 NP_001354785 NP_899144 NP_001361572 NP_001369388 Location (UCSC) Chr 19: 35.76 – 35.77 Mb Chr 7: 30.24 – 30.25 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Chromosome 19 open reading frame 55 (C19orf55), also known as PROSER3 or Proline And Serine-Rich Protein 3, is an uncharacterized human protein-coding gene. PROSER3 (accession: NM_001039887) is found on the plus strand of chromosome 19 at gene locus q.13.12 at the span of 12,991 base pairs, see Figure "Ideogram of chromosome 19 showing PROSER3 in Humans". There are no paralogs of this gene, and it does not interact with any of its immediate gene neighborhood.   In an analysis of human tissue expression, PROSER3 was found to be expressed ubiquitously at low levels with up to 30-fold expression level variation among tissues. PROSER3 takes part in regulating cell growth and apoptosis in papillary thyroid cancer (PTC) cells, and targeting it can enhance treatment efficacy and decrease PTC recurrence. The probability of PROSER3 having a role in centrosome function is considerable.

mRNA

There are 10 exons contained within PROSER3’s mRNA sequence as well as 28 different mRNA variations. Some features of isoform 2 include a major polyA site, an alternative polyA site, and 3 disordered regions once translated.

Protein

The Proline and Serine-rich 3 protein in Homo sapiens is encoded by the PROSER3 gene. A FASTA translation in NCBI reveals that the protein-coding sequence produces 101 serine and 116 proline amino acids out of a total of 724 amino acids within that protein-coding sequence. The protein is localized to the Golgi apparatus as well as co-localized with γ-tubulin or pericentrin (PCNT) in the centrosome, suggesting Proline and Serine-rich 3 is a centrosome component. In mammalian cells, the centrosome and Golgi apparatus are closely positioned during interphase and have a functional relationship. The Golgi apparatus transports vesicles via microtubules arranged by the centrosome, and the positioning of the centrosome influences the organization of the Golgi apparatus, which is critical for cell polarization and migration and suggests potential significance of PROSER3's role in it. The PROSER3 protein has two partial homologous amino acid sequences that are well conserved in bacteria and viruses. One is the UL36 tegument protein, while the other is the DNA polymerase III subunit gamma/tau.

The UL36 tegument protein, which is present in viruses such as the Herpes Simplex Virus 1, includes residues linked to catalysis and is known to actively deubiquitinate host cells in vitro. Ubiquitination is essential for proteolysis and cell cycle control, both of which play vital roles in centrosome formation.

DNA polymerase III subunits gamma/tau in E. coli create a highly effective replication apparatus that concurrently duplicates both strands of the duplex DNA by assembling the core interface that joins two DNA polymerases with a single clamp-loading complex that is responsible for quick and precise DNA replication. In order to control microtubule stability, dynamics, and cytoskeletal architecture, tau, a microtubule-associated protein, possesses microtubule-binding domains that rely on sequence motifs and helices to mediate interactions with tubulin.

Gene Ontology

Mature microRNA hsa-miR-212-5p is involved in miRNA-mediated post-transcriptional gene silencing, negative regulation of canonical Wnt signaling pathway, and enables mRNA base-pairing translational repressor activity.

Evolutionary Aspects

PROSER3 retains sequence identity exclusively with the domain Eukarya, specifically the animal kingdom and, more precisely, one of the oldest invertebrates: sponges. The bacteria and archaea domains have no sequence identity, nor do the protists, plants, or fungi kingdoms. It is expected that the PROSER3 gene first arose around 758 million years ago. PROSER3 has no gene family.

PROSER3 orthologs are found in every extant class of vertebrates except birds and crocodiles, and partial orthologs are found in certain invertebrates. In decreasing order of divergence, these invertebrates include Sponges (Porifera), Mollusks, Cnidaria, and Echinoderms.

Orthologs

Non-primate orthologs of PROSER3 were found below 60% sequence identity and 64% sequence similarity. Although the Mammalia class has an identity and similarity score of more than 30%, the range is very wide, going from 30% to 99%. Taxonomic classes prior to Mammalia have lower similarity and identity scores, although this range is narrower despite the larger divergence (439 million years ago) compared to Mammalia's 160 million years of diversification.

Protein Divergence

In the figure titled "Informational context of PROSER3 human protein..." the human PROSER3 protein, in contrast to the conserved m cytochrome C—as seen by its lower slope— is evolving quickly over time similar to fibrinogen alpha. However, fibrinogen alpha continues to evolve more quickly than the PROSER3 protein.

Multiple Sequence Alignment

Exon 2 at amino acid K is in a highly conserved/unchanged amino acid sequence VVAKYI between aa 170 and 180. The following are highly conserved unchanged amino acid sequences even in distant orthologs: FWWL at aa 206 and DDILYQWR…RRKLEQA at aa 463. The figures titled "Multiple Sequence Alignment of Distant PROSER3 Orthologs" show a snippet of the most important conserved regions in the PROSER3 protein.

Protein Analysis

All proteins that are known to physically interact with PROSER3 exhibit a shared consensus. Based on their functions and subcellular localizations, PROSER3 plays a role in centriole biogenesis and the organization of microtubules. PROSER3 protein's subcellular location is likely on top of the Golgi apparatus. Further research into microtubule organization and location reveals that there are two microtubule populations, axonemal microtubules and cytoplasmic microtubules. Microtubule plus ends grow out from the microtubule-organizing center nucleated by the basal body and the minus ends are tethered to the adjacent centriole at the base of the connecting cilium. There are only four types of proteins that interact non-physically. The three proteins CEP128, CEP135, and NINL are proximity-based interaction types, while MIF is an association-type interaction. Considering the subcellular location of these interaction proteins is either near or in the same area where PROSER3 protein localizes, and because the activities of these interaction proteins are extremely similar to the hypothesized function of PROSER3 protein, there is a strong probability that these protein interactions with PROSER3 protein are real. Proving these interactions could be done with co-immunoprecipitation to pull the target protein out of a cell lysate along with any proteins bound to it, forming a protein complex that can then be analyzed by western blotting. Additionally, co-expression of the Proline and Serine-rich 3 protein is observed with proteins coded by the genes C19orf44, CFAP100, DNAAF3, CCDC38, and C10orf67, indicating these proteins may be functionally related or involved in similar biological processes. Co-expression between PROSER3 and C19orf44 is accompanied by a strong correlation in the co-occurence, indicating a potential functional link between the two.

Conceptual Translation

Depicted on the right is a PDF for the conceptual translation of the human PROSER3 isoform 2 (full mRNA) with annotations to the right-hand side.

SNPs

There are 6413 SNPs catalogued in NCBI's Variation Viewer, none of which have publications or clinical significance records. rs1187661251 is a single nucleotide variant that overlaps with the conserved region VVAKYI and, when mutated, prevents the RNA-binding protein FUS from binding. Potential resulting side effects may include promotion of neurodegenerative diseases like ALS or FTLD, neuronal dysfunction, decreased damage response signaling and repair, and RNA dysregulation. rs1971047914 is a C insertion variant overlapping the transcription factor ZNF384 (C2H2 zinc finger factors) and RNA-binding protein ELAVL2 which may have potential significance for chromatin remodeling and neuronal differentiation/function. If mutated by the C insertion, ZNF384 would no longer be able to bind to the DNA sequence and downregulate the cell’s ability to remodel chromatin, initiating or promoting oncogenesis. Additionally, ELAVL2 would lose its ability to bind, which could result in risk-associated diseases such as frontotemporal dementia/ALS and lung cancer.

Further Links and Articles

• AlphaFold can be used to predict the tertiary structure of the PROSER3 protein.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000167595 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000036864 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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7. Fagerberg, Linn; Hallström, Björn M.; Oksvold, Per; Kampf, Caroline; Djureinovic, Dijana; Odeberg, Jacob; Habuka, Masato; Tahmasebpoor, Simin; Danielsson, Angelika; Edlund, Karolina; Asplund, Anna; Sjöstedt, Evelina; Lundberg, Emma; Szigyarto, Cristina Al-Khalili; Skogs, Marie (February 2014). "Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics". Molecular & Cellular Proteomics. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMC 3916642. PMID 24309898.
8. He, Jingni; Tian, Zhong; Yao, Xu; Yao, Baiyu; Liu, Yuan; Yang, Jiapeng (April 2020). "A novel RNA sequencing-based risk score model to predict papillary thyroid carcinoma recurrence". Clinical & Experimental Metastasis. 37 (2): 257–267. doi:10.1007/s10585-019-10011-4. ISSN 0262-0898. PMID 31792675.
9. "PROSER3 proline and serine rich 3 [Homo sapiens (human)] - Gene - NCBI".
10. Gupta, Gagan D.; Coyaud, Étienne; Gonçalves, João; Mojarad, Bahareh; Liu, Yi; Wu, Qianzhu; Gheiratmand, Ladan; Comartin, David; Tkach, Johnny; Cheung, Sally; Bashkurov, Mikhail; Hasegan, Monica; Knight, James; Lin, Zhen-Yuan; Schueler, Markus (2015). "A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface". Cell. 163 (6): 1484–1499. doi:10.1016/j.cell.2015.10.065. ISSN 0092-8674. PMC 5089374. PMID 26638075.
11. Sütterlin, Christine; Colanzi, Antonino (2010-03-08). "The Golgi and the centrosome: building a functional partnership". Journal of Cell Biology. 188 (5): 621–628. doi:10.1083/jcb.200910001. ISSN 1540-8140. PMC 2835931. PMID 20212314.
12. McNabb DS, Courtney RJ.1992.Analysis of the UL36 open reading frame encoding the large tegument protein (ICP1/2) of herpes simplex virus type 1. J Virol66:.https://doi.org/10.1128/jvi.66.12.7581-7584.1992
13. Thermus thermophilis dnaX Homolog Encoding γ- and τ-like Proteins of the Chromosomal Replicase *Yurieva, Olga et al.
14. Reiko Takemura, Shigeo Okabe, Takashige Umeyama, Yoshimitsu Kanai, Nicholas J. Cowan, Nobutaka Hirokawa; Increased microtubule stability and alpha tubulin acetylation in cells transfected with microtubule-associated proteins MAP1B, MAP2 or tau. J Cell Sci 1 December 1992; 103 (4): 953–964. doi: https://doi.org/10.1242/jcs.103.4.953
15. The Intraflagellar Transport Protein IFT20 Is Associated with the Golgi Complex and Is Required for Cilia Assembly John A. Follit, Richard A. Tuft, Kevin E. Fogarty, and Gregory J. Pazour, Molecular Biology of the Cell 2006 17:9, 3781-3792
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21. PROSER3 Antibody (NBP2-30902) by Novus, Part of Bio-Techne. (n.d.). Retrieved December 11, 2024, from https://www.bio-techne.com/p/antibodies/proser3-antibody_nbp2-30902#tab-citations_reviews
22. Troutt, L.L., Wang, E., Pagh-Roehl, K. et al. Microtubule nucleation and organization in teleost photoreceptors: Microtubule recovery after elimination by cold. J Neurocytol 19, 213–223 (1990). https://doi.org/10.1007/BF01217299
23. Frank Zach, Felix Grassmann, Thomas Langmann, Nasrin Sorusch, Uwe Wolfrum, Heidi Stöhr, The retinitis pigmentosa 28 protein FAM161A is a novel ciliary protein involved in intermolecular protein interaction and microtubule association, Human Molecular Genetics, Volume 21, Issue 21, 1 November 2012, Pages 4573–4586, https://doi.org/10.1093/hmg/dds268
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26. Ishigaki, S., & Sobue, G. (2018). Importance of Functional Loss of FUS in FTLD/ALS. Frontiers in Molecular Biosciences, 5. https://doi.org/10.3389/fmolb.2018.00044
27. "Variation Viewer". www.ncbi.nlm.nih.gov. Retrieved 2024-12-07.
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29. Cai, H., Zheng, D., Yao, Y., Yang, L., Huang, X., & Wang, L. (2022). Roles of Embryonic Lethal Abnormal Vision-Like RNA Binding Proteins in Cancer and Beyond. Frontiers in Cell and Developmental Biology, 10. (https://doi.org/10.3389/fcell.2022.847761)
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• Genes on human chromosome 19