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PROSER3

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Gene

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PROSER3
Identifiers
AliasesPROSER3, C19orf55, proline and serine rich 3
External IDsMGI: 2681861; HomoloGene: 134643; GeneCards: PROSER3; OMA:PROSER3 - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 7: 30.24 – 30.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. [5] [6] 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.[7] 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.[8] The probability of PROSER3 having a role in centrosome function is considerable.

Ideogram of Chromosome 19 Showing PROSER3 in Humans
Gene Neighborhood of PROSER3 in Humans

mRNA

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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.5

Protein

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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.[9] 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.5, [10] 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.[11] The PROSER3 protein has two extremely similar amino acid sequences that are well conserved in prokaryotes. 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.[12]

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.[13] 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.[14][15]

Gene Ontology

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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.

Table 1. Conserved Sites of hsa-miR-212-5p for miRNA families broadly conserved among vertebrates
Conservation Site Type Position Pairing
High 7mer-A1 113-119 CCAAGGA

GGUUCCA

Poor 7mer-m8 257-263 GCCAAGG

CGGUUCC

Poor 7mer-m8 2676-2682 GCCAAGG

CGGUUCC

Poor 7mer-m8 3220-3226 GCCAAGG

CGGUUCC

Evolutionary Aspects

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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

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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.

Evolutionary Divergence in orthologs of PROSER3 including the following: puma, elephant, eel, rabbit, koala, house mouse, cow, sheep, Komodo dragon, river lamprey, common frog, and Burmese python.
Table 2. Orthologs of PROSER3 protein in order of increasing divergence from Homo sapiens
Taxonomic Class Genus and species Common Name Taxonomic Order Date of Divergence (MYA) Accension number Sequence Length (aa) Sequence Identity (%) Sequence Similarity (%)
Mammailia Homo sapians Human Primates 0 AAI10894.1 480 100 100
Mammailia Gorilla gorilla gorilla Gorilla Primates 8.6 XP_055224997.1 770 91.7 92.6
Mammailia Oryctolagus cuniculus Rabbit Lagomorpha 87 XP_051692036.1 710 40.2 44.5
Mammailia Mus musculus House Mouse Rodentia 87 NP_001361572.1 660 34.2 39.9
Mammailia Bos taurus Domestic Cow Artiodactyla 94 XP_024834460.1 666 34.3 38.8
Mammailia Ovis aries Sheep Artiodactyla 94 XP_027833195.2 687 35.3 39.4
Mammailia Canis lupus familiaris Dog Carnivora 94 XP_038513300.1 823 33 37.5
Mammailia Puma concolor Puma Carnivora 94 XP_025770589.1 485 56.8 64
Mammailia Loxodonta africana African Elephant Proboscidea 99 XP_064149597.1 574 30.8 34.7
Mammailia Phascolarctos cinereus Koala Diprotodontia 160 XP_020832844.1 643 27.6 34.5
Reptilia Varanus komodoensis Komodo Dragon Squamata 319 XP_044291264.1 615 24 33.4
Reptilia Python bivittatus Burmease Python Squamata 319 XP_007430618.1 619 24.8 34
Amphibia Rana temporaria Frog Anura 352 XP_040183035.1 568 26 35.7
Amphibia Rhinatrema bivittatum Two-lined caecilian Gymnophiona 352 XP_029432023.1 688 23.7 32.4
Actinopterygii Anguilla anguilla European Eel Anguilliformes 429 XP_035286751.1 703 22.4 28.9
Actinopterygii Lethenteron reissneri River Lampray Petromyzontiformes 563 XP_061407033.1 735 20.1 30.2
Asteroidea Acanthaster planci Starfish Valvatida 619 XP_022088550 887 15.5 20.7
Anthozoa Exaiptasia diaphana Brown Anemone Actiniaria 685 KXJ13057 635 21.2 28.9
Gastropoda Haliotis rubra Abalone Lepetellida 686 XP_046554919 816 17.4 23.2
Homoscleromorpha Oscarella lobularis Sponge Homosclerophorida 758 XM_065990070 530 18.9 25.8

Protein Divergence

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Informational Context of PROSER3 Human Protein in Comparison to Cytochrome C and Fibrinogen Alpha Through Alignment of 15 Orthologs

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

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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

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Multiple Sequence Alignment of Distant PROSER3 Orthologs pt.1
Multiple Sequence Alignment of Distant PROSER3 Orthologs pt.2

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.[16][17][18] PROSER3 protein's subcellular location is likely on top of the Golgi apparatus.[19][20][21] 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.[22][23] 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.[24] Co-expression between PROSER3 and C19orf44 is accompanied by a strong correlation in the co-occurence, indicating a potential functional link between the two.[25]

Table 3. Physical protein interactions with human PROSER3
Protein IDs Identification Function Subcellular Location
Centrosomal Protein of 135 kDa CEP135 Proximity Label-MS Centrosomal microtubule-binding protein acting as a scaffolding protein in centriole biogenesis. Centriole, Centrosome, Microtubule Organizing Center
Ninein-like Protein NINL Proximity Label-MS Microtubule organization in interphase cells, overexpression induces fragmentation of the Golgi + lysosome dispersal. Centriole, Centrosome, Microtubule Organizing Center
Centrosomal Protein of 128 kDa CEP128 Proximity Label-MS Organelle assembly, microtubule organization. Centriole, Centrosome, Microtubule Organizing Center
Nucleoside Diphosphate Kinase Homolog 7 NME7 Two-hybrid array Component of the gamma-tubulin ring complex, implicated in the regulation of microtubule-nucleating activity in Centrosome. DMT is implicated in motile cilia beating. Centriole, Centrosome, Microtubule Organizing Center, Nucleus, Cilium Axoneme
Coiled-coil Alpha-helical Rod Protein 1 CCHCR1 Two-hybrid array May be a regulator of keratinocyte proliferation or differentiation. Centriole
IQ Domain-containing Protein C IQCC Two-hybrid array N/A N/A
Coiled-coil Domain Containing Protein 146 CCDC146 Two-hybrid array Sperm flagellum biogenesis and male fertility. Centriole, Centrosome, Flagellum, Microtubule Organizing Center
Cell Division Cycle Protein 23 Homolog CDC23 Two-hybrid array Component of anaphase-promoting complex/cyclosome. Cytosol, Nucleoplasm
Zinc Finger Protein 396 ZNF396 Two-hybrid array May act as a DNA-dependent transcriptional repressor. Nucleus, Cytoplasm
Coiled-coil Domain-containing Protein 57 CCDC57 Two-hybrid array Pleiotropic regulator of centriole duplication, mitosis, and ciliogenesis. Localizes to and interacts with microtubules. Centriole, Centrosome, Spindle, Microtubule Organizing Center
ELAV-like Protein 1 ELAVL1 Affinity Capture-RNA RNA binding protein binding to poly U elements, AU-rich elements in 3' UTR, increasing stability. ESC differentiation preferentially binds non-methylated mRNAs. Cytoplasm, Nucleus, Stress Granule, P-body
Replicase Polyprotein 1ab (SARS-CoV-2) NSP12AB Affinity Capture-MS Viral proliferation: Transcription and replication of viral RNAs, has proteinases for cleavage of polyprotein. Inhibits host translation by endonucleolytic cleavage near 5' UTR of host mRNA. Modifies viral mRNA caps for immune evasion. Host Cytoplasm, Endosome, Golgi Apparatus, ER
Nesprin-3 SYNE3 Proximity Label-MS Component linker of nucleoskeleton and cytoskeleton complex, involved in nucleocytoplasmic interactions and mechanical forces across the nuclear envelope, nuclear movement, and positioning. Regulation of aortic epithelial cell morphology. Required for flow-induced Centrosome polarization and directional migration in aortic endothelial cells. Perinuclear space, Rough ER, Nucleus Envelope, Nucleus Outer Membrane
Ninein NIN Proximity Label-MS Centrosomal protein required in positioning and anchorage of microtubule minus-end to mother centriole in epithelial cells. Centrosome, Microtubule Organizing Center, Centriole
Macrophage Migration Inhibitory Factor MIF Affinity Capture-MS Pro-inflammatory cytokine mediator secreted by macrophages in response to bacterial pathogen LPS. Secreted, Cytoplasm
Cell Migration-inducing and Hyaluronan-binding Protein CEMIP Affinity Capture-MS Mediates depolymerization of hyaluronic acid via clathrin-coated pit endocytic pathway. Positively regulates epithelial-mesenchymal transition, and promotes cancer cell dissemination, invasion, and growth. Nucleus, ER, Secreted, Cytoplasm
Mex-3 RNA Binding Family Member B MEX3B Proximity Label-MS May be involved in post-transcriptional regulatory mechanisms. Cytoplasmic Granule, P-body, Cytosol, Nucleoplasm
Bicaudal D Homolog 1 (Drosophila) BICD1 Proximity Label-MS Regulates coat complex coatomer protein 1 independent Golgi- ER transport by recruiting dynein-dynactin motor complex. Golgi Apparatus, Centrosome, Cytoplasmic vesicle, Cytosol
SAGA-associated Factor 29 SGF29/

CCDC101

Two-hybrid array Chromatin reader component of histone acetyltransferase, recognizes and binds methylated Lys-4 of histone H3. Involved in ER stress response, recruiting SAGA complex. Nucleoplasm, Mitotic Spindle

Conceptual Translation

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Conceptual Translation of PROSER3 human gene and protein (isoform 2) with PTMs, 3D structures, and other annotations

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

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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.[26] 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.[27][28][29]

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  • AlphaFold can be used to predict the tertiary structure of the PROSER3 protein.[30]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167595 – Ensembl, May 2017
  2. ^ a b c 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.
  5. ^ "GeneCards".
  6. ^ "Genome Browser".
  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
  16. ^ "Results - mentha: the interactome browser". mentha.uniroma2.it. Retrieved 2024-12-07.
  17. ^ "PROSER3 Result Summary | BioGRID". thebiogrid.org. Retrieved 2024-12-07.
  18. ^ "IntAct Portal". www.ebi.ac.uk. Retrieved 2024-12-07.
  19. ^ "SOSUI WWW Server". harrier.nagahama-i-bio.ac.jp. Retrieved 2024-12-12.
  20. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2024-12-12.
  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
  24. ^ "PROSER3 protein (human) - STRING interaction network". string-db.org. Retrieved 2024-10-19.
  25. ^ "PROSER3 protein expression summary - The Human Protein Atlas". v20.proteinatlas.org. Retrieved 2024-10-19.
  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.
  28. ^ Liu B, Yip RKh, Zhou Z. Chromatin remodeling, DNA damage repair and aging. Curr Genomics. 2012 Nov;13(7):533-47. doi: 10.2174/138920212803251373. PMID: 23633913; PMCID: PMC3468886.
  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)
  30. ^ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2024-12-11.
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