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Lysine-rich nucleolar protein 1 (KNOP1) Is a protein encoding gene that encodes KNOP1. The known aliases for KNOP1 are TSG118, C16orf88, and FAM191A[1]. It is located at 16p12.3.[2]

Gene

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KNOP1 is located on the [negative DNA strand] of chromosome 16 at 16p12.3. It covers 15.21 kb, from 19729556 to 19714347 and has 6 exons [3]. KNOP1 has 2 different Isoforms that differ in the 5' UTR and coding sequence. The result is shorter at the N-terminus. Isoform B and C do not contain exon 1 shifting the start codon to exon 2. Isoform C does not contain exon 4 which contains the DUF5595 domain.

Human_chromosome_16_ideogram_from_GHR

Gene Neighborhood

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The genes surrounding KNOP1 are VPS35L which is upstream and IQCK which is downstream of KNOP1. The IQCK gene was identified to be a potential candidate for obsessive-compulsive disorder in a genome-wide association study[4]. The VPS35L encodes the protein VPS35L that acts as a component of the retriever complex which[5].

Gene Expression

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KNOP1 expression in Human tissues[6]

KNOP1 is shown to have high levels of expression superior cervical ganglion[7], testis, placenta, and in early stages of hear and lung development[8]. KNOP1 showed low levels of expression in the liver and pancreas.


Species distribution

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There are many orthologs of KNOP1 in many different species of animals but not in the other kingdoms. No paralogs of KNOP1 were found. Table 1 lists select KNOP1 orthologs.

Table 1: KNOP1 Orthologs
Genus, Species Divergence from Homo sapiens (MYA)[9] NCBI accession number Sequence Length (AA) Sequence Similarity to Homo sapien KNOP1[10]
Homo sapiens -- NP_001335456.1 518 100%
Pan paniscus 6 XP_034795825.1 604 85.1%
Mus musculus 89 NP_075686.2 532 65.8%
Lagenorhynchus obliquidens 94 XP_026953897.1 454 72.6%
Galemys pyrenaicus 94 KAG8513613.1 534 67.1%
Phyllostomus discolor 94 KAF6125017.1 434 64.3%
Monodelphis domestica 160 XP_016279153.1 601 47.1%
Ornithorhynchus anatinus 180 XP_028910011.1 544 47.2%
Tyto alba 318 XP_042654773.1 627 42.1%
Gallus gallus 318 XP_004945520.2 548 32.4%
Bufo bufo 352 XP_040296565.1 513 37.7%
Danio rerio 433 XP_687135.1 475 40.4%
Branchiostoma floridae 637 XP_035694713.1 666 34.2%
[Owenia fusiformis] 787 CAC9610945.1 553 34.7%

Protein

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The exact function of KNOP1 is not yet understood it is hypothesized to mimic nucleostemin, a nucleolar protein linked to the proliferation potential of stem cells[11]. The protein is 518 amino acids long[12], Isoform B is 458 amino acids[13], and Isoform C is 435 amino acids[14] . It has a molecular weight of 58 kdal and an isoelectric point of 9.92 [15] The protein is rich in lysine[16] and has a lysine-rich region from amino acid 123-355[17]. There is a region of the protein that interacts with the protein ZNF106[18]. Some papers have associated it with the surface of the condensed chromosomes[19].

Domains

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Domains of KNOP1:The green box is domain DUF5595:The blue box is domain SMAP:The green line is region of interaction for ZNF106[20]

KNOP1 has two domains Duf5595 (Not found in isoform C) and SMAP located at the end of the protein[21]. DUF5595 is found in Nude C 80 (Ndc80) proteins which can be found in species such as Homo sapiens. Ndc80 protein complexes are a core component of the end-on attachment sites for kinetochore microtubules[22]. SMAP (Small acidic protein family) is found in eukaryotes, and is approximately 70 amino acids in length. There is a single completely conserved residue G that may be functionally important at G441 [23].

KNOP1 Conceptual Translation

Interacting protein

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KNOP1 has been shown to interact with ZNF106[24] and has been confirmed by Grasberger, H., & Bell, G. I.[25]. This study concluded that the rapid downregulation of KNOP1 expression during in vitro terminal differentiation coincides with a loss of nucleolar ZFP106.

References

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  1. ^ GeneCards (https://www.genecards.org/cgi-bin/carddisp.pl?gene=KNOP1)
  2. ^ U.S. National Library of Medicine. (n.d.). ACEVIEW: Gene:c16orf88, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView. National Center for Biotechnology Information. Retrieved October 4, 2021, from https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=C16orf88&submit=Go
  3. ^ (NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/400506#genomic-context)
  4. ^ U.S. National Library of Medicine. (n.d.). IQCK IQ motif containing K [homo sapiens (human)] - gene - NCBI. National Center for Biotechnology Information. Retrieved December 18, 2021, from https://www.ncbi.nlm.nih.gov/gene/124152
  5. ^ McNally, K. E., Faulkner, R., Steinberg, F., Gallon, M., Ghai, R., Pim, D., Langton, P., Pearson, N., Danson, C. M., Nägele, H., Morris, L. L., Singla, A., Overlee, B. L., Heesom, K. J., Sessions, R., Banks, L., Collins, B. M., Berger, I., Billadeau, D. D., Burstein, E., … Cullen, P. J. (2017). Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nature cell biology, 19(10), 1214–1225. https://doi.org/10.1038/ncb3610
  6. ^ NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:213235_at)
  7. ^ NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:213235_at)
  8. ^ NCBI RNA-seq data (https://www.ncbi.nlm.nih.gov/gene/400506#genomic-context)
  9. ^ TimeTree (http://www.timetree.org/)
  10. ^ NCBI BLAST
  11. ^ Grasberger, H., & Bell, G. I. (2005). Subcellular recruitment by TSG118 and TSPYL implicates a role for zinc finger protein 106 in a novel Developmental pathway. The International Journal of Biochemistry & Cell Biology, 37(7), 1421–1437. https://doi.org/10.1016/j.biocel.2005.01.013
  12. ^ NCBI Protein (https://www.ncbi.nlm.nih.gov/protein/1143077058)
  13. ^ NCBI KNOP1 Isoform B (https://www.ncbi.nlm.nih.gov/protein/1142736531)
  14. ^ NCBI KNOP1 Isoform C (https://www.ncbi.nlm.nih.gov/protein/NP_001335461.1)
  15. ^ Expasy-Compute pI/Mw (https://web.expasy.org/compute_pi/)
  16. ^ Statistical Analysis of Protein Sequences (https://www.ebi.ac.uk/Tools/seqstats/saps/)
  17. ^ Motif Scan (https://myhits.sib.swiss/cgi-bin/motif_scan)
  18. ^ UniProt (https://www.uniprot.org/uniprot/Q1ED39)
  19. ^ Larsson, M., Brundell, E., Jörgensen, P. M., Ståhl, S., & Höög, C. (1999). Characterization of a novel nucleolar protein that transiently associates with the condensed chromosomes in mitotic cells. European journal of cell biology, 78(6), 382-390.
  20. ^ ProSite (https://prosite.expasy.org/cgi-bin/prosite/mydomains/)
  21. ^ MOTIF Search (https://www.genome.jp/tools/motif/)
  22. ^ DUF5595 (https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam18077)
  23. ^ SMAP (https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam15477)
  24. ^ String Protein-Protein Interaction Networks(https://string-db.org/cgi/network?taskId=bKzRFr03O9Lu&sessionId=b92QrR5MM6wa)
  25. ^ Grasberger, H., & Bell, G. I. (2005). Subcellular recruitment by TSG118 and TSPYL implicates a role for zinc finger protein 106 in a novel developmental pathway. The international journal of biochemistry & cell biology, 37(7), 1421–1437. https://doi.org/10.1016/j.biocel.2005.01.013
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