KNOP1

Lysine-rich nucleolar protein 1 (KNOP1) is a protein which in human's is encoded by the KNOP1 gene. Aliases for KNOP1 include TSG118, C16orf88, and FAM191A.[1]

Gene

KNOP1 is located on the negative DNA strand of chromosome 16 at 16p12.3. It spans 15.21 kb, from 19729556 to 19714347 and has 6 exons which are alternatively spliced in the RNA to create three main transcript isoforms.[2] Two of the KNOP1 isoforms, B and C, lack exon 1, shifting the start codon used to the one found in exon 2, and so the proteins encoded by these lack sequence at N-terminus. Isoform C also does not contain exon 4, which encodes the C-terminal DUF5595 domain.

Human chromosome 16 ideogram from GHR

Gene Neighborhood

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.[3] The VPS35L encodes the protein VPS35L that acts as a component of the retriever complex.[4]

Gene Expression
KNOP1 expression in Human tissues[5]

KNOP1 has high levels of expression in the superior cervical ganglion,[6] testis, placenta, and in early stages of hear and lung development.[7] KNOP1 showed low levels of expression in the liver and pancreas.

Species distribution

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, SpeciesDivergence from Homo sapiens (MYA)[8]NCBI accession numberSequence Length (AA)Sequence Similarity to Homo sapien KNOP1[9]
Homo sapiens--NP_001335456.1518100%
Pan paniscus6XP_034795825.160485.1%
Mus musculus89NP_075686.253265.8%
Lagenorhynchus obliquidens94XP_026953897.145472.6%
Galemys pyrenaicus94KAG8513613.153467.1%
Phyllostomus discolor94KAF6125017.143464.3%
Monodelphis domestica160XP_016279153.160147.1%
Ornithorhynchus anatinus180XP_028910011.154447.2%
Tyto alba318XP_042654773.162742.1%
Gallus gallus318XP_004945520.254832.4%
Bufo bufo352XP_040296565.151337.7%
Danio rerio433XP_687135.147540.4%
Branchiostoma floridae637XP_035694713.166634.2%
Owenia fusiformis787CAC9610945.155334.7%

Protein

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.[10] The protein is 518 amino acids long,[11] Isoform B is 458 amino acids,[12] and Isoform C is 435 amino acids.[13] It has a molecular weight of 58 kdal and an isoelectric point of 9.92 [14] The protein is rich in lysine[15] and has a lysine-rich region from amino acid 123–355.[16] There is a region of the protein that interacts with the protein ZNF106.[17] Some papers have associated it with the surface of the condensed chromosomes.[18]

Domains
Domains of KNOP1:The green box is domain DUF5595:The blue box is domain SMAP:The green line is region of interaction for ZNF106[19]

KNOP1 has two domains Duf5595 (Not found in isoform C) and SMAP located at the end of the protein.[20] 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.[21] 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 [22]

KNOP1 Conceptual Translation

Interacting protein

KNOP1 has been shown to interact with ZNF106[23] and has been confirmed by Grasberger, H., & Bell, G. I.[24] This study concluded that the rapid downregulation of KNOP1 expression during in vitro terminal differentiation coincides with a loss of nucleolar ZFP106.

References
  1. GeneCards (https://www.genecards.org/cgi-bin/carddisp.pl?gene=KNOP1)
  2. (NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/400506#genomic-context)
  3. 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
  4. 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
  5. NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:213235_at)
  6. NCBI GEO (https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:213235_at)
  7. NCBI RNA-seq data (https://www.ncbi.nlm.nih.gov/gene/400506#genomic-context)
  8. TimeTree (http://www.timetree.org/)
  9. NCBI BLAST
  10. 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
  11. NCBI Protein (https://www.ncbi.nlm.nih.gov/protein/1143077058)
  12. NCBI KNOP1 Isoform B (https://www.ncbi.nlm.nih.gov/protein/1142736531)
  13. NCBI KNOP1 Isoform C (https://www.ncbi.nlm.nih.gov/protein/NP_001335461.1)
  14. Expasy-Compute pI/Mw (https://web.expasy.org/compute_pi/)
  15. Statistical Analysis of Protein Sequences (https://www.ebi.ac.uk/Tools/seqstats/saps/)
  16. Motif Scan (https://myhits.sib.swiss/cgi-bin/motif_scan)
  17. UniProt (https://www.uniprot.org/uniprot/Q1ED39)
  18. 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.
  19. ProSite (https://prosite.expasy.org/cgi-bin/prosite/mydomains/)
  20. MOTIF Search (https://www.genome.jp/tools/motif/)
  21. DUF5595 (https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam18077)
  22. SMAP (https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam15477)
  23. String Protein-Protein Interaction Networks(https://string-db.org/cgi/network?taskId=bKzRFr03O9Lu&sessionId=b92QrR5MM6wa)
  24. 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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