Biology:REPIN1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Replication initiator 1 is a protein that in humans is encoded by the REPIN1 gene.[1][2] The protein helps enable RNA binding activity as a replication initiation-region protein. The make up of REPIN 1 include three zinc finger hand clusters that organize polydactyl zinc finger proteins containing 15 zinc finger DNA- binding motifs.[3] It has also been predicted to help in regulation of transcription via RNA polymerase II with it being located in the nucleoplasm. Expression of this protein has been seen in the colon, spleen, kidney, and 23 other tissues within the human body throughout.[4]

History

REPIN 1 originally was first identified in a study focusing on replication of dihydrofolate reductase gene (dhfr) in Chinese hamsters, with it initiating near stable bent DNA that binds to multiple factors. In the paper scientists used protein DNA cross linking experiments that revealed the 60-kDa polypeptide, with it being labeled by its alternative name RIP60.[5] Due to the cofractionating of ATP-dependent DNA helicase with DNA-binding activity that was origin specific, the study suggested that RIP60 was involved with chromosomal DNA synthesis in mammalian cells.[6]

Genetics

REPIN 1 can be found on chromosome 7q36.1 according to the National Center for Biotechnology Information within humans.[7] REPIN 1 acts as a specific sequence binding protein in human DNA which is required for the start of chromosomal replication. Located in the nucleoplasm and part of the nuclear origin of replication recognition complex within the nucleus, it first binds on 5'-ATT'3' of the sequence. It does this on reiterated sequences downstream of the origin of bidirectional replication (OBR), and at a second 5'-ATT-3' homologous sequence opposite of the orientation within the OBR zone.[8] It encodes proteins containing fifteen C2H2 zinc finger DNA binding motifs to three clusters referred to as hands Z1 (ZFs 1-5), Z2 (ZFs 6-8), and Z3 (ZFs 9-15) with proline rich areas being present between them.[9]

Function

The function of REPIN 1 is to act as a replication initiator and sequence binding protein for chromosomal replication. Like other zinc finger proteins its physiological functions, molecular mechanisms, and regulations are not fully understood. However due to its high expression in adipose tissue and livers found in sub congenic and congenic rat strains some scientists have seen in as a participant in the regulation of genes. More specifically in those that are involved in lipid droplet formation and fusion, adipogenesis, as well as glucose and fatty acid transport in adipocytes. [10] Human in vitro data also suggests REPIN 1's role in adipocyte function and a possible therapeutic target for treating obesity.[11]

References

  1. ↑ "The dhfr oribeta-binding protein RIP60 contains 15 zinc fingers: DNA binding and looping by the central three fingers and an associated proline-rich region". Nucleic Acids Research 28 (2): 570–581. January 2000. doi:10.1093/nar/28.2.570. PMID 10606657. 
  2. ↑ "Entrez Gene: REPIN1 replication initiator 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29803. 
  3. ↑ "Replication initiator 1 in adipose tissue function and human obesity". Vitamins and Hormones (Academic Press) 91: 97–105. 2013-01-01. doi:10.1016/B978-0-12-407766-9.00005-5. ISBN 9780124077669. PMID 23374714. 
  4. ↑ "REPIN1 replication initiator 1 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/29803#gene-expression. 
  5. ↑ "Metabolic effects of genetic variation in the human REPIN1 gene". International Journal of Obesity 43 (4): 821–831. April 2019. doi:10.1038/s41366-018-0123-0. PMID 29915365. https://ul.qucosa.de/id/qucosa%3A37375. 
  6. ↑ "Purification of RIP60 and RIP100, mammalian proteins with origin-specific DNA-binding and ATP-dependent DNA helicase activities". Molecular and Cellular Biology 10 (12): 6225–6235. December 1990. doi:10.1128/mcb.10.12.6225-6235.1990. PMID 2174103. 
  7. ↑ "REPIN1 replication initiator 1 [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/29803. 
  8. ↑ "UniProt". https://www.uniprot.org/uniprotkb/Q9BWE0/entry#names_and_taxonomy. 
  9. ↑ "Triplet repeat in the Repin1 3'-untranslated region on rat chromosome 4 correlates with facets of the metabolic syndrome". Diabetes/Metabolism Research and Reviews 23 (5): 406–410. July 2007. doi:10.1002/dmrr.713. PMID 17173329. 
  10. ↑ "Repin1 maybe involved in the regulation of cell size and glucose transport in adipocytes" (in en-US). Biochemical and Biophysical Research Communications 400 (2): 246–251. September 2010. doi:10.1016/j.bbrc.2010.08.049. PMID 20727851. 
  11. ↑ "Replication initiator 1 in adipose tissue function and human obesity". Vitamins and Hormones (Academic Press) 91: 97–105. January 2013. doi:10.1016/B978-0-12-407766-9.00005-5. ISBN 9780124077669. PMID 23374714. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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