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REPIN1
Identifiers
Aliases	REPIN1, AP4, RIP60, ZNF464, Zfp464, replication initiator 1
External IDs	MGI: 1889817; HomoloGene: 22810; GeneCards: REPIN1; OMA:REPIN1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) Band 7q36.1 Start 150,368,189 bp End 150,374,044 bp
Gene location (Mouse) Chr. Chromosome 6 (mouse) Band 6|6 B2.3 Start 48,570,817 bp End 48,576,016 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube muscle of thigh mucosa of transverse colon Pituitary Gland Skeletal muscle tissue of biceps brachii gastrocnemius muscle left adrenal cortex right adrenal cortex anterior pituitary thymus Top expressed in ascending aorta aortic valve cumulus cell lumbar subsegment of spinal cord Pituitary Gland pineal gland supraoptic nucleus lobe of cerebellum cerebellar vermis suprachiasmatic nucleus More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding metal ion binding nucleic acid binding RNA binding Cellular component nuclear origin of replication recognition complex nucleus Biological process DNA replication Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 29803 58887 Ensembl ENSG00000214022 ENSMUSG00000052751 UniProt Q9BWE0 Q5U4E2 RefSeq (mRNA) NM_001099695 NM_001099696 NM_013400 NM_014374 NM_001362745 NM_001362746 NM_001362747 NM_001079901 NM_001079902 NM_001079903 NM_001079904 NM_001079905 NM_175099 RefSeq (protein) NP_001093165 NP_001093166 NP_037532 NP_001349674 NP_001349675 NP_001349676 NP_001073370 NP_001073371 NP_001073372 NP_001073373 NP_001073374 NP_780308 Location (UCSC) Chr 7: 150.37 – 150.37 Mb Chr 6: 48.57 – 48.58 Mb PubMed search
Wikidata
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Replication initiator 1 is a protein that in humans is encoded by the REPIN1 gene. 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. 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.

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. 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.

Genetics

REPIN 1 can be found on chromosome 7q36.1 according to the National Center for Biotechnology Information within humans. 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. 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.

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. Human in vitro data also suggests REPIN 1's role in adipocyte function and a possible therapeutic target for treating obesity.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000214022 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000052751 – 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. Houchens CR, Montigny W, Zeltser L, Dailey L, Gilbert JM, Heintz NH (January 2000). "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. doi:10.1093/nar/28.2.570. PMC 102514. PMID 10606657.
6. "Entrez Gene: REPIN1 replication initiator 1".
7. Heiker JT, Klöting N (2013-01-01). Litwack G (ed.). "Replication initiator 1 in adipose tissue function and human obesity". Vitamins and Hormones. 91. Academic Press: 97–105. doi:10.1016/B978-0-12-407766-9.00005-5. ISBN 9780124077669. PMID 23374714.
8. "REPIN1 replication initiator 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-10-18.
9. Krüger J, Berger C, Weidle K, Schleinitz D, Tönjes A, Stumvoll M, et al. (April 2019). "Metabolic effects of genetic variation in the human REPIN1 gene". International Journal of Obesity. 43 (4): 821–831. doi:10.1038/s41366-018-0123-0. PMID 29915365. S2CID 49297306.
10. Dailey L, Caddle MS, Heintz N, Heintz NH (December 1990). "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. doi:10.1128/mcb.10.12.6225-6235.1990. PMC 362897. PMID 2174103.
11. "REPIN1 replication initiator 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-10-18.
12. "UniProt". www.uniprot.org. Retrieved 2023-10-18.
13. Klöting N, Wilke B, Klöting I (July 2007). "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. doi:10.1002/dmrr.713. PMID 17173329. S2CID 84633542.
14. Ruschke K, Illes M, Kern M, Klöting I, Fasshauer M, Schön MR, et al. (September 2010). "Repin1 maybe involved in the regulation of cell size and glucose transport in adipocytes". Biochemical and Biophysical Research Communications. 400 (2): 246–251. doi:10.1016/j.bbrc.2010.08.049. PMID 20727851.
15. Heiker JT, Klöting N (January 2013). Litwack G (ed.). "Replication initiator 1 in adipose tissue function and human obesity". Vitamins and Hormones. 91. Academic Press: 97–105. doi:10.1016/B978-0-12-407766-9.00005-5. ISBN 9780124077669. PMID 23374714.

Further reading

• Dailey L, Caddle MS, Heintz N, Heintz NH (December 1990). "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. doi:10.1128/mcb.10.12.6225. PMC 362897. PMID 2174103.
• Caddle MS, Dailey L, Heintz NH (December 1990). "RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication". Molecular and Cellular Biology. 10 (12): 6236–6243. doi:10.1128/mcb.10.12.6236. PMC 362898. PMID 2247056.
• Mastrangelo IA, Held PG, Dailey L, Wall JS, Hough PV, Heintz N, Heintz NH (August 1993). "RIP60 dimers and multiples of dimers assemble link structures at an origin of bidirectional replication in the dihydrofolate reductase amplicon of Chinese hamster ovary cells". Journal of Molecular Biology. 232 (3): 766–778. doi:10.1006/jmbi.1993.1430. PMID 8355269.
• Montigny WJ, Houchens CR, Illenye S, Gilbert J, Coonrod E, Chang YC, Heintz NH (May 2001). "Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells". Nucleic Acids Research. 29 (9): 1982–1988. doi:10.1093/nar/29.9.1982. PMC 37261. PMID 11328883.
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, et al. (June 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–716. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
• Kim MY, Jeong BC, Lee JH, Kee HJ, Kook H, Kim NS, et al. (August 2006). "A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells". Proceedings of the National Academy of Sciences of the United States of America. 103 (35): 13074–13079. Bibcode:2006PNAS..10313074K. doi:10.1073/pnas.0601915103. PMC 1551900. PMID 16924111.

External links

• REPIN1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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