POT1

POT1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1XJV, 3KJO, 3KJP
Identifiers
Aliases	POT1 , CMM10, HGLM9, protection of telomeres 1
External IDs	OMIM: 606478; MGI: 2141503; HomoloGene: 32263; GeneCards: POT1; OMA:POT1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q31.33 Start 124,822,386 bp [1] End 124,929,983 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 A3.1 Start 25,743,736 bp [2] End 25,809,245 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte germinal epithelium Achilles tendon sperm Epithelium of choroid plexus gastric mucosa gonad tibia ventricular zone retinal pigment epithelium Top expressed in genital tubercle tail of embryo zygote cumulus cell Gonadal ridge renal corpuscle ventricular zone primitive streak epiblast thymus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding telomeric DNA binding single-stranded telomeric DNA binding DEAD/H-box RNA helicase binding protein binding G-rich strand telomeric DNA binding telomerase inhibitor activity G-rich single-stranded DNA binding telomeric D-loop binding telomeric G-quadruplex DNA binding 8-hydroxy-2'-deoxyguanosine DNA binding Cellular component nuclear telomere cap complex nucleoplasm chromosome telomere nucleus shelterin complex Biological process negative regulation of telomerase activity DNA duplex unwinding positive regulation of helicase activity positive regulation of telomerase activity establishment of protein localization to telomere telomere assembly positive regulation of DNA strand elongation telomere maintenance telomere capping regulation of DNA helicase activity positive regulation of DNA helicase activity telomeric D-loop disassembly telomere maintenance via telomerase regulation of telomere maintenance via telomerase negative regulation of telomere maintenance via telomerase positive regulation of telomere maintenance via telomerase Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25913 101185 Ensembl ENSG00000128513 ENSMUSG00000029676 UniProt Q9NUX5 Q91WC1 RefSeq (mRNA) NM_001042594 NM_015450 NM_133931 RefSeq (protein) NP_001036059 NP_056265 NP_001036059.1 NP_598692 Location (UCSC) Chr 7: 124.82 – 124.93 Mb Chr 6: 25.74 – 25.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protection of telomeres protein 1 is a protein that in humans is encoded by the POT1 gene. ^{[5] [6] [7]}

Function

This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein functions as a member of a multi-protein complex known as shelterin, that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate recombination, catastrophic chromosome instability, and abnormal chromosome segregation. Alternatively spliced transcript variants have been described. ^[7]

The absence of POT1 in mouse embryonic fibroblasts and chicken cells leads to a detrimental DNA damage response on telomeres resulting in telomere dysfunction-induced foci (TIFs). POT1 is required for telomere protection because it allows for telomere inhibition of DNA damage response factors. The protein also serves a role in the regulation of telomerase activity on telomeres. In vitro experiments utilizing human POT1 have shown that reduction in POT1 levels result in the elongation of telomeres. ^[8]

Interactions

POT1 has been shown to interact with ACD ^{[9] [10] [11]} and TINF2. ^{[10] [11] [12]}

Pathology

• Increased transcriptional expression of this gene is associated with stomach carcinogenesis and its progression.
• Mutations in this gene have also been associated to the acquisition of the malignant features of chronic lymphocytic leukemia. ^[13]
• POT1 loss-of-function variants predispose to familial melanoma ^[14] and glioma. ^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000128513 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029676 – 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. Baumann P, Cech TR (May 2001). "Pot1, the putative telomere end-binding protein in fission yeast and humans". Science. 292 (5519): 1171–5. Bibcode:2001Sci...292.1171B. doi:10.1126/science.1060036. PMID   11349150. S2CID   11248384.
6. Baumann P, Podell E, Cech TR (November 2002). "Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing". Molecular and Cellular Biology. 22 (22): 8079–87. doi:10.1128/MCB.22.22.8079-8087.2002. PMC   134737 . PMID   12391173.
7. "Entrez Gene: POT1 POT1 protection of telomeres 1 homolog (S. pombe)".
8. Bauman P, Carolyn P (2010). "Pot1 and telomere maintenance". FEBS Letters. 584 (17): 3779–3784. doi:10.1016/j.febslet.2010.05.024. PMC   2942089 . PMID   20493859.
9. Rual JF, Venkatesan K, Hao T, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
10. Ye JZ, Hockemeyer D, Krutchinsky AN, et al. (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes & Development. 18 (14): 1649–54. doi:10.1101/gad.1215404. PMC   478187 . PMID   15231715.
11. Liu D, Safari A, O'Connor MS, et al. (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology. 6 (7): 673–80. doi:10.1038/ncb1142. PMID   15181449. S2CID   11543383.
12. Loayza D, De Lange T (June 2003). "POT1 as a terminal transducer of TRF1 telomere length control". Nature. 423 (6943): 1013–8. Bibcode:2003Natur.423.1013L. doi:10.1038/nature01688. PMID   12768206. S2CID   4370276.
13. Ramsay AJ, Quesada V, Foronda M, et al. (May 2013). "POT1 mutations cause telomere dysfunction in chronic lymphocytic leukemia". Nature Genetics. 45 (5): 526–30. doi:10.1038/ng.2584. hdl: 10651/19019 . PMID   23502782. S2CID   9482133.^{[ permanent dead link ]}
14. Robles-Espinoza CD, Harland M, Ramsay AJ, et al. (May 2014). "POT1 loss-of-function variants predispose to familial melanoma". Nature Genetics. 46 (5): 478–481. doi:10.1038/ng.2947. PMC   4266105 . PMID   24686849.
15. Bainbridge MN, Armstrong GN, Gramatges MM, et al. (January 2015). "Germline mutations in shelterin complex genes are associated with familial glioma". Journal of the National Cancer Institute. 107 (1): 384. doi:10.1093/jnci/dju384. PMC   4296199 . PMID   25482530.

Further reading

• de Lange T (September 2005). "Shelterin: the protein complex that shapes and safeguards human telomeres". Genes & Development. 19 (18): 2100–10. doi: 10.1101/gad.1346005 . PMID   16166375.
• Bonaldo MF, Lennon G, Soares MB (September 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Loayza D, De Lange T (June 2003). "POT1 as a terminal transducer of TRF1 telomere length control". Nature. 423 (6943): 1013–8. Bibcode:2003Natur.423.1013L. doi:10.1038/nature01688. PMID   12768206. S2CID   4370276.
• Colgin LM, Baran K, Baumann P, et al. (May 2003). "Human POT1 facilitates telomere elongation by telomerase". Current Biology. 13 (11): 942–6. Bibcode:2003CBio...13..942C. doi: 10.1016/S0960-9822(03)00339-7 . PMID   12781132. S2CID   17801176.
• Loayza D, Parsons H, Donigian J, et al. (March 2004). "DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal binding site, sequence specificity, and internal binding to multimeric sites". The Journal of Biological Chemistry. 279 (13): 13241–8. doi: 10.1074/jbc.M312309200 . PMID   14715659.
• Kondo T, Oue N, Yoshida K, et al. (January 2004). "Expression of POT1 is associated with tumor stage and telomere length in gastric carcinoma". Cancer Research. 64 (2): 523–9. doi: 10.1158/0008-5472.CAN-03-1196 . PMID   14744765.
• Armbruster BN, Linardic CM, Veldman T, et al. (April 2004). "Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1". Molecular and Cellular Biology. 24 (8): 3552–61. doi:10.1128/MCB.24.8.3552-3561.2004. PMC   381596 . PMID   15060173.
• Liu D, Safari A, O'Connor MS, et al. (July 2004). "PTOP interacts with POT1 and regulates its localization to telomeres". Nature Cell Biology. 6 (7): 673–80. doi:10.1038/ncb1142. PMID   15181449. S2CID   11543383.
• Ye JZ, Hockemeyer D, Krutchinsky AN, et al. (July 2004). "POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex". Genes & Development. 18 (14): 1649–54. doi:10.1101/gad.1215404. PMC   478187 . PMID   15231715.
• Lei M, Podell ER, Cech TR (December 2004). "Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection". Nature Structural & Molecular Biology. 11 (12): 1223–9. doi:10.1038/nsmb867. PMID   15558049. S2CID   21018496.
• Veldman T, Etheridge KT, Counter CM (December 2004). "Loss of hPot1 function leads to telomere instability and a cut-like phenotype". Current Biology. 14 (24): 2264–70. Bibcode:2004CBio...14.2264V. doi: 10.1016/j.cub.2004.12.031 . PMID   15620654. S2CID   18198999.
• Kelleher C, Kurth I, Lingner J (January 2005). "Human protection of telomeres 1 (POT1) is a negative regulator of telomerase activity in vitro". Molecular and Cellular Biology. 25 (2): 808–18. doi:10.1128/MCB.25.2.808-818.2005. PMC   543404 . PMID   15632080.
• Yang Q, Zheng YL, Harris CC (February 2005). "POT1 and TRF2 cooperate to maintain telomeric integrity". Molecular and Cellular Biology. 25 (3): 1070–80. doi:10.1128/MCB.25.3.1070-1080.2005. PMC   544002 . PMID   15657433.
• Lei M, Zaug AJ, Podell ER, et al. (May 2005). "Switching human telomerase on and off with hPOT1 protein in vitro". The Journal of Biological Chemistry. 280 (21): 20449–56. doi: 10.1074/jbc.M502212200 . PMID   15792951.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Protection of telomeres protein 1 (POT1)