Telomerase-binding protein EST1A

Details

Name

Telomerase-binding protein EST1A

Synonyms

• 3.1.-.-
• C17orf31
• EST1-like protein A
• EST1A
• Ever shorter telomeres 1A
• hSmg5/7a
• KIAA0732
• Smg-6 homolog
• Telomerase subunit EST1A

Gene Name

SMG6

Organism

Humans

Amino acid sequence

>lcl|BSEQ0004866|Telomerase-binding protein EST1A
MAEGLERVRISASELRGILATLAPQAGSRENMKELKEARPRKDNRRPDLEIYKPGLSRLR
NKPKIKEPPGSEEFKDEIVNDRDCSAVENGTQPVKDVCKELNNQEQNGPIDPENNRGQES
FPRTAGQEDRSLKIIKRTKKPDLQIYQPGRRLQTVSKESASRVEEEEVLNQVEQLRVEED
ECRGNVAKEEVANKPDRAEIEKSPGGGRVGAAKGEKGKRMGKGEGVRETHDDPARGRPGS
AKRYSRSDKRRNRYRTRSTSSAGSNNSAEGAGLTDNGCRRRRQDRTKERPRLKKQVSVSS
TDSLDEDRIDEPDGLGPRRSSERKRHLERNWSGRGEGEQKNSAKEYRGTLRVTFDAEAMN
KESPMVRSARDDMDRGKPDKGLSSGGKGSEKQESKNPKQELRGRGRGILILPAHTTLSVN
SAGSPESAPLGPRLLFGSGSKGSRSWGRGGTTRRLWDPNNPDQKPALKTQTPQLHFLDTD
DEVSPTSWGDSRQAQASYYKFQNSDNPYYYPRTPGPASQYPYTGYNPLQYPVGPTNGVYP
GPYYPGYPTPSGQYVCSPLPTSTMSPEEVEQHMRNLQQQELHRLLRVADNQELQLSNLLS
RDRISPEGLEKMAQLRAELLQLYERCILLDIEFSDNQNVDQILWKNAFYQVIEKFRQLVK
DPNVENPEQIRNRLLELLDEGSDFFDSLLQKLQVTYKFKLEDYMDGLAIRSKPLRKTVKY
ALISAQRCMICQGDIARYREQASDTANYGKARSWYLKAQHIAPKNGRPYNQLALLAVYTR
RKLDAVYYYMRSLAASNPILTAKESLMSLFEETKRKAEQMEKKQHEEFDLSPDQWRKGKK
STFRHVGDDTTRLEIWIHPSHPRSSQGTESGKDSEQENGLGSLSPSDLNKRFILSFLHAH
GKLFTRIGMETFPAVAEKVLKEFQVLLQHSPSPIGSTRMLQLMTINMFAVHNSQLKDCFS
EECRSVIQEQAAALGLAMFSLLVRRCTCLLKESAKAQLSSPEDQDDQDDIKVSSFVPDLK
ELLPSVKVWSDWMLGYPDTWNPPPTSLDLPSHVAVDVWSTLADFCNILTAVNQSEVPLYK
DPDDDLTLLILEEDRLLSGFVPLLAAPQDPCYVEKTSDKVIAADCKRVTVLKYFLEALCG
QEEPLLAFKGGKYVSVAPVPDTMGKEMGSQEGTRLEDEEEDVVIEDFEEDSEAEGSGGED
DIRELRAKKLALARKIAEQQRRQEKIQAVLEDHSQMRQMELEIRPLFLVPDTNGFIDHLA
SLARLLESRKYILVVPLIVINELDGLAKGQETDHRAGGYARVVQEKARKSIEFLEQRFES
RDSCLRALTSRGNELESIAFRSEDITGQLGNNDDLILSCCLHYCKDKAKDFMPASKEEPI
RLLREVVLLTDDRNLRVKALTRNVPVRDIPAFLTWAQVG

Number of residues

1419

Molecular Weight

160460.34

Theoretical pI

7.03

GO Classification

Functions

endoribonuclease activity / metal ion binding / telomeric DNA binding

Processes

gene expression / mRNA export from nucleus / nuclear-transcribed mRNA catabolic process, nonsense-mediated decay / regulation of dephosphorylation / RNA phosphodiester bond hydrolysis, endonucleolytic / telomere maintenance

Components

chromosome, telomeric region / cytoplasm / cytosol / nucleolus / nucleus / telomerase holoenzyme complex

General Function

Telomeric dna binding

Specific Function

Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.

Pfam Domain Function

• EST1 (PF10374)
• EST1_DNA_bind (PF10373)
• PIN_4 (PF13638)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0011773|Telomerase-binding protein EST1A (SMG6)
ATGGAGACATTCCCTGCAGTGGCTGAGAAGGTCCTCAAGGAGTTCCAGGTGTTACTGCAG
CACAGCCCCTCTCCCATTGGAAGTACCCGCATGCTGCAGCTTATGACCATCAATATGTTT
GCAGTACACAACTCCCAGCTGAAAGACTGCTTCTCGGAGGAGTGCCGCTCTGTGATCCAG
GAACAAGCCGCAGCTCTGGGCTTGGCCATGTTTTCTCTACTGGTCCGCCGCTGCACCTGC
TTACTTAAGGAGTCCGCCAAAGCTCAGCTGTCCTCTCCTGAGGACCAGGATGACCAAGAC
GACATCAAGGTGTCTTCCTTTGTCCCGGACCTGAAGGAGCTGCTCCCCAGTGTCAAAGTC
TGGTCAGATTGGATGCTCGGCTACCCGGACACCTGGAATCCTCCTCCCACATCCCTGGAT
CTGCCCTCGCATGTTGCTGTGGATGTATGGTCGACGCTGGCTGATTTCTGTAACATACTG
ACTGCAGTGAATCAGTCTGAGGTGCCACTGTACAAGGACCCGGATGATGACCTCACCCTT
CTTATCCTGGAAGAGGATCGGCTTCTCTCGGGCTTTGTCCCCTTGCTGGCTGCCCCTCAG
GACCCCTGCTACGTGGAGAAAACCTCGGATAAGGTTATTGCAGCTGACTGCAAAAGGGTC
ACAGTGCTGAAGTATTTTCTGGAAGCCCTTTGTGGACAAGAAGAGCCTCTGCTGGCATTC
AAGGGTGGAAAGTATGTGTCAGTGGCACCCGTCCCAGACACCATGGGAAAGGAAATGGGA
AGCCAAGAGGGAACACGACTGGAAGATGAGGAGGAGGATGTGGTGATTGAAGACTTTGAG
GAAGATTCAGAGGCTGAAGGCAGCGGAGGCGAGGATGACATCAGGGAGCTTCGGGCCAAG
AAGCTGGCTCTGGCCAGGAAGATAGCTGAGCAGCAGCGTCGCCAGGAAAAGATCCAGGCT
GTCCTGGAGGACCACAGTCAGATGAGGCAGATGGAGCTCGAAATCAGACCTTTGTTCCTC
GTACCAGACACCAACGGCTTCATTGACCACCTGGCCAGTCTGGCGCGGCTGCTGGAGAGC
AGGAAGTACATCCTGGTGGTGCCCCTCATCGTGATCAATGAGCTGGACGGCCTGGCCAAG
GGGCAGGAGACAGACCACCGGGCTGGGGGCTACGCCCGTGTGGTACAAGAGAAGGCCCGC
AAGTCCATCGAGTTCCTCGAGCAGCGATTCGAGAGTCGGGACTCTTGCCTGCGAGCCCTG
ACCAGCCGTGGCAATGAACTCGAATCCATCGCCTTCCGCAGTGAGGACATCACTGGCCAG
CTGGGTAACAACGATGATCTCATCCTGTCCTGCTGCCTCCACTACTGCAAAGACAAGGCT
AAGGACTTCATGCCCGCCAGCAAAGAGGAGCCAATCCGGCTACTGCGGGAGGTGGTGCTG
TTGACGGATGACCGGAACCTGCGTGTGAAGGCGCTCACAAGGAATGTTCCTGTACGGGAC
ATCCCAGCCTTCCTCACGTGGGCCCAGGTGGGCTGA

Chromosome Location

17

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	Q86US8
UniProtKB Entry Name	EST1A_HUMAN
GenBank Gene ID	AY145883
GenAtlas ID	SMG6
HGNC ID	HGNC:17809

General References

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2. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Oct 30;5(5):277-86. [Article]
3. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [Article]
4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
5. Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L: Functional conservation of the telomerase protein Est1p in humans. Curr Biol. 2003 Apr 15;13(8):698-704. [Article]
6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
7. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
9. Chiu SY, Serin G, Ohara O, Maquat LE: Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA. 2003 Jan;9(1):77-87. [Article]
10. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
11. Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E: SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA. 2008 Dec;14(12):2609-17. doi: 10.1261/rna.1386208. Epub 2008 Oct 30. [Article]
12. Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH: SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol. 2009 Jan;16(1):49-55. doi: 10.1038/nsmb.1530. Epub 2008 Dec 7. [Article]
13. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
14. Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE: A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science. 2009 Jan 30;323(5914):644-8. doi: 10.1126/science.1165357. [Article]
15. Kashima I, Jonas S, Jayachandran U, Buchwald G, Conti E, Lupas AN, Izaurralde E: SMG6 interacts with the exon junction complex via two conserved EJC-binding motifs (EBMs) required for nonsense-mediated mRNA decay. Genes Dev. 2010 Nov 1;24(21):2440-50. doi: 10.1101/gad.604610. Epub 2010 Oct 7. [Article]
16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
17. Glavan F, Behm-Ansmant I, Izaurralde E, Conti E: Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J. 2006 Nov 1;25(21):5117-25. Epub 2006 Oct 19. [Article]
18. Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M: Crystal structure of the PIN domain of human telomerase-associated protein EST1A. Proteins. 2007 Sep 1;68(4):980-9. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB05036	Grn163l	investigational	unknown		Details