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Telomerase-binding protein EST1A

 
Known also as: EST1-like protein A,Ever shorter telomeres 1A,Smg-6 homolog,Telomerase subunit EST1A,hSmg5/7a

Known abbreviations: SMG6, C17orf31, EST1A, KIAA0732

 

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)4GTGT-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. 
 
COFACTOR:
 
Manganese. 
 
SUBUNIT STRUCTURE:
 
Component of the telomerase holoenzyme complex at least composed of TERT, DKC1, WRAP53/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 and a telomerase RNA template component (TERC). Interacts with TERT, independently of the telomerase RNA. Interacts with PP2A catalytic subunits, SMG1, UPF1, UPF2 and UPF3B. 
 
CELLULAR LOCALIZATION:
 
Nucleus › nucleolus. Chromosome › telomere (Probable). Cytoplasm › cytosol. Note: Particularly enriched in the nucleolus.
 
TISSUE SPECIFICITY:
 
Ubiquitous. 
 
DOMAIN:
 
The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion.



Activities in which Telomerase-binding protein EST1A is involved: Pathways in which Telomerase-binding protein EST1A is involved:

NCBI GI number(s): 378744173
378744172
378744171
378744170
115511020
115511019
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q86US8 Q86US8
BRENDA - -
KEGG hsa:23293 hsa:23293
PFAM: PF10374
PF10373
PF10374
PF10373
InterPro: IPR018834
IPR019458
IPR006596
IPR011990
IPR018834
IPR019458
IPR006596
IPR011990
CATH: - -
SCOP: - -
Solved crystal structures: 2HWW
2HWX
2DOK
[PDB] [details]
[PDB] [details]
[PDB] [details]


Protein sequence:
MAEGLERVRISASELRGILATLAPQAGSRENMKELKEARPRKDNRRPDLE
IYKPGLSRLRNKPKIKEPPGSEEFKDEIVNDRDCSAVENGTQPVKDVCKE
LNNQEQNGPIDPENNRGQESFPRTAGQEDRSLKIIKRTKKPDLQIYQPGR
RLQTVSKESASRVEEEEVLNQVEQLRVEEDECRGNVAKEEVANKPDRAEI
EKSPGGGRVGAAKGEKGKRMGKGEGVRETHDDPARGRPGSAKRYSRSDKR
RNRYRTRSTSSAGSNNSAEGAGLTDNGCRRRRQDRTKERPRLKKQVSVSS
TDSLDEDRIDEPDGLGPRRSSERKRHLERNWSGRGEGEQKNSAKEYRGTL
RVTFDAEAMNKESPMVRSARDDMDRGKPDKGLSSGGKGSEKQESKNPKQE
LRGRGRGILILPAHTTLSVNSAGSPESAPLGPRLLFGSGSKGSRSWGRGG
TTRRLWDPNNPDQKPALKTQTPQLHFLDTDDEVSPTSWGDSRQAQASYYK
FQNSDNPYYYPRTPGPASQYPYTGYNPLQYPVGPTNGVYPGPYYPGYPTP
SGQYVCSPLPTSTMSPEEVEQHMRNLQQQELHRLLRVADNQELQLSNLLS
RDRISPEGLEKMAQLRAELLQLYERCILLDIEFSDNQNVDQILWKNAFYQ
VIEKFRQLVKDPNVENPEQIRNRLLELLDEGSDFFDSLLQKLQVTYKFKL
EDYMDGLAIRSKPLRKTVKYALISAQRCMICQGDIARYREQASDTANYGK
ARSWYLKAQHIAPKNGRPYNQLALLAVYTRRKLDAVYYYMRSLAASNPIL
TAKESLMSLFEETKRKAEQMEKKQHEEFDLSPDQWRKGKKSTFRHVGDDT
TRLEIWIHPSHPRSSQGTESGKDSEQENGLGSLSPSDLNKRFILSFLHAH
GKLFTRIGMETFPAVAEKVLKEFQVLLQHSPSPIGSTRMLQLMTINMFAV
HNSQLKDCFSEECRSVIQEQAAALGLAMFSLLVRRCTCLLKESAKAQLSS
PEDQDDQDDIKVSSFVPDLKELLPSVKVWSDWMLGYPDTWNPPPTSLDLP
SHVAVDVWSTLADFCNILTAVNQSEVPLYKDPDDDLTLLILEEDRLLSGF
VPLLAAPQDPCYVEKTSDKVIAADCKRVTVLKYFLEALCGQEEPLLAFKG
GKYVSVAPVPDTMGKEMGSQEGTRLEDEEEDVVIEDFEEDSEAEGSGGED
DIRELRAKKLALARKIAEQQRRQEKIQAVLEDHSQMRQMELEIRPLFLVP
DTNGFIDHLASLARLLESRKYILVVPLIVINELDGLAKGQETDHRAGGYA
RVVQEKARKSIEFLEQRFESRDSCLRALTSRGNELESIAFRSEDITGQLG
NNDDLILSCCLHYCKDKAKDFMPASKEEPIRLLREVVLLTDDRNLRVKAL
TRNVPVRDIPAFLTWAQVG

Telomerase-binding protein EST1A (Homo sapiens) is product of expression of SMG6 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A. Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M Acta Crystallogr Sect F Struct 2006-07-01 (62) 16820686
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). 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, K Genome Res 2004-10-01 (14) 15489334
SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH Nat Struct Mol Biol 2009-02-01 (16) 19060897
SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E RNA 2008-12-01 (14) 18974281
Functional conservation of the telomerase protein Est1p in humans. Snow BE, Erdmann N, Cruickshank J, Goldman H, Gill RM, Robinson MO, Harrington L Curr Biol 2003-04-15 (13) 12699629
Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. Chiu SY, Serin G, Ohara O, Maquat LE RNA 2003-02-01 (9) 12554878
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem 2009-06-01 (81) 19413330
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
The full-ORF clone resource of the German cDNA Consortium. 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 BMC Genomics 2007-01-01 (8) 17974005
A human homolog of yeast Est1 associates with telomerase and uncaps chromosome ends when overexpressed. Reichenbach P, Hoss M, Azzalin CM, Nabholz M, Bucher P, Lingner J Curr Biol 2003-04-01 (13) 12676087
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. Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O DNA Res 1998-10-01 (5) 9872452
Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T DNA Res 2002-06-01 (9) 12168954
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal 2009-01-01 (2) 19690332
A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, Terns MP, Artandi SE Science 2009-02-01 (323) 19179534
Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. Glavan F, Behm-Ansmant I, Izaurralde E, Conti E EMBO J 2006-11-01 (25) 17053788
Crystal structure of the PIN domain of human telomerase-associated protein EST1A. Takeshita D, Zenno S, Lee WC, Saigo K, Tanokura M Proteins 2007-09-01 (68) 17557331



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Last modification of this entry: 2012-07-05 14:41:13
Edited by a user: kaja
Edited content: Changed structures and publications.

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