EST1A_MOUSE
ID EST1A_MOUSE Reviewed; 1418 AA.
AC P61406; Q5NC64;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Telomerase-binding protein EST1A {ECO:0000305};
DE EC=3.1.-.-;
DE AltName: Full=Ever shorter telomeres 1A {ECO:0000250|UniProtKB:Q86US8};
DE AltName: Full=Nonsense mediated mRNA decay factor SMG6 {ECO:0000312|MGI:MGI:2144117};
DE AltName: Full=Smg-6 homolog {ECO:0000250|UniProtKB:Q86US8};
GN Name=Smg6 {ECO:0000312|MGI:MGI:2144117};
GN Synonyms=Est1a {ECO:0000250|UniProtKB:Q86US8},
GN Kiaa0732 {ECO:0000250|UniProtKB:Q86US8};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 447-1418.
RC TISSUE=Fetal brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331; THR-470; SER-869 AND
RP SER-873, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-405 AND ARG-432, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Component of the telomerase ribonucleoprotein (RNP) complex
CC that is essential for the replication of chromosome termini. May have a
CC general role in telomere regulation. Promotes in vitro the ability of
CC TERT to elongate telomeres. Overexpression induces telomere uncapping,
CC chromosomal end-to-end fusions (telomeric DNA persists at the fusion
CC points) and did not perturb TRF2 telomeric localization. Binds to the
CC single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a
CC telomerase RNA template component (TER).
CC {ECO:0000250|UniProtKB:Q86US8}.
CC -!- FUNCTION: Plays a role in nonsense-mediated mRNA decay. Is thought to
CC provide a link to the mRNA degradation machinery as it has endonuclease
CC activity required to initiate NMD, and to serve as an adapter for UPF1
CC to protein phosphatase 2A (PP2A), thereby triggering UPF1
CC dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA
CC or dsRNA. {ECO:0000250|UniProtKB:Q86US8}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC -!- SUBUNIT: May form homooligomers. Associated component of the telomerase
CC holoenzyme complex. Interacts with TERT, independently of the
CC telomerase RNA. Interacts with SMG1, SMG5, SMG7, UPF1, UPF2, UPF3B and
CC the PP2A catalytic subunits. Also interacts with the exon junction
CC complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A;
CC required for the process of nonsense-mediated mRNA decay. Interacts
CC with DHX34; the interaction is RNA-independent (By similarity).
CC {ECO:0000250|UniProtKB:Q86US8}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q86US8}. Chromosome, telomere
CC {ECO:0000250|UniProtKB:Q86US8}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q86US8}. Note=Particularly enriched in the
CC nucleolus. {ECO:0000250|UniProtKB:Q86US8}.
CC -!- DOMAIN: The PINc domain confers endonuclease activity and is expected
CC to bind the catalytic metal ion. {ECO:0000250|UniProtKB:Q86US8}.
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DR EMBL; AL603905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL604066; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC066040; AAH66040.1; -; mRNA.
DR EMBL; AK129203; BAC98013.1; -; mRNA.
DR CCDS; CCDS25039.1; -.
DR RefSeq; NP_001002764.1; NM_001002764.1.
DR AlphaFoldDB; P61406; -.
DR SMR; P61406; -.
DR BioGRID; 222140; 5.
DR IntAct; P61406; 1.
DR STRING; 10090.ENSMUSP00000043555; -.
DR iPTMnet; P61406; -.
DR PhosphoSitePlus; P61406; -.
DR EPD; P61406; -.
DR jPOST; P61406; -.
DR MaxQB; P61406; -.
DR PaxDb; P61406; -.
DR PeptideAtlas; P61406; -.
DR PRIDE; P61406; -.
DR ProteomicsDB; 275801; -.
DR Antibodypedia; 50527; 75 antibodies from 13 providers.
DR Ensembl; ENSMUST00000045281; ENSMUSP00000043555; ENSMUSG00000038290.
DR GeneID; 103677; -.
DR KEGG; mmu:103677; -.
DR UCSC; uc007kcz.1; mouse.
DR CTD; 23293; -.
DR MGI; MGI:2144117; Smg6.
DR VEuPathDB; HostDB:ENSMUSG00000038290; -.
DR eggNOG; KOG2162; Eukaryota.
DR GeneTree; ENSGT00940000155300; -.
DR HOGENOM; CLU_004735_0_0_1; -.
DR InParanoid; P61406; -.
DR OMA; KDFMPPQ; -.
DR OrthoDB; 556396at2759; -.
DR PhylomeDB; P61406; -.
DR TreeFam; TF327119; -.
DR Reactome; R-MMU-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR BioGRID-ORCS; 103677; 22 hits in 77 CRISPR screens.
DR ChiTaRS; Smg6; mouse.
DR PRO; PR:P61406; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P61406; protein.
DR Bgee; ENSMUSG00000038290; Expressed in spermatid and 221 other tissues.
DR ExpressionAtlas; P61406; baseline and differential.
DR Genevisible; P61406; MM.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0035145; C:exon-exon junction complex; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:HGNC-UCL.
DR GO; GO:0005697; C:telomerase holoenzyme complex; IBA:GO_Central.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:MGI.
DR GO; GO:0004521; F:endoribonuclease activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0070034; F:telomerase RNA binding; ISO:MGI.
DR GO; GO:0042162; F:telomeric DNA binding; ISS:HGNC-UCL.
DR GO; GO:1904354; P:negative regulation of telomere capping; ISO:MGI.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; ISS:UniProtKB.
DR GO; GO:0032204; P:regulation of telomere maintenance; ISS:HGNC.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR018834; DNA/RNA-bd_Est1-type.
DR InterPro; IPR045153; Est1/Ebs1-like.
DR InterPro; IPR019458; Est1_N.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR002716; PIN_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR15696; PTHR15696; 1.
DR Pfam; PF10374; EST1; 1.
DR Pfam; PF10373; EST1_DNA_bind; 1.
DR Pfam; PF13638; PIN_4; 1.
DR SMART; SM00670; PINc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
PE 1: Evidence at protein level;
KW Chromosome; Coiled coil; Cytoplasm; DNA-binding; Endonuclease; Hydrolase;
KW Manganese; Metal-binding; Methylation; Nonsense-mediated mRNA decay;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; Telomere.
FT CHAIN 1..1418
FT /note="Telomerase-binding protein EST1A"
FT /id="PRO_0000087070"
FT DOMAIN 1245..1396
FT /note="PINc"
FT REGION 23..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..59
FT /note="EJC-binding motif 1; mediates interaction with the
FT EJC"
FT /evidence="ECO:0000250"
FT REGION 102..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 132..152
FT /note="EJC-binding motif 2; mediates interaction with the
FT EJC"
FT /evidence="ECO:0000250"
FT REGION 178..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..468
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 820..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 856..882
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 566..600
FT /evidence="ECO:0000255"
FT COILED 1196..1243
FT /evidence="ECO:0000255"
FT COMPBIAS 30..83
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..121
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..230
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..332
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 366..402
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 860..882
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1250
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 1352
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 1391
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 405
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 432
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 470
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 478
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86US8"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86US8"
FT MOD_RES 830
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86US8"
FT MOD_RES 869
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 1418 AA; 160496 MW; DC48C12B38C6EB8A CRC64;
MAEGLERVRI SASELRGILA TLAPQAGSRE NMKELKEPRQ RKDNRRPDLE IYKPGLSRLR
NRPKTKEASG NEEFKDEIVN DRDSSAVGND TQLIQVCKEL DSQQQNGPID AENSQAQETF
PKTVGLEDRS LKIIKRSKKP DLQIYQPGRR LQTITKESAG RADEEEILNQ VEQLRIEEDE
CKGEAIKEEV NNKPDKTEIE KHQSNDRVRT AKGEKGKKIE KGEGSKKVAD DSVPGKPGSV
KRYSRSDKRR NRYRTCSTSS AGSNNSAEGA GLTDNGCRRR RQDRAKERPR LKKQVSLSST
DSLDEDRVDE PDVLGSRRSS ERKKHLERNW SGCGEGEQKS NGKENRSALR VTFDAETMSK
DSPVVRSVKD NVDRMKSDKG PSSGGKGSEK QELRHPRQEL RDRGRGILIL PAHTALSVSS
SGSPESTPLG PRLLFGSGSK GSRSWGRGGT TRRLWDPNNP DQKPALKSQT PQLHFLDTDD
EISPTSWGDS RQAQASYYKF QNSDNPYYYP RTPGPASQYP YAGYSPLQYP VGPTNGMYPG
AYYPGYPAPS GQYVCSPLPA STMSPEEIEQ HVRNMQQQEL HRLLRVADNQ ELQLSNLLSR
DRISTEGMEK MAQLRTELLQ LYERCILLDI EFSDSQNVDQ ILWKNAFYQV IEKFRQLLKD
PNSENPEQIR NRLLELLDEG SDFFDSLLQK LQVTYKFKLE DYMDGLAIRS KPLRKTVKYA
LISAQRSMIC QGDISRYREQ ANDTANYGKA RSWYLKAQHI APKNGRPYNQ LALLAVYTRR
KLDAVYYYMR SLAASNPILT AKESLMSLFE ETKRKAEQME KKQHEEFDMS PDKWRKGKKS
TFRHVGDDTT RLEIWIHPSH SRSAQGTESG KDSEQENGLG SLSPSDLNKR FILSFLHAHG
KLFTRIGMET FPAVAEKVLK EFQVLLQHSP SPIGSTRMLQ LMTINMFAVH NSQLKDCFSE
ECRSVIQEQA ASLGLAMFSL LVQRCTCLLK DSAKAQLSSP EDQEDQDDIK VSSFVPDLKE
LLPSVKVWSD WMLGYPDTWN PPPTSLDLPL QVAVDVWSTL ADFCNILTAV NQSEVPLYKD
PDDDLTLLIL EEDRLLSGFV PLLAAPQDPC YVEKTSDKVI AADCKRVTVL KYFLEALCGQ
EEPLLAFKGG KYVSVAPVPD TMGKEMGSQE GKQLEDEEED VVIEDFEEDS EAEGSGGEDD
IRELRAKKLA LARKIAEQQR RQEKIQAVLE DQSQMRQMEL EIRPLFLVPD TNGFIDHLAS
LARLLESRKY ILVVPLIVIN ELDGLAKGQE TDHRAGGYAR VVQEKARKSI EFLERRFESR
DSCLRALTSR GNELESIAFR SEDITGQLGN NDDLILSCCL HYCKDKAKDY MPTSKEEPIR
LLREVVLLTD DRNLRVKALT RNVPVRDIPA FLTWAQVG
