Human Gene SMG6 (uc002fub.1) Description and Page Index
  Description: Homo sapiens smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans) (SMG6), transcript variant 1, mRNA.
RefSeq Summary (NM_017575): This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014].
Transcript (Including UTRs)
   Position: hg19 chr17:1,963,133-2,207,069 Size: 243,937 Total Exon Count: 19 Strand: -
Coding Region
   Position: hg19 chr17:1,964,786-2,207,014 Size: 242,229 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr17:1,963,133-2,207,069)mRNA (may differ from genome)Protein (1419 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Telomerase-binding protein EST1A; EC=3.1.-.-; AltName: Full=EST1-like protein A; AltName: Full=Ever shorter telomeres 1A; AltName: Full=Smg-6 homolog; AltName: Full=Telomerase subunit EST1A; AltName: Full=hSmg5/7a;
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).
FUNCTION: 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: 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.
INTERACTION: Q92900-2:UPF1; NbExp=2; IntAct=EBI-3232100, EBI-373492;
SUBCELLULAR LOCATION: Nucleus, nucleolus. Chromosome, telomere (Probable). Cytoplasm, cytosol. Note=Particularly enriched in the nucleolus.
DOMAIN: The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion.
SIMILARITY: Contains 1 PINc domain.
SEQUENCE CAUTION: Sequence=AAH64916.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA34452.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): SMG6
CDC HuGE Published Literature: SMG6
Positive Disease Associations: Aorta , Aortic root size , Coronary Artery Disease
Related Studies:
  1. Aorta
    Ramachandran S Vasan et al. JAMA : the journal of the American Medical Association 2009, Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data., JAMA : the journal of the American Medical Association. [PubMed 19584346]
    We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
  2. Aortic root size
    Vasan ,et al. 2009, Genetic Variants Associated with Cardiac Structure and Function: A Meta-analysis and Replication of Genome-wide Association Data, JAMA 2009 302- 2 : 168-78. [PubMed 19584346]
    We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance.
  3. Coronary Artery Disease
    Heribert Schunkert et al. Nature genetics 2011, Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease., Nature genetics. [PubMed 21378990]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: SMG6
Diseases sorted by gene-association score: tricuspid valve insufficiency (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.48 RPKM in Testis
Total median expression: 366.77 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -34.8055-0.633 Picture PostScript Text
3' UTR -658.061653-0.398 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR018834 - DNA/RNA-bd_Est1-type
IPR019458 - EST1
IPR006596 - PINc_nuc-bd
IPR011990 - TPR-like_helical

Pfam Domains:
PF10373 - Est1 DNA/RNA binding domain
PF10374 - Telomerase activating protein Est1
PF13638 - PIN domain

SCOP Domains:
88723 - PIN domain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q86US8
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details  Gene DetailsGene Details 
Gene Sorter  Gene SorterGene Sorter 
  Protein SequenceProtein SequenceProtein Sequence 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0004518 nuclease activity
GO:0004519 endonuclease activity
GO:0004521 endoribonuclease activity
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0042162 telomeric DNA binding
GO:0043021 ribonucleoprotein complex binding
GO:0046872 metal ion binding
GO:0070034 telomerase RNA binding
GO:0070182 DNA polymerase binding

Biological Process:
GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0006406 mRNA export from nucleus
GO:0032204 regulation of telomere maintenance
GO:0032210 regulation of telomere maintenance via telomerase
GO:0035303 regulation of dephosphorylation
GO:0043487 regulation of RNA stability
GO:0051972 regulation of telomerase activity
GO:0090305 nucleic acid phosphodiester bond hydrolysis
GO:0090502 RNA phosphodiester bond hydrolysis, endonucleolytic
GO:1904354 negative regulation of telomere capping

Cellular Component:
GO:0000781 chromosome, telomeric region
GO:0005634 nucleus
GO:0005694 chromosome
GO:0005697 telomerase holoenzyme complex
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0000333 telomerase catalytic core complex
GO:0035145 exon-exon junction complex

-  Descriptions from all associated GenBank mRNAs
  AK024131 - Homo sapiens cDNA FLJ14069 fis, clone HEMBB1001562, weakly similar to CYLICIN II.
AK074270 - Homo sapiens cDNA FLJ23690 fis, clone HEP10195.
AY145883 - Homo sapiens telomerase subunit EST1A mRNA, complete cds.
AB018275 - Homo sapiens KIAA0732 mRNA for KIAA0732 protein.
BC064916 - Homo sapiens Smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans), mRNA (cDNA clone IMAGE:6070108), complete cds.
AK302964 - Homo sapiens cDNA FLJ53500 complete cds, highly similar to Telomerase-binding protein EST1A.
AY168921 - Homo sapiens Est1p-like protein A mRNA, complete cds.
BC148373 - Synthetic construct Homo sapiens clone IMAGE:100015319, MGC:182986 Smg-6 homolog, nonsense mediated mRNA decay factor (C. elegans) (SMG6) mRNA, encodes complete protein.
KJ902319 - Synthetic construct Homo sapiens clone ccsbBroadEn_11713 SMG6 gene, encodes complete protein.
AB385377 - Synthetic construct DNA, clone: pF1KA0732, Homo sapiens SMG6 gene for Smg-6 homolog, nonsense mediated mRNA decay factor, complete cds, without stop codon, in Flexi system.
CU687964 - Synthetic construct Homo sapiens gateway clone IMAGE:100022848 5' read SMG6 mRNA.
LF209193 - JP 2014500723-A/16696: Polycomb-Associated Non-Coding RNAs.
AL133597 - Homo sapiens mRNA; cDNA DKFZp434E042 (from clone DKFZp434E042).
MA444770 - JP 2018138019-A/16696: Polycomb-Associated Non-Coding RNAs.
AK093007 - Homo sapiens cDNA FLJ35688 fis, clone SPLEN2019375.
AX747853 - Sequence 1378 from Patent EP1308459.
AL080204 - Homo sapiens mRNA; cDNA DKFZp434F072 (from clone DKFZp434F072).
JD128262 - Sequence 109286 from Patent EP1572962.
JD280753 - Sequence 261777 from Patent EP1572962.
JD537117 - Sequence 518141 from Patent EP1572962.
JD385287 - Sequence 366311 from Patent EP1572962.
JD133595 - Sequence 114619 from Patent EP1572962.
JD072516 - Sequence 53540 from Patent EP1572962.
JD552004 - Sequence 533028 from Patent EP1572962.
JD076760 - Sequence 57784 from Patent EP1572962.
JD121612 - Sequence 102636 from Patent EP1572962.
JD468157 - Sequence 449181 from Patent EP1572962.
JD077724 - Sequence 58748 from Patent EP1572962.
JD253723 - Sequence 234747 from Patent EP1572962.
JD134433 - Sequence 115457 from Patent EP1572962.
JD398096 - Sequence 379120 from Patent EP1572962.
LF326729 - JP 2014500723-A/134232: Polycomb-Associated Non-Coding RNAs.
JD171310 - Sequence 152334 from Patent EP1572962.
JD391922 - Sequence 372946 from Patent EP1572962.
JD464364 - Sequence 445388 from Patent EP1572962.
JD371498 - Sequence 352522 from Patent EP1572962.
JD525777 - Sequence 506801 from Patent EP1572962.
JD367993 - Sequence 349017 from Patent EP1572962.
JD525773 - Sequence 506797 from Patent EP1572962.
LF326728 - JP 2014500723-A/134231: Polycomb-Associated Non-Coding RNAs.
JD423626 - Sequence 404650 from Patent EP1572962.
JD444950 - Sequence 425974 from Patent EP1572962.
JD496487 - Sequence 477511 from Patent EP1572962.
JD422301 - Sequence 403325 from Patent EP1572962.
JD272618 - Sequence 253642 from Patent EP1572962.
JD429171 - Sequence 410195 from Patent EP1572962.
JD174914 - Sequence 155938 from Patent EP1572962.
JD220937 - Sequence 201961 from Patent EP1572962.
JD148520 - Sequence 129544 from Patent EP1572962.
LF326727 - JP 2014500723-A/134230: Polycomb-Associated Non-Coding RNAs.
JD524644 - Sequence 505668 from Patent EP1572962.
JD405651 - Sequence 386675 from Patent EP1572962.
JD369316 - Sequence 350340 from Patent EP1572962.
JD278490 - Sequence 259514 from Patent EP1572962.
JD255877 - Sequence 236901 from Patent EP1572962.
JD055588 - Sequence 36612 from Patent EP1572962.
JD276975 - Sequence 257999 from Patent EP1572962.
JD144117 - Sequence 125141 from Patent EP1572962.
JD067798 - Sequence 48822 from Patent EP1572962.
LF326726 - JP 2014500723-A/134229: Polycomb-Associated Non-Coding RNAs.
MA562306 - JP 2018138019-A/134232: Polycomb-Associated Non-Coding RNAs.
MA562305 - JP 2018138019-A/134231: Polycomb-Associated Non-Coding RNAs.
MA562304 - JP 2018138019-A/134230: Polycomb-Associated Non-Coding RNAs.
MA562303 - JP 2018138019-A/134229: Polycomb-Associated Non-Coding RNAs.
LF209191 - JP 2014500723-A/16694: Polycomb-Associated Non-Coding RNAs.
MA444768 - JP 2018138019-A/16694: Polycomb-Associated Non-Coding RNAs.
DQ596371 - Homo sapiens piRNA piR-34437, complete sequence.
DQ589762 - Homo sapiens piRNA piR-56874, complete sequence.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q86US8 (Reactome details) participates in the following event(s):

R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-927802 Nonsense-Mediated Decay (NMD)
R-HSA-8953854 Metabolism of RNA

-  Other Names for This Gene
  Alternate Gene Symbols: C17orf31, EST1A, EST1A_HUMAN, KIAA0732, NM_017575, NP_060045, O94837, Q86US8, Q86VH6, Q9UF60, uc002fud.2
UCSC ID: uc002fub.1
RefSeq Accession: NM_017575
Protein: Q86US8 (aka EST1A_HUMAN or ESTA_HUMAN)
CCDS: CCDS11016.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_017575.4
exon count: 19CDS single in 3' UTR: no RNA size: 5968
ORF size: 4260CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6933.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.