製品: TERT Antibody
カタログ: AF5413
タンパク質の説明: Rabbit polyclonal antibody to TERT
アプリケーション: WB
反応性: Human
予測: Pig, Dog
分子量: 127 kDa; 127kD(Calculated).
ユニプロット: O14746
RRID: AB_2837897

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製品説明

ソース:
Rabbit
アプリケーション:
WB 1:500-1:2000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

反応性:
Human
予測:
Pig(86%), Dog(86%)
クローナリティ:
Polyclonal
特異性:
TERT Antibody detects endogenous levels of total TERT.
RRID:
AB_2837897
引用形式: Affinity Biosciences Cat# AF5413, RRID:AB_2837897.
コンジュゲート:
Unconjugated.
精製:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
別名:

折りたたみ/展開

CMM9; DKCA2; DKCB4; EST2; HEST2; htert; hTRT; PFBMFT1; TCS1; Telomerase associated protein 2; Telomerase catalytic subunit; Telomerase reverse transcriptase; Telomerase-associated protein 2; Telomere Reverse Transcriptase; TERT; TERT_HUMAN; TP2; TRT;

免疫原

免疫原:
Uniprot:
遺伝子(ID):
発現特異性:
O14746 TERT_HUMAN:

Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes.

タンパク質の説明:
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme.
タンパク質配列:
MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGAATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRLVETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEILAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTIPQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTLLCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNLRKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTFNRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLPFHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLLKLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAANPALPSDFKTILD

種類予測

種類予測:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
86
Dog
86
Bovine
71
Sheep
71
Horse
0
Xenopus
0
Zebrafish
0
Chicken
0
Rabbit
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - O14746 基板として

Site PTM Type Enzyme
T26 Phosphorylation
Y122 Phosphorylation
S134 Phosphorylation
S227 Phosphorylation P31749 (AKT1)
S349 Phosphorylation
S457 Phosphorylation
S679 Phosphorylation
T692 Phosphorylation
Y707 Phosphorylation P12931 (SRC)
T767 Phosphorylation
S797 Phosphorylation
S824 Phosphorylation P31749 (AKT1)
S948 Phosphorylation
Y949 Phosphorylation
K1059 Acetylation
T1113 Phosphorylation
S1125 Phosphorylation

研究背景

機能:

Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.

PTMs:

Phosphorylation at Tyr-707 under oxidative stress leads to translocation of TERT to the cytoplasm and reduces its antiapoptotic activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention. Phosphorylation at Ser-227 by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-457 by DYRK2 promotes ubiquitination by the EDVP complex and degradation.

Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-457 by DYRK2. Ubiquitinated leads to proteasomal degradation.

(Microbial infection) In case of infection by HIV-1, the EDVP complex is hijacked by HIV-1 via interaction between HIV-1 Vpr and DCAF1/VPRBP, leading to ubiquitination and degradation.

細胞の位置付け:

Nucleus>Nucleolus. Nucleus>Nucleoplasm. Nucleus. Chromosome>Telomere. Cytoplasm. Nucleus>PML body.
Note: Shuttling between nuclear and cytoplasm depends on cell cycle, phosphorylation states, transformation and DNA damage. Diffuse localization in the nucleoplasm. Enriched in nucleoli of certain cell types. Translocated to the cytoplasm via nuclear pores in a CRM1/RAN-dependent manner involving oxidative stress-mediated phosphorylation at Tyr-707. Dephosphorylation at this site by SHP2 retains TERT in the nucleus. Translocated to the nucleus by phosphorylation by AKT.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
組織特異性:

Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes.

サブユニット構造:

Catalytic component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase. Interacts directly with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed. Interacts with RAN; the interaction promotes nuclear export of TERT. Interacts with XPO1. Interacts with PTPN11; the interaction retains TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT. Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling (By similarity). Interacts with MCRS1 (isoform MCRS2); the interaction inhibits in vitro telomerase activity. Interacts with PIF1; the interaction has no effect on the elongation activity of TERT (By similarity). Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity. Interacts with GNL3L (By similarity). Interacts with isoform 1 and isoform 2 of NVL. Interacts with DHX36.

タンパク質ファミリー:

The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers.

The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity.

The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis.

Belongs to the reverse transcriptase family. Telomerase subfamily.

研究領域

· Human Diseases > Infectious diseases: Viral > Human papillomavirus infection.

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

参考文献

1). hTERT promotes the invasion of gastric cancer cells by enhancing FOXO3a ubiquitination and subsequent ITGB1 upregulation. GUT, 2017 (PubMed: 26370108) [IF=24.5]

Application: WB    Species: human    Sample: human gastric cancer

Figure 1 Human telomerase reverse transcriptase (hTERT) promotes the invasion of gastric cancer cells by upregulating integrin β1 (ITGB1). (A) Western blot analysis of hTERT in U2OS, SGC-7901 and HGC-27 cells. The cells were infected with lenti-hTERT and the corresponding control lentivirus. (B) Transwell analysis of the effects of hTERT on the invasion of the cancer cells. After 48 h of incubation on the top of the Transwell insert, the cells were fixed and stained, and the number of invasion cells was calculated. (C) Ten candidate molecules with more than fivefold (log ratio) increases in hTERT-overexpressed U2OS cells, revealed by proteomics analysis. (D) Western blot analysis of the expression of the above candidates in hTERT-overexpressed cancer cells and corresponding control cells. (E) Western blot analysis of knockdown of ITGB1 after hTERT overexpression. Stable SGC-7901 and HGC-27 cells were transfected with siRNA targeting ITGB1. Forty-eight hours later, the cells were harvested for western blot analysis. (F) ITGB1-mediated cell adhesion assay after knockdown of ITGB1. Cells were treated as in (E) in six-well plates, and then adhesion assays were performed. (G) Cell invasion assays after knockdown of ITGB1. Six hours after the transfection of siRNAs against ITGB1 in the stable cells, SGC-7901 and HGC-27 cells were resuspended and seeded in Transwells for another 48 h, and the number of invasion cells was calculated. *p<0.05, **p<0.01.

Application: IHC    Species: human    Sample: human gastric cancer

Figure 2 Human telomerase reverse transcriptase (hTERT) expression parallels that of integrin β1 (ITGB1) in gastric cancer tissues, and both are correlated with poor prognosis. (A) Representative immunohistochemical staining of hTERT and ITGB1 in gastric cancer tissues and corresponding adjacent non-cancerous tissues. (B) The association between hTERT/ITGB1 expression and TNM stage/lymphatic metastasis in patients with gastric cancer (p<0.01). (C) The correlations between the protein levels of hTERT and ITGB1 (p<0.01). (D) The receiver operating characteristic (ROC) curves for predicting patients’ survival time using hTERT or ITGB1 expression. (E) Kaplan–Meier analyses of overall survival according to hTERT or ITGB1 expression levels (p<0.01). (F) Kaplan–Meier analyses of overall survival according to the combination of the above two indices (p<0.01). AUC, area under the curve; TNM, tumour node metastases.

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