Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Nucleus. Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body Nucleus, nucleolus. Endoplasmic reticulum membrane Peripheral membrane protein Cytoplasmic side Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Isoform PML-1 can shuttle between the nucleus and cytoplasm. Isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6 are nuclear isoforms whereas isoform PML-7 and isoform PML-14 lacking the nuclear localization signal are cytoplasmic isoforms. Detected in the nucleolus after DNA damage. Acetylation at Lys-487 is essential for its nuclear localization. Within the nucleus, most of PML is expressed in the diffuse nuclear fraction of the nucleoplasm and only a small fraction is found in the matrix-associated nuclear bodies (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends on its phosphorylation and sumoylation. The B1 box and the RING finger are also required for the localization in PML-NBs. Also found in specific membrane structures termed mitochondria-associated membranes (MAMs) which connect the endoplasmic reticulum (ER) and the mitochondria. Sequestered in the cytoplasm by interaction with rabies virus phosphoprotein. |
Domain |
PF12126 Protein of unknown function (DUF3583) PF00643 B-box zinc finger |
Function |
Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.; FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HCMV) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. |
Biological Process |
GO:0000075 cell cycle checkpoint GO:0000077 DNA damage checkpoint GO:0000082 G1/S transition of mitotic cell cycle GO:0000723 telomere maintenance GO:0001525 angiogenesis GO:0001558 regulation of cell growth GO:0001666 response to hypoxia GO:0001667 ameboidal-type cell migration GO:0001763 morphogenesis of a branching structure GO:0001818 negative regulation of cytokine production GO:0006282 regulation of DNA repair GO:0006302 double-strand break repair GO:0006606 protein import into nucleus GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006913 nucleocytoplasmic transport GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0006979 response to oxidative stress GO:0006997 nucleus organization GO:0007050 cell cycle arrest GO:0007093 mitotic cell cycle checkpoint GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007182 common-partner SMAD protein phosphorylation GO:0007184 SMAD protein import into nucleus GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007346 regulation of mitotic cell cycle GO:0007568 aging GO:0007569 cell aging GO:0007623 circadian rhythm GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress GO:0009306 protein secretion GO:0009314 response to radiation GO:0009411 response to UV GO:0009416 response to light stimulus GO:0009615 response to virus GO:0009648 photoperiodism GO:0009649 entrainment of circadian clock GO:0009894 regulation of catabolic process GO:0009895 negative regulation of catabolic process GO:0010212 response to ionizing radiation GO:0010332 response to gamma radiation GO:0010498 proteasomal protein catabolic process GO:0010522 regulation of calcium ion transport into cytosol GO:0010761 fibroblast migration GO:0010948 negative regulation of cell cycle process GO:0010950 positive regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0010959 regulation of metal ion transport GO:0016049 cell growth GO:0016525 negative regulation of angiogenesis GO:0016925 protein sumoylation GO:0017038 protein import GO:0018205 peptidyl-lysine modification GO:0019058 viral life cycle GO:0019076 viral release from host cell GO:0022612 gland morphogenesis GO:0030099 myeloid cell differentiation GO:0030308 negative regulation of cell growth GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0030522 intracellular receptor signaling pathway GO:0030575 nuclear body organization GO:0030578 PML body organization GO:0030879 mammary gland development GO:0031329 regulation of cellular catabolic process GO:0031330 negative regulation of cellular catabolic process GO:0031396 regulation of protein ubiquitination GO:0031397 negative regulation of protein ubiquitination GO:0031570 DNA integrity checkpoint GO:0031571 mitotic G1 DNA damage checkpoint GO:0032200 telomere organization GO:0032204 regulation of telomere maintenance GO:0032206 positive regulation of telomere maintenance GO:0032469 endoplasmic reticulum calcium ion homeostasis GO:0032507 maintenance of protein location in cell GO:0032611 interleukin-1 beta production GO:0032612 interleukin-1 production GO:0032651 regulation of interleukin-1 beta production GO:0032652 regulation of interleukin-1 production GO:0032691 negative regulation of interleukin-1 beta production GO:0032692 negative regulation of interleukin-1 production GO:0032844 regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0032922 circadian regulation of gene expression GO:0033044 regulation of chromosome organization GO:0034341 response to interferon-gamma GO:0034504 protein localization to nucleus GO:0034599 cellular response to oxidative stress GO:0034976 response to endoplasmic reticulum stress GO:0035239 tube morphogenesis GO:0036293 response to decreased oxygen levels GO:0036473 cell death in response to oxidative stress GO:0042176 regulation of protein catabolic process GO:0042177 negative regulation of protein catabolic process GO:0042752 regulation of circadian rhythm GO:0042770 signal transduction in response to DNA damage GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043153 entrainment of circadian clock by photoperiod GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044744 protein targeting to nucleus GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044773 mitotic DNA damage checkpoint GO:0044774 mitotic DNA integrity checkpoint GO:0044783 G1 DNA damage checkpoint GO:0044819 mitotic G1/S transition checkpoint GO:0044843 cell cycle G1/S phase transition GO:0045165 cell fate commitment GO:0045185 maintenance of protein location GO:0045341 MHC class I biosynthetic process GO:0045343 regulation of MHC class I biosynthetic process GO:0045345 positive regulation of MHC class I biosynthetic process GO:0045765 regulation of angiogenesis GO:0045786 negative regulation of cell cycle GO:0045787 positive regulation of cell cycle GO:0045861 negative regulation of proteolysis GO:0045862 positive regulation of proteolysis GO:0045926 negative regulation of growth GO:0045930 negative regulation of mitotic cell cycle GO:0048144 fibroblast proliferation GO:0048145 regulation of fibroblast proliferation GO:0048146 positive regulation of fibroblast proliferation GO:0048384 retinoic acid receptor signaling pathway GO:0048511 rhythmic process GO:0048514 blood vessel morphogenesis GO:0048525 negative regulation of viral process GO:0048732 gland development GO:0048754 branching morphogenesis of an epithelial tube GO:0050663 cytokine secretion GO:0050701 interleukin-1 secretion GO:0050702 interleukin-1 beta secretion GO:0050704 regulation of interleukin-1 secretion GO:0050706 regulation of interleukin-1 beta secretion GO:0050707 regulation of cytokine secretion GO:0050708 regulation of protein secretion GO:0050709 negative regulation of protein secretion GO:0050710 negative regulation of cytokine secretion GO:0050711 negative regulation of interleukin-1 secretion GO:0050713 negative regulation of interleukin-1 beta secretion GO:0050792 regulation of viral process GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051052 regulation of DNA metabolic process GO:0051054 positive regulation of DNA metabolic process GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051224 negative regulation of protein transport GO:0051235 maintenance of location GO:0051457 maintenance of protein location in nucleus GO:0051480 regulation of cytosolic calcium ion concentration GO:0051607 defense response to virus GO:0051651 maintenance of location in cell GO:0051924 regulation of calcium ion transport GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0055074 calcium ion homeostasis GO:0060249 anatomical structure homeostasis GO:0060333 interferon-gamma-mediated signaling pathway GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0060443 mammary gland morphogenesis GO:0060444 branching involved in mammary gland duct morphogenesis GO:0060562 epithelial tube morphogenesis GO:0060603 mammary gland duct morphogenesis GO:0061138 morphogenesis of a branching epithelium GO:0061180 mammary gland epithelium development GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070482 response to oxygen levels GO:0070670 response to interleukin-4 GO:0070838 divalent metal ion transport GO:0071156 regulation of cell cycle arrest GO:0071158 positive regulation of cell cycle arrest GO:0071346 cellular response to interferon-gamma GO:0071353 cellular response to interleukin-4 GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:0072331 signal transduction by p53 class mediator GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator GO:0072395 signal transduction involved in cell cycle checkpoint GO:0072401 signal transduction involved in DNA integrity checkpoint GO:0072413 signal transduction involved in mitotic cell cycle checkpoint GO:0072422 signal transduction involved in DNA damage checkpoint GO:0072431 signal transduction involved in mitotic G1 DNA damage checkpoint GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0072595 maintenance of protein localization in organelle GO:0090068 positive regulation of cell cycle process GO:0090398 cellular senescence GO:0097191 extrinsic apoptotic signaling pathway GO:0097193 intrinsic apoptotic signaling pathway GO:0098542 defense response to other organism GO:1901342 regulation of vasculature development GO:1901343 negative regulation of vasculature development GO:1901796 regulation of signal transduction by p53 class mediator GO:1901987 regulation of cell cycle phase transition GO:1901988 negative regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1901991 negative regulation of mitotic cell cycle phase transition GO:1902186 regulation of viral release from host cell GO:1902187 negative regulation of viral release from host cell GO:1902400 intracellular signal transduction involved in G1 DNA damage checkpoint GO:1902402 signal transduction involved in mitotic DNA damage checkpoint GO:1902403 signal transduction involved in mitotic DNA integrity checkpoint GO:1902593 single-organism nuclear import GO:1902806 regulation of cell cycle G1/S phase transition GO:1902807 negative regulation of cell cycle G1/S phase transition GO:1903050 regulation of proteolysis involved in cellular protein catabolic process GO:1903051 negative regulation of proteolysis involved in cellular protein catabolic process GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903321 negative regulation of protein modification by small protein conjugation or removal GO:1903362 regulation of cellular protein catabolic process GO:1903363 negative regulation of cellular protein catabolic process GO:1903531 negative regulation of secretion by cell GO:1903900 regulation of viral life cycle GO:1903901 negative regulation of viral life cycle GO:1904950 negative regulation of establishment of protein localization GO:2000021 regulation of ion homeostasis GO:2000045 regulation of G1/S transition of mitotic cell cycle GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000059 negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000116 regulation of cysteine-type endopeptidase activity GO:2000134 negative regulation of G1/S transition of mitotic cell cycle GO:2000181 negative regulation of blood vessel morphogenesis GO:2000779 regulation of double-strand break repair GO:2001020 regulation of response to DNA damage stimulus GO:2001056 positive regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001238 positive regulation of extrinsic apoptotic signaling pathway GO:2001252 positive regulation of chromosome organization |
Molecular Function |
GO:0031625 ubiquitin protein ligase binding GO:0032182 ubiquitin-like protein binding GO:0032183 SUMO binding GO:0044389 ubiquitin-like protein ligase binding GO:0046332 SMAD binding |
Cellular Component |
GO:0000781 chromosome, telomeric region GO:0000784 nuclear chromosome, telomeric region GO:0005635 nuclear envelope GO:0005769 early endosome GO:0010008 endosome membrane GO:0016363 nuclear matrix GO:0016604 nuclear body GO:0016605 PML body GO:0019898 extrinsic component of membrane GO:0031312 extrinsic component of organelle membrane GO:0031901 early endosome membrane GO:0031965 nuclear membrane GO:0034399 nuclear periphery GO:0042406 extrinsic component of endoplasmic reticulum membrane GO:0044440 endosomal part GO:0044454 nuclear chromosome part GO:0098687 chromosomal region |
KEGG |
hsa04120 Ubiquitin mediated proteolysis hsa04144 Endocytosis |
Reactome |
R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling R-HSA-877300: Interferon gamma signaling R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804758: Regulation of TP53 Activity through Acetylation R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-3108214: SUMOylation of DNA damage response and repair proteins R-HSA-3700989: Transcriptional Regulation by TP53 |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between PML and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between PML and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of PML in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of PML in various data sets.
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Points in the above scatter plot represent the mutation difference of PML in various data sets.
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Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PML. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PML. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PML. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PML. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of PML expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between PML and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | PML |
Name | promyelocytic leukemia |
Aliases | MYL; TRIM19; RNF71; PP8675; PML/RARA fusion; RING finger protein 71; probable transcription factor PML; prom ...... |
Chromosomal Location | 15q24.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting PML collected from DrugBank database. |
Details on drugs targeting PML.
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