Human Gene PML (ENST00000268059.10) from GENCODE V44
Description: Homo sapiens PML nuclear body scaffold (PML), transcript variant 9, mRNA. (from RefSeq NM_033239) RefSeq Summary (NM_033239): The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000268059.10 Gencode Gene: ENSG00000140464.20 Transcript (Including UTRs) Position: hg38 chr15:73,994,717-74,036,394 Size: 41,678 Total Exon Count: 8 Strand: + Coding Region Position: hg38 chr15:73,994,813-74,035,951 Size: 41,139 Coding Exon Count: 8
ID:PML_HUMAN DESCRIPTION: RecName: Full=Protein PML; AltName: Full=Promyelocytic leukemia protein; AltName: Full=RING finger protein 71; AltName: Full=Tripartite motif-containing protein 19; FUNCTION: Key component of PML nuclear bodies that regulate a large number of cellular processes by facilitating post- translational modification of target proteins, promoting protein- protein contacts, or by sequestering proteins. Functions as tumor suppressor. Required for normal, caspase-dependent apoptosis in response to DNA damage, FAS, TNF, or interferons. Plays a role in transcription regulation, DNA damage response, DNA repair and chromatin organization. Plays a role in processes regulated by retinoic acid, regulation of cell division, terminal differentiation of myeloid precursor cells and differentiation of neural progenitor cells. Required for normal immunity to microbial infections. Plays a role in antiviral response. In the cytoplasm, plays a role in TGFB1-dependent processes. Regulates p53/TP53 levels by inhibiting its ubiquitination and proteasomal degradation. Regulates activation of p53/TP53 via phosphorylation at 'Ser-20'. Sequesters MDM2 in the nucleolus after DNA damage, and thereby inhibits ubiquitination and degradation of p53/TP53. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates RB1 phosphorylation and activity. Required for normal development of the brain cortex during embryogenesis. Can sequester herpes virus and varicella virus proteins inside PML bodies, and thereby inhibit the formation of infectious viral particles. Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum (By similarity). Regulates transcription activity of ELF4. Inhibits specifically the activity of the tetrameric form of PKM. Together with SATB1, involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Regulates PTEN compartmentalization through the inhibition of USP7-mediated deubiquitination. SUBUNIT: Key component of PML bodies. PML bodies are formed by the interaction of PML homodimers (via SUMO-binding motif) with sumoylated PML, leading to the assembly of higher oligomers. Several types of PML bodies have been observed. PML bodies can form hollow spheres that can sequester target proteins inside. Interacts (via SUMO-binding motif) with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 phosphorylation at 'Ser-20' and prevents its proteasomal degradation. Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby preventing ubiquitination of p53/TP53. Interaction with PML-RARA oncoprotein and certain viral proteins causes disassembly of PML bodies and abolishes the normal PML function. Interacts with HIPK2, TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C- terminus). Interacts with Lassa virus Z protein and rabies virus phosphoprotein. Interacts with ITPR3 (By similarity). Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts (via the coiled-coil domain and when sumoylated) with SATB1. Interacts with UBE2I; the interaction is enhanced by arsenic binding. Interacts (PML-RARA oncoprotein, via the coiled-coil domain) with UBE2I; the interaction is enhanced by arsenic binding and is required for PML-RARA oncoprotein sumoylation and inhibition of RARA transactivational activity. Interacts with RB1, PPP1A, SMAD2, SMAD3, DAXX, RPL11 and MTOR. INTERACTION: P03243-1:- (xeno); NbExp=2; IntAct=EBI-304008, EBI-1927377; P68400:CSNK2A1; NbExp=2; IntAct=EBI-295890, EBI-347804; Q9UER7:DAXX; NbExp=6; IntAct=EBI-295890, EBI-77321; P25445:FAS; NbExp=4; IntAct=EBI-295890, EBI-494743; Q9Y2M5:KLHL20; NbExp=4; IntAct=EBI-295890, EBI-714379; Q13164:MAPK7; NbExp=6; IntAct=EBI-295890, EBI-1213983; Q00987:MDM2; NbExp=6; IntAct=EBI-304008, EBI-389668; P25788:PSMA3; NbExp=2; IntAct=EBI-295890, EBI-348380; P63165:SUMO1; NbExp=2; IntAct=EBI-295890, EBI-80140; P04637:TP53; NbExp=3; IntAct=EBI-295890, EBI-366083; Q05516:ZBTB16; NbExp=7; IntAct=EBI-295890, EBI-711925; SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body. Nucleus, nucleolus. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Sumoylated forms localize to the PML nuclear bodies. The B1 box and the RING finger are also required for this nuclear localization. Isoforms lacking a nuclear localization signal are cytoplasmic. Detected in the nucleolus after DNA damage. Sequestered in the cytoplasm by interaction with rabies virus phosphoprotein. DOMAIN: Interacts with PKM via its coiled-coil domain. DOMAIN: Binds arsenic via the RING-type zinc finger. PTM: Ubiquitinated; mediated by RNF4, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation. 'Lys-6'-, 'Lys-11'-, 'Lys- 48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent. Ubiquitination by UHRF1 leads to subsequent proteasomal degradation. PTM: Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites is required for nuclear body formation. Sumoylation on Lys-160 is a prerequisite for sumoylation on Lys-65. The PML-RARA fusion protein requires the coiled-coil domain for sumoylation. Desumoylated by SENP2 and SENP6. Arsenic induces PML and PML-RARA oncogenic fusion proteins polysumoylation and their subsequent RNF4-dependent ubiquitination and proteasomal degradation, and is used as treatment in acute promyelocytic leukemia (APL). PTM: Phosphorylated in response to DNA damage, probably by ATR. Stabilized by HIPK2-mediated phosphorylation at Ser-8 and Ser-38 in response to DNA damage. PTM: Acetylation may promote sumoylation and enhance induction of apoptosis. DISEASE: Note=A chromosomal aberration involving PML may be a cause of acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) with RARA. The PML breakpoints (type A and type B) lie on either side of an alternatively spliced exon. SIMILARITY: Contains 2 B box-type zinc fingers. SIMILARITY: Contains 1 RING-type zinc finger. SEQUENCE CAUTION: Sequence=AAA60351.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAA60352.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAA60388.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAA60390.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAB62809.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA; Sequence=BAD92648.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PMLID41.html";
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.
ModBase Predicted Comparative 3D Structure on P29590
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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.
Biological Process: GO:0001666 response to hypoxia GO:0001932 regulation of protein phosphorylation GO:0002230 positive regulation of defense response to virus by host GO:0002376 immune system process GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006605 protein targeting GO:0006606 protein import into nucleus GO:0006915 apoptotic process 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:0007050 cell cycle arrest GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007182 common-partner SMAD protein phosphorylation GO:0007569 cell aging GO:0008285 negative regulation of cell proliferation GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress GO:0009411 response to UV GO:0010332 response to gamma radiation GO:0010522 regulation of calcium ion transport into cytosol GO:0010761 fibroblast migration GO:0016032 viral process GO:0016525 negative regulation of angiogenesis GO:0030099 myeloid cell differentiation GO:0030155 regulation of cell adhesion GO:0030308 negative regulation of cell growth GO:0030578 PML body organization GO:0031065 positive regulation of histone deacetylation GO:0032206 positive regulation of telomere maintenance GO:0032211 negative regulation of telomere maintenance via telomerase GO:0032469 endoplasmic reticulum calcium ion homeostasis GO:0032922 circadian regulation of gene expression GO:0032938 negative regulation of translation in response to oxidative stress GO:0034097 response to cytokine GO:0042752 regulation of circadian rhythm GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator GO:0043153 entrainment of circadian clock by photoperiod GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045087 innate immune response GO:0045165 cell fate commitment GO:0045343 regulation of MHC class I biosynthetic process GO:0045345 positive regulation of MHC class I biosynthetic process GO:0045892 negative regulation of transcription, DNA-templated GO:0045930 negative regulation of mitotic cell cycle GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048146 positive regulation of fibroblast proliferation GO:0048384 retinoic acid receptor signaling pathway GO:0048511 rhythmic process GO:0050711 negative regulation of interleukin-1 secretion GO:0050713 negative regulation of interleukin-1 beta secretion GO:0050821 protein stabilization GO:0051457 maintenance of protein location in nucleus GO:0051607 defense response to virus GO:0051974 negative regulation of telomerase activity GO:0060058 positive regulation of apoptotic process involved in mammary gland involution GO:0060333 interferon-gamma-mediated signaling pathway GO:0060444 branching involved in mammary gland duct morphogenesis GO:0065003 macromolecular complex assembly GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0071353 cellular response to interleukin-4 GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator GO:0090398 cellular senescence GO:0097191 extrinsic apoptotic signaling pathway GO:1901796 regulation of signal transduction by p53 class mediator GO:1902187 negative regulation of viral release from host cell GO:1904816 positive regulation of protein localization to chromosome, telomeric region GO:1990830 cellular response to leukemia inhibitory factor GO:2000059 negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000779 regulation of double-strand break repair GO:2001235 positive regulation of apoptotic signaling pathway GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
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