| Description | 560 amino acids, 70 KDa (longest isoform); composed successively, from the N- to the C-terminus, by: 1- a proline-rich N-terminus 2- a so-called "tripartite motif", cysteine-histidine rich, composed of a RING finger structure and 2 B box domains, with putative DNA-binding function 3- a coiled-coil motif corresponding to a dimerization interface 4- a basic sequence with a nuclear localization domain, and 5- a serine-proline rich C-terminal region, of unknown function, variable in length (alternative splicing) and containing phosphorylation sites |
| Expression | in a wide variety of tissues. In hematopoietic tissue, expression apparently restricted to myeloid precursors |
| Localisation | nuclear, as part of a multiproteic complex located into multiple subnuclear PML oncogenic domains (PODs) |
| Function | unknown to date; putative transcription factor; in conjunction with other proteins included in the PODs, it would play a role as tumor suppressor and in apoptosis |
| Homology | with (numerous) other RING finger / B box proteins |
| Entity | t(15;17)(q22;q21) / acute promyelocytic leukemia (APL) -->PML- RARA |
| Disease | typical APL (or M3 ANLL, FAB classification), approximately 98% of APL cases; abnormal promyelocytes with Auer rods and bundles (faggots); disruption of the PODs with a microspeckeled pattern; maturation response to all-trans retinoic acid (ATRA) therapy |
| Prognosis | immediate prognosis impaired by intravascular disseminated coagulopathy; long term prognosis is favorable with treatment combining ATRA plus chemotherapy |
| Cytogenetics | variant or complex t(15;17) translocation in 5% of cases, no known prognosis implication; secondary chromosomal abnormalities in 30 to 35% of APL at diagnosis; association with +8 in 17 to 28% of cases; other associations are rare but recurrent: del(7q), del(9q), ider(17)t(15;17), +21 |
| Hybrid/Mutated Gene | the crucial fusion transcript is 5'PML-3'RARA, encoded by der(15) chromosome; the counterpart 5'RARA-3'PML encoded by der(17) is inconstant breakpoint in RARA gene is always located in intron between A and B domains three breakpoint clusters in PML gene: bcr1 (70% of patients), bcr2 (10%) and bcr3 (20%), giving rise respectively to the long (L), intermediate (V) and short (S) length hybrid PML-RARAtranscripts; V form would be linked to ATRA decreased sensitivity and S form to association with an excess of secondary chromosome changes. |
| Abnormal Protein | 106 Kda fusion protein; role in the leukemogenic process by probable interference with the signalling pathway leading to differentiation and maturation of myeloid precursors (mainly dysregulation of retinoid-inducible genes involved in myeloid differentiation) |
| | |
| Nomenclature | | HGNC (Hugo) | PML 9113 |
| Entrez_Gene (NCBI) | PML 5371 promyelocytic leukemia |
| Cards |
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| Atlas | PMLID41 |
| GeneCards (Weizmann) | PML |
| Ensembl (Hinxton) | ENSG00000140464 [Gene_View] PML [Vega] |
| AceView (NCBI) | PML |
| Genatlas (Paris) | PML |
| euGene (Indiana) | 5371 |
| SOURCE (Stanford) | NM_002675 NM_033238 NM_033239 NM_033240 NM_033244 NM_033246 NM_033247 NM_033249 NM_033250
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| Genomic and cartography |
|---|
| GoldenPath (UCSC) | PML - 15q22 chr15:72074067-72122770 + 15q22 [Description] (hg18-Mar_2006) |
| Ensembl | PML - 15q22 [CytoView] |
| Mapping of homologs : NCBI | PML [Mapview] |
| OMIM | 102578 |
| Gene and transcription |
| Gene : Genbank (Entrez) | AB208950 AB209051 AB209411 AF230401 AF230402 |
| Reference sequence (RefSeq transcript) :SRS | NM_002675 NM_033238 NM_033239 NM_033240 NM_033244 NM_033246 NM_033247 NM_033249 NM_033250 |
| Reference transcript : Entrez | NM_002675 NM_033238 NM_033239 NM_033240 NM_033244 NM_033246 NM_033247 NM_033249 NM_033250 |
| RefSeq genomic : SRS | AC_000058 AC_000147 NC_000015 NT_010194 NW_001838218 NW_925884 |
| RefSeq genomic : Entrez | AC_000058 AC_000147 NC_000015 NT_010194 NW_001838218 NW_925884 |
| Consensus coding sequences : CCDS NCBI | PML |
| Cluster EST : Unigene | Hs.526464 [ SRS ] Hs.526464 [ NCBI ] |
| Alternative Splicing : Fast-db (Paris) | 18056 |
| Protein : pattern, domain, 3D structure |
|---|
| Protein : UniProt/SwissProt | P29590 (SRS) P29590 (Expasy) P29590 (Uniprot) |
| With graphics : InterPro | P29590 |
| Splice isoforms : VarSplice FASTA | P29590(VarSplice FASTA) |
| Domaine pattern : Prosite (SRS) | ZF_BBOX (PS50119) ZF_RING_1 (PS00518) ZF_RING_2 (PS50089) |
| Domain pattern : Prosite (Expaxy) | ZF_BBOX (PS50119) ZF_RING_1 (PS00518) ZF_RING_2 (PS50089) |
| Domains : Interpro (SRS) | Znf_B-box Znf_RING Znf_RING/FYVE/PHD |
| Domains : Interpro (EBI) | Znf_B-box Znf_RING Znf_RING/FYVE/PHD |
| Related proteins : CluSTr | P29590 |
| Domain families : Pfam SRS | zf-B_box (PF00643) zf-C3HC4 (PF00097) |
| Domain families : Pfam Sanger | zf-B_box (PF00643) zf-C3HC4 (PF00097) |
| Domain families : Pfam NCBI | pfam00643 pfam00097 |
| Domain families : Smart EMBL | BBOX (SM00336)RING (SM00184) |
| Blocks (Seattle) | P29590 |
| Crystal structure of protein : PDB SRS | 1BOR |
| Crystal structure of protein : PDBSum | 1BOR |
| Crystal structure of protein : IMB | 1BOR |
| Crystal structure of protein : PDB RSDB | 1BOR |
| HPRD | 00023 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | P29590 |
| IntAct (EBI) | P29590 |
| Polymorphism : SNP, mutations, diseases |
|---|
| Single Nucleotide Polymorphism (SNP) : dbSNP NCBI | PML |
| SNP : GeneSNP Utah | PML |
| SNP : HGBase | PML |
| Genetic variants : HAPMAP | PML |
| Somatic Mutations in Cancer : COSMIC | PML |
| Translocation Breakpoints in Cancer : TICdb | PML |
| Mutations and Diseases : HGMD | PML |
| Hereditary diseases : OMIM | 102578 |
| Hereditary diseases : GENETests | 102578 |
| Diseases : Genetic Association | PML |
| General knowledge |
|---|
| Homologs : HomoloGene | PML |
| Homology/Alignments : Family Browser UCSC | PML |
| Phylogenetic Trees/Animal Genes : TreeFam | PML |
| Chemical/Protein Interactions : CTD | 5371 |
| Keywords Ontology : AmiGO | response to hypoxia DNA binding intracellular insoluble fraction nucleus nucleoplasm nucleolus cytoplasm regulation of transcription, DNA-dependent protein complex assembly induction of apoptosis activation of caspase activity DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest cell cycle arrest common-partner SMAD protein phosphorylation SMAD protein nuclear translocation cell aging zinc ion binding negative regulation of cell proliferation response to UV response to gamma radiation nuclear matrix negative regulation of transcription negative regulation of angiogenesis PML body PML body myeloid cell differentiation negative regulation of cell growth transcription regulator activity PML body organization nuclear membrane SUMO polymer binding response to cytokine stimulus DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis protein homodimerization activity interspecies interaction between organisms regulation of MHC class I biosynthetic process SMAD binding metal ion binding retinoic acid receptor signaling pathway maintenance of protein location in nucleus |
| Keywords Ontology : EGO-EBI | response to hypoxia DNA binding intracellular insoluble fraction nucleus nucleoplasm nucleolus cytoplasm regulation of transcription, DNA-dependent protein complex assembly induction of apoptosis activation of caspase activity DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest cell cycle arrest common-partner SMAD protein phosphorylation SMAD protein nuclear translocation cell aging zinc ion binding negative regulation of cell proliferation response to UV response to gamma radiation nuclear matrix negative regulation of transcription negative regulation of angiogenesis PML body PML body myeloid cell differentiation negative regulation of cell growth transcription regulator activity PML body organization nuclear membrane SUMO polymer binding response to cytokine stimulus DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis protein homodimerization activity interspecies interaction between organisms regulation of MHC class I biosynthetic process SMAD binding metal ion binding retinoic acid receptor signaling pathway maintenance of protein location in nucleus |
| Pathways : BIOCARTA | Regulation of transcriptional activity by PML [Genes] |
| Pathways : KEGG | |
| Other databases |
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| Other database | PML at 15q22 in normal cells (Bari) |
| Probes |
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| Probes : Imagenes | PML Related clones (RZPD - Berlin) |
| Literature |
|---|
| PubMed | 198 Pubmed reference(s) in Entrez |
| PubGene | PML |
| The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. |
| de Thˆ© H, Chomienne C, Lanotte M, Degos L, Dejean A |
| Nature. 1990 ; 347 (6293) : 558-561. |
| PMID 2170850 |
| |
| Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. |
| Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM |
| Cell. 1991 ; 66 (4) : 663-674. |
| PMID 1652368 |
| |
| Characterization of the PML-RAR alpha chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation. |
| Nervi C, Poindexter EC, Grignani F, Pandolfi PP, Lo Coco F, Avvisati G, Pelicci PG, Jetten AM |
| Cancer research. 1992 ; 52 (13) : 3687-3692. |
| PMID 1319828 |
| |
| Retinoic acid regulatory pathways, chromosomal translocations, and acute promyelocytic leukemia. |
| Chen Z, Tong JH, Dong S, Zhu J, Wang ZY, Chen SJ |
| Genes, chromosomes & cancer. 1996 ; 15 (3) : 147-156. |
| PMID 8721678 |
| |
| Genetics of APL and the molecular basis of retinoic acid treatment. |
| Casini T, Grignani F, Pelicci PG |
| International journal of cancer. Journal international du cancer. 1997 ; 70 (4) : 473-474. |
| PMID 9033658 |
| |
| Structure, organization, and dynamics of promyelocytic leukemia protein nuclear bodies. |
| Hodges M, Tissot C, Howe K, Grimwade D, Freemont PS |
| American journal of human genetics. 1998 ; 63 (2) : 297-304. |
| PMID 9683622 |
| |
| The pathogenesis of acute promyelocytic leukaemia: evaluation of the role of molecular diagnosis and monitoring in the management of the disease. |
| Grimwade D |
| British journal of haematology. 1999 ; 106 (3) : 591-613. |
| PMID 10468848 |
| |
| Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. |
| Melnick A, Licht JD |
| Blood. 1999 ; 93 (10) : 3167-3215. |
| PMID 10233871 |
| |
| The transcriptional role of PML and the nuclear body. |
| Zhong S, Salomoni P, Pandolfi PP |
| Nature cell biology. 2000 ; 2 (5) : E85-E90. |
| PMID 10806494 |
| |
