| 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 | | Hugo | PML |
| GDB | PML |
| Entrez_Gene | PML 5371 promyelocytic leukemia |
| Cards |
|---|
| Atlas | PMLID41 |
| GeneCards | PML |
| Ensembl | PML [Search_View] ENSG00000140464 [Gene_View] |
| Genatlas | PML |
| GeneLynx | PML |
| eGenome | PML |
| euGene | 5371 |
| Genomic and cartography |
|---|
| GoldenPath | PML - 15q22 chr15:72074067-72127206 + 15q22 (hg18-Mar_2006) |
| Ensembl | PML - 15q22 [CytoView] |
| NCBI | Mapview |
| OMIM | Disease map [OMIM] |
| HomoloGene | PML |
| Gene and transcription | | Genbank | AB208950 [ ENTREZ ] |
| Genbank | AB209051 [ ENTREZ ] |
| Genbank | AB209411 [ ENTREZ ] |
| Genbank | AF230401 [ ENTREZ ] |
| Genbank | AF230402 [ ENTREZ ] |
| RefSeq | NM_002675 [ SRS ] NM_002675 [ ENTREZ ] |
| RefSeq | NM_033238 [ SRS ] NM_033238 [ ENTREZ ] |
| RefSeq | NM_033239 [ SRS ] NM_033239 [ ENTREZ ] |
| RefSeq | NM_033240 [ SRS ] NM_033240 [ ENTREZ ] |
| RefSeq | NM_033244 [ SRS ] NM_033244 [ ENTREZ ] |
| RefSeq | NM_033246 [ SRS ] NM_033246 [ ENTREZ ] |
| RefSeq | NM_033247 [ SRS ] NM_033247 [ ENTREZ ] |
| RefSeq | NM_033249 [ SRS ] NM_033249 [ ENTREZ ] |
| RefSeq | NM_033250 [ SRS ] NM_033250 [ ENTREZ ] |
| RefSeq | AC_000058 [ SRS ] AC_000058 [ ENTREZ ] |
| RefSeq | NC_000015 [ SRS ] NC_000015 [ ENTREZ ] |
| RefSeq | NT_010194 [ SRS ] NT_010194 [ ENTREZ ] |
| RefSeq | NW_925884 [ SRS ] NW_925884 [ ENTREZ ] |
| AceView | PML AceView - NCBI |
| Unigene | Hs.526464 [ SRS ] Hs.526464 [ NCBI ]
HS526464 [ spliceNest ] |
| Fast-db | 18056 (alternative variants) |
| Protein : pattern, domain, 3D structure |
|---|
| SwissProt | P29590 [ SRS] P29590 [ EXPASY ] P29590 [ INTERPRO ] |
| Prosite | PS50119 ZF_BBOX [ SRS ] PS50119 ZF_BBOX [ Expasy ] |
| Prosite | PS00518 ZF_RING_1 [ SRS ] PS00518 ZF_RING_1 [ Expasy ] |
| Prosite | PS50089 ZF_RING_2 [ SRS ] PS50089 ZF_RING_2 [ Expasy ] |
| Interpro | IPR000315 Znf_Bbox [ SRS ] IPR000315 Znf_Bbox [ EBI ] |
| Interpro | IPR001841 Znf_RING [ SRS ] IPR001841 Znf_RING [ EBI ] |
| Interpro | IPR013083 Znf_RING/FYVE/PHD [ SRS ] IPR013083 Znf_RING/FYVE/PHD [ EBI ] |
| CluSTr | P29590 |
| Pfam | PF00643 zf-B_box [ SRS ] PF00643 zf-B_box [ Sanger ] pfam00643 [ NCBI-CDD ] |
| Pfam | PF00097 zf-C3HC4 [ SRS ] PF00097 zf-C3HC4 [ Sanger ] pfam00097 [ NCBI-CDD ] |
| Smart | SM00336 BBOX [EMBL] |
| Smart | SM00184 RING [EMBL] |
| Blocks | P29590 |
| PDB | 1BOR [ SRS ] 1BOR [ PdbSum ], 1BOR [ IMB ] 1BOR [ RSDB ] |
| HPRD | 00023 |
| Protein Interaction databases |
|---|
| DIP | P29590 |
| IntAct | P29590 |
| Polymorphism : SNP, mutations, diseases |
|---|
| OMIM | 102578 [ map ] |
| GENECLINICS | 102578 |
| SNP | PML [dbSNP-NCBI] |
| SNP | NM_002675 [SNP-NCI] |
| SNP | NM_033238 [SNP-NCI] |
| SNP | NM_033239 [SNP-NCI] |
| SNP | NM_033240 [SNP-NCI] |
| SNP | NM_033244 [SNP-NCI] |
| SNP | NM_033246 [SNP-NCI] |
| SNP | NM_033247 [SNP-NCI] |
| SNP | NM_033249 [SNP-NCI] |
| SNP | NM_033250 [SNP-NCI] |
| SNP | PML [GeneSNPs - Utah] PML] [HGBASE - SRS] |
| HAPMAP | PML [HAPMAP] |
| COSMIC | PML [Somatic mutation (COSMIC-CGP-Sanger)] |
| HGMD | PML |
| General knowledge |
|---|
| Family Browser | PML [UCSC Family Browser] |
| SOURCE | NM_002675 |
| SOURCE | NM_033238 |
| SOURCE | NM_033239 |
| SOURCE | NM_033240 |
| SOURCE | NM_033244 |
| SOURCE | NM_033246 |
| SOURCE | NM_033247 |
| SOURCE | NM_033249 |
| SOURCE | NM_033250 |
| SMD | Hs.526464 |
| SAGE | Hs.526464 |
| GO | response to hypoxia [Amigo] response to hypoxia |
| GO | nucleic acid binding [Amigo] nucleic acid binding |
| GO | DNA binding [Amigo] DNA binding |
| GO | protein binding [Amigo] protein binding |
| GO | protein binding [Amigo] protein binding |
| GO | intracellular [Amigo] intracellular |
| GO | insoluble fraction [Amigo] insoluble fraction |
| GO | nucleus [Amigo] nucleus |
| GO | nucleoplasm [Amigo] nucleoplasm |
| GO | nucleolus [Amigo] nucleolus |
| GO | cytoplasm [Amigo] cytoplasm |
| GO | DNA repair [Amigo] DNA repair |
| GO | transcription [Amigo] transcription |
| GO | regulation of transcription, DNA-dependent [Amigo] regulation of transcription, DNA-dependent |
| GO | protein complex assembly [Amigo] protein complex assembly |
| GO | induction of apoptosis [Amigo] induction of apoptosis |
| GO | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [Amigo] DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest |
| GO | zinc ion binding [Amigo] zinc ion binding |
| GO | zinc ion binding [Amigo] zinc ion binding |
| GO | response to ionizing radiation [Amigo] response to ionizing radiation |
| GO | negative regulation of transcription [Amigo] negative regulation of transcription |
| GO | negative regulation of angiogenesis [Amigo] negative regulation of angiogenesis |
| GO | transcription repressor activity [Amigo] transcription repressor activity |
| GO | PML body [Amigo] PML body |
| GO | PML body [Amigo] PML body |
| GO | negative regulation of cell growth [Amigo] negative regulation of cell growth |
| GO | PML body organization and biogenesis [Amigo] PML body organization and biogenesis |
| GO | SUMO binding [Amigo] SUMO binding |
| GO | DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis [Amigo] DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis |
| GO | metal ion binding [Amigo] metal ion binding |
| BIOCARTA | Regulation of transcriptional activity by PML [Genes] |
| PubGene | PML |
| TreeFam | PML |
| Other databases |
|---|
| Other database | PML at 15q22 in normal cells (Bari) |
| Probes |
|---|
| Probe | PML Related clones (RZPD - Berlin) |
| PubMed |
|---|
| PubMed | 165 Pubmed reference(s) in LocusLink |
| 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 |
| |