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Symbol PML contributors: shn - updated : 21-05-2016
HGNC name promyelocytic leukemia
HGNC id 9113
Corresponding disease
PML acute promyelocytic leukemia (APL)
Location 15q24.1      Physical location : 74.287.013 - 74.340.153
Synonym name
  • tripartite motif protein TRIM19
  • promyelocytic leukemia, inducer of
  • RING finger protein 71
  • Synonym symbol(s) MYL, TRIM19, PP8675, RNF71
    TYPE functioning gene
    text a megabase-scale insertion/deletion polymorphism 3' to PML (see GLP)
    STRUCTURE 53.14 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    Binding site   HRE
    text structure
  • flanked by two CpG islands
  • interferon stimulated response element and GAS motif in the 5'utr
  • MAPPING cloned Y linked N status confirmed
    Map cen - D15S215 - D15S1026 - PML PML - D15S160 - D15S965 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 5600 97.4 882 nuclear PML isoform 2011 21115099
    also called variant alpha
    7 splicing 3751 67.3 611 nuclear PML isoform 2011 21115099
  • also called variant beta
  • different 3'UTR and 3' coding region compared to variant 1
  • 8 splicing 3096 61.9 560 nuclear PML isoform 2011 21115099
  • also called variant epsilon
  • different 3'UTR and 3' coding region compared to variant 1
  • 8 splicing 2254 69.9 633 nuclear PML isoform 2011 21115099
  • also called variant zeta, PML-IV, PML-X and TRIM19zeta
  • different 3'UTR and 3' coding region compared to variant 1
  • GNL3 prevents telomere damage by promoting PML-IV recruitment to SUMOylated TERF1
  • 6 splicing 1851 47.4 423 nuclear PML isoform 2011 21115099
  • variant eta
  • multiple differences in the coding region compared to variant 1 which results in a translational frameshift
  • 5 splicing 1797 48.5 435 nuclear PML isoform 2011 21115099
  • also called variant theta
  • multiple differences in the coding region compared to variant 1 which results in a translational frameshift
  • 8 splicing 3088 90.6 829 - 2011 21115099
    D. variant kappa
  • different 3'UTR and 3' coding region compared to variant 1
  • 7 splicing 2110 64.9 585 - 2011 21115099
  • variant lambda
  • multiple differences in the coding region compared to variant 1 which results in a translational frameshift
  • 7 splicing 2944 85.6 781 - 2011 21115099
  • also called variant 11
  • multiple differences in the coding region compared to variant 1 which results in a translational frameshift
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon moderately
     pancreas exocrine   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuterus  highly
     female systemovary  predominantly
     female systembreastmammary gland moderately
     male systemprostate  moderately
    Respiratorylung   moderately
    Skin/Tegumentskin   moderately
    Urinarybladder   highly
     kidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage restricted to neural progenitor cells (NPCs) in the developing neocortex of the mouse
    cell lines
    fluid/secretion blood
    at STAGE
    cell cycle     cell cycle, G1, S, G2, M
  • an N-terminal RING zinc finger domain
  • two B boxes (a B-box type 1 and a B-box type 2)
  • a leucine coiled-coil domain
  • a RBCC/TRIM motif comprising several cysteine-rich zinc-binding domains (RING and B-boxes) and a coiled-coil domain
  • a nuclear localization signal (NLS)
  • conjugated PhosphoP , Other
    mono polymer homomer , dimer , complex
    interspecies ortholog to Pml, Rattus norvegicus
    ortholog to PML, Pan troglodytes
  • B box family, RBCC (TRIM family)
  • member of the tripartite motif (TRIM) family
  • C-V TRIM family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm,nuclear bodies
  • extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca2+) transport and in induction of apoptosis
  • basic FUNCTION
  • recruiting the nuclear corepressor histone deacetylase complex, essential for multiple apoptotic pathways in early hematopoiesis and late erythropoiesis
  • acting as a putative controller of genes devoted to MHC class I antigen presentation
  • mediating the interferon induced antiviral state against a complex retrovirus (foamy virus, via its association with the viral transactivator)
  • may play an important role in recruitment of ELF4 into PML nuclear bodies
  • acting as a critical inhibitor of neoangiogenesis in both ischaemic and neoplastic conditions, through the control of protein translation
  • negatively regulating the synthesis rate of hypoxia-inducible factor 1alpha (HIF-1alpha) by repressing mammalian target of rapamycin (mTOR)
  • cytoplasmic Pml is an essential modulator of TGF-beta signaling
  • plays an important role in cell growth and survival
  • role of PML/Nur77 interaction in regulating cell growth and apoptosis
  • role for PML in the regulation of TP53 by CSNK1A1
  • central regulator of cell proliferation and apoptosis
  • role in controlling the function of neural progenitor cells in the central nervous system
  • regulates the size of the cerebral cortex
  • broadly regulate the early (and transcription independent) apoptotic response, and regulates apoptosis at endoplasmic reticulum by modulating calcium release
  • PML and the key Wnt signaling regulator AXIN1 regulate TP53-dependent apoptosis in response to DNA damage
  • physiological role of PML in apoptosis
  • functions as a positive regulator of IFNG signaling
  • through its scaffold properties is able to control cell growth and survival at many different levels (
  • exerts its essential role in hematopoietic stem cell maintenance through regulation of PPAR signaling and fatty-acid oxidation
  • selectively associate with transcriptionally active genomic regions, including the gene-rich major histocompatibility (MHC) locus
  • is a coregulator of IFNG-induced MHC class II expression
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, repair, recombination
    nucleotide, transcription, regulation
    protein, ubiquitin dependent proteolysis
  • negative regulation of cell proliferation and angiogenesis
  • negative regulation of transcription
  • induction of apoptosis
  • myeloid cell differentiation
    a component
  • colocalizing and interacting with CREBBP, TIF2A and with DAXX in special (PML/SP100) nuclear bodies(NB/POD), to form a retinoic acid (RA) dependent growth suppressive RRXA, RARA nuclear
  • AXIN1, PML and TP53 form a ternary complex
    DNA binding to interferon stimulated response element (ISRE) and GAS motif in the 5'UTR
    small molecule metal binding,
  • Zn2+
  • protein
  • HDAC1
  • HAT
  • viral transactivator
  • inhibits NR4A1 (NUR77) mediated transcription
  • SIRT1
  • TOPBP1
  • TRIM27 and TRIM69
  • C-terminus of ELF4
  • Lassa virus Z protein
  • mTOR
  • several transcription factors and their coactivators: HIPK2 and EP300
  • HIPK2
  • Aurora Kinase A (AURKA)
  • p53 ubiquitin-ligase Mdm2
  • Oncoprotein Mdm2
  • nucleolar protein L11
  • Myc
  • bonds and augments the transcriptional activities of Aryl hydrocarbon receptor nuclear translocator (ARNT)
  • cyclin T1 (CCNT1)
  • Checkpoint protein with FHA and ring finger domains (CHFR)
  • death-domain associated protein (DAXX)
  • Eukaryotic translation initiation factor 4E (eIF4E)
  • involved in the AP-1 complex and can modulate Fos-mediated transcriptional activity
  • GATA binding protein 2 (GATA2)
  • Histone deacetylase 1 and 2 (HDAC1, HDAC2)
  • proline-rich homeodomain protein PRH
  • inhibitor of SAPK2/p38 mitogen-activated protein kinase
  • retinoic acid receptor-alpha (RARalpha), c-Ski, N-CoR, mSin3A and tumor suppressor Mad
  • c-Myb
  • Interacts and inhibits Nur77-mediated transcription
  • regulate the subcellular distribution of the retinoblastoma protein (pRb) and the protein phosphatase 1 alpha (PP1a), triggering pRb dephosphorylation
  • is a transcriptional repressor of NF-kappaB by interacting with RelA/p65
  • prostate-apoptosis-response-4 (Par-4)
  • Transcription factor Sp1
  • Serum response factor (SRF)
  • STAT3, PIC1
  • thymine DNA glycosylase (TDG)
  • Tif1alpha
  • stabilizes the DNA damage response protein TopBP1
  • acts as a transcriptional co-activator with p53
  • Ret finger protein (rfp)
  • Promyelocytic leukemia zinc finger (PLZF)
  • ring finger protein 36 (RNF36)
  • ankyrin repeat domain 2 (ANKRD2)
  • CREB binding protein (CREBBP)
  • immediate target gene regulated by IRF8 in response to IFNG activation
  • PML/RARA binds to FAS and blocks FAS-mediated apoptosis in acute promyelocytic leukemia (APL) by forming an apoptotic inhibitory complex with CFLAR
  • PML and TBX2 act in an autoregulatory loop to control the effective execution of the senescence program 7)
  • circadian clock regulator that can physically interact with PER2
  • PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA
  • regulates endothelial cell migration, in part, by modulating expression of downstream genes, such as ITGB1
  • undergoes ubiquitination-mediated degradation facilitated by an E3 ligase UHRF1
  • PML is required for efficient IFNG1-induced MHC II gene transcription through regulation of the class II transactivator (CIITA), and mediates this function through protection of CIITA from proteasomal degradation
  • AKT1-mediated phosphorylation of KAT6A suppresses the interaction between PML and KAT6A
  • NDN bound to PIAS1 central domains that are highly conserved among PIAS family proteins and suppressed PIAS1-dependent sumoylation of the substrates STAT1 and PML
  • NACC1 cooperates with PML protein
  • accumulation of HIPK2 in nuclear speckles and association with promyelocytic leukemia protein (PML) in response to DNA damage were also dependent on ABL1 activity
  • CACUL1 is a novel regulator that negatively controls TP53 activity through the regulation of PML SUMOylation
  • cell & other
    inhibited by IFN-gamma and LPS
    Other regulated by casein kinase 2 at protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517
    ubiquitinated via the action of UBE3A
    upregulated by oncogenic RAS
    acetylated at K487 and its deacetylation by SIRT1 promotes PML control of PER2 nuclear localization
    corresponding disease(s) PML
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    mutated in acute promyelocytic leukemia with associates with poor prognosis and RA unresponsiveness
    tumoral fusion      
    fused with RARA int (15;17) in acute promyelocytic leukemia
    Susceptibility to Paget disease (PDB)
    Variant & Polymorphism other
  • rs5742915 strongly associated with PDB
  • Candidate gene
    Therapy target
    PML-RARA degradation or therapy-triggered degradation of oncoproteins could be a general strategy to eradicate cancer stem cells
  • PMLRAR alpha transgenic mice exhibited neutrophil differentiation impairment and acute promyelocytic leukemia
  • Pml–/– mice had smaller brains and hippocampus than Pml+/+ and Pml+/– mice although the overall organization of the brain did not appear to be affected
  • PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia