Homo sapiens Gene: PML
Summary
InnateDB Gene IDBG-21462.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol PML
Gene Name promyelocytic leukemia
Synonyms MYL; PP8675; RNF71; TRIM19;
Species Homo sapiens
Ensembl Gene ENSG00000140464
Encoded Proteins
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
promyelocytic leukemia
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway.
Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms. (Demonstrated in murine model)
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Pml, a member of the Trim protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway.
[Mus musculus] Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms.
Entrez Gene
Summary 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]
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]
Gene Information
Type Protein coding
Genomic Location Chromosome 15:73994673-74047812
Strand Forward strand
Band q24.1
Transcripts
ENST00000268058 ENSP00000268058
ENST00000359928 ENSP00000353004
ENST00000268059 ENSP00000268059
ENST00000354026 ENSP00000315434
ENST00000395135 ENSP00000378567
ENST00000395132 ENSP00000378564
ENST00000436891 ENSP00000394642
ENST00000435786 ENSP00000395576
ENST00000565898 ENSP00000455838
ENST00000564428 ENSP00000457023
ENST00000566068 ENSP00000458061
ENST00000564725
ENST00000569161
ENST00000570213
ENST00000565317
ENST00000567543 ENSP00000456277
ENST00000567606 ENSP00000457669
ENST00000563500 ENSP00000457032
ENST00000569965 ENSP00000456486
ENST00000562086 ENSP00000456329
ENST00000569477 ENSP00000455612
ENST00000565239 ENSP00000456989
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 277 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.
Experimentally validated
Total 277 [view]
Protein-Protein 275 [view]
Protein-DNA 2 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 22 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003713 transcription coactivator activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0031625 ubiquitin protein ligase binding
GO:0032183 SUMO binding
GO:0042803 protein homodimerization activity
GO:0046332 SMAD binding
GO:0046982 protein heterodimerization activity
GO:0050897 cobalt ion binding
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:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006461 protein complex assembly
GO:0006605 protein targeting
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:0007184 SMAD protein import into nucleus
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:0016032 viral process
GO:0016525 negative regulation of angiogenesis
GO:0019221 cytokine-mediated signaling pathway
GO:0030099 myeloid cell differentiation
GO:0030308 negative regulation of cell growth
GO:0030578 PML body organization
GO:0031065 positive regulation of histone deacetylation
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 (InnateDB)
GO:0045165 cell fate commitment
GO:0045343 regulation of MHC class I biosynthetic process
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045930 negative regulation of mitotic cell cycle
GO:0048384 retinoic acid receptor signaling pathway
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: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:1902187 negative regulation of viral release from host cell
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
Cellular Component
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016363 nuclear matrix
GO:0016605 PML body
GO:0031901 early endosome membrane
GO:0031965 nuclear membrane
GO:0042406 extrinsic component of endoplasmic reticulum membrane
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
TGF_beta_Receptor pathway
TNFalpha pathway
REACTOME
Cytokine Signaling in Immune system pathway
Interferon Signaling pathway
Immune System pathway
Interferon gamma signaling pathway
KEGG
Ubiquitin mediated proteolysis pathway
Endocytosis pathway
Pathways in cancer pathway
Acute myeloid leukemia pathway
INOH
PID BIOCARTA
Regulation of transcriptional activity by pml [Biocarta view]
PID NCI
Direct p53 effectors
mTOR signaling pathway
p73 transcription factor network
C-MYC pathway
TGF-beta receptor signaling
Validated transcriptional targets of TAp63 isoforms
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.526464 Hs.593486
RefSeq NM_002675 NM_033238 NM_033239 NM_033240 NM_033244 NM_033246 NM_033247 NM_033249 NM_033250
HUGO
OMIM
CCDS CCDS10255 CCDS10256 CCDS10257 CCDS10258 CCDS45297 CCDS45298 CCDS45299 CCDS45300 CCDS58386
HPRD 00023
IMGT
EMBL
GenPept
RNA Seq Atlas