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Symbol PMAIP1 contributors: mct/npt/pgu - updated : 05-06-2015
HGNC name phorbol-12-myristate-13-acetate-induced protein 1
HGNC id 9108
Location 18q21.32      Physical location : 57.567.191 - 57.571.538
Synonym name
  • adult T cell leukemia-derived PMA-responsive
  • cellular immediate-early-response protein APR
  • PMA-induced protein 1
  • ATL-derived PMA-responsive gene
  • pro-apoptotic BH3-only protein
  • Synonym symbol(s) APR, NOXA
    TYPE functioning gene
    STRUCTURE 4.35 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • three transcripts, controlled by the same promoter with two TP53 consensus-binding sites, were inducible by TP53
  • promoter contains sites also for E2F-1, Myc, and HIF-1
  • a conserved FOXxO-binding site (DBE; DAF-16 binding element) in the promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    TXNL 18q21.2 thioredoxin-like, 32kDa WDR7 18q21.1-q22 WD repeat domain 7 MGC33608 18q21.31 hypothetical protein MGC33608 SIAT8C 18q21.2 sialyltransferase 8C (alpha2,3Galbeta1,4GlcNAcalpha 2,8-sialyltransferase) ONECUT2 18q21.1-q21.2 one cut domain, family member 2 FECH 18q21.2 ferrochelatase (protoporphyria) NARS 18q21.2-q21.3 asparaginyl-tRNA synthetase ATP8B1 18q21 ATPase, Class I, type 8B, member 1 LOC284288 18q21.31 similar to Ribosomal protein L24-like LOC388476 18 similar to Nonhistone chromosomal protein HMG-14 (High-mobility group nucleosome binding domain 1) NEDD4L 18q21.2 neural precursor cell expressed, developmentally down-regulated 4-like HAK 18q21.31-q21.32 heart alpha-kinase MALT1 18q21 mucosa associated lymphoid tissue lymphoma translocation gene 1 FLJ10697 LOC390858 18 similar to RIKEN cDNA 5330437I02 gene LOC388477 18 LOC388477 LOC90701 18q21.32 similar to signal peptidase complex (18kD) GRP 18q21.31 gastrin-releasing peptide RAX 18q21.31 retina and anterior neural fold homeobox CPLX4 18q21.32 complexin 4 LMAN1 18q21.3-q22 lectin, mannose-binding, 1 FLJ30681 18q21.32 KIAA1983 protein LOC219542 18q21.32 similar to 40S ribosomal protein S26 LOC390859 18 similar to Chain A, Crystal Structure Of The R463a Mutant Of Human Glutamate Dehydrogenase LOC390860 18 similar to 60S acidic ribosomal protein P0 (L10E) PMAIP1 18q21.32 phorbol-12-myristate-13-acetate-induced protein 1 LOC147072 18q21.32 similar to nuclear factor (erythroid-derived 2)-like 3; NF-E2-related factor 3 LOC388478 18 similar to serologically defined colon cancer antigen 3 LOC284289 18q21.32 similar to TERA protein LOC388479 18 similar to 40S ribosomal protein S3a LOC342784 18q21.32 similar to TFIIH basal transcription factor complex p62 subunit (Basic transcription factor 62 kDa subunit) (BTF2-p62) (General transcription factor IIH polypeptide 1) MC4R 18q21.32 melanocortin 4 receptor MRPS5P4 18q21 mitochondrial ribosomal protein S5 pseudogene LOC220147 18q21.32 similar to C-terminal binding protein 2 isoform 2; ribeye CDH20 18q22-q23 cadherin 20, type 2 LOC388480 18 LOC388480 RNF152 18q21.33 ring finger protein 152 PIGN 18q21.32 phosphatidylinositol glycan, class N KIAA1468 18q21.33 KIAA1468 TNFRSF11A 18q21.3-q22.1 tumor necrosis factor receptor superfamily, member 11a, activator of NFKB LOC390861 18 similar to FKSG30 ZCCHC2 18q21.32 zinc finger, CCHC domain containing 2 PLEKHE1 18q21.32 pleckstrin homology domain containing, family E (with leucine rich repeats) member 1 BCL2 18q21.33 B-cell CLL/lymphoma 2
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1954 5.8 54 - 2010 20085765
  • exons 1 and 3
  • - - - - 136 - 2008 18630524
  • also called Noxa splicing variant-1 or NSV-1
  • exon-1, partially spliced exon-2, and exon-3
  • is unlikely to play a role in apoptosis regulation
  • - - - - 70 - 2008 18630524
  • also called NSV-2
  • 100p100 identical to the first 70 amino acids of NSV-1
  • is unlikely to play a role in apoptosis regulation
    Rna function
  • mRNA expression level low in osteoblasts but high in osteoclasts
  • Type
       expressed in (based on citations)
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines adult T-cell leukemia cell line
    at STAGE
  • mitochondrial targeting domain (MTD) responsible for inducing fragmentation with two leucine residue playing a key role in the process
    interspecies homolog to murine Pmaip1
  • BH3-only pro-apoptotic Bcl-2 family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • being an essential mediator of TP53-dependent apoptosis
  • important component of the innate immune response of cells to viral infection, leading to enhanced cellular apoptosis that may play a role in limiting viral dissemination
  • with BCL2L11, establish a connection between FKHRL1 and mitochondria, and both BH3-only proteins are critically involved in FKHRL1-induced apoptosis in neuroblastoma
  • may play an important role in the progression of pancreatic cancer
  • suppressor of Myc-induced lymphomagenesis
  • HIF1A-induced proapoptotic gene that mediates hypoxic cell death by generation of ROS
  • promotes activation of caspases and apoptosis
  • promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria
  • promotes proteasomal degradation of MCL1
  • competes with BAK1 for binding to MCL1
  • causes mitochondrial fragmentation
  • role in mitochondrial dynamics and cell death
  • having proapoptotic activity and functions downstream of the TP53-mediated apoptotic pathway, to selectively induce apoptosis in tumor cells
  • TP53 transcriptional target involved in the response to DNA-damaging agents
  • participated in triggering mitochondrial dysfunction in multiple apoptotic pathways through distinct mechanisms
  • crucial regulator of osteoclast apoptosis
  • plays a critical role in the regulation of the number of osteoclasts, which may be determined by the level of osteoclast differentiation or survival
  • BIK is a stronger inducer of apoptosis than PMAIP1, and when expressed simultaneously, a combinative effect was observed
  • a function of PMAIP1 was at least in part neutralization of induced myeloid leukemia cell differentiation protein (MCL1) in neutrophils and progenitors
  • apoptosis regulated by BCL2L11- and PMAIP1-driven loss of MCL1 is thus the final step in neutrophil differentiation, required for the termination of neutrophil function and neutrophil-dependent inflammation
  • is involved in the modulation of MCL1 expression
  • triggers the degradation of MCL1 at the mitochondria according to the exclusive location of PMAIP1 at this compartment
  • apoptosis, regulated by PMAIP1, is a critical factor for the selection of high-affinity clones during B cell expansion after antigen triggering
  • sensor of 26S proteasome integrity
  • BCL2L1, and PMAIP1 co-ordinately regulate oxidative stress-induced apoptosis
  • PMAIP1 and, albeit to a lesser extent, BBC3 are essential for DNA damage induced TP63-mediated killing of primordial follicle oocytes
  • PMAIP1 and BBC3 are critical for DNA damage-induced, TP63-mediated oocyte apoptosis
  • important regulator of the number of memory cells formed during infection
  • CELLULAR PROCESS cell life, cell death/apoptosis
  • Hippo/MST1-FOXO1-PMAIP1 pathway
  • a component
    small molecule
  • interacting with MCL1 and BAX
  • strongly upregulated and became associated with both MCL1 and BCL2L11 during apoptosis induced by proteasome inhibition
  • interaction with HRAS (HRAS-induced expression of PMAIP1 and Beclin-1 promotes autophagic cell death) (
  • interacting with HSPA5 (HSPA5 confers resistance to apoptosis induced by BIK and PMAIP)
  • favors the interaction between MCL1 and HUWE1 and consequently affects MCL1 ubiquitination
  • controls HUWE1-dependent MCL1 ubiquitination through the regulation of the MCL1/USP9X interaction
  • PMAIP1 band BBC3 are target genes for TP53
  • TP63 but not TP53 is essential for DNA damage triggered transcriptional induction of BBC3 and PMAIP1 in primordial follicle oocytes
  • TP63 acts via transcriptional induction of the BH3-only proteins, BBC3 and PMAIP1 to cause apoptosis of DNA-damaged primordial follicle oocytes
  • BBC3 like BCL2L11, PMAIP1, is able to act as a direct BAK1 activator
  • MTD domain of PMAIP1 causes mitochondrial damage by opening mitochondrial permeability transition pore (mPTP) through VDACs, especially VDAC2, during necrotic cell death
  • cell & other
    activated by MST1, that stimulates transcription of the proapoptotic mediator PMAIP1 in a FOXO1-dependent manner
    induced by highly induced by TNFSF11 during osteoclast maturation
    Other up-regulated by p53
    HRK, BBC3, and PMAIP1 are transcriptionally induced in severe hypoxia and their expression is abrogated by RNA interference against ATF4
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    results in an increase in the osteoclast number without affecting osteoclast differentiation and function
    Susceptibility to bleomycin sensitivity (BLM)
    Variant & Polymorphism other
  • genetic variant on 18q21 near the PMAIP1 that is associated with BLM sensitivity
  • Candidate gene
    Therapy target
    promising target for suppressing pathological bone destruction
    PMAIP1-triggered BBC3-mediated apoptosis may be a powerful target for cancer therapy, especially early-stage cancer
  • mice lacking Noxa exhibit a severe osteoporotic phenotype due to an increased number of osteoclasts
  • upon influenza infection Noxa(-/-) mice generate a memory compartment of increased size and clonal diversity
  • Noxa(-/-) mice mount low affinity antibody responses compared with wild-type animals