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FLASH GENE
Symbol PTTG1 contributors: mct/pgu - updated : 18-04-2017
HGNC name pituitary tumor-transforming 1
HGNC id 9690
Location 5q34      Physical location : 159.848.864 - 159.855.745
Synonym name
  • ESP1 associated protein 1
  • securin
  • securin sister chromatid separation inhibitor
  • Synonym symbol(s) PTTG, TUTR1, EAP1, HPTTG, SECURIN, PDS1p, MGC126883, MGC138276
    DNA
    TYPE functioning gene
    STRUCTURE 6.94 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor   HRE
    text structure
  • NF-Y sites at the promoter exhibited a synergistic effect on upregulation of PTTG1 through interacting with EP300
  • a binding site for a tumor suppressor protein, Kruppel-like factor 6 (KLF6), in the PTTG1 promoter
  • promoter contains a putative androgen response element (ARE), which localizes in the -851 to -836 region of the promoter
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC348938 5q33.3 hypothetical protein LOC348938 ADAM19 5q32-q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) SOX30 5q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) LOC389341 5 similar to RIKEN cDNA 4921536K21 FLJ20546 5q33.3 hypothetical protein FLJ20546 LSM11 5q33.3 U7 snRNA-associated Sm-like protein ENTH 5q23.1-q33.3 U7 snRNA-associated Sm-like protein LOC391843 5 similar to 60S acidic ribosomal protein P2 LOC345471 5q33.3 similar to Hsp90 co-chaperone Cdc37 (Hsp90 chaperone protein kinase-targeting subunit) (p50Cdc37) LOC285721 5q33.3 hypothetical LOC285721 EBF 5q34 early B-cell factor FLJ31951 5q33.3 hypothetical protein FLJ31951 MGC10067 5q33.3 hypothetical protein MGC10067 IL12B 5q31.1-q33.1 interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) ADRA1B 5q33.1 adrenergic, alpha-1B-, receptor TTC1 5q32-q33.2 tetratricopeptide repeat domain 1 KIAA1935 5q34 KIAA1935 protein FABP6 5q23-q35 fatty acid binding protein 6, ileal (gastrotropin) FLJ14166 5q34 hypothetical protein FLJ14166 C1QTNF2 5q33.3 C1q and tumor necrosis factor related protein 2 LOC63920 5q34 transposon-derived Buster3 transposase-like SLU7 5q34 step II splicing factor SLU7 PTTG1 5q35.1 pituitary tumor-transforming 1 FLJ21477 5q34 hypothetical protein FLJ21477 GABRB2 5q33.1-q34 gamma-aminobutyric acid (GABA) A receptor, beta 2 GABRA6 5q33.1-q33.2 gamma-aminobutyric acid (GABA) A receptor, alpha 6 GABRA1 5q33.2 gamma-aminobutyric acid (GABA) A receptor, alpha 1 GABRG2 5q31.3-q33.2 gamma-aminobutyric acid (GABA) A receptor, gamma 2 MRP63P6 5q34 mitochondrial ribosomal protein 63 pseudogene 6 CCNG1 5q32-q34 cyclin G1 LOC134492 5q34 similar to RIKEN cDNA 2700047N05 HMMR 5q33.3 hyaluronan-mediated motility receptor (RHAMM)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 786 - 202 - 2009 19539243
    5 - 1093 - 202 - 2009 19539243
    6 - 947 - 202 - 2009 19539243
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   lowly
    Digestiveintestinelarge intestinecolon lowly
    Nervousbrainforebraincerebral cortex highly
    Reproductivemale systemtestis  highly
    Respiratorylung   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatid
    Reproductivespermatocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text liver, brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • protein proline-rich containing a N terminal basic domain
  • two PXXP motifs
  • several putative SH3-binding sites
  • a C terminal acidic domain
  • HOMOLOGY
    Homologene
    FAMILY
  • securin family
  • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    text
  • mainly located in cytosol but partly in nucleus
  • although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm
  • basic FUNCTION
  • mitotic checkpoint protein which inhibits sister chromatid separation during mitosis
  • maintenance of euploidy and chromosomal stability
  • involved in tumor angiogenesis and mitogenesis
  • playing a potential role in modulating cell proliferation and FGF2 expression during neurogenesis
  • involved in proliferation, and aggressiveness of prolactin pituitary tumors
  • proto-oncogene implicated in the pathogenesis of thyroid tumours
  • involved in multiple cellular pathways including cell transformation, apoptosis, DNA repair, genomic instability, mitotic control and angiogenesis induction
  • new functional role of PTTG1 and separase in the modulation of membrane traffic and protein secretion that implicates regulation of V-ATPase assembly and function
  • is a tumor cell marker to predict anti-neoplastic treatment outcomes
  • role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration
  • participate in maintaining chromosomal integrity during the cell cycle through regulation of metaphase-anaphase transition, DNA damage repair, and apoptosis
  • enhances proliferation and suppresses early differentiation of keratinocytes
  • regulator of sister chromatid separation and transition from metaphase to anaphase
  • enhances the migratory and invasive properties of breast cancer cells by inducing epithelial to mesenchymal transition
  • oncogene implicated in malignant progression of both endocrine and nonendocrine malignancies
  • having a central role in thyroid autocrine signaling mechanisms via growth factors, with profound implications for promotion of transformed cell growth
  • securin is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis)
  • implicated in the regulation of homotypic spacing between specific types of retinal neurons
  • promotes the progression of ovarian cancer cells, and its loss resists tumor development, in part, by regulating cellular metabolic reprogramming that supports cell growth and proliferation via MYC pathway
  • PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling
  • CELLULAR PROCESS cell cycle,division,meiosis
    cell cycle, checkpoint
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a complex with proteins involved in microtubule nucleation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inhibiting the anaphase specific autocleavage of separin (ESPL1)
  • cohesins CDC20, APC (for sister chromatin cohesion)
  • specifically interacting with KUP70 in the Ku heterodimer association prevented by DNA double-strand breaks
  • PTTG1 and its binding factor PTTG1IP repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake
  • FGF2
  • competes with CDC20 for binding to securin, and thereby the interaction between BUB1B and PTTG1 is greatly increased by the depletion of CDC20
  • interaction between TERT and PTTG1 by association of XRCC6 might be important for the enhancement of the limited self-renewal activity of MSCs and for understanding the regulatory mechanisms of self-renewal
  • RASGRF1 is an important upstream component of signal transduction pathways regulating PTTG1 expression and controlling beta cell development and physiological responses
  • PTTG1 is likely a novel downstream target gene of androgen receptor and take part in prostate cancer proliferation and metastasis
  • cell & other
    REGULATION
    repressed by HDAC3 (decreased PTTG1 promoter activity)
    KLF6
    Phosphorylated by GSK3B (GSK3B phosphorylates securin to promote its proteolysis via the SKP1-CUL1-F-box protein (SCF) complex E3 ubiquitin ligase)
    Other regulated by EP300 (overexpression of histone acetyltransferase (HAT) p300 upregulated PTTG1 at the levels of promoter activity, mRNA and protein expression)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in T-cell leukemia
    tumoral     --over  
    in Jurkat cells in hematopoietic malignancies, pituitary, adrenal, kidney, liver, ovarian, testicular, thyroid, breast cancer
    tumoral     --over  
    is higher in aggressive brain tumors including medulloblastomas, glioblastoma multiforme IV, and astrocytoma III, whereas in more benign tumors, PTTG immunoexpression is lower
    tumoral   amplification    
    in clear cell renal cell carcinoma
    tumoral     --over  
    in breast cancer patients, compared with normal tissues
    constitutional     --over  
    in normal human fibroblasts caused chromosome instability, which subsequently induced TP53-dependent senescence through activation of DNA-damage response pathway
    tumoral     --over  
    PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer
    tumoral     --over  
    in metastasis prostate cancer tissue
    tumoral     --low  
    in breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential new prognosticator for treatment decisions concerning breast cancer patients
  • CDC27 and PTTG1 appear promising biomarkers for applications in predicting disease progression, prognostication of breast cancer
  • is a promising target for gastric cancer diagnosis and therapy
  • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    may offer a novel therapeutic target of pathologic significance in aggressive clear cell renal cell carcinoma
    cancerreproductivebreast
    may represent a new therapeutic target for malignant breast cancer
    cancerdigestivepancreas
    may represent a potential therapeutic target for the treatment of pancreatic cancer
    cancer  
    MTOR-PTTG1 signaling axis may be targeted for the treatment of tumors with MTOR hyperactivation
    ANIMAL & CELL MODELS
  • mice lacking Pttg1 developed spontaneous mammary tumors