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FLASH GENE
Symbol PINX1 contributors: mct - updated : 25-04-2017
HGNC name PIN2/TERF1 interacting, telomerase inhibitor 1
HGNC id 30046
Location 8p23.1      Physical location : 10.622.883 - 10.697.299
Synonym name
  • PIN2-interacting protein 1
  • 67-11-3 protein
  • hepatocellular carcinoma-related putative tumor suppressor
  • TRF1-interacting protein 1
  • liver-related putative tumor suppressor
  • Synonym symbol(s) LPTS, TRF1, LPTL, MGC8850, FLJ20565
    DNA
    TYPE functioning gene
    STRUCTURE 74.94 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure 5'-flanking region is GC-rich, lacks canonical TATA box, but contains potential binding sites for a variety of transcription factors
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC389623 8 LOC389623 MSRA 8p23.1 methionine sulfoxide reductase A LOC346702 8p23.1 similar to tryptophan/serine protease RP1L1 8p23 retinitis pigmentosa 1-like 1 LOC203076 8p23.1 similar to 4930578I06Rik protein SOX7 8p22 SRY (sex determining region Y)-box 7 PINX1 8p23 SRY (sex determining region Y)-box 7 LOC389624 8 LOC389624 LOC286046 8p23.1 hypothetical protein LOC286046 C8orf5 8p22 chromosome 8 open reading frame 5 C8orf15 8p23.1 chromosome 8 open reading frame 15 C8orf6 8p23.1 chromosome 8 open reading frame 6 C8orf7 8p22 chromosome 8 open reading frame 7 LOC392193 8 similar to 60S ribosomal protein L19 LOC157740 8p23.1 hypothetical protein C8orf9 MTMR9 8p23-p22 myotubularin related protein 9 AMAC 8p22 acyl-malonyl condensing enzyme TDH 8p22 L-threonine dehydrogenase C8orf12 8p22 chromosome 8 open reading frame 12 C8orf13 8p22 chromosome 8 open reading frame 13 BLK 8p23-p22 B lymphoid tyrosine kinase C8orf14 8p22 chromosome 8 open reading frame 14 GATA4 8p23.1 GATA binding protein 4 NEIL2 8p23.1 nei like 2 (E. coli) LOC389625 8 similar to Activated RNA polymerase II transcriptional coactivator p15 (Positive cofactor 4) (PC4) (p14) FDFT1 8p23.1-p22 farnesyl-diphosphate farnesyltransferase 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1047 - 328 - 2015 26194824
    6 - 1493 - 174 - 2015 26194824
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveesophagus   highly
     salivary gland   highly
    Endocrinepancreas   lowly
    Nervousbrain   lowly
    Respiratoryrespiratory tractlarynx  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal glycin-rich nucleic binding domain
  • one G-patch domain
  • two direct TERT-binding domains separately allocated to its N-terminal (AA 1-142)
  • a lysine-rich domain
  • C-terminal (AA 254-328), telomerase inhibitory domain of 74AA (TID), fragment 290328, localized in nucleolus contains a telomerase inhibitory domain required for the inhibition of telomere elongation and the induction of cell crisis , and C-terminal region of PINX1 is responsible for its nucleolar localization and binding with TERT, a catalytic component of telomerase , with C-terminal fragment of PINX1(290-328) containing a telomerase inhibitory domain that is required for the inhibition of telomere elongation and the induction of cell crisis
  • HOMOLOGY
    Homologene
    FAMILY
  • PINX1 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nucleus,nucleolus
    text
  • nucleoli and telomeres in interphase and relocates to the periphery of chromosomes and the outer plate of the kinetochores in mitosis
  • mainly co-localizes with nucleolin at chromosome periphery in prometaphase (li 2009)
  • co-localizes with TERF1 to telomeres and in the nucleolus
  • basic FUNCTION
  • potent telomerase inhibitor involved in negative regulation of cell proliferation, telomerase-dependent telomere maintenance, negative regulation of cell cycle
  • having an effect on mediating TERT nucleolar localization, effect mediated by a novel domain enclosed within the central section of the polypeptide
  • microtubules binding protein, essential for faithful chromosome segregation
  • recruited to chromosome periphery by Nucleolin and a complex of PINX1 and nucleolin is essential for faithful chromosome congression
  • has the unique property of directly interacting with the telomerase catalytic component, TERT, and potently inhibiting telomerase catalytic activity
  • potent telomerase inhibitor that inhibits telomere elongation
  • recruited to telomeres by TERF1, providing a crucial link between TERF1 and inhibition of telomere elongation by telomerase to help maintain telomere homeostasis
  • one function of PINX1 is likely to stabilize TERF1 during mitosis, perhaps to promote transition into M phase of the cell cycle
  • role of PINX1 in telomerase function regulation by mediating its localization inside cells
  • PINX1 overexpression significantly inhibited telomerase activity
  • may be a potential suppressive gene in the progression of gliomas
  • inhibits telomerase activity, which leads to the shortening of telomeres
  • could maintain telomere integrity and plays an important role in regulating telomerase activity
  • playing a vital role in maintaining telomeres length and chromosome stability
  • PINX1 is a telomerase regulator and the aberrant expression of PINX1 causes telomere shortening
  • novel mechanism that regulates telomerase activation through the interaction between NPM1, PINX1 and the telomerase complex
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TERT (inhibition of its activity)
  • interacting with EST1B
  • association with TERT within nucleoli might be through an indirect interaction and is mediated by a novel domain within the central region of PINX (interaction between PINX1 and TERT within the nucleolus might constitute a rapid responsive mechanism on telomerase functional modulation, important for cellular homeostasis)
  • interacts with nucleolin, a chromosome periphery protein, through its C-termini
  • interaction with TERF1 may play a role in the stabilization of telomeres
  • PINX1 domains mediating interaction with TERF1 and TERT are different (AAs 254289 specifically bind to TERF1, and the N-terminal 1253 and C-terminal 290328 fragments bind to TERT)
  • interacting with TERF1 (is recruited to telomeres by TERF1 and provides a critical link between TERF1 and telomerase inhibition to prevent telomere elongation and help maintain telomere homeostasis)
  • TERF1-PINX1 interaction is required not only for targeting PINX1 to telomeres but also for PINX1 to prevent telomere elongation in cells
  • endogenous PINX1 associates with telomeres primarily at mitosis
  • PINX1 may maintain telomere integrity by regulating TERF1 stability and TERT may act as both a positive and a negative regulator of TERF1 homeostasis in a PINX1-dependent manner
  • PINX1 interacts with the N-terminal domain of ESR1 and functions as a corepressor of ESR1
  • stability of PINX1 is maintained in nucleolus in the presence of TERT, suggesting a role of TERT in the regulation of PINX1 steady-state levels
  • directly interacts with nucleophosmin (NPM1), a protein that has been shown to positively correlate with telomerase activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in hepatocellular carcinoma especially with HBV infections and medulloblastoma
    tumoral   LOH   loss of function
    hypoacetylation of histone H4 in the 5' UTR of PINX1 associated with reduced expression in gastric carcinoma
    tumoral     --over  
    suppresses telomerase activity, resulting in shortened telomeres
    tumoral     --low  
    in some cancer and associated with cancer prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may serve as a prognostic and predictive biomarker for gliomas
  • may be a new potential diagnostic biomarker and therapeutic target for human cancers, and may play different roles in different human cancers
  • Therapy target
    ANIMAL & CELL MODELS