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FLASH GENE
Symbol TPP1 contributors: mct - updated : 14-10-2016
HGNC name tripeptidyl peptidase I
HGNC id 2073
Corresponding disease
CLN2 ceroid-lipofuscinosis, neuronal, 2
SCAAR1 spinocerebellar ataxia 1
Location 11p15.4      Physical location : 6.633.996 - 6.640.692
Synonym name
  • tripeptidyl aminopeptidase
  • lysosomal peptidase, pepstatin-insensitive
  • cell growth-inhibiting gene 1 protein
  • lysosomal pepstatin insensitive protease
  • Synonym symbol(s) TPPI, LPPI, LINCL, GIG1, MGC21297, TPP I, CLN2, LPIC, SCAR7, TPP-1
    EC.number 3.4.14.9
    DNA
    TYPE functioning gene
    STRUCTURE 6.70 kb     13 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map pter - AT3IRS - TPP1 - TAF10 /ILK - cen
    Authors Liu (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 3540 59.3 563 - 2001 11054422
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Cardiovascularheart   highly
    Nervousbrainforebraincerebral cortex  
    Reproductivefemale systemplacenta  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text brain, spleen, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an OB-fold domain that provides an interface to recruit telomerase, and a region adjacent to the OB-fold domain of TPP1 is involved in telomere length regulation via telomerase recruitment
  • a small patch of amino acids on the surface of the chromosome end-binding protein TPP1, the TEL patch, binds telomerase to enable both its recruitment to telomeres and its high-processivity extension of telomeric DNA
  • conjugated GlycoP
    isoforms Precursor inactive 62 kDa precursor autocatalytically converted to an active 46kDa acidic serine protease
    HOMOLOGY
    interspecies homolog to murine Tpp1
    homolog to rattus Cln2
    Homologene
    FAMILY
  • peptidase family S53
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • pepstatin-insensitive, carboxyl-dependent tripeptidyl-peptidase
  • acting as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases
  • a minor endoprotease activity
  • predominant proteolytic enzyme responsible for the intracellular degradation of neuromedin B
  • catalyzes the cleavage of Bid (Autefage 2009)
  • plays a role in TNF-induced cell death (Autefage 2009)
  • has essential roles in telomere maintenance and, together with POT1, is required for the repression of DNA damage signaling at telomeres
  • is a newly identified substrate for RNF8, indicating a previously unrecognized role for RNF8 in telomere end protection
  • seven separation-of-function mutations map to a patch of amino acids on the surface of TPP1, the TEL patch, that both recruits telomerase to telomeres and promotes high-processivity DNA synthesis
  • has recently emerged as a primary contributor in protecting telomere DNA and in recruiting telomerase to the telomere ends
  • has critical functions in telomeric protein complex assembly and telomerase recruitment and regulation
  • telomerase localization to telomeres requires an interaction with a region on the surface of TPP1 known as the TEL patch
  • TPP1 and the TEN domain of the telomerase catalytic subunit TERT regulate telomerase recruitment
  • blocks an ATR-mediated resection mechanism at telomeres
  • plays critical roles in chromosome end protection and telomere length regulation
  • essential role of TPP1 in protecting cigarette smoke (CS)-induced telomeric DNA damage and cellular senescence
  • recruits telomerase, the enzyme responsible for synthesis of telomere DNA, to the telomere
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS development , nervous system
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
  • part of Shelterin complex (TERF1, TERF2, POT1, TERF2IP, TINF2, and TPP1)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • can associate with another OB fold-containing protein, OBFC1/AAF44 (Wan 2009)
  • TINF2 stabilize TPP1/POT1 on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling
  • in the absence of RNF8, TPP1 is unstable, resulting in telomere shortening and chromosome fusions through the alternative nonhomologous end-joining (A-NHEJ) repair pathway
  • potential interface for telomerase-TPP1 interaction required for telomere maintenance and implicate defective telomerase recruitment in telomerase-related disease
  • TPP1 interacts with TINF2 N terminus, which contains overlapping mitochondrial and telomeric targeting sequences, and controls TINF2 localization
  • AKT1 regulates TPP1 homodimerization and telomere protection
  • USP7 is a novel interacting protein of the oligonucleotide/oligosaccharide-binding fold of TPP1, which was previously known to recruit telomerase to telomeres
  • interacts with the cell cycle regulator kinase NEK6 in human cells, and NEK6-mediated phosphorylation of TPP1 Ser255 in G2/M phase regulates the association between telomerase activity and TPP1
  • RFX5 can strongly bind to the tripeptidyl peptidase 1 (TPP1) promoter region and then increase its transcriptional activity
  • cell & other
    REGULATION
    Other Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment
    ASSOCIATED DISORDERS
    corresponding disease(s) CLN2 , SCAAR1
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS