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FLASH GENE
Symbol TINF2 contributors: mct/npt/pgu - updated : 25-04-2017
HGNC name TERF1 (TRF1)-interacting nuclear factor 2
HGNC id 11824
Corresponding disease
ATXP ataxia–pancytopenia
DKC5 dyskeratosis congenita 5
ERBMF exudative retinopathy with bone marrow failure
Location 14q11.2      Physical location : 24.708.852 - 24.711.880
Synonym name (TRF1)-interacting nuclear factor 2 variant 1
Synonym symbol(s) TIN2, TIN2L
DNA
TYPE functioning gene
STRUCTURE 3.03 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site
text structure
  • binding sites for SP1 and NFKB
  • important roles that Sp1 and NFKB play in regulating the expression of the human telomere-binding protein TINF2 (
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1869 50 451 - 2009 19229133
  • TIN2L
  • differs from the originally described TIN2 isoform (TIN2S) in two ways: TIN2L contains an additional 97 AAs, and associates strongly with the nuclear matrix
  • 6 - 2196 39.3 354 - 2009 19229133
    TIN2S
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   moderately
    Endocrinepancreas   highly
    Nervousbrain   moderately
    Reproductivemale systemprostate  moderately
    Respiratorylung   moderately
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal TRF1-interacting domain
  • HOMOLOGY
    interspecies homolog to C.elegans Y75b8a.22
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome,telomere
    text
  • can specifically localize to the mitochondria
  • basic FUNCTION
  • negative regulator of telomerase length, stabilising TTAGGG repeats
  • ADPRT modulator in the TERF1 complex and contributing to the regulation of the telomere length
  • crucial for anchoring the TPP1-POT1-telomerase complex to the telomeres
  • plays a central role in the assembly and function of the six-protein complex, connecting the double-stranded DNA-binding proteins TERF1 (telomere repeat binding factor) and TERF2 to the single-stranded DNA-binding unit TPP1/POT1
  • dual role for TINF2 in mediating the function of the shelterin complex and tethering telomeres to the nuclear matrix
  • TINF2-anchored ACD plays a major role in the recruitment of telomerase to telomeres in cells
  • participate in the TPP1-dependent recruitment of telomerase activity
  • recruits the telomerase in a TPP1-dependent manner
  • may specifically regulate the telomerase that has been recruited to the telomeres rather than total telomerase activity
  • essential for early embryonic development and for development of a variety of malignancies
  • preferential recruitment of shelterin complex to areas of the telomere where ss- and ds-DNA are in close proximity, such as the 3prime-telomeric overhang, telomeric DNA bubbles and the D-loop at the base of T-loops
  • SIAH2-mediated removal of TINF2 may allow dynamic remodeling of the shelterin complex and its associated factors during the cell cycle
  • also affected the TERF2-dependent repression of ATM kinase signaling but not to TERF2-mediated inhibition of telomere fusions
  • likely a direct role for TINF2 in mediating telomere length through telomerase, separable from its role in telomere protection
  • CELLULAR PROCESS cell life, senescence
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with ACD, POT1 and TERF2IP to ensure proper maintenance of telomeres (high-molecular-mass telomeric complex, the telosome that contains the six core proteins TERF1, TERF2, TERF2IP, POT1 and ACD)
  • telomere-binding protein complex that serves to cap and protect mammalian chromosome ends
  • part of Shelterin complex (TERF1, TERF2, POT1, TERF2IP, TINF2, and TPP1)
  • INTERACTION
    DNA binding to the interstitial TTAGGG repeats
    RNA
    small molecule
    protein
  • TERF1-interacting protein that mediates TERF1 function and also interacting with TERF2
  • TINF2-mediated cooperative binding of TERF1 and TERF2 to telomeres has important implications for the mechanism of telomere length regulation and protection
  • coordinated interactions among ACD, TERF1, and TERF2 may ensure robust assembly of the telosome, telomere targeting of its subunits, and, ultimately, regulated telomere maintenance
  • TINF2 binds to SIAH2 and is ubiquitylated
  • has a minor contribution to the repression of ATM by TERF2, its major role is to stabilize TPP1/POT1 on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling
  • TPP1 interacts with TINF2 N terminus, which contains overlapping mitochondrial and telomeric targeting sequences, and controls TINF2 localization
  • binds to TERF1 and TERF2, improving the telomeric localization of TERF2 and its function
  • cell & other
    REGULATION
    Other TINF2 stability is regulated by the E3 ligase SIAH2
    potential mitotic regulation of TINF2 by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s) DKC5 , ATXP , ERBMF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in familial pulmonary fibrosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS