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FLASH GENE
Symbol TNIP1 contributors: mct/npt/shn/pgu - updated : 28-05-2010
HGNC name TNFAIP3 interacting protein 1
HGNC id 16903
Location 5q33.1      Physical location : 150.409.507 - 150.460.997
Synonym name
  • HIV-1 Nef-interacting protein
  • Nef-associated factor 1 SNP
  • TNFAIP3-interacting protein 1
  • hVAN
  • virion-associated nuclear shuttling protein
  • A20 binding and inhibitor of NF-kappaB
  • Synonym symbol(s) VAN, NAF1, ABIN-1, KIAA0113, Nip40-1, ABIN1
    DNA
    TYPE functioning gene
    STRUCTURE 51.49 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map cen - D5S640 - D5S470 - TNIP1 - D5S2077 - D5S673 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 splicing 3268 71.9 636 - 2002 12220502
  • also called : variant alpha (NAF1 alpha)
  • phosphorylated by the EGF/MEK/ERK2 signal transduction pathway
  • attenuator of activated ERK2 signaling.
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestine  highly
     intestinelarge intestinecolon highly
     liver   moderately
    Endocrinepancreas   highly
    Lymphoid/Immunespleen   highly
     spleen   moderately
    Nervousbrain   lowly
    Reproductivefemale systemplacenta  moderately
     female systemovary  moderately
     male systemprostate  moderately
     male systemtestis  lowly
    Respiratorylung   moderately
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatum  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four coiled-coil structures
  • ABIN homology domain 1 (AHD1 and AHD2)
  • an ubiquitin-binding domain that is essential for their NF-kappaB inhibitory and anti-apoptotic activities
  • HOMOLOGY
    interspecies ortholog to Tnip1, mus musculus
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text shuttling between the nucleus and the cytoplasm in a CRM1-dependent manner
    basic FUNCTION
  • inhibiting the activity of NF-kappaB
  • a negative regulator of NF-
  • B via two sequential activities: de-ubiquitination of Lys63-based chains and synthesis of Lys48-based chains on the TNF receptor-interacting protein (RIP)
  • regulating matrix nuclear localization
  • attenuates epidermal growth factor (EGF)/extracellular-signal-regulated kinase2 (ERK2) nuclear signaling
  • atypical nuclear receptor coregulator, reducing RAR activity
  • A20-binding protein that is also known to attenuate NF-kappaB activation, and inhibits NFKB1 processing
  • important role in the regulation of immunity and tissue homeostasis
  • sequential action of SHQ1 and TNIP1 is required for functional assembly of H/ACA RNPs
  • cannot bind directly to the H/ACA domain of TERC, and requires the core trimer DKC1-NOP10-NHP2 to be efficiently incorporated into the pre-RNP
  • negative regulator of antiviral signaling
  • cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
  • essential anti-inflammatory component of TLR-signaling pathways that controls CEBPB activity
  • CELLULAR PROCESS cell life, antiapoptosis
    protein
    PHYSIOLOGICAL PROCESS immunity/defense
    text defense response
    PATHWAY
    metabolism
    signaling
    a component
  • potential role for the TNFAIP3/ABIN complex in the negative feedback regulation of NF-kappaB activation
  • INTERACTION
    DNA
    RNA
    small molecule polyubiquitin chains
    protein
  • tumor necrosis factor, alpha-induced protein 3, TNFAIP3
  • Nef of human immunodeficiency virus
  • human immunodeficiency virus type 1 matrix, HIV1
  • mitogen-activated protein kinase 1, MAPK1
  • RARalpha and RARgamma (TNIP1 repression of RARs in the presence of RA places it in a small category of corepressors of agonist-bound nuclear receptors)
  • NFKB1 (effects of TNIP1 on NFKB1 processing and of NFKB1 on stabilizing TNIP1 act to potentiate the NF-kappaB inhibitory activity of TNIP1)
  • ubiquitin-editing nuclear factor-kappaB (NF-kappaB) inhibitor protein TNFAIP3
  • TNI1 and TAX1BP1 together disrupted the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKBKE to attenuate lysine 63-linked polyubiquitination of TBK1/IKBKE
  • requires its ubiquitin binding domain and cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue of systemic sclerosis
    Susceptibility to SLE systemic lupus erythematosus
    Variant & Polymorphism SNP
  • variant (rs7708392 within an intron of TNIP1 significantly associated with SLE
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • . delivery of the NF-kappaB inhibitory protein ABIN-1 (TNIP1) to the lung epithelium of murine model of allergen-induced asthma results in a considerable reduction of allergen-induced eosinophil infiltration into the lungs
  • mice deficient for ABIN-1 (TNIP1) die during embryogenesis with fetal liver apoptosis, anaemia and hypoplasia
  • Abin1-deficient mice develop a progressive, lupus-like inflammatory disease characterized by expansion of myeloid cells, leukocyte infiltrations in different parenchymatous organs, activated T and B lymphocytes, elevated serum Ig levels, and the appearance of autoreactive antibodies