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FLASH GENE
Symbol TSLP contributors: mct/npt - updated : 26-01-2013
HGNC name thymic stromal lymphopoietin
HGNC id 30743
Location 5q22.1      Physical location : 110.407.389 - 110.413.722
DNA
TYPE functioning gene
STRUCTURE 6.33 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • several NFKB binding sites located in the proximal region of the TSLP promoter are critical for TSLP modulation in intestinal epithelial cells
  • MAPPING cloned Y linked N status provisional
    Physical map
    LOC391817 5 similar to protease (prosome, macropain) 26S subunit, ATPase 1 EFNA5 5q21 ephrin-A5 LOC391818 5 similar to Ubiquitin carboxyl-terminal hydrolase 7 (Ubiquitin thiolesterase 7) (Ubiquitin-specific processing protease 7) (Deubiquitinating enzyme 7) (Herpesvirus associated ubiquitin-specific protease) LOC345576 5q21.3 similar to Ubiquitin carboxyl-terminal hydrolase 7 (Ubiquitin thiolesterase 7) (Ubiquitin-specific processing protease 7) (Deubiquitinating enzyme 7) (Herpesvirus associated ubiquitin-specific protease) FBXO13 5q21.3 F-box only protein 13 RPS20P3 5q13-q23 ribosomal protein S20 pseudogene 3 FER 5q21 fer (fps/fes related) tyrosine kinase (phosphoprotein NCP94) GJA1P1 5q21.3 gap junction protein, alpha 1, 43kDa (connexin 43) pseudogene 1 PJA2 5q21.1 praja 2, RING-H2 motif containing LOC391819 5 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) MAN2A1 5q21-q22 mannosidase, alpha, class 2A, member 1 LOC153778 5q22.1 hypothetical LOC153778 LOC255338 5q22.1 hypothetical LOC255338 LOC91137 5q22.2 hypothetical protein BC017169 LOC134433 5q22.2 similar to Zinc finger DHHC domain containing protein 8 (Zinc finger protein 378) LOC285639 5q22.2 similar to Bcl-2-associated transcription factor TSLP 5q22.2 thymic stromal lymphopoietin TA-WDRP 5q22.2 T-cell activation WD repeat protein LOC133744 5q22.2 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 CAMK4 5q21-q23 calcium/calmodulin-dependent protein kinase IV STARD4 5q21.3 START domain containing 4, sterol regulated C5orf13 5q22.1 chromosome 5 open reading frame 13 TIGA1 5q21-q22 TIGA1 EPB41L4A 5q22.1 erythrocyte membrane protein band 4.1 like 4A FLJ11235 5q22.2 hypothetical protein FLJ11235 APC 5q21-q22 adenomatosis polyposis coli SRP19 5q21 signal recognition particle 19kDa DP1 5q22-q23 polyposis locus protein 1 XBPP1 5q14.3-q15 X-box binding protein pseudogene 1 U2AF1L1 5q22 U2(RNU2) small nuclear RNA auxillary factor 1-like 1 DCP2 5q22.3 decapping enzyme hDcp2 MCC 5q21 mutated in colorectal cancers STK22D 5q22.2 serine/threonine kinase 22D (spermiogenesis associated) LOC389316 5 LOC389316 FLJ21940 5q22.3 FLJ21940 protein KCNN2 5q22.3 potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 2629 18.1 159 - 2009 19770269
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    Nervousbrain    
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion in human breast milk
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 28-residue signal sequence
  • 6 cysteines and 2 N-glycosylation sites
  • secondary structure several predicted alpha-helical regions in TSLP, a structure characterizing many classical antimicrobial peptides (AMPs)
    HOMOLOGY
    Homologene
    FAMILY
  • B cell-stimulating factors family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    text
  • constitutively secreted by intestinal epithelial cells
  • basic FUNCTION
  • enhancing the dendritic cells maturation process
  • with IL7, use different mechanisms to regulate human CD4(+) T cell homeostasis
  • may be an important player in the acute phase of HIV-1 infection by creating an environment that is conducive for sustaining the small dose of the initial virus inoculum that crosses the mucosal barrier
  • induces tight junction protein claudin-7 via NF-kappaB in dendritic cells
  • plays an important role in extravillous trophoblast invasion and placentation in human early pregnancy
  • potential key mediator of both the initiation and maintenance of Th2 responsiveness and thereby the allergic inflammatory cascade
  • acts on multiple lineages, including dendritic cells (DCs), T cells, NKT cells, eosinophils, and mast cells, mediating proliferation and survival and linking innate and adaptive immune responses
  • epithelial-derived cytokine TSLP triggers chemokinesis of resting primary human dendritic cells in a cell-autonomous manner
  • could elicit basophil responses in both IL3/IL3R-sufficient and -deficient environments
  • its expression may influence susceptibility to multiple allergic diseases by regulating basophil haematopoiesis
  • may regulate basophil haematopoiesis in the bone marrow
  • role for TSLP in promoting basophil haematopoiesis, peripheral basophilia and altering the functional capacity of basophils
  • its antimicrobial activity is primarily mediated by the C-terminal part of the protein
  • capable of activating dendritic cells to promote T helper (Th) 2 immune responses
  • induces the invasion of human trophoblasts and plays a role in embryo implantation
  • might downregulate NME1 expression via STAT3 signaling pathway, affecting TIMP1 expression in influencing trophoblast invasion
  • implicated in the development and progression of allergic diseases such as atopic dermatitis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TSLP/CRLF2 plays a significant role in the amplification of polarization and chemokine production, thereby contributing to allergic inflammation
  • both IL3 and TSLP can promote basophil maturation from bone-marrow-resident precursor cells and promote survival of mature basophils isolated from the periphery
  • can be expressed and produced through caspase-1 and NFKB in mast cells
  • cell & other
    REGULATION
    Other calcium regulates the level of TSLP through RIP2/caspase-1/NFKB/IKBKA signal
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to esophagitis, eosinophilic (See EOE2)
  • Variant & Polymorphism SNP A allele of rs1837253, associated with protection from asthma, atopic asthma, and airway hyperresponsiveness
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionfertilityfemale
    potential therapeutic target for recurrent spontaneous abortion
    immunologyinfectious 
    possibility of targeting TSLP as a strategy against mucosal HIV-1 transmission and/or TSLP as a potential modulator of antigen-specific immune responses induced by candidate vaccines delivered at these mucosal viral entry sites
    ANIMAL & CELL MODELS
  • in rhesus macaques inoculated with simian immunodeficiency virus (SIV) by the vaginal route, dramatic increases in TSLP expression and SIV replication in the vaginal tissues within the first 2 weeks after virus exposure