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FLASH GENE
Symbol STIP1 contributors: mct - updated : 08-03-2019
HGNC name stress-induced-phosphoprotein 1
HGNC id 11387
Location 11q13.1      Physical location : 63.953.586 - 63.972.020
Synonym name
  • Hsp70/Hsp90-organizing protein
  • NY-REN-11 antigen
  • transformation-sensitive protein IEF SSP 3521
  • Synonym symbol(s) HOP, P60, STI1L, IEF-SSP-3521, STI1, HEL-S-94n
    DNA
    TYPE functioning gene
    STRUCTURE 19.28 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D13S1357 - SERPING1 - SSRP1 - CNTF - D11S1765 - MS4A1 - MS4A2 - AHNAK - CD5 - FTH1 - ROM1 - FAU - STIP1 - D11S913 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2219 63 543 - 1992 1569099
    14 - 2766 - 590 - 1992 1569099
    14 - 2147 - 519 - 1992 1569099
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Visualeyeanterior segment  highly Homo sapiens
    cell lineage
    cell lines SV40 transformed MRC-5 fibroblasts
    fluid/secretion
    at STAGE
    Text trabecular meshwork (HTM), non-pigmented ciliary epithelium ((19150991)
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • TPR protein containing at least six copies of tetra-tricopeptide repeat (TPR2A and TPR2B); TPR1, TPR2A and TPR2B, bind a single S100A1 dimer with significantly different affinities and that the TPR2B domain possesses the highest affinity for S100A1
  • TPR2a containing the HSP90-binding site is also the primary site for dimerisation
  • secondary structure butterfly-like quaternary structure
    conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae STI1
    Homologene
    FAMILY
    CATEGORY adaptor , chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    text the nucleus of SV40 transformed MRC-5 fibroblasts
    basic FUNCTION
  • may would be involved in response to stress
  • tetratricopeptide repeat domain (TPR)-containing co-chaperone Hsp-organising protein, plays a critical role in mediating interactions between HSP70 and HSP90 as part of the cellular assembly machine
  • having a functional role on the physiology of gliomas, and promoting glioma proliferation through MAPK and PI3K pathways
  • is critically involved in endothelial cell migration and angiogenesis, and is important for endothelial cell migration
  • essential roles for intracellular and extracellular STI1 in cellular resilience
  • is a unique co-chaperone that undergoes an ATP-dependent conformational change
  • secreted form of the co-chaperone STIP1 has been described as a prion protein partner that is involved in several processes of the nervous system, such as neurite outgrowth, neuroprotection, astrocyte development, and the self-renewal of neural progenitor cells
  • participates in RND1-induced signal transduction pathways that are involved in the dynamics of the actin cytoskeleton
  • STIP1 promoted the growth, colony formation and migration of cancer cells
  • CELLULAR PROCESS nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to the EEVD motif of HSP70 and HSP90 families through the TPR domain
  • likely binds to both monomers of HSP90 in the form of a clamp, interacting with residues in the middle domain of HSP90, thus preventing ATP hydrolysis, possibly by the prevention of association of N-terminal and middle domains in individual HSP90 monomers
  • interacting with WDR36
  • interacting with PRNP (enhances neuronal PRNP synthesis via MTOR)
  • directly binds to chaperones to regulate their activities
  • interacts with tubulin and colocalizes with microtubules in endothelial cells
  • direct interaction between STIP1 and PIAS1 is involved in the accumulation of nuclear STIP1, and this retention mechanism could facilitate nuclear chaperone activity
  • cytoplasmic STIP1 directly interacts with the GTPase RND1
  • may be part of the cancer gene signature induced by a combination of mutant TP53 and mutated RAS that is associated with cellular transformation
  • STIP1 acts as a scaffold promoting the interaction between KDM1A and GSK3B
  • STIP1 interacted with Axin, enhanced the interaction between Axin and DVL2, thus activated beta-catenin/TCF signaling
  • IL7 stimulation induced the phosphorylation of the proteins STIP1, ATIC and HNRNPH, involved in pathways related to survival, proliferation and gene expression, respectively, and increased the phosphorylation of CRKL
  • is a co-chaperone of HSPA4 and HSP90AA1 that regulates a number of cell biology processes via interactions with cellular proteins
  • STIP1 stabilises EMD and loss of STIP1 alters nuclear structure via EMD degradation
  • cell & other
  • cell surface ligand for cellular prion (PrP(C)), which leads to the activation of several signal transduction pathways, some of which modulate cell survival
  • REGULATION
    induced by stress
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation   protein chimeric
    chimeric protein gamma-heregulin (5'-STIP1-NRG1-3') resulting from the translocation t(8;11) (p12;q13) and the fusion with neuregulin
    tumoral     --over  
    in hepatocellular carcinoma and associated with poor clinical prognosis
    constitutional     --low  
    reduced STIP1 levels can contribute to phenotypes related to ASD
    Susceptibility to variations in corticosteroid response in asthmatic subjects with reduced lung function
    Variant & Polymorphism other
  • genetic variations might play a role in regulating corticosteroid response in asthmatic subjects with reduced lung function
  • Candidate gene ideal candidate gene for glaucoma
    Marker
  • STIP1 expression might be used as a prognostic biomarker for cancer treatment
  • is a secreted biomarker for human ovarian cancer and promotes cancer cell proliferation
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    STIP1 might be a therapeutic target in hepatocellular carcinoma
    ANIMAL & CELL MODELS