Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol STUB1 contributors: mct/pgu - updated : 31-01-2017
HGNC name STIP1 homology and U-Box containing protein 1
HGNC id 11427
Corresponding disease
SCA48 spinocerebellar ataxia 48
SCAR16 spinocerebellar ataxia, autosomal recessive 16
Location 16p13.3      Physical location : 730.114 - 732.767
Synonym name
  • U-box dependent E3 ubiquitin ligase-chaperone protein
  • serologically defined colon cancer antigen NY-CO-7
  • carboxyl terminus of the Hsc70-interacting protein
  • Synonym symbol(s) CHIP, NY-CO-7, HSPABP2, SDCCAG7, UBOX1, SCA48, SCAR16
    EC.number 2.3.2.27
    DNA
    TYPE functioning gene
    STRUCTURE 2.39 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1340 - 303 - 1999 10330192
    7 - 1429 - 231 - 1999 10330192
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestivesalivary gland   highly
    Lymphoid/Immunetonsils   highly
    Nervousnerve   highly
    Reproductivemale systemtestis  highly Homo sapiens
    Skin/Tegumentskin   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three 34-amino acid TPR domains, required for the promotion of aggregation at its N terminus, binding to the TPR acceptor sites on Hsp90 and Hsp70 proteins
  • a central domain rich in charged residues,
  • an adjacent charged domain
  • two potential nuclear localization signals
  • a C terminal Ubox (ubiquitin ligase domain), and it serves as an E3 ubiquitin ligase through this Ubox domain
  • HOMOLOGY
    interspecies homolog to yeast STIP1
    ortholog to murine Stub1
    homolog to drosophila CHIP
    homolog to C.elegans T09B4.10
    Homologene
    FAMILY
    CATEGORY chaperone/stress , enzyme , regulatory , antigen
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • being a negative regulator of chaperone functions
  • ubiquitylation of HSC70 (ubiquitin ligase activity)
  • decreasing net ATPase activity and reducing chaperone efficiency, and implicated in the negative regulation of the forward reaction of the HSC70-HSP70 substrate-binding cycle
  • Hsp70 co-chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic stress
  • inhibits anchorage-independent cell growth and metastatic potential by degrading oncogenic proteins including NCOA3
  • plays an important role in regulation NOS2 activity
  • serves as an E3 ubiquitin ligase that regulates RUNX1 protein stability via an ubiquitination and degradation mechanism that is independent of Hsp70/90
  • preferentially ubiquitinates Hsp70-bound substrates
  • mediates the ubiquitylation and suppresses the aggregation of polyglutamine (polyQ) proteins, such as huntingtin or ataxin-3
  • chaperone-associated ligase, regulating SENP3 stability
  • represents a new pathway for modulating telomerase activity in cancer
  • STUB1-dependent TP53 regulation occurs specifically during senescence
  • U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins
  • regulates NFKB1-mediated cell invasion via the down-regulation of TRAF2
  • UBE2N and STUB1 are novel factors in the regulation of cell surface availability of GHR
  • by regulating HDAC6 levels, influences potentially protein triage decisions by modulating the refolding and degradation activities of HDAC6
  • regulates the EIF5A protein stability via a protein degradation mechanism
  • E3 ubiquitin ligase STUB1 ubiquitinates and degrades its substrate ARNTL and thereby alleviates hydrogen peroxide-induced cell senescence
  • CELLULAR PROCESS protein, post translation, folding
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to the C terminus of heat shock proteins HSP70 and HSC70
  • interaction with MAPT (inducing ubiquitination of MAPT and increasing MAPT aggregation)
  • interacting with SMAD(inhibiting the transcriptional activities of the SMAD1/SMAD4 complex induced by BMP signal)
  • associates not only with the polyQ-expanded ataxin-1 but also with the normal ataxin-1
  • binds the co-chaperone/ubiquitin ligase STUB1 (C terminus of Hsc-70-interacting protein) through a unique N-terminal PEST domain in FBXO2
  • with the N-terminus of HSF1 (this interaction requires conformational change of HSF1 by heat stress)
  • binding to the RAF1/Hsp90 complex
  • stabilizes malin by modulating the activity of HSPA4 (NHLRC1 is unstable, and the aggregate-prone protein and co-chaperone STUB1 can modulate its stability)
  • UBE2N and UBE2D1 had distinct effects on the conformational dynamics of STUB1, suggesting different roles of the STUB1-E2 interaction in the ubiquitination of substrates and interaction with chaperones
  • STUB1 and Hsp90 interplay with a client alternately under non-stress and stress conditions, and the choice between stabilization and degradation is made by the redox state of the client
  • STUB1 and USP2 show antagonistic functions in the control of AIFM1-mediated cell death, and implicate the role of the enzymes as a switch for cells to live or die under stresses that cause truncated AIFM1 release
  • strongly inhibited the nuclear localization and the transcriptional activity of NFKB1
  • FBXO2 interacts with another protein known for glycoprotein homeostasis, STUB1, a co-chaperon with ubiquitin ligase properties
  • STUB1 binds, ubiquitinates and regulates expression of histone deacetylase 6 (HDAC6)
  • may also facilitate MAPT degradation by abrogating the protein folding function of HDAC6
  • RNF8 interacts with UBE2N in a manner that is similar to that of the RING-type E3 ubiquitin ligase TRAF6 and the U-box-type E3 ubiquitin ligase, STUB1
  • ER stress reduced the binding between MAPT and STUB1, ubiquitin E3 ligase for MAPT (STUB1 binds to MAPT and is thought to promote the degradation of MAPT by its ubiquitination through ubiquitin–proteasome system)
  • is a CARD11 associated protein
  • UBE2N activity and its interaction with STUB1 precede endocytosis of GHR
  • dynamic C-terminal region of HSPA8 provides for flexibility between STUB1 and the chaperone
  • USP47 plays a crucial role in the control of axonal growth during neuronal development by antagonizing STUB1-mediated KATNA1 degradation
  • EIF5A is a target of STUB1, an E3 ligase with a U-box domain
  • STUB1 ubiquitinated FMR1 for proteasomal degradation in a molecular chaperone-independent manner
  • E3 ubiquitin ligase STUB1 is a negative regulator of both RUNX1 and RUNX1-RUNX1T1
  • STUB1, a chaperone-dependent E3 ubiquitin ligase, modulates TFEB activity by preferentially targeting inactive phosphorylated TFEB for degradation by the ubiquitin-proteasome pathway
  • DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by HSPA4/HSPA8 and the E3 ubiquitin ligase STUB1
  • STUB1 is a ubiquitin ligase for OTUD3
  • STUB1 is a negative regulator of OTUD3 and suppresses lung cancer metastasis through inhibiting OTUD3-HSPA5 signaling axis
  • cell & other
    REGULATION
    inhibited by BAG2 (inhibits its ubiquitin ligase activity by abrogating the STUB1/E2 cooperation and stimulates the chaperone-assisted maturation of CFTR)
    ASSOCIATED DISORDERS
    corresponding disease(s) SCAR16 , SCA48
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    Sertoli-specific expression of STUB1 was significantly decreased in the human testes with impaired spermatogenesis
    constitutional     --over  
    in CD4(+)T cells of SLE patients compared to healthy subjects
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmuneLupus
    modulation of STUB1 activity may provide a novel therapeutic approach for SLE
    ANIMAL & CELL MODELS