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FLASH GENE
Symbol STUB1 contributors: mct/pgu - updated : 31-01-2015
HGNC name STIP1 homology and U-Box containing protein 1
HGNC id 11427
Corresponding disease
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
    DNA
    TYPE functioning gene
    STRUCTURE 2.65 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    MRPL28 16p13.3 mitochondrial ribosomal protein L28 TMEM8 16p13.3 transmembrane protein 8 (five membrane-spanning domains) LOC388197 16 hypothetical gene supported by BC028568 NME4 16p13 non-metastatic cells 4, protein expressed in DECR2 16p13.3 2,4-dienoyl CoA reductase 2, peroxisomal Rab11-FIP3 16p13.3 eferin SOLH 16p13.3 small optic lobes homolog (Drosophila) LOC146325 16p13.3 similar to hypothetical protein FLJ13841 FLJ36208 16p13.3 hypothetical protein FLJ36208 PIGQ 16p13.3 phosphatidylinositol glycan, class Q RAB40C 16p13.3 RAB40C, member RAS oncogene family WFIKKN 16p13.3 RAB40C, member RAS oncogene family MGC13114 16p13.3 hypothetical protein MGC13114 LOC388198 16 LOC388198 MGC15416 16p13.3 hypothetical protein MGC15416 KIAA1924 16p13.3 hypothetical protein KIAA1924 LOC197336 16p13.3 similar to RIKEN cDNA 3230401M21 [Mus musculus] ARHT2 16p13.3 ras homolog gene family, member T2 RHBDL1 16p13.3 rhomboid, veinlet-like 1 (Drosophila) STUB1 16p13.3 STIP1 homology and U-Box containing protein 1 LOC339123 16p13.3 similar to RIKEN cDNA 2610003J06 DKFZp434F054 16p13.3 hypothetical protein DKFZp434F054 MGC33974 16p13.3 hypothetical protein MGC33974 MGC2601 16p13.3 hypothetical protein MGC2601 MGC2494 16p13.3 hypothetical protein MGC2494 FLJ34512 16p13.3 hypothetical protein FLJ34512 HAGHL 16p13.3 hydroxyacyl glutathione hydrolase-like NARFL 16p13.3 nuclear prelamin A recognition factor-like MSLN 16p13.3 mesothelin RLUCL CHTF18 16p13.3 CTF18, chromosome transmission fidelity factor 18 homolog (S. cerevisiae) GNG13 16p13.3 guanine nucleotide binding protein (G protein), gamma 13 LOC388199 16 LOC388199 FLJ12681 16p13.3 hypothetical protein FLJ12681
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1646 - 303 - 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 systemprostate  highly
    Skin/Tegumentskin   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    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
    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
  • 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
  • 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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS