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FLASH GENE
Symbol DNAJA1 contributors: mct - updated : 27-08-2019
HGNC name DnaJ (Hsp40) homolog, subfamily A, member 1
HGNC id 5229
Corresponding disease
IDSD intellectual disability and seizure disorder
Location 9p21.1      Physical location : 33.025.208 - 33.039.062
Synonym name
  • heat shock protein DNAJ-like 2
  • DnaJ protein homolog 2
  • heat shock 40 kDa protein 4
  • neural precursor cell expressed, developmentally down-regulated 7
  • Synonym symbol(s) HSPF4, HSJ2, DJ2, HDH2, DNAJ1, HDJ2 , HSDJ, NEDD7
    DNA
    TYPE functioning gene
    STRUCTURE 14.70 kb     9 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
    9 splicing 1538 - 397 - 2019 30566031
    localized to the nucleus
    8 splicing 2228 - 240 - 2019 30566031
  • observed throughout the cell, consistent with the elimination of a nuclear localization signal sequence as a result of the alternative splicing
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   moderately
    Cardiovascularheart   highly
    Digestiveliver   moderately
    Endocrinepancreas   highly
    Nervousbrain   highly
    Reproductivemale systemprostate  highly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a DJA domain
  • a DR domain
  • C-terminus of DNAJA1 having a CAAX box for farnesylation
  • conjugated LipoP , Other
    HOMOLOGY
    interspecies homolog to murine Dnaja1
    homolog to Drosophila CG8863
    homolog to C.elegans dnj-12
    homolog to yeast S.cerevisiae HSJ2
    Homologene
    FAMILY
    CATEGORY chaperone/stress , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleolus
    text
  • colocalizing with Hsp70 (HSPA*),DNAJA2,BAG1 after heat shock
  • membrane-bound
  • identified in the mammalian cytosol (Abdul 2002)
  • basic FUNCTION
  • transport of certain proteins into the mitochondria and endoplasmic reticulum
  • positive cochaperone of Hsp70
  • having a heat shock protein activity
  • critical role of DNAJA1 in spermiogenesis, suggesting that likely DNAJA1 and DNAJA2 are not functionally equivalent
  • with DNAJA2, cause a decrease in the amount of KCNH2 complexed with Hsc70, indicating a preferential degradation of the complex (Walker 2010)
  • role for the DJA proteins in regulating degradation suggesting that they act at a critical point in secretory pathway quality control (Walker 2010)
  • although functions of DNAJA2 and DNAJA1 independent of HSPA8 are possible, it is generally thought that their main roles are as co-chaperones of HSPA8
  • DNAJA1 is likely co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an HSPA4 cochaperone-independent manner
  • DNAJA1 interacts with GORASP1 to enhance Golgi structure formation through the promotion of GORASP1 trans-oligomerization
  • 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
  • CELLULAR PROCESS protein, post translation, folding
    PHYSIOLOGICAL PROCESS cellular trafficking transport , mitochondrial transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • DNAJA1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AICDA protein levels in B cells
  • antagonizes constitutive HSPA4-mediated stabilization of MAPT
  • essential role of specific DJA domains of DNAJA1 and DNAJA2 in the folding mechanism of HSPA8
  • DNAJA1 controls the fate of misfolded mutant TP53 through the mevalonate pathway
  • DNAJA1 is a novel GORASP1-binding protein
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IDSD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in Colorectal cancer tissues and positively correlated with serosa invasion, lymph node metastasis
    tumoral     --low  
    in pancreatic cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • targeted as a biomarker for pancreatic cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivepancreas
    farnesylated DNAJA1 is a crucial chaperone in maintaining mutant TP53 stabilization and targeting farnesylated DNAJA1 by atorvastatin will be critical for inhibiting TP53 mutant cancer
    immunologyinfectious 
    Targeting the interactions between polymerase subunits and DnaJA1 may provide a novel strategy to develop antiviral drugs
    ANIMAL & CELL MODELS
  • loss of DjA1 in mice led to severe defects in spermatogenesis that involve aberrant androgen signaling