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FLASH GENE
Symbol JUN contributors: mct/pgu/shn - updated : 26-02-2016
HGNC name jun proto-oncogene
HGNC id 6204
Location 1p32.1      Physical location : 59.246.463 - 59.249.785
Synonym name
  • jun oncogene
  • enhancer binding protein AP-1
  • enhancer-binding protein AP1
  • v-jun sarcoma virus 17 oncogene homolog (avian)
  • v-jun avian sarcoma virus 17 oncogene homolog
  • v-jun sarcoma virus 17 oncogene homolog
  • activator protein 1
  • proto-oncogene c-jun
  • Jun activation domain binding protein
  • proto-oncogene c-Jun
  • transcription factor AP-1
  • Synonym symbol(s) AP1, C-JUN, p39, AP-1
    DNA
    TYPE functioning gene
    STRUCTURE 3.32 kb     1 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • GAGCCTC putative response element in the promoter
  • MAPPING cloned Y linked N status provisional
    Map pter - D1S2752 - D1S2700 - JUN - D1S220 - D1S2831 - cen
    Physical map
    PCSK9 1p32.3 proprotein convertase subtilisin/kexin type 9 USP24 1p32.2-p31.2 ubiquitin specific protease 24 LOC388634 1 similar to Ubiquitin carboxyl-terminal hydrolase 24 (Ubiquitin thiolesterase 24) (Ubiquitin-specific processing protease 24) (Deubiquitinating enzyme 24) LOC388635 1 LOC388635 LOC391042 1 similar to glycogenin LOC391043 1 similar to Aspartate aminotransferase, mitochondrial precursor (Transaminase A) (Glutamate oxaloacetate transaminase-2) LOC127406 1p32.2 similar to 33K laminin receptor homolog - bovine PPAP2B 1pter-p22.1 phosphatidic acid phosphatase type 2B PRKAA2 1p31 protein kinase, AMP-activated, alpha 2 catalytic subunit LOC199920 1p32.2 hypothetical protein LOC199920 C8A 1p32 complement component 8, alpha polypeptide C8B 1p32 complement component 8, beta polypeptide DAB1 1p32-p31 disabled homolog 1 (Drosophila) MPRP-1 1p32.1 metalloprotease related protein 1 TACSTD2 1p32-p31 tumor-associated calcium signal transducer 2 AK2B 1p32.1 adenylate kinase 2 pseudogene KIAA1915 1p32.1 KIAA1915 protein JUN 1p32-p31 v-jun sarcoma virus 17 oncogene homolog (avian) LOC391044 1 similar to prohibitin FLJ10986 1p32.1 hypothetical protein FLJ10986 HOOK1 1p32.1 hook homolog 1 (Drosophila) CYP2J2 1p31.3-p31.2 cytochrome P450, family 2, subfamily J, polypeptide 2 MGC34837 1p32.1 hypothetical protein MGC34837 NFIA 1p31.3-p31.2 nuclear factor I/A BBP 1p32.1 beta-amyloid binding protein precursor INADL 1p32.1-p31.3 beta-amyloid binding protein precursor FLJ10884 1p32.1 hypothetical protein FLJ10884 LOC388637 1 similar to LOC163782 protein USP1 1p32.1-p31.3 ubiquitin specific protease 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 3338 - 331 - 1992 1631061
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic leucine zipper (bZIP) protein, binding to DNA as monomers prior to folding and homodimerization
  • conjugated PhosphoP
    mono polymer heteromer , dimer , trimer
    HOMOLOGY
    interspecies homolog to avian sarcoma virus 17 (v-jun) oncogene
    ortholog to Jun, Mus musculus
    ortholog to Jun, Rattus norvegicus
    ortholog to jun, Danio rerio
    ortholog to JUN, Pan troglodytes
    Homologene
    FAMILY
  • AP1 family of transcription factors
  • bZIP family
  • Jun subfamily
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,chromatin/chromosome
    text localized to endosomes and/or the trans Golgi network (TGN)
    basic FUNCTION
  • an essential function in hepatogenesis
  • essential substrate of JNK signalling during kainate-induced neuronal apoptosis
  • prevents apoptosis by antagonizing p53 activity
  • regulating intestinal tumorigenesis by interaction with TCF4 (by integrating JNK and APC/beta-catenin, two distinct pathways activated by WNT signaling)
  • regulate stromal-epithelial interactions via paracrine signals, and stromally expressed JUN may promote prostatic epithelial proliferation through IGF1 as a paracrine signal that, in turn, can promote prostate epithelial proliferation.
  • involved in the metastasis of breast cancer
  • JUN and AP3B1 are involved in the formation of distinct types of clathrin-coated vesicles, each of which is characterized by the incorporation of specific cargo membrane proteins
  • XRCC5-JUN activates JUN expression by binding to the GAGCCTC element in the JUN promoter and XRCC6 may also serve a role
  • controls the ability of IL12 to induce IL10 production from memory CD4+ T cells
  • promote monocytic differentiation
  • synergistic role for TAF4B and JUN and other AP1 family members on the promoter of ITGA6, underlining the existence of a specific mechanism related to gene expression control
  • have distinct roles in the basal versus suprabasal epidermis, confirming that its function is required for normal terminal differentiation, and potentially have a different role in normal epidermis versus cancer progression
  • critical for glucocorticoid receptor (GR)-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive JUN-GR interaction network
  • required for successful axonal regeneration
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forming heterodimers with JUN, JUNB, JUND, FOS, FOSB to form the transcription factor AP1 major target of mitogen-activated signal transduction pathway
  • forming a ternary complex with JUN, CTNNB1 (beta-cetanin)
  • BATF forms a heterodimeric complex with JUNB and JUN, induced upregulation of matrix-degrading enzymes and downregulation of cartilage matrix molecules in chondrocytes
  • INTERACTION
    DNA
  • H ferritin promoter
  • bind to the promoters of a multitude of genes involved in critical cellular responses such as cell growth and proliferation, cell cycle regulation, embryonic development and cancer
  • cAMP-responsive element (CRE) in the PII promoter-proximal region
  • RNA
    small molecule
    protein
  • MyoD
  • CREB
  • ribosomal protein L18a
  • TBP and TFIIB
  • Maf and Nrl
  • DNA topoisomerase II, topo II
  • CRE-BP1
  • tissue inhibitor of metalloproteinases-1, TIMP-1 and c-Ets-1
  • GHF-1
  • TFIIE-34, TFIIF-30, and TFIIF-74
  • B-ATF
  • Ubc9
  • JAB1
  • ETS2
  • alpha chain of the nascent polypeptide-associated complex, alpha-NAC
  • retinoblastoma protein, Rb
  • Steroid receptor coactivator-1, SRC-1
  • Ergp55 and Fos
  • Smad3 and Smad4
  • Nrf2 and Nrf1
  • retinoblastoma protein, Rb
  • SPI-B
  • vitamin D3 receptor, VDR
  • NF-kappaB and AP-1 components c-Fos
  • steroidogenic factor 1, SF-1
  • Stat3
  • Bcl3
  • C/EBP homologous protein 10, CHOP
  • Silencing mediator of retinoic acid and thyroid hormone receptors, SMRT
  • SUMO-1
  • ASC-2
  • BAF60a
  • Cbfa and Runt
  • TAF(II)250
  • TG-interacting factor, TGIF
  • estrogen receptor alpha, ERalpha
  • Pin1
  • homeodomain-containing protein Hex
  • Cbfa1
  • hypoxia-inducible factor 1, HIF-1
  • coactivator of activating protein-1 (AP-1) and estrogen receptors, CAPER
  • STAT4
  • DEAD-box RNA helicase RHII/Gu
  • PIAS1 and PIASxbeta
  • nuclear factor Y, NFY
  • Protein kinase D, PKD
  • Ski
  • BRCA1
  • BCL-6
  • Receptor-interacting protein 140, RIP140
  • Human COP1, huCOP1
  • histone deacetylase 3, HDAC3
  • Jun B
  • Cofactor of BRCA1, COBRA1
  • promyelocytic leukemia, PML
  • DNA topoisomerase I, Topo I
  • TCF4
  • histone deacetylase-related protein, HDRP
  • COOH-terminal Src kinase, CSK
  • interaction of GAK with adaptor protein 1 (JUN) regulates lysosomal enzyme sorting
  • F-box protein Fbl10/JHDM1B
  • calcineurin, CaN
  • SIRT1
  • c-Fos and MAZ
  • p21(Cip1)
  • c-Myc
  • RING domain AP-1 co-activator-1, RACO-1
  • Mbd3
  • STAT6 and JUN proteins were found to physically cooperate with each other and upregulated IL24 gene transcription
  • STRAP
  • metastasis-associated protein 1, MTA1
  • receptor for activated C-kinase 1, Rack1
  • FOSB and JUN can derepress transcription from the SERPINB2 promoter which may have general significance for SERPINB2-expressing cells
  • AATF is a nucleolar stress sensor, which is required as a cofactor for JUN-mediated apoptosis
  • PAX2 promotes proliferation of colon cancer cells through JUN
  • AFF2 is an upstream regulator of FOS and JUN, and further link deregulation of the immediate early response genes to the pathology of intellectual disability (ID)- and FRAXE-associated ID in particular
  • KRIT1 loss of function causes a ROS-dependent upregulation of JUN
  • RBPMS physically and functionally interacts with JUN
  • role of APPL1 as a positive regulator of DVL2-dependent transcriptional activity of JUN
  • COPS6 is involved in positively regulating the stability of JUN
  • overexpression of COPS6 correlates with the upregulation of JUN target gene expression in cancer
  • JUN can suppress adipocyte differentiation through the down-regulation of KLF15 at the transcriptional level
  • BATF/JUNB and BATF/JUN complexes play important roles in osteoarthritic cartilage destruction through regulating anabolic and catabolic gene expression in chondrocytes
  • JUN may cooperate with other partners to regulate FDX1 in Leydig cells
  • HIPK1-phosphorylated PAGE4 (HIPK1-PAGE4) potentiates JUN, whereas CLK2-phosphorylated PAGE4 (CLK2-PAGE4) attenuates JUN activity
  • hyperphosphorylation of PAGE4 by CLK2 attenuates this interaction with JUN
  • cell & other
    REGULATION
    activated by Vav
    induced by ligand induced
    inhibited by DACH1
    repressed by F-box protein Fbl10/JHDM1B
    Phosphorylated by GSK3
    c-Abl
    mitogen-activated protein-serine (MAP) kinases (pp54 and pp42/44)
    Vav
    Protein kinase D, PKD
    MKK-4, MKK-7, and JNK complex
    ultraviolet B, UVB
    COOH-terminal Src kinase, CSK
    5/6-kinase
    CK2 and PKD
    Other coactivated by COD5 is abrogated by CDKN1B
    regulated by both phosphorylation and sumoylation
    regulated by two SUMO-specific proteases (SUMO1 and SENP1) through entirely different mechanisms
    regulated by CDCA4 (transcriptional co-factor CDCA4 participates in the regulation of JUN oncogene expression)
    regulated by FOSL1 (posttranslational regulator of c-Jun stability in RAS transformation)
    sumoylated by PIAS1 and PIASxbeta
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    constitutional     --over  
    in in sudden infant death (in the brain)
    tumoral     --over  
    in breast cancer with liver metastasis
    tumoral     --other  
    dysregulation of JUN expression is a primary molecular aberrancy that contributes to the etiology and pathogenesis of juvenile myelomonocytic leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    opportunity for development of anti-JUN strategies in breast cancer therapy
    cancerhemopathy 
    potential pharmacologic interventions that may reduce JUN function or expression, (inhibition of JUN phosphorylation or expression could inhibit mutant PTPN11-induced monocytic differentiation) thus providing a novel therapeutic approach for juvenile myel
    cancer  
    autoregulatory loop between JUN and FOSL1 might represent an important determinant for the increased JUN activity and a novel target for therapeutic intervention in tumorigenesis
    ANIMAL & CELL MODELS
  • mouse embryonic stem (ES) cells lacking c-Jun are viable and have a normal in vitro differentiation capacity
  • primary Jun-/- fibroblasts have a severe proliferation defect and undergo premature senescence in vitro
  • mouse primary JunAA (serines 63 and 73 mutated to alanines) fibroblasts have proliferation- and stress-induced apoptotic defects, accompanied by reduced AP-1 activity, and JunAA mice are viable and fertile, smaller than controls and resistant to epileptic seizures and neuronal apoptosis induced by the excitatory amino acid kainate
  • mouse primary hepatocytes lacking c-Jun showed increased sensitivity to TNF-alpha-induced apoptosis
  • embryos lacking c-Jun die at mid- to late-gestation and exhibit impaired hepatogenesis, altered fetal liver erythropoiesis and generalized oedema
  • Absence of mouse neuronal Jun reduced the speed of axonal regeneration following crush, and prevented most cut axons from reconnecting to their target, significantly reducing functional recovery (