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FLASH GENE
Symbol COPS5 contributors: mct/ - updated : 28-05-2014
HGNC name COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis)
HGNC id 2240
Location 8q13.1      Physical location : 67.955.317 - 67.974.562
Synonym name
  • Jun-activation domain binding protein 1
  • 38 kDa Mov34 homolog
  • COP9 (constitutive photomorphogenic, Arabidopsis, homolog) subunit 5
  • signalosome subunit 5
  • Synonym symbol(s) JAB1, MOV34, SGN5, CSN5, MGC3149,
    EC.number 3.4.-.-
    DNA
    TYPE functioning gene
    STRUCTURE 19.25 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC392227 8 similar to peptidylprolyl isomerase A FLJ10511 8q12.3 armadillo repeat containing protein CHPPR 8q12.3 likely ortholog of chicken chondrocyte protein with a poly-proline region PDE7A 8q13 phosphodiesterase 7A MGC26226 8q12.3 beta cysteine string protein RNF29 8q12.3 ring finger protein 29 CRH 8q13 corticotropin releasing hormone RRS1 8q12.3 RRS1 ribosome biogenesis regulator homolog (S. cerevisiae) ADHFE1 8q12.3 alcohol dehydrogenase, iron containing, 1 MGC33510 8q12.3 hypothetical protein MGC33510 MYBL1 8q22 v-myb myeloblastosis viral oncogene homolog (avian)-like 1 VCIP135 8q13 valosin-containing protein (p97)/p47 complex-interacting protein p135 FLJ11267 8q13.1 hypothetical protein FLJ11267 PTTG3 8q13.1 hypothetical protein FLJ11267 SGKL 8q12.3-q13.1 serum/glucocorticoid regulated kinase-like FLJ25692 8q13.1 hypothetical protein FLJ25692 LOC392228 8 similar to hypothetical class II basic helix-loop-helix protein LOC286187 8q13.1 similar to RIKEN cDNA 1700011J18 COPS5 8q13.1 COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis) FLJ22490 8q13.1 hypothetical protein FLJ22490 BIG1 8q13 hypothetical protein FLJ22490 LOC389666 8 LOC389666 LOC392229 8 similar to 60S ribosomal protein L17 (L23) (Amino acid starvation-induced protein) (ASI) CPA6 8q12.3 carboxypeptidase A6 FLJ12987 8q13.1 hypothetical protein FLJ12987 VEST1 8q13 vestibule-1 protein LOC389667 8 similar to tropomyosin 4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1510 - 334 - 2010 20034471
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Nervousbrain   highly
    Reproductivemale systemprostate  highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cell lineage
    cell lines lung cancer cells
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a MPN domain-containing N-terminal portion that is sufficient for interacting with TYK2, although the intact JAMM motif is not necessary
  • PCI (Proteasome, COP9, initiation factor 3) domain
  • INT6 domain
  • NIP1 and TRIP15 domain
  • one JAB/MPN domain (JAMM), a domain of COPS5 that is essential
  • a catalytic domain that brings essential elements to understand its activity control
  • HOMOLOGY
    interspecies homolog to rattus Cops5 (99.10 pc)
    homolog to murine Cops5 (99.40 pc)
    intraspecies paralog to components of regulatory subunits of the 26S proteasome
    paralog to EIF3s family
    Homologene
    FAMILY
  • peptidase M67A family
  • CSN5 subfamily
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text colocolizing with UCHL1 in the nucleus in lung cancer and in cytoplasm in contact inhibited cells
    basic FUNCTION
  • potential cellular regulator modulating multiple signaling pathways
  • coactivator increasing the target specificity of AP-1 transcription factor
  • cleaving through JAMM domain NEDD8 from the CUL1 subunit of SCF ubiquitin ligase
  • phosphorylating IKBA, JUN, NFKB1
  • involved in numerous cell processes, including regulation of transcription and protein turnover
  • regulating the transcriptional activity of HAND2 in a unique manner that may account, in part, for the apparent ability of this bHLH factor to regulate gene expression through numerous mechanisms
  • important effector that mediates a novel signal transduction pathway for F2RL1-dependent gene expression
  • having a function critical for the proliferation and maintenance of hematopoietic progenitors
  • playing a critical role for cell proliferation/survival and the eventual pathway to control tumorigenesis
  • negative regulator of TP53 and a plausible oncogene
  • implicated in regulating TP53 activity and is overexpressed in various tumors
  • regulates the degradation rate of EDNRA and EDNRB by modulating ubiquitination of these receptors, leading to changes in EDNRA and EDNRB levels
  • promotes degradation of EDNRA by enhancing its ubiquitination
  • multifunctional protein that participates in the control of cell proliferation and the stability of multiple protein
  • essential for efficient DNA repair and mechanistically linked to the maintenance of genome integrity and to cell survival
  • important regulator in cancer development
  • affects RAD51 protein expression through TP53 transcriptional regulation
  • controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle
  • regulates ubiquitin-dependent protein degradation by deneddylation of cullin-based ubiquitin ligases and, therefore, plays a central role in regulating proliferation and apoptosis
  • represses chondrocyte hypertrophy, likely in part by downregulating BMP signaling and RUNX2 activity
  • endothelial COPS5 attenuates NFKB-dependent pro-inflammatory gene expression suggesting that it might serve as a negative regulator of atherogenesis
  • role as a multifunctional cell cycle regulator
  • COPS5 is a RANBP9-interacting protein that robustly increases APP generation
  • COPS5 may play a pathological role in AD
  • positively regulates the basal protein stability of IFN receptor and the IFN response by antagonizing the neddylation pathway (pMID: 24043623)
  • has a positive role in the IFNA-induced cell responses (pMID: 24043623)
  • may constitute a key molecule in the pathogenesis of dysmyelinating neuropathies (pMID: 24344238)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of a signalosome complex GPS1 450kDa including COPS3, COPS4, COPS5/JAB1, COPS6, COPS7A, COPS7B, GPS1, TRIP15
  • subunit of translation initiation factor 3 (EIF3)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • c-Jun (JUN) coactivator, JUND
  • integrin LFA1 to modulate AP-1 actvity
  • AP1
  • binding directly to the HLH domain of HAND2 and increasing HAND2 transcription-stimulating activity
  • interaction between the glucose-regulated destruction domain (GRDD)of TOP2A and MPN domain of CSN5
  • interacting with RNF139 (RNF139-induced growth suppression is COPS5 (and COPS6) dependent)
  • interacting partner of F2RL1
  • interacting with NRBP1 (NRBP1 inhibits COPS5-induced phosphorylation of c-Jun and AP-1 activation)
  • interacting with oncoprotein SMYD3 (suppressed transcription of CDKN2A in cooperation with COPS5)
  • interaction with ZDHHC16 (the zf-DHHC domain and the C-terminal of COPS5 were confirmed to be critical for the interaction)
  • critical regulator of both TP53 and MDM2 (CSN5 expression results in stabilization of MDM2 through reducing MDM2 self-ubiquitination and decelerating turnover rate of MDM2)
  • interacting with S100A7
  • physical association between FAM188A and COPS5 (FAM188A functioning as a novel tumor suppressor by modulating several key G(1)/S-regulatory proteins by interacting with COPS5)
  • is essential for BCL6 expression, a transcriptional repressor required for germinal center formation
  • COPS5 promoted the ubiquitination and proteasome-dependent degradation of BRSK2
  • CUL4B E3 ubiquitin ligase plays a key role in targeting COPS5 for degradation, potentially revealing a previously undocumented mechanism for regulation of the BMP signaling pathway involved with the CUL4B-based E3 complex
  • is a novel binding partner of CREB3 which negatively regulates the activity of Luman by promoting its degradation
  • directly interacts with both CENPT and CENPW and regulates the stability of the inner kinetochore components CENPT and CENPW
  • increases APP generation by stabilizing RANBP9 protein levels
  • is a TYK2 binding partner
  • acts potentially as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway
  • may be involved in the IFNAR1 protein level through CSN deneddylation activity
  • PDLIM7 binding to COPS5 prevents the binding and subsequent degradation of SMAD4, SMAD5, and SMAD7 causing increased accumulation of osteogenic SMADs in cells
  • a COPS5/CTNNB1/SIAH1 interaction network that might control CTNNB1 degradation in colorectal cancer cells
  • cell & other
    REGULATION
    inhibited by MIF
    Other promoting the transport and the degradation of CDKN1B
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in several cancer cells
    tumoral     --over  
    may indicate a poor prognosis for patients with esophageal squamous cell carcinoma
    tumoral     --over  
    in human hepatocellular carcinoma
    constitutional     --over  
    of COPS5 levels in the Alzheimer brain may increase the levels of RANBP9 and, consequently, APP levels
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential target for cancer therapy
    cancerdigestiveliver
    maybe an attractive molecular target for systemic Hepatocellular carcinoma therapy
    neurologyneurodegenerativealzheimer
    lowering COPS5 levels may be an effective therapeutic approach for AD
    ANIMAL & CELL MODELS
    defects in DSB repair in Jab1 gene-targeted embryos contribute to premature cell death in homozygous Jab1 knockout mice