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FLASH GENE
Symbol PACS2 contributors: mct/pgu - updated : 12-06-2018
HGNC name phosphofurin acidic cluster sorting protein 2
HGNC id 23794
Corresponding disease
EIEE66 epileptic encephalopathy, early infantile, 66
Location 14q32.33      Physical location : 105.781.080 - 105.864.484
Synonym name
  • phosphofurin acidic cluster sorting protein 1-like
  • PACS1-like protein
  • Synonym symbol(s) PACS1L, KIAA0602, FLJ25488, PACS-2
    DNA
    TYPE functioning gene
    STRUCTURE 97.43 kb     24 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 6332 98 893 - 2005 15692567
  • isoform 1
  • 24 - 6667 97.6 889 - 2005 15692567
    24 - 6189 - 814 - 2005 15692567
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrinepancreas   highly
    Nervousbrain     Homo sapiensFetal
     spinal cord   highly Homo sapiens
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    Nervouscentralwhite matter  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a cargo(furin)-binding region (FBR) that bind cargo proteins, sorting adaptors, and cellular kinase
  • HOMOLOGY
    interspecies ortholog to murine Pacs1l
    intraspecies paralog to PACS1
    Homologene
    FAMILY
  • PACS family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text mainly localized at the ER
    basic FUNCTION
  • multifunctional sorting protein indirectly controlling juxtaposition of the organelles through BCAP31-dependent fission and perinuclear clustering of mitochondria
  • cytosolic sorting protein, integrating ER-mitochondria communication, ER homeostasis, and apoptosis and controling the apposition of mitochondria with the ER
  • through its functions, is an important regulator of apoptosis onset
  • regulates GGA3 binding to cargo
  • is required for localizing polycystin-2 to the ER
  • TRAIL effector required for killing virally infected hepatocytes
  • endocytic sorting pathway involved in HIV-1 immunoevasion
  • ER trafficking machinery is pirated by KSHV
  • in the nucleus, PACS2 controls the SIRT1-TP53 axis to promote cell cycle arrest following DNA damage response by directly inhibiting SIRT1-dependent deacetylation of TP53, and in the cytoplasm, regulates endoplasmic reticulum (ER) homeostasis, ER-mitochondria communication, autophagy, and endosomal trafficking of ion channels, receptors, and enzymes
  • PACS2 is an in vivo mediator of the SIRT1-TP53-CDKN1A axis that modulates the DNA damage response
  • role for PACS2 selectively in NFKB1 activation in response to DNA damage
  • multifunctional sorting protein involved in nuclear gene expression and pathway traffic regulation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with calnexin (distributes calnexin between the rough ER, the MAM, mitochondria-associated membrane, and the plasma membrane)
  • binding cargo proteins, adaptors and signalling molecules
  • interaction of HIV1 Nef with the sorting proteins PACS1 and PACS2 mediates key signaling and trafficking steps required for Nef-mediated MHC-I down-regulation
  • TNFSF10 -induced lysosomal membrane permeabilization is mediated by the multifunctional sorting protein PACS2 and repressed by the E3 ligases BIRC2 and BIRC3
  • BIRC2, BIRC3 constitutively downregulate PACS2 by polyubiquitination and proteasomal degradation, thereby restraining TNFSF10-induced killing of liver cancer cells
  • PACS2 regulates SIRT1-mediated deacetylation of TP53 to modulate the DNA damage response
  • PACS2 is a regulator of ADAM17 trafficking and ErbB signalling
  • is a mediator of the ATM and NFkB1-dependent induction of BCL2L1 that promotes cell survival in response to DNA damage
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEE66
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    frequently deleted in sporadic cases of colorectal cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Pacs-2(-/-) thymocytes exhibit a blunted induction of Bcl2l1, increased mitochondrial outer membrane permeabilization (MOMP) and accelerated apoptosis
  • Pacs2-deficient mice display significantly reduced levels of phosphorylated EGFR and intestinal proliferation