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FLASH GENE
Symbol STAG2 contributors: mct - updated : 13-06-2018
HGNC name stromal antigen 2
HGNC id 11355
DNA
TYPE functioning gene
STRUCTURE 142.10 kb     34 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
35 - 6277 145.8 1268 - 2002 12034751
35 - 6186 145.8 1268 - 2002 12034751
34 - 6075 141.3 1231 - 2002 12034751
33 - 6010 141.3 1231 - 2002 12034751
34 - 6054 - 1231 - 2002 12034751
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Nervousbrain    
Reproductivemale systemprostate   
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
one SCD (stromalin conservative) domain.
HOMOLOGY
Homologene
FAMILY SCC3 family
CATEGORY DNA associated
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm,cytosolic
intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
intracellular,nucleus,nucleoplasm
intracellular,nucleus,chromatin/chromosome,nucleosome
basic FUNCTION
  • complex required for the cohesion of sister chromatids after DNA replication
  • may also play a role in spindle pole assembly during mitosis
  • able to enhance the activity of the tumor necrosis factor alpha, the CD69, and the human immunodeficiency virus long terminal repeat promoters in a NF-kappaB-dependent manner
  • role for STAG/Scc3 in transcriptional regulation
  • its phosphorylation is essential for cohesin dissociation during prophase and prometaphase, but is not required for cohesin cleavage by separase
  • maintaining sister chromatid cohesion during the diplotene stage of meiosis
  • cohesin(STAG1) and cohesin(STAG2) are differentially required for telomere and centromere cohesion, respectively
  • component of the cohesin complex identified as a candidate gene that could participate in XCI through its association with CTCF
  • regulates the separation of sister chromatids during cell division
  • likely to function as a “caretaker” tumor suppressor gene that when inactivated results in chromosomal instability, similar to other caretaker genes like MLH1 and MSH2 that, when inactivated, result in nucleotide instability
  • STAG2, RAD21, SMC1A, SMC3 mutations participate in leukemogenesis through the deregulated expression of genes that are involved in myeloid development and differentiation
  • STAG1 and STAG2 participate in the DNA damage response, coordinately protecting genome integrity in human cells through unique ways
  • STAG2 promotes the correction of kinetochore-microtubule (kMT) attachment errors to ensure faithful chromosome segregation during mitosis
  • is a dosage-sensitive gene and heterozygous loss-of-function variants lead to a cohesinopathy
  • STAG1 and STAG2 share high sequence identity, encode mutually exclusive cohesin subunits and retain partially overlapping functions
  • cohesin ring is a protein complex composed of four core subunits: SMC1A, SMC3, RAD21 and STAG1/STAG2 and is involved in chromosome segregation, DNA repair, chromatin organization and transcription regulation
  • STAG1 is required for telomere cohesion and STAG2 for centromere cohesion
  • STAG2 functions likely at intermediate DNA structures during DNA transactions in genome maintenance pathways
  • predominantly functions in sister chromatid cohesion and segregation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with RAD21 in several stages of meiosis
  • subunit of the cohesin complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the viral transactivator TAT and enhances the TAT-mediated activation of the human immunodeficiency virus long terminal repeat promoter
  • critical target of PLK1 in the cohesin dissociation pathway
  • interacting with SSU72 (a RAD21-binding protein that directly interacts with RAD21 and STAG2)
  • interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit STAG2 and specific regions of the C-terminal tail of CTCF
  • STAG2 is the main complex corecruited with the cohesin-loading factor NIPBL to DNA damage sites in an S/G(2)-phase-specific manner
  • SGO1 binds directly to STAG2 and further shields cohesin from WAPL, protecting sister-chromatid cohesion during mitosis, particularly at centromeres
  • STAG1 preferentially contributes to the stabilization of topologically associating domain boundaries together with CTCF, whereas STAG2 promotes cell-type-specific contacts between enhancers and promoters independently of CTCF
  • cell & other
    REGULATION
    Other regulated by SSU72 (may be involved in the dephosphorylation or hypophosphorylation of STAG2)
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,nucleosome
    basic FUNCTION
  • may be playing a role in spindle pole assembly during mitosis
  • complex required for the cohesion of sister chromatids after DNA replication
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    Other regulated by SSU72 (may be involved in the dephosphorylation or hypophosphorylation of STAG2)
    ASSOCIATED DISORDERS
    corresponding disease(s) SRXID
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    in STAG2-depleted cells telomere cohesion is normal, but centromere cohesion is prematurely lost
    tumoral somatic mutation      
    in myelodysplastic syndromes, chronic myelogenous leukemia , chronic myelomonocytic leukemia and acute myeloid leukemia
    constitutional germinal mutation     loss of function
    in a syndrome with developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features
    constitutional        
    STAG2 silencing in normal human cells that lack telomerase led to increased recombination at telomeres, delayed telomere shortening, and postponed senescence onset
    tumoral     --other  
    abnormal expression of STAG2 could cause aneuploidy in normal bladder cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS