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FLASH GENE
Symbol SMARCAL1 contributors: mct/pgu - updated : 30-03-2017
HGNC name SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1
HGNC id 11102
Corresponding disease
SIOD Schimke immunoosseous dysplasia
Location 2q35      Physical location : 217.277.136 - 217.347.772
Synonym name
  • hepA related protein
  • SMARCA-like protein 1
  • sucrose nonfermenting protein 2-like 1
  • Synonym symbol(s) HHARP, HARP
    EC.number 3.6.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 70.64 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3281 - 954 - 2000 10857751
    18 - 3095 - 954 - 2000 10857751
  • differs in the 5'UTR, compared to the other variant
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemtestis  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    not specificchondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal RPA1-binding motif, which is necessary and sufficient for the binding of SMARCAL1 to RPA1
  • two conserved HARP domains, (2HP) domain that dictates the annealing helicase activity
  • one helicase ATP-binding domain
  • one helicase C-terminal domain
  • HOMOLOGY
    interspecies ortholog to C.elegans CE-HARP
    homolog to E.coli RNA polymerase-binding protein HepA
    homolog to murine (syntenic chromosome 1)
    ortholog to drosophila Marcal1
    intraspecies homolog to SF2 and SNF2 helicases
    Homologene
    FAMILY
  • SNF2/RAD54 helicase family
  • SWI2/SNF2 protein family
  • annealing helicase, ATP-driven DNA-rewinding motor proteins family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • localize to transcriptionally active chromatin, modulate gene expression and have epistatic interactions with transcription factors
  • basic FUNCTION
  • actin-dependent regulator of chromatin structure (chromatin remodelling enzyme)
  • having a cell autonomous function
  • may be regulating cellular proliferation
  • playing a regulatory role in the proliferation of chondrocytes, lymphocytes and spermatozoa, as well as in the development or maintenance of cardiomyocytes and in vascular homoeostasis
  • replication stress response protein that maintains genome integrity at stalled replication forks
  • ATP-dependent annealing helicase activity toward RPA-unwound DNA
  • may be involved in the vicinity of ssDNA regions for the regeneration of dsDNA
  • may stabilize stalled replication forks during cell proliferation
  • DNA damage-binding protein involved in replication fork stabilization
  • important role in DNA structure and dynamics
  • has ATP-dependent annealing helicase activity, which helps to stabilize stalled replication forks and facilitate DNA repair during replication
  • SMARCAL1 annealing helicase buffers fluctuations in gene expression and alterations in gene expression contribute to the penetrance of SIOD
  • at both the molecular and genetic levels, SMARCAL1 plays a role in modulating gene expression
  • maintains the duplex status of DSBs to ensure proper recruitment of NHEJ factors to DSB sites
  • maintains telomere integrity during DNA replication
  • endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes
  • stabilizes replication forks during DNA damage
  • replication stress response protein SMARCAL1 is a critical regulator of alternative lengthening of telomeres (ALT) activity
  • functions to limit DNA damage during replication of difficult-to-replicate telomere sequences
  • stabilizes DNA replication forks and prevents replication fork collapse, a cause of DNA breaks and apoptosis
  • DNA annealing helicase with roles in DNA replication fork restart, DNA repair, and gene expression modulation
  • CELLULAR PROCESS nucleotide, repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component component of the DNA damage response
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • interacting with RPA32
  • binding domain A of RPA1 and thus is recruited to stalled replication forks
  • phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity
  • SMARCAL1 negatively regulates MYC transcription by altering the conformation of its promoter region during differentiation
  • SMARCAL1 associates with ALT telomeres to resolve replication stress and ensure telomere stability
  • SMARCA4 and SMARCAL1, both members of the ATP-dependent chromatin remodeling protein family, regulate each other (SMARCA4 binds to the SMARCAL1 promoter, while SMARCAL1 binds to the SMARCA4 promoter)
  • cell & other
    REGULATION
    Phosphorylated by ATR (ATR phosphorylates SMARCAL1 on S652, thereby limiting its fork regression activities and preventing aberrant fork processing)
    Other phosphorylated by ATM, ATR or PRKDC in response to replication-associated DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s) SIOD
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • significant inhibition of lymphomagenesis in mice lacking one or both alleles of Smarcal1