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FLASH GENE
Symbol HLTF contributors: mct/pgu - updated : 14-04-2015
HGNC name helicase-like transcription factor
HGNC id 11099
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Mus musculusFetal
 heart     Mus musculusAdult
Nervousbrain   highly Mus musculusFetal
 brain     Mus musculusAdult
 brainlimbic systemhippocampusdentate gyrus  Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal   Mus musculus
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text late
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two bromodomain motifs
  • seven helicase motifs
  • a DNA dependent ATPase domain
  • a RING motif exclusively shared by saccharomyces RAD16, RAD5, RAD8
  • embedded within a SWI/SNF helicase domain
  • an HIRAN domain, that may have a role in recruiting repair activities to damaged DNA
  • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae SWI/SNF2 general transcriptional activator Rad5
    Homologene
    FAMILY
  • SNF2/Rad54 helicase family
  • SWI/SNF family of chromatin remodeling complex
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • mainly localized inside the nucleus
  • basic FUNCTION
  • involved in the basal expression of PAI1
  • binding the myosin light chain enhancer and likely, many other targets
  • required for error-free postreplication repair of damaged DNA (in keeping with its cancer-suppression role)
  • actin-dependent regulator of chromatin structure
  • promotes PCNA polyubiquitination
  • playing a role in promoting RAD6A/RAD18- and UBE2V2-UE2N-dependent PCNA polyubiquitination (implicates its involvement in promoting error-free postreplication repair through DNA lesions)
  • can facilitate fork regression and has a role in replication of damaged DNA
  • promotes the restart of replication forks blocked at DNA lesions and can promote error-free replication of damaged DNA
  • may be preventing mutagenesis and carcinogenesis
  • modulates basal expression of SERPINE1 involved in regulation of cell migration
  • HLTF and SHPRH suppress mutagenesis in a damage-specific manner
  • HLTF and SHPRH may coordinate the two main branches of postreplication repair to choose the proper bypass mechanism for minimizing mutagenesis
  • exhibits ubiquitin ligase activity for proliferating cell nuclear antigen (PCNA) polyubiquitylation as well as double-stranded DNA translocase activity for remodeling stalled replication fork by fork reversal
  • has an ATP hydrolysis-dependent protein remodeling activity, by which it can remove proteins bound to the replication fork
  • crucial role for SMARCA3 in S100A10-dependent neurogenic and behavioral response to chronic antidepressant administration
  • is involved in a RAD51-independent D-loop branch of template switch pathway that can promote repair of gaps formed during replication of damaged DNA
  • regulates transcription, remodels chromatin, and coordinates DNA damage repair
  • regulates G2/M transition, WT1/GATA4/HIF1A cardiac transcription networks, and collagen biogenesis
  • CELLULAR PROCESS nucleotide, chromatin organization
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • S100A10/ANXA2/HLTF pathway mediates both neurogenic and behavioral responses to selective serotonin reuptake inhibitors (SSRIs)
  • a component
  • component of chromatin remodeling complexes
  • part of USP7-HLTF-PCNA molecular network controlling DNA damage response
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • actin
  • ATP11B
  • CHFR-interacting protein
  • interact with a RING-finger binding protein (RFBP), which is a splice variant of the Type IV P-type ATPase, ATP11B
  • PAXIP1 and RPA1, both involved in DNA replication and DNA repair, are HLTF-interacting proteins although cells depleted of HLTF did not show defects in cellular responses to DNA damage
  • promotes the Lys-63-linked polyubiquitination of proliferating cell nuclear antigen (PCNA) that is required for maintaining genomic stability
  • USP7 is a novel regulator of HLTF stability
  • HLTF, chromatin-remodeling factor, is a target for the S100A10/ANXA2 heterotetrameric complex
  • S100A10/ANXA2 not only increases the DNA-binding affinity of HLTF but also anchors HLTF to the nuclear matrix presumably via the interaction of ANXA2 with actin and PIP2
  • cell & other
  • binding to the HIV long terminal repeat
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    aberrantly tumors regulated in malignant cells
    tumoral        
    in colon cancer by promoter methylation
    tumoral       loss of function
    in colorectal and gastric cancers
    tumoral       loss of function
    by hypermethylation in a significant number of colon, gastric and uterine tumors
    tumoral       loss of function
    promotes the malignant transformation of intestinal or colonic adenomas to carcinomas by inducing genomic instability
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    CHFR-mediated downregulation of HLTF may help protect against cancer
    ANIMAL & CELL MODELS