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FLASH GENE
Symbol SHFM1 contributors: mct - updated : 26-10-2016
HGNC name split hand/foot malformation (ectrodactyly) type 1
HGNC id 10845
Corresponding disease
DEL7Q21 chromosome 7q21 interstitial deletion
SHFM1 split hand and foot malformation 1
Location 7q21.3      Physical location : 96.318.080 - 96.339.203
Synonym name
  • candidate for split hand/foot malformation type 1
  • deleted in split-hand/split-foot 1 region
  • 26S proteasome complex subunit DSS1
    • Synonym symbol(s) ECD, DSS1, SEM1, SHFD1, SHSF1, FLJ42280, Shfdg1
    DNA
    TYPE functioning gene
    STRUCTURE 21.12 kb     3 Exon(s)
    regulatory sequence Binding site
    text structure
  • TP63 binds to an enhancer element in the SHFM1 locus and this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 509 - 70 - 1994 7987313
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue   
    Nervousbrainlimbic systemhippocampus  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text limb bud, craniofacial primordia and skin
    IMPRINTING maternally
    text maternally imprinted in osteoblasts
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • an PSMD3-interacting motif (R3IM), located at AAs 15 to 21 of the N-terminus, sufficient to replace the ability of SHFM1 to pull down proteasome complexes and protein substrates with high-molecular mass ubiquitin conjugates
    • HOMOLOGY
    interspecies homolog to yeast S.cerevisiae sem2
    homolog to murine Dss1
    Homologene
    FAMILY
  • DSS1/SEM1 family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION
    basic FUNCTION
  • may play a role in the completion of the cell cycle
  • novel subunit of the 26S proteasome and playing a role in ubiquitin-dependent proteolysis
  • required for DNA damage-induced RAD51 focus formation and for the maintenance of genomic stability
  • required for the stability of BRCA2
  • through R3IM motif, in conjunction with the complexes of 19S RP and 20S core particle (CP), regulates proteasome interaction through RPN3/S3 molecule, and utilizes a specific subset of poly-ubiquitinated TP53 as a substrate
  • plays an important role in the regulation of gene transcription and cell proliferation and may be involved in the maintenance of genomic integrity
  • is necessary to rescue cells from DNA damage, but high SHFM1 expression increases drug resistance
  • is a small acidic intrinsically disordered protein (IDP) that can fold upon binding with PCID2 TREX-2
  • by targeting RPA1 and mimicking DNA, SHFM1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression
    • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the C-terminal of BRCA2 and RAD51 (may be required for the BRCA2-RAD51 complex to become associated with sites of DNA damage)
  • mammalian SHFM1 makes a critical contribution to the function of BRCA2 in mediating HRR, and hence to genomic stability
  • is required for BRCA2 stability and function, making a critical contribution to the BRCA2 function in mediating homologous recombination
  • plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them
  • BRCA2 repair factor, which binds to SHFM1, also associates with PCID2 in the cell
  • binding to PCID2 with its hydrophobic core of seven AAs favorable to the binding of PCID2
  • acts as a DNA mimic to attenuate the affinity of RPA1 for ssDNA
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SHFM1 , DEL7Q21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    syndromic ectrodactyly (see SHFD1)
    tumoral   deletion   loss of function
    in breast and ovarian cancer
    tumoral     --over  
    in breast cancers with worse prognosis and shorter relapse-free survival times
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • its expression expression could be a useful marker for drug resistance in breast cancers
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    might be a specific, robust and reliable target for treatment of cervical cancer
    ANIMAL & CELL MODELS