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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue       Nervous brain limbic system hippocampus

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer reproductive breast might be a specific, robust and reliable target for treatment of cervical cancer

ANIMAL & CELL MODELS