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FLASH GENE

Symbol

SPDEF

contributors: mct/npt/pgu - updated : 01-12-2015

HGNC name	SAM pointed domain containing ets transcription factor
HGNC id	17257

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two putative PEST sequences : one near the N terminus and the other at the center of the protein
	a central pointed domain, which is characteristic of some ETS family members
	an ETS DNA-binding domain

mono polymer

complex

HOMOLOGY

interspecies

ortholog to murine Spdef (88.3pc)

Homologene

FAMILY

ETS (epithelial-specific E26 transforming sequence) family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	androgen independent transcriptional activator of the PSA promoter
	regulator of prostate gland or prostate cancer development
	acting as a transcriptional activator for SERPINB5 promoter
	critical regulator of genes involved in cell motility, invasion, and adhesion of prostate cancer cells
	in multiple invasive breast cancer cells, its expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization
	regulates goblet cell hyperplasia in the airway epithelium
	important role in regulating intestinal epithelial cell homeostasis and differentiation, and regulates terminal differentiation and maturation of intestinal goblet cells
	is potentially a negative regulator of tumor progression by modulating the expression of growth and migration promoting genes
	required for mucous gland cell function in the gastric antrum
	plays a critical role in regulating a transcriptional network mediating IL13-induced MUC5AC synthesis dependent on STAT6
	negative regulator of tumor progression and metastasis
	plays a significant role in tumorigenesis in prostate, breast, colon, and ovarian cancer, and functions as a tumor metastasis suppressor

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to 5'-GGAT- 3' DNA sequences

RNA

small molecule

protein	the DNA-binding domain of the androgen receptor
	NKX3-1
	STMN1 is downregulated by PDEF, suggesting that PDEF may inhibit prostate cancer progression by transcriptional downregulation of oncogenic STMN expression
	involved in G2/M transition and degradation of several transcription factors, CDK11A directly interacts with and phosphorylates SPDEF on serine residues, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway
	GADD45A and GADD45G, directly interact with CDK11A and thereby inhibit CDK11A activity, and consequentially SPDEF phosphorylation and degradation, ultimately reducing prostate cancer cell migration and invasion

cell & other

REGULATION

induced by

by interleukin (IL13)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in prostate cancer and in metastatic breast cancer in axillary lymph node tumoral     --low   leads to a morphologic change, increased migration and invasiveness in prostate cancer cells, reminiscent of transforming growth factor beta (TGFbeta) function and epithelial-to-mesenchymal transition tumoral     --over   prostate tumor cells where it regulates prostate-specific antigen gene expression and is an androgen receptor co-regulator

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	up-regulation is associated with a favorable prognosis in patients with clinically localized prostate cancer
Therapy target
	System Type Disorder Pubmed neurosensorial ear   ATOH1 and SPDEF could be the therapeutic targets for otitis media associated with mucous cell metaplasia which is frequently considered "intractable" in the clinical settings

ANIMAL & CELL MODELS