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FLASH GENE

Symbol

TMEFF2

contributors: mct - updated : 20-12-2011

HGNC name	transmembrane protein with EGF-like and two follistatin-like domains 2
HGNC id	11867

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	at least, three isoforms distinguished by their cytoplasmic domains

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed TMEFF2 - - 1810 - 368 - 2000 10903839 secreted form 1 - - - - - - 1999 10600548 with EGF-like domain secreted form 2 - - - - - - 1999 10600548 without EGF-like domain TMEFF2-S - - 3362 - 175 prostate cancer cells 2006 16439095 truncated after the first four coding exons, eliminating both the EGF-like and the transmembrane domains NM_016192 10 - 1814 - 374 - 2000 10903839

EXPRESSION

Type	restricted

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 intestine small intestine       Nervous brain diencephalon hypothalamus   highly Homo sapiens   brain limbic system hippocampus dentate gyrus highly Homo sapiens Reproductive male system prostate     highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal signal peptide,
	putative extracellular domain with signal peptide,
	two follistatin-like and EGF-like domains,followed by a transmembrane region, including two potential glycosaminoglycan attachment sites
	a cytosolic tail G protein activating motif
	TMEFF2 ectodomain promoting cell growth

HOMOLOGY

interspecies

homolog to murine Tmeff2

Homologene

FAMILY

EGF/neurogulin family of growth factors

CATEGORY

tumor suppressor , signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	type I transmembrane protein
	localization to the membrane but also to the cytoplasm, where it appears in a punctate pattern

basic FUNCTION	potential survival factors for hippocampal and mesencephalic neurons
	silencing of TMEFF2 by methylation increase probability of neoplastic transformation
	androgen-regulated gene exhibiting antiproliferative effects in prostate cancer cells
	having tumor suppressive and pro-apoptotic activity (
	its tumor suppressor activity requires the cytoplasmic/transmembrane portion of the protein and correlates with its ability to bind to SARDH and to modulate the level of sarcosine
	modulates SARDH activity to promote changes in cell growth and/or invasion
	TMEFF1 and TMEFF2 could be playing similar roles in different tissues and/or developmental stages
	can function to regulate PDGF signaling and is hypermethylated and downregulated in glioma and several other cancers, thereby suggesting an important role for this protein in the etiology of cancers

CELLULAR PROCESS	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

text	antiapoptosis for hippocampal including dopaminergic mesencephalic neurons

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	activation of the STAT1 pathway likely represents the principal mediator of its tumor suppressive properties (
	interaction of SARDH with TMEFF2
	interacts with PDGFA through its extracellular domain

cell & other

REGULATION

Other

regulated by androgens

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by hypermethylation in sporadic colorectal and bladder cancer and in ulcerative colitis associated colorectal carcinoma tumoral     --over   in androgen-dependent prostate cancer tumoral     --low   in brain cancers and is negatively correlated with PDGFA expression tumoral     --low   silencing by methylation in esophageal squamous cell carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	methylated SFRP2 and TMEFF2 detected in 94.2 p100, and 71.2 p100 of colorecal cancer (CRC), and methylation testing of fecal DNA may be a simple and promising non-invasive screening method for CRC and precancerous lesions
Therapy target	immunotherapeutic target for the treatment of prostate cancer

ANIMAL & CELL MODELS