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FLASH GENE

Symbol

LEFTY2

contributors: mct/npt - updated : 25-05-2010

HGNC name	left-right determination factor 2
HGNC id	3122

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HTX9 abnormal left-right axis with visceral heterotaxy (situs ambiguus), 9
Location	1q42.12      Physical location : 226.124.297 - 226.129.083
Synonym name	transforming growth factor, beta 4
	endometrial bleeding associated factor (left-right determination, factor A; transforming growth factor beta superfamily)
	protein lefty-A
	protein lefty-2
Synonym symbol(s)	EBAF, TGFB4, LEFTYA, LEFTA

DNA

TYPE	functioning gene
STRUCTURE	4.62 kb     4 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003240 4 - 2187 NP_003231 - 366 - Kosaki (1999) NM_001172425 - - 2085 NP_001165896 - 332 - Kosaki (1999)

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 Reproductive female system uterus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining endometrium

cell lineage
cell lines	adenocarcinomas that exhibited a mucinous differentiation including colonic, duodenal, and ovarian adenocarcinomas
fluid/secretion

at STAGE

physiological period

embryo, fetal, pregnancy

Text	transiently expressed before and during menstrual bleeding
	the left side of the embryo, more strongly in the floor plate and notochord than in the lateral mesoderm
	seemed to be exclusively expressed by a certain population of cells in the early human embryoid bodies that does not overlap with the population expressing the ESC marker OCT4 (Dvash 2007)

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N-terminal signal peptide
	a TGFB4 sequence
	two cleavage sites

conjugated

GlycoP

isoforms

Precursor

HOMOLOGY

interspecies

homolog to murine Lefty2

Homologene

FAMILY

TGF-beta family of growth factors

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION
text	is secreted and released into body fluids

basic FUNCTION	playing a role with LEFTYB, NODAL and PITX2 in left-right asymmetry determination of organ systems during development
	may also play a role in endometrial bleeding
	antagonizing NODAL
	its expression controlled by NODAL appears to have a substantial role in mesodermal origin cell population establishment, since inhibition of NODAL activity downregulated expression not only of LEFTY1 and LEFTY2 but also of BRACHYURY, an early mesodermal marker (Dvash 2007)
	regulating endometrial MMP9
	acts as a molecular switch that modulates both the induction of decidual differentiation and the maintenance of a decidualized state (Tang 2010)

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein

cell & other

REGULATION

activated by

transcription factor SMAD2/3

inhibited by

progesterone

Other

high expression requires activin-linked kinases (ALK) 4, 5 and 7

ASSOCIATED DISORDERS

corresponding disease(s)

HTX9

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs constitutional         some types of infertility are associated with a dysregulated expression of the gene in the endometrium

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

lefty 1-/- mutant mice have bilateral expression of Nodal and left isomerism