Lefty2 left-right determination factor 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lefty2provided by MGI
Official Full Name: left-right determination factor 2provided by MGI
Primary source: MGI:MGI:2443573
See related: Ensembl:ENSMUSG00000066652 AllianceGenome:MGI:2443573
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Ebaf; Lefta; Leftb; lefty-2; lefty-B; 6030463A22Rik
Summary: This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in left-right asymmetry determination of organ systems during development. This protein is also important in self-renewal and differentiation of mouse embryonic stem cells. Mice lacking a functional copy of this gene exhibit defects in axial and left-right patterning. [provided by RefSeq, Aug 2016]
Expression: Broad expression in CNS E18 (RPKM 1.4), adrenal adult (RPKM 1.0) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 1 H4; 1 84.46 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (180720673..180726672)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (180893108..180899107)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-beta1/Smad3 pathway.
Title: LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-β1/Smad3 pathway.
Endometrial receptivity is negatively regulated by LEFTY2. LEFTY2 inhibits the expression of key murine receptivity genes. LEFTY2 downregulates the expression of Orai1 and inhibits SOCE. LEFTY2 and the Orai1 blockers 2-APB, MRS-1845, and YM-58483 inhibit COX2, BMP2, and WNT4 expression in endometrial cells. Targeting LEFTY2 and Orai1 may represent a novel approach for treating unexplained infertility.
Title: LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca(2+) entry.
LEFTY2 regulates the expression and activity of ENaC in endometrial epithelial cells via SGK1.
Title: LEFTYA Activates the Epithelial Na+ Channel (ENaC) in Endometrial Cells via Serum and Glucocorticoid Inducible Kinase SGK1.
Results indicate that microRNA miR-127 accelerates mesendoderm differentiation of embryonic stem cells through nodal signaling by targeting left-right determination factor 2 (Lefty2).
Title: MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2.
Studies indicate that the pair of Nodal and Lefty (Lefty1 and Lefty2) has a conserved role in left-right asymmetry.
Title: TGFβ signaling in establishing left-right asymmetry.
Taken together, these results suggest that optimal expression of Lefty1 and Lefty2 is critical for the balanced differentiation of mESCs into three germ layers.
Title: Lefty1 and lefty2 control the balance between self-renewal and pluripotent differentiation of mouse embryonic stem cells.
ectopic expression of the Nodal inhibitor Lefty2 in the node of Nodal(neo/+) embryos resulted in a phenotype similar to that of the Nodal(neo/neo) mutant
Title: Left-right patterning of the mouse lateral plate requires nodal produced in the node.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (2) 1 citation

General gene information

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Markers

AV214969 (e-PCR)
- UniSTS:165126

Lefty2 (e-PCR), detects polymorphism
- UniSTS:532677

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables transforming growth factor beta receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in anterior/posterior axis specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: left-right determination factor 2

Names: endometrial bleeding associated factor; left-right determination factor B; left-right determination, factor A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_177099.4 → NP_796073.1 left-right determination factor 2 preproprotein

See identical proteins and their annotated locations for NP_796073.1

Status: REVIEWED

Source sequence(s)

AK031621, BE994648

Consensus CDS

CCDS15575.1

UniProtKB/Swiss-Prot

P57785, Q8BMF7

UniProtKB/TrEMBL

A0A0R5T0P8

Related

ENSMUSP00000082952.6, ENSMUST00000085797.6

Conserved Domains (2) summary

pfam00019
Location:263 → 355

TGF_beta; Transforming growth factor beta like domain

pfam00688
Location:106 → 211

TGFb_propeptide; TGF-beta propeptide