Lefty1 left right determination factor 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lefty1provided by MGI
Official Full Name: left right determination factor 1provided by MGI
Primary source: MGI:MGI:107405
See related: Ensembl:ENSMUSG00000038793 AllianceGenome:MGI:107405
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; Leftb; Stra3; Tgfb4; lefty; lefty-1
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. Mice lacking a functional copy of this gene exhibit embryonic lethality and defects in left-right patterning. [provided by RefSeq, Aug 2016]
Expression: Broad expression in adrenal adult (RPKM 9.4), colon adult (RPKM 6.0) and 21 other tissues See more
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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 (180762587..180765966)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (180935022..180938401)

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?

Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways.
Title: Lefty1 Ameliorates Post-infarction Fibrosis by Suppressing p-Smad2 and p-ERK1/2 Signaling Pathways.
Lefty-1 inhibits renal epithelial-mesenchymal transition by antagonizing the TGF-beta/Smad signaling pathway.
Title: Lefty-1 inhibits renal epithelial-mesenchymal transition by antagonizing the TGF-β/Smad signaling pathway.
A cell that experiences the highest level of Nodal signaling begins to express Lefty1 and becomes an L1(epi) cell. Deletion of Lefty1 alone or together with Lefty2 increased the number of prospective DVE cells
Title: Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos.
Lefty1 may ameliorate renal tubulointerstitial inflammation by suppressing NFkappaB signaling.
Title: Anti-inflammatory effects of Lefty-1 in renal tubulointerstitial inflammation via regulation of the NF-κB pathway.
results show that TET-mediated oxidation of 5-methylcytosine modulates Lefty-Nodal signalling by promoting demethylation in opposition to methylation by DNMT3A and DNMT3B; findings reveal a fundamental epigenetic mechanism featuring dynamic DNA methylation and demethylation crucial to regulation of key signalling pathways in early body plan formation
Title: TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.
exogenous lefty1 administered to mice restored the endogenous expression levels of lefty1. The present study demonstrated that lefty1 attenuated renal interstitial injury by inhibiting the Smaddependent TGFb1 signaling pathway
Title: Lefty1 alleviates renal tubulointerstitial injury in mice with unilateral ureteral obstruction.
Lefty-1 may prevent TGFB1-induced fibroblast-myofibroblast transdifferentiation in part via modulation of Smad3, JNK-3, and BMP-5 signaling.
Title: Lefty-1 alleviates TGF-β1-induced fibroblast-myofibroblast transdifferentiation in NRK-49F cells.
The expression of lefty in RCC cells was lower than that in adjacent non-tumor cells, which may result in the overexpression of nodal, thereby promoting the growth of RCC.
Title: Nodal activates smad and extracellular signal-regulated kinases 1/2 pathways promoting renal cell carcinoma proliferation.
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.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Variation

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Alleles

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

Targeted (6) 1 citation
Endonuclease-mediated (2)

General gene information

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Markers

NoName (e-PCR)
- UniSTS:234280

AI450052 (e-PCR)
- UniSTS:158899

Z73151 (e-PCR)
- UniSTS:125940

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables nodal binding	IPI Inferred from Physical Interaction more info	PubMed
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
acts_upstream_of_or_within anterior/posterior axis specification	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cell migration involved in gastrulation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in determination of left/right symmetry	IDA Inferred from Direct Assay more info	PubMed
involved_in heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of nodal receptor complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of nodal signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within response to retinoic acid	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: left-right determination factor 1

Names: TGF-beta-4; left-right determination, factor B; protein lefty-1; stimulated by retinoic acid gene 3 protein; transforming growth factor beta-4

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_010094.4 → NP_034224.1 left-right determination factor 1 preproprotein

See identical proteins and their annotated locations for NP_034224.1

Status: REVIEWED

Source sequence(s)

AA216877, AC117673, AK131943

Consensus CDS

CCDS15577.1

UniProtKB/Swiss-Prot

Q3V2A9, Q64280

UniProtKB/TrEMBL

A0A0R5T0P8

Related

ENSMUSP00000041427.9, ENSMUST00000037361.9

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