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

    Gene ID: 320202, updated on 11-Apr-2024

    Summary

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    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

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    See Lefty2 in Genome Data Viewer
    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_000067.7Genomic Context describing neighboring genes Neighboring gene CapStarr-seq enhancer MGSCv37_chr1:182805483-182805670 Neighboring gene predicted gene, 18036 Neighboring gene predicted gene, 39714 Neighboring gene CapStarr-seq enhancer MGSCv37_chr1:182814007-182814116 Neighboring gene STARR-seq mESC enhancer starr_03220 Neighboring gene STARR-positive B cell enhancer ABC_E2592 Neighboring gene STARR-positive B cell enhancer mm9_chr1:182834193-182834494 Neighboring gene pyrroline-5-carboxylate reductase family, member 2 Neighboring gene predicted gene, 32199

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca(2+) entry. Salker MS, et al. J Mol Med (Berl), 2018 Feb. PMID 29230527, Free PMC Article
    2. Lefty1 and lefty2 control the balance between self-renewal and pluripotent differentiation of mouse embryonic stem cells. Kim DK, et al. Stem Cells Dev, 2014 Mar 1. PMID 24147624, Free PMC Article
    3. LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-β1/Smad3 pathway. Yang YR, et al. Mol Immunol, 2020 Oct. PMID 32745796
    4. TGFβ signaling in establishing left-right asymmetry. Shiratori H, et al. Semin Cell Dev Biol, 2014 Aug. PMID 24704359
    5. Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. Nakamura T, et al. Dev Cell, 2006 Oct. PMID 17011489

    See all (163) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    Submit: New GeneRIF Correction

    Variation

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    Alleles

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

    Pathways from PubChem

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    General gene information

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    Markers

    Homology

    Clone Names

    • MGC98569

    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 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 multicellular organism development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 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)

    1. 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

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000067.7 Reference GRCm39 C57BL/6J

      Range
      180720673..180726672
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P57785.2 GenPept UniProtKB/Swiss-Prot:P57785

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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