LEFTY2 left-right determination factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LEFTY2provided by HGNC
Official Full Name: left-right determination factor 2provided by HGNC
Primary source: HGNC:HGNC:3122
See related: Ensembl:ENSG00000143768 MIM:601877; AllianceGenome:HGNC:3122
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EBAF; LEFTA; TGFB4; LEFTYA
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. The protein may also play a role in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. This gene is closely linked to both a related family member and a related pseudogene. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]
Expression: Biased expression in endometrium (RPKM 129.5) and ovary (RPKM 10.7) See more
Orthologs: mouse all
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Genomic context

Location:: 1q42.12

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (225936603..225941220, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (225124381..225129000, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (226124303..226128920, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population.
Title: Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population.
Requirements of LEFTY and Nodal overexpression for tumor cell survival under hypoxia in glioblastoma.
Title: Requirements of LEFTY and Nodal overexpression for tumor cell survival under hypoxia in glioblastoma.
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.
The present study demonstrates a novel role of LEFTY2 in up-regulating transcript levels and protein abundance of the Na+ coupled glucose transporter SGLT1, thus stimulating cellular glucose uptake and cellular formation of glycogen in endometrial cancer cells.
Title: LEFTY2/endometrial bleeding-associated factor up-regulates Na+ Coupled Glucose Transporter SGLT1 expression and Glycogen Accumulation in Endometrial Cancer Cells.
In a reaction-diffusion pattern, the effective range of Nodal is 3.5 times narrower than that of Lefty2.
Title: Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty.
functional role of LEFTY during progesterone therapy for endometrial carcinoma
Title: A functional role of LEFTY during progesterone therapy for endometrial carcinoma.
LeftyA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization, cell softening and cell shrinkage.
Title: LeftyA decreases Actin Polymerization and Stiffness in Human Endometrial Cancer Cells.
LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration.
Title: LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion Kinase Activity (FAK) and miRNA-200a.
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.
Lefty A may account for the tumor suppressive activity of human adult stem cells.
Title: Role of Lefty in the anti tumor activity of human adult liver stem cells.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

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
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA 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
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: left-right determination factor 2

Names: TGF-beta-4; endometrial bleeding-associated factor; left-right determination factor A; protein lefty-2; protein lefty-A; 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.

Genomic

NG_008118.1 RefSeqGene

Range

5001..9618

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001172425.3 → NP_001165896.1 left-right determination factor 2 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1. This isoform (2) lacks a portion of the mature peptide compared to isoform 1, but may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AK075344, AK304549, AL117348

Consensus CDS

CCDS53479.1

UniProtKB/Swiss-Prot

O00292

Related

ENSP00000388009.2, ENST00000420304.6

Conserved Domains (2) summary

pfam00019
Location:229 → 319

TGF_beta; Transforming growth factor beta like domain

pfam00688
Location:110 → 180

TGFb_propeptide; TGF-beta propeptide
NM_003240.5 → NP_003231.2 left-right determination factor 2 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_003231.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA922485, AK027520, DA269806

Consensus CDS

CCDS1549.1

UniProtKB/Swiss-Prot

B3KNH4, B4E332, E9PDM4, O00292, O75611, Q5TE89, Q8NBQ9

Related

ENSP00000355785.5, ENST00000366820.10

Conserved Domains (2) summary

pfam00019
Location:263 → 353

TGF_beta; Transforming growth factor beta like domain

pfam00688
Location:106 → 214

TGFb_propeptide; TGF-beta propeptide

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

225936603..225941220 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544266.2 → XP_011542568.1 left-right determination factor 2 isoform X1

Conserved Domains (1) summary

pfam00688
Location:63 → 214

TGFb_propeptide; TGF-beta propeptide