LEFTY2
Left-right determination factor 2
Also known as: EBAF, LEFTA, LEFTYA, LFTY2_HUMAN, TGFB4
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O00292
- Gene
- LEFTY2
- Ensembl
- ENSG00000143768
- Chromosome
- 1
- Canonical length
- 366 aa
- Protein class
- Disease related genes, Predicted secreted proteins
- Secretome location
- Secreted in other tissues
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
366 residues, UniProt reviewed canonical sequence.
>O00292|LEFTY2
1 MWPLWLCWAL WVLPLAGPGA ALTEEQLLGS LLRQLQLSEV PVLDRADMEK LVIPAHVRAQ
61 YVVLLRRSHG DRSRGKRFSQ SFREVAGRFL ASEASTHLLV FGMEQRLPPN SELVQAVLRL
121 FQEPVPKAAL HRHGRLSPRS AQARVTVEWL RVRDDGSNRT SLIDSRLVSV HESGWKAFDV
181 TEAVNFWQQL SRPRQPLLLQ VSVQREHLGP LASGAHKLVR FASQGAPAGL GEPQLELHTL
241 DLRDYGAQGD CDPEAPMTEG TRCCRQEMYI DLQGMKWAKN WVLEPPGFLA YECVGTCQQP
301 PEALAFNWPF LGPRQCIASE TASLPMIVSI KEGGRTRPQV VSLPNMRVQK CSCASDGALV
361 PRRLQPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against LEFTY2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.34
- Highest tissue expression
- 160 nTPM
Expression across tissuesHPA
Tissue
- endometrium: 160 nTPM
- cervix: 89 nTPM
- choroid plexus: 50 nTPM
- ovary: 41 nTPM
- smooth muscle: 35 nTPM
- blood vessel: 20 nTPM
Single-cell type
- endometrial stromal cells: 1.7 nCPM
- leydig cells: 1.6 nCPM
- erythrocytes: 1.5 nCPM
- decidual stromal cells: 1.1 nCPM
- pituicytes/fscs: 1.1 nCPM
- late spermatids: 1 nCPM
Immune cell
- basophil: 0.2 nTPM
- naive CD4 T-cell: 0.1 nTPM
- neutrophil: 0.1 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
Brain region
- choroid plexus: 34 nTPM
- thalamus: 1.6 nTPM
- hippocampal formation: 1.3 nTPM
- hypothalamus: 0.6 nTPM
- white matter: 0.4 nTPM
- basal ganglia: 0.3 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about LEFTY2.
Disease | AllUniProt
Conditions LEFTY2 is implicated in, by any mechanism.
- Left-right axis malformations (LRAM) MIM:601877
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.95
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.58
- DepMap mean gene effect
- 0.07
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads LEFTY2 as an antibody target. Whether an autoantibody or antibody against LEFTY2 could matter depends on whether native LEFTY2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
LEFTY2 is annotated as secreted, so native LEFTY2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label LEFTY2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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