NODAL
Nodal homolog
Also known as: NODAL_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q96S42
- Gene
- NODAL
- Ensembl
- ENSG00000156574
- Chromosome
- 10
- Canonical length
- 347 aa
- Protein class
- Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins
- Secretome location
- Secreted to blood
- Quaternary structure
- Homodimer
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 regulates early embryonic development. This protein is required for maintenance of human embryonic stem cell pluripotency and may play a role in human placental development. Mutations in this gene are associated with heterotaxy, a condition characterized by random orientation of visceral organs with respect to the left-right axis. [provided by RefSeq, Aug 2016]
Canonical amino-acid sequenceUniProt
347 residues, UniProt reviewed canonical sequence.
>Q96S42|NODAL
1 MHAHCLPFLL HAWWALLQAG AATVATALLR TRGQPSSPSP LAYMLSLYRD PLPRADIIRS
61 LQAEDVAVDG QNWTFAFDFS FLSQQEDLAW AELRLQLSSP VDLPTEGSLA IEIFHQPKPD
121 TEQASDSCLE RFQMDLFTVT LSQVTFSLGS MVLEVTRPLS KWLKHPGALE KQMSRVAGEC
181 WPRPPTPPAT NVLLMLYSNL SQEQRQLGGS TLLWEAESSW RAQEGQLSWE WGKRHRRHHL
241 PDRSQLCRKV KFQVDFNLIG WGSWIIYPKQ YNAYRCEGEC PNPVGEEFHP TNHAYIQSLL
301 KRYQPHRVPS TCCAPVKTKP LSMLYVDNGR VLLDHHKDMI VEECGCLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against NODAL 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)
- 0.38
- Highest tissue expression
- 2.6 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 2.6 nTPM
- testis: 1.8 nTPM
- cerebellum: 1.2 nTPM
- retina: 1.2 nTPM
- skin: 0.9 nTPM
- adipose tissue: 0.8 nTPM
Single-cell type
- late spermatids: 60 nCPM
- early spermatids: 25 nCPM
- epicardial cells: 16 nCPM
- myonuclei: 8.8 nCPM
- retinal bipolar cells: 5.5 nCPM
- endometrial glandular cells: 5.2 nCPM
Immune cell
- memory CD8 T-cell: 0.3 nTPM
- neutrophil: 0.2 nTPM
- classical monocyte: 0.1 nTPM
- MAIT T-cell: 0.1 nTPM
- memory CD4 T-cell: 0.1 nTPM
- naive B-cell: 0.1 nTPM
Brain region
- cerebellum: 5.5 nTPM
- medulla oblongata: 2.2 nTPM
- pons: 2.2 nTPM
- amygdala: 2.1 nTPM
- basal ganglia: 2.1 nTPM
- hypothalamus: 2 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about NODAL.
Disease | AllUniProt
Conditions NODAL is implicated in, by any mechanism.
- Heterotaxy, visceral, 5, autosomal (HTX5) MIM:270100
Disease | GeneticClinVar
16 pathogenic / likely-pathogenic of 186 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Heterotaxy, visceral, 5, autosomal
- Visceral heterotaxy
- NODAL-related disorder
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)
- 0.31
- gnomAD pLI
- 0.97
- gnomAD missense Z
- 0.97
- DepMap mean gene effect
- -0.08
- 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
- apoptotic signaling pathway
- brain development
- cell migration involved in gastrulation
- cell population proliferation
- cell surface receptor protein serine/threonine kinase signaling pathway
- determination of left/right asymmetry in lateral mesoderm
- digestive tract morphogenesis
- embryonic cranial skeleton morphogenesis
- embryonic pattern specification
- embryonic placenta development
- embryonic process involved in female pregnancy
- endodermal cell differentiation
- formation of anatomical boundary
- germ cell development
- heart looping
- inhibition of neuroepithelial cell differentiation
- left lung morphogenesis
- liver development
- maternal placenta development
- maternal process involved in parturition
- mesendoderm development
- negative regulation of androgen receptor signaling pathway
- negative regulation of cell development
- negative regulation of chorionic trophoblast cell proliferation
- negative regulation of transcription by RNA polymerase II
- negative regulation of trophoblast cell migration
- neural fold formation
- nodal signaling pathway
- placenta development
- positive regulation of angiogenesis
- positive regulation of cell-cell adhesion
- positive regulation of epithelial cell proliferation
- positive regulation of ERK1 and ERK2 cascade
- positive regulation of SMAD protein signal transduction
- positive regulation of transcription by RNA polymerase II
- positive regulation of vascular endothelial growth factor production
- primitive streak formation
- regulation of gastrulation
- regulation of stem cell population maintenance
- somatic stem cell population maintenance
- transforming growth factor beta receptor signaling pathway
- trophectodermal cellular morphogenesis
- vasculature development
- axial mesodermal cell fate specification
- epiblast cell-extraembryonic ectoderm cell signaling
- floor plate morphogenesis
- polarity specification of proximal/distal axis
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads NODAL as an antibody target. Whether an autoantibody or antibody against NODAL could matter depends on whether native NODAL is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
NODAL is annotated as secreted, so native NODAL 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 NODAL as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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