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Q96S42 (NODAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nodal homolog
Gene names
Name:NODAL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length347 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Essential for mesoderm formation and axial patterning during embryonic development By similarity.

Subunit structure

Homodimer; disulfide-linked By similarity.

Subcellular location

Secreted By similarity.

Involvement in disease

Heterotaxy, visceral, 5, autosomal (HTX5) [MIM:270100]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. HTX5 clinical features include situs inversus viscerum or situs ambiguus, congenital heart defect, transposition of the great vessels ventricular septal defect, atrial septal defect, truncus communis, and dextrocardia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.6

Sequence similarities

Belongs to the TGF-beta family.

Ontologies

Keywords
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Heterotaxy
   DomainSignal
   Molecular functionCytokine
Developmental protein
Growth factor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSMAD protein signal transduction

Inferred from electronic annotation. Source: Ensembl

axial mesodermal cell fate specification

Inferred from electronic annotation. Source: Ensembl

brain development

Inferred from electronic annotation. Source: Ensembl

cell migration involved in gastrulation

Inferred from electronic annotation. Source: Ensembl

digestive tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic cranial skeleton morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryonic pattern specification

Inferred from electronic annotation. Source: Ensembl

embryonic placenta development

Inferred from electronic annotation. Source: Ensembl

embryonic process involved in female pregnancy

Inferred from electronic annotation. Source: Ensembl

endodermal cell differentiation

Inferred from mutant phenotype PubMed 21741376. Source: BHF-UCL

epiblast cell-extraembryonic ectoderm cell signaling involved in anterior/posterior axis specification

Inferred from electronic annotation. Source: Ensembl

floor plate morphogenesis

Inferred from electronic annotation. Source: Ensembl

formation of anatomical boundary

Inferred from electronic annotation. Source: Ensembl

growth

Inferred from electronic annotation. Source: InterPro

heart looping

Inferred from electronic annotation. Source: Ensembl

inhibition of neuroepithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

left lung morphogenesis

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

maternal placenta development

Inferred from electronic annotation. Source: Ensembl

maternal process involved in parturition

Inferred from electronic annotation. Source: Ensembl

mesendoderm development

Inferred from mutant phenotype PubMed 21741376. Source: BHF-UCL

negative regulation of androgen receptor signaling pathway

Inferred from direct assay PubMed 21656830. Source: BHF-UCL

negative regulation of chorionic trophoblast cell proliferation

Inferred from direct assay PubMed 15150278. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

negative regulation of trophoblast cell migration

Inferred from direct assay PubMed 21356369. Source: BHF-UCL

neural fold formation

Inferred from electronic annotation. Source: Ensembl

nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Inferred from electronic annotation. Source: Ensembl

placenta development

Inferred from mutant phenotype PubMed 21356369. Source: BHF-UCL

polarity specification of proximal/distal axis

Inferred from electronic annotation. Source: Ensembl

positive regulation of ERK1 and ERK2 cascade

Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL

positive regulation of SMAD protein import into nucleus

Inferred from mutant phenotype PubMed 21741376. Source: BHF-UCL

positive regulation of activin receptor signaling pathway

Inferred from genetic interaction PubMed 15150278. Source: BHF-UCL

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL

positive regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL

positive regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 15150278. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from direct assay PubMed 21656830. Source: BHF-UCL

positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from mutant phenotype PubMed 21741376. Source: BHF-UCL

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation vascular endothelial growth factor production

Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL

regulation of gastrulation

Inferred from electronic annotation. Source: Ensembl

regulation of stem cell maintenance

Traceable author statement PubMed 21630377. Source: BHF-UCL

stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

transforming growth factor beta receptor signaling pathway involved in primitive streak formation

Inferred from electronic annotation. Source: Ensembl

trophectodermal cellular morphogenesis

Inferred from electronic annotation. Source: Ensembl

vasculature development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular space

Inferred from direct assay PubMed 21656830. Source: BHF-UCL

   Molecular_functionmorphogen activity

Non-traceable author statement PubMed 21159651. Source: BHF-UCL

type I activin receptor binding

Inferred from mutant phenotype PubMed 21356369. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Propeptide27 – 237211 Potential
PRO_0000033998
Chain238 – 347110Nodal homolog
PRO_0000033999

Amino acid modifications

Glycosylation721N-linked (GlcNAc...) Potential
Glycosylation1991N-linked (GlcNAc...) Potential
Disulfide bond247 ↔ 313 By similarity
Disulfide bond276 ↔ 344 By similarity
Disulfide bond280 ↔ 346 By similarity
Disulfide bond312Interchain By similarity

Natural variations

Natural variant1651H → R. Ref.1
Corresponds to variant rs1904589 [ dbSNP | Ensembl ].
VAR_038193
Natural variant1831R → Q in HTX5. Ref.4
Corresponds to variant rs104894169 [ dbSNP | Ensembl ].
VAR_015111
Natural variant2031E → K in HTX5; decrease in signal transduction. Ref.6
Corresponds to variant rs10999334 [ dbSNP | Ensembl ].
VAR_038194
Natural variant2601G → R in HTX5; decrease in signal transduction. Ref.6
VAR_062281
Natural variant2751R → C in HTX5; decrease in signal transduction. Ref.6
VAR_062282
Natural variant2791E → K in a colorectal cancer sample; somatic mutation. Ref.5
VAR_036202
Natural variant2841V → F in HTX5; decrease in signal transduction. Ref.6
VAR_062283

Secondary structure

................ 347
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q96S42 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 0D52352B9711650C

FASTA34739,561
        10         20         30         40         50         60 
MHAHCLPFLL HAWWALLQAG AATVATALLR TRGQPSSPSP LAYMLSLYRD PLPRADIIRS 

        70         80         90        100        110        120 
LQAEDVAVDG QNWTFAFDFS FLSQQEDLAW AELRLQLSSP VDLPTEGSLA IEIFHQPKPD 

       130        140        150        160        170        180 
TEQASDSCLE RFQMDLFTVT LSQVTFSLGS MVLEVTRPLS KWLKHPGALE KQMSRVAGEC 

       190        200        210        220        230        240 
WPRPPTPPAT NVLLMLYSNL SQEQRQLGGS TLLWEAESSW RAQEGQLSWE WGKRHRRHHL 

       250        260        270        280        290        300 
PDRSQLCRKV KFQVDFNLIG WGSWIIYPKQ YNAYRCEGEC PNPVGEEFHP TNHAYIQSLL 

       310        320        330        340 
KRYQPHRVPS TCCAPVKTKP LSMLYVDNGR VLLDHHKDMI VEECGCL 

« Hide

References

« Hide 'large scale' references
[1]"Human Nodal-related gene."
Tate Genshu T.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-165.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain cortex and Fetal brain.
[4]"X-linked situs abnormalities result from mutations in ZIC3."
Gebbia M., Ferrero G.B., Pilia G., Bassi M.T., Aylsworth A.S., Penman-Splitt M., Bird L.M., Bamforth J.S., Burn J., Schlessiner D., Nelson D.L., Casey B.
Nat. Genet. 17:305-308(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HTX5 GLN-183.
[5]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-279.
[6]"Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations."
Mohapatra B., Casey B., Li H., Ho-Dawson T., Smith L., Fernbach S.D., Molinari L., Niesh S.R., Jefferies J.L., Craigen W.J., Towbin J.A., Belmont J.W., Ware S.M.
Hum. Mol. Genet. 18:861-871(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HTX5 LYS-203; ARG-260; CYS-275 AND PHE-284, CHARACTERIZATION OF VARIANTS HTX5 LYS-203; ARG-260; CYS-275 AND PHE-284.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB067632 Genomic DNA. Translation: BAB62524.1.
AC022532 Genomic DNA. No translation available.
BC033585 mRNA. Translation: AAH33585.1.
BC104976 mRNA. Translation: AAI04977.1.
BC112025 mRNA. Translation: AAI12026.1.
RefSeqNP_060525.3. NM_018055.4.
UniGeneHs.370414.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4N1DX-ray1.91A257-313[»]
ProteinModelPortalQ96S42.
SMRQ96S42. Positions 246-346.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000287139.

Polymorphism databases

DMDM166214958.

Proteomic databases

PaxDbQ96S42.
PRIDEQ96S42.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287139; ENSP00000287139; ENSG00000156574.
GeneID4838.
KEGGhsa:4838.
UCSCuc001jrc.2. human.

Organism-specific databases

CTD4838.
GeneCardsGC10M072191.
H-InvDBHIX0008897.
HGNCHGNC:7865. NODAL.
HPAHPA045201.
MIM270100. phenotype.
601265. gene.
neXtProtNX_Q96S42.
Orphanet93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
157769. Situs ambiguus.
101063. Situs inversus totalis.
PharmGKBPA31669.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG278576.
HOGENOMHOG000113815.
HOVERGENHBG108195.
InParanoidQ96S42.
KOK04666.
OMAHRVPSTC.
OrthoDBEOG7DFXD1.
PhylomeDBQ96S42.
TreeFamTF316134.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
SignaLinkQ96S42.

Gene expression databases

ArrayExpressQ96S42.
BgeeQ96S42.
CleanExHS_NODAL.
GenevestigatorQ96S42.

Family and domain databases

InterProIPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNODAL.
GenomeRNAi4838.
NextBio18642.
PROQ96S42.
SOURCESearch...

Entry information

Entry nameNODAL_HUMAN
AccessionPrimary (citable) accession number: Q96S42
Secondary accession number(s): Q2M3A5, Q8N4V3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 10, 2003
Last sequence update: January 15, 2008
Last modified: April 16, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM