Q96S42 (NODAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nodal homolog

Gene names

Name:

NODAL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	347 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Heterotaxy
Domain	Signal
Molecular function	Cytokine Developmental protein Growth factor
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	SMAD protein signal transduction Inferred from electronic annotation. Source: Compara axial mesodermal cell fate specification Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cell migration involved in gastrulation Inferred from electronic annotation. Source: Compara digestive tract morphogenesis Inferred from electronic annotation. Source: Compara embryonic cranial skeleton morphogenesis Inferred from electronic annotation. Source: Compara embryonic pattern specification Inferred from electronic annotation. Source: Compara embryonic placenta development Inferred from electronic annotation. Source: Compara embryonic process involved in female pregnancy Inferred from electronic annotation. Source: Compara 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: Compara floor plate morphogenesis Inferred from electronic annotation. Source: Compara formation of anatomical boundary Inferred from electronic annotation. Source: Compara growth Inferred from electronic annotation. Source: InterPro heart looping Inferred from electronic annotation. Source: Compara inhibition of neuroepithelial cell differentiation Inferred from electronic annotation. Source: Compara left lung morphogenesis Inferred from electronic annotation. Source: Compara liver development Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of trophoblast cell migration Inferred from direct assay PubMed 21356369. Source: BHF-UCL neural fold formation Inferred from electronic annotation. Source: Compara nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry Inferred from electronic annotation. Source: Compara placenta development Inferred from mutant phenotype PubMed 21356369. Source: BHF-UCL polarity specification of proximal/distal axis Inferred from electronic annotation. Source: Compara 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 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: Compara positive regulation vascular endothelial growth factor production Inferred from mutant phenotype PubMed 21116837. Source: BHF-UCL regulation of gastrulation Inferred from electronic annotation. Source: Compara regulation of stem cell maintenance Traceable author statement PubMed 21630377. Source: BHF-UCL stem cell maintenance Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway involved in primitive streak formation Inferred from electronic annotation. Source: Compara trophectodermal cellular morphogenesis Inferred from electronic annotation. Source: Compara vasculature development Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from direct assay PubMed 21656830. Source: BHF-UCL
Molecular_function	morphogen 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Propeptide	27 – 237	211	Potential		PRO_0000033998
	Chain	238 – 347	110	Nodal homolog		PRO_0000033999
Amino acid modifications
	Glycosylation	72	1	N-linked (GlcNAc...) Potential
	Glycosylation	199	1	N-linked (GlcNAc...) Potential
	Disulfide bond	247 ↔ 313		By similarity
	Disulfide bond	276 ↔ 344		By similarity
	Disulfide bond	280 ↔ 346		By similarity
	Disulfide bond	312		Interchain By similarity
Natural variations
	Natural variant	165	1	H → R. Ref.1 Corresponds to variant rs1904589 [ dbSNP | Ensembl ].		VAR_038193
	Natural variant	183	1	R → Q in HTX5. Ref.4		VAR_015111
	Natural variant	203	1	E → K in HTX5; decrease in signal transduction. Ref.6 Corresponds to variant rs10999334 [ dbSNP | Ensembl ].		VAR_038194
	Natural variant	260	1	G → R in HTX5; decrease in signal transduction. Ref.6		VAR_062281
	Natural variant	275	1	R → C in HTX5; decrease in signal transduction. Ref.6		VAR_062282
	Natural variant	279	1	E → K in a colorectal cancer sample; somatic mutation. Ref.5		VAR_036202
	Natural variant	284	1	V → F in HTX5; decrease in signal transduction. Ref.6		VAR_062283

Sequences

	Sequence		Length	Mass (Da)
	Q96S42 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: 0D52352B9711650C	FASTA	347	39,561
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00045497.
RefSeq	NP_060525.3. NM_018055.4.
UniGene	Hs.370414.
3D structure databases
ProteinModelPortal	Q96S42.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000287139.
Polymorphism databases
DMDM	166214958.
Proteomic databases
PaxDb	Q96S42.
PRIDE	Q96S42.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287139; ENSP00000287139; ENSG00000156574.
GeneID	4838.
KEGG	hsa:4838.
UCSC	uc001jrc.2. human.
Organism-specific databases
CTD	4838.
GeneCards	GC10M072191.
H-InvDB	HIX0008897.
HGNC	HGNC:7865. NODAL.
HPA	HPA045201.
MIM	270100. phenotype. 601265. gene.
neXtProt	NX_Q96S42.
Orphanet	93925. 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.
PharmGKB	PA31669.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG278576.
HOGENOM	HOG000113815.
HOVERGEN	HBG108195.
InParanoid	Q96S42.
KO	K04666.
OMA	HRVPSTC.
OrthoDB	EOG4NGGNG.
PhylomeDB	Q96S42.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
ArrayExpress	Q96S42.
Bgee	Q96S42.
CleanEx	HS_NODAL.
Genevestigator	Q96S42.
GermOnline	ENSG00000156574. Homo sapiens.
Family and domain databases
InterPro	IPR001839. TGF-b_C. IPR001111. TGF-b_N. IPR015615. TGF-beta-rel. IPR017948. TGFb_CS. [Graphical view]
PANTHER	PTHR11848. PTHR11848. 1 hit.
Pfam	PF00019. TGF_beta. 1 hit. PF00688. TGFb_propeptide. 1 hit. [Graphical view]
SMART	SM00204. TGFB. 1 hit. [Graphical view]
PROSITE	PS00250. TGF_BETA_1. 1 hit. PS51362. TGF_BETA_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4838.
NextBio	18642.
SOURCE	Search...

Entry information

Entry name

NODAL_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.