Q96S42 (NODAL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nodal homolog

Gene names

Name:

NODAL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in NODAL are the cause of visceral heterotaxy autosomal type 5 (HTX5) [MIM:270100]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy autosomal type 5 include situs inversus viscerum or situs ambiguus, congenital heart defect, transposition of the great vessels ventricular septal defect, atrial septal defect, truncuscommunis, and dextrocardia. 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	growth Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW growth factor activity Inferred from electronic annotation. Source: UniProtKB-KW
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: 15164054] [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: 15489334] [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: 9354794] [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: 16959974] [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: 19064609] [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.
SMR	Q96S42. Positions 241-346.
ModBase	Search...
Protein-protein interaction databases
STRING	Q96S42.
Polymorphism databases
DMDM	166214958.
Proteomic databases
PRIDE	Q96S42.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287139; ENSP00000287139; ENSG00000156574.
GeneID	4838.
KEGG	hsa:4838.
UCSC	uc001jrc.1. human.
Organism-specific databases
CTD	4838.
GeneCards	GC10M072191.
H-InvDB	HIX0008897.
HGNC	HGNC:7865. NODAL.
MIM	270100. phenotype. 601265. gene.
neXtProt	NX_Q96S42.
PharmGKB	PA31669.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11275.
GeneTree	ENSGT00600000084167.
HOGENOM	HBG713475.
HOVERGEN	HBG108195.
InParanoid	Q96S42.
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]
KO	K04666.
PANTHER	PTHR11848. TGFbeta. 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
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:	January 25, 2012
This is version 81 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.