ID   NODAL_HUMAN             Reviewed;         347 AA.
AC   Q96S42; Q2M3A5; Q8N4V3;
DT   10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 2.
DT   25-JAN-2012, entry version 81.
DE   RecName: Full=Nodal homolog;
DE   Flags: Precursor;
GN   Name=NODAL;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-165.
RA   Tate Genshu T.;
RT   "Human Nodal-related gene.";
RL   Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA   Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA   Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA   Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA   Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA   Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA   Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA   Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA   Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA   Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA   Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA   Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA   Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA   Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA   Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA   Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA   Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA   Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex, and Fetal brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   VARIANT HTX5 GLN-183.
RX   MEDLINE=98016414; PubMed=9354794; DOI=10.1038/ng1197-305;
RA   Gebbia M., Ferrero G.B., Pilia G., Bassi M.T., Aylsworth A.S.,
RA   Penman-Splitt M., Bird L.M., Bamforth J.S., Burn J., Schlessiner D.,
RA   Nelson D.L., Casey B.;
RT   "X-linked situs abnormalities result from mutations in ZIC3.";
RL   Nat. Genet. 17:305-308(1997).
RN   [5]
RP   VARIANT [LARGE SCALE ANALYSIS] LYS-279.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
RN   [6]
RP   VARIANTS HTX5 LYS-203; ARG-260; CYS-275 AND PHE-284, AND
RP   CHARACTERIZATION OF VARIANTS HTX5 LYS-203; ARG-260; CYS-275 AND
RP   PHE-284.
RX   PubMed=19064609; DOI=10.1093/hmg/ddn411;
RA   Mohapatra B., Casey B., Li H., Ho-Dawson T., Smith L., Fernbach S.D.,
RA   Molinari L., Niesh S.R., Jefferies J.L., Craigen W.J., Towbin J.A.,
RA   Belmont J.W., Ware S.M.;
RT   "Identification and functional characterization of NODAL rare variants
RT   in heterotaxy and isolated cardiovascular malformations.";
RL   Hum. Mol. Genet. 18:861-871(2009).
CC   -!- FUNCTION: Essential for mesoderm formation and axial patterning
CC       during embryonic development (By similarity).
CC   -!- SUBUNIT: Homodimer; disulfide-linked (By similarity).
CC   -!- SUBCELLULAR LOCATION: Secreted (By similarity).
CC   -!- DISEASE: Defects in NODAL are the cause of visceral heterotaxy
CC       autosomal type 5 (HTX5) [MIM:270100]. A form of visceral
CC       heterotaxy, a complex disorder due to disruption of the normal
CC       left-right asymmetry of the thoracoabdominal organs. It results in
CC       an abnormal arrangement of visceral organs, and a wide variety of
CC       congenital defects. Clinical features of visceral heterotaxy
CC       autosomal type 5 include situs inversus viscerum or situs
CC       ambiguus, congenital heart defect, transposition of the great
CC       vessels ventricular septal defect, atrial septal defect,
CC       truncuscommunis, and dextrocardia.
CC   -!- SIMILARITY: Belongs to the TGF-beta family.
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DR   EMBL; AB067632; BAB62524.1; -; Genomic_DNA.
DR   EMBL; AC022532; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC033585; AAH33585.1; -; mRNA.
DR   EMBL; BC104976; AAI04977.1; -; mRNA.
DR   EMBL; BC112025; AAI12026.1; -; mRNA.
DR   IPI; IPI00045497; -.
DR   RefSeq; NP_060525.3; NM_018055.4.
DR   UniGene; Hs.370414; -.
DR   ProteinModelPortal; Q96S42; -.
DR   SMR; Q96S42; 241-346.
DR   STRING; Q96S42; -.
DR   DMDM; 166214958; -.
DR   PRIDE; Q96S42; -.
DR   Ensembl; ENST00000287139; ENSP00000287139; ENSG00000156574.
DR   GeneID; 4838; -.
DR   KEGG; hsa:4838; -.
DR   UCSC; uc001jrc.1; human.
DR   CTD; 4838; -.
DR   GeneCards; GC10M072191; -.
DR   H-InvDB; HIX0008897; -.
DR   HGNC; HGNC:7865; NODAL.
DR   MIM; 270100; phenotype.
DR   MIM; 601265; gene.
DR   neXtProt; NX_Q96S42; -.
DR   PharmGKB; PA31669; -.
DR   eggNOG; prNOG11275; -.
DR   GeneTree; ENSGT00600000084167; -.
DR   HOGENOM; HBG713475; -.
DR   HOVERGEN; HBG108195; -.
DR   InParanoid; Q96S42; -.
DR   OMA; HRVPSTC; -.
DR   OrthoDB; EOG4NGGNG; -.
DR   PhylomeDB; Q96S42; -.
DR   Reactome; REACT_111045; Developmental Biology.
DR   NextBio; 18642; -.
DR   ArrayExpress; Q96S42; -.
DR   Bgee; Q96S42; -.
DR   CleanEx; HS_NODAL; -.
DR   Genevestigator; Q96S42; -.
DR   GermOnline; ENSG00000156574; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0040007; P:growth; IEA:InterPro.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR001111; TGF-b_N.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   KO; K04666; -.
DR   PANTHER; PTHR11848; TGFbeta; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   SMART; SM00204; TGFB; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Complete proteome; Cytokine;
KW   Developmental protein; Disease mutation; Disulfide bond; Glycoprotein;
KW   Growth factor; Heterotaxy; Polymorphism; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL        1     26       Potential.
FT   PROPEP       27    237       Potential.
FT                                /FTId=PRO_0000033998.
FT   CHAIN       238    347       Nodal homolog.
FT                                /FTId=PRO_0000033999.
FT   CARBOHYD     72     72       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    199    199       N-linked (GlcNAc...) (Potential).
FT   DISULFID    247    313       By similarity.
FT   DISULFID    276    344       By similarity.
FT   DISULFID    280    346       By similarity.
FT   DISULFID    312    312       Interchain (By similarity).
FT   VARIANT     165    165       H -> R (in dbSNP:rs1904589).
FT                                /FTId=VAR_038193.
FT   VARIANT     183    183       R -> Q (in HTX5).
FT                                /FTId=VAR_015111.
FT   VARIANT     203    203       E -> K (in HTX5; decrease in signal
FT                                transduction; dbSNP:rs10999334).
FT                                /FTId=VAR_038194.
FT   VARIANT     260    260       G -> R (in HTX5; decrease in signal
FT                                transduction).
FT                                /FTId=VAR_062281.
FT   VARIANT     275    275       R -> C (in HTX5; decrease in signal
FT                                transduction).
FT                                /FTId=VAR_062282.
FT   VARIANT     279    279       E -> K (in a colorectal cancer sample;
FT                                somatic mutation).
FT                                /FTId=VAR_036202.
FT   VARIANT     284    284       V -> F (in HTX5; decrease in signal
FT                                transduction).
FT                                /FTId=VAR_062283.
SQ   SEQUENCE   347 AA;  39561 MW;  0D52352B9711650C CRC64;
     MHAHCLPFLL HAWWALLQAG AATVATALLR TRGQPSSPSP LAYMLSLYRD PLPRADIIRS
     LQAEDVAVDG QNWTFAFDFS FLSQQEDLAW AELRLQLSSP VDLPTEGSLA IEIFHQPKPD
     TEQASDSCLE RFQMDLFTVT LSQVTFSLGS MVLEVTRPLS KWLKHPGALE KQMSRVAGEC
     WPRPPTPPAT NVLLMLYSNL SQEQRQLGGS TLLWEAESSW RAQEGQLSWE WGKRHRRHHL
     PDRSQLCRKV KFQVDFNLIG WGSWIIYPKQ YNAYRCEGEC PNPVGEEFHP TNHAYIQSLL
     KRYQPHRVPS TCCAPVKTKP LSMLYVDNGR VLLDHHKDMI VEECGCL
//