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NODAL_MOUSE
ID   NODAL_MOUSE             Reviewed;         354 AA.
AC   P43021; Q8BH87;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   03-AUG-2022, entry version 164.
DE   RecName: Full=Nodal;
DE   Flags: Precursor;
GN   Name=Nodal;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Embryo;
RX   PubMed=8429908; DOI=10.1038/361543a0;
RA   Zhou X., Sasaki H., Lowe L., Hogan B.L., Kuehn M.R.;
RT   "Nodal is a novel TGF-beta-like gene expressed in the mouse node during
RT   gastrulation.";
RL   Nature 361:543-547(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION.
RX   PubMed=8582278; DOI=10.1242/dev.121.11.3651;
RA   Jones C.M., Kuehn M.R., Hogan B.L.M., Smith J.C., Wright C.V.E.;
RT   "Nodal-related signals induce axial mesoderm and dorsalize mesoderm during
RT   gastrulation.";
RL   Development 121:3651-3662(1995).
CC   -!- FUNCTION: Essential for mesoderm formation and axial patterning during
CC       embryonic development. {ECO:0000269|PubMed:8429908,
CC       ECO:0000269|PubMed:8582278}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in the node during gastrulation.
CC       Expression is first detected in primitive streak-stage embryos at about
CC       the time of mesoderm formation. It then becomes highly localized in the
CC       node at the anterior of the primitive streak.
CC       {ECO:0000269|PubMed:8429908}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR   EMBL; X70514; CAA49914.1; -; mRNA.
DR   EMBL; AK049290; BAC33661.1; -; mRNA.
DR   EMBL; AK082823; BAC38637.1; -; mRNA.
DR   EMBL; CH466553; EDL32144.1; -; Genomic_DNA.
DR   CCDS; CCDS23878.1; -.
DR   PIR; S29718; S29718.
DR   RefSeq; NP_038639.2; NM_013611.5.
DR   AlphaFoldDB; P43021; -.
DR   SMR; P43021; -.
DR   BioGRID; 201801; 2.
DR   STRING; 10090.ENSMUSP00000039653; -.
DR   GlyGen; P43021; 1 site.
DR   PaxDb; P43021; -.
DR   PRIDE; P43021; -.
DR   Antibodypedia; 29029; 325 antibodies from 35 providers.
DR   DNASU; 18119; -.
DR   Ensembl; ENSMUST00000049339; ENSMUSP00000039653; ENSMUSG00000037171.
DR   GeneID; 18119; -.
DR   KEGG; mmu:18119; -.
DR   UCSC; uc007ffy.2; mouse.
DR   CTD; 4838; -.
DR   MGI; MGI:97359; Nodal.
DR   VEuPathDB; HostDB:ENSMUSG00000037171; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   GeneTree; ENSGT00940000160223; -.
DR   HOGENOM; CLU_020515_1_0_1; -.
DR   InParanoid; P43021; -.
DR   OMA; SWRAREG; -.
DR   OrthoDB; 1518399at2759; -.
DR   PhylomeDB; P43021; -.
DR   TreeFam; TF316134; -.
DR   BioGRID-ORCS; 18119; 0 hits in 72 CRISPR screens.
DR   ChiTaRS; Nodal; mouse.
DR   PRO; PR:P43021; -.
DR   Proteomes; UP000000589; Chromosome 10.
DR   RNAct; P43021; protein.
DR   Bgee; ENSMUSG00000037171; Expressed in mesoderm and 139 other tissues.
DR   Genevisible; P43021; MM.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB.
DR   GO; GO:0070698; F:type I activin receptor binding; ISO:MGI.
DR   GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IMP:MGI.
DR   GO; GO:0009948; P:anterior/posterior axis specification; IMP:MGI.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR   GO; GO:0048327; P:axial mesodermal cell fate specification; IMP:MGI.
DR   GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR   GO; GO:0007420; P:brain development; IMP:MGI.
DR   GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR   GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR   GO; GO:0016477; P:cell migration; IMP:MGI.
DR   GO; GO:0042074; P:cell migration involved in gastrulation; IDA:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR   GO; GO:0007368; P:determination of left/right symmetry; IDA:MGI.
DR   GO; GO:0055123; P:digestive system development; IMP:MGI.
DR   GO; GO:0048546; P:digestive tract morphogenesis; IMP:MGI.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR   GO; GO:0035050; P:embryonic heart tube development; IMP:MGI.
DR   GO; GO:0009880; P:embryonic pattern specification; IMP:MGI.
DR   GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
DR   GO; GO:0060136; P:embryonic process involved in female pregnancy; IMP:MGI.
DR   GO; GO:0007492; P:endoderm development; IMP:MGI.
DR   GO; GO:0035987; P:endodermal cell differentiation; ISO:MGI.
DR   GO; GO:0060802; P:epiblast cell-extraembryonic ectoderm cell signaling involved in anterior/posterior axis specification; IMP:MGI.
DR   GO; GO:0033505; P:floor plate morphogenesis; IMP:MGI.
DR   GO; GO:0048859; P:formation of anatomical boundary; IMP:MGI.
DR   GO; GO:0007369; P:gastrulation; IMP:MGI.
DR   GO; GO:0001702; P:gastrulation with mouth forming second; IMP:MGI.
DR   GO; GO:0007281; P:germ cell development; IMP:MGI.
DR   GO; GO:0007507; P:heart development; IMP:MGI.
DR   GO; GO:0001947; P:heart looping; IGI:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR   GO; GO:0002085; P:inhibition of neuroepithelial cell differentiation; IMP:MGI.
DR   GO; GO:0060460; P:left lung morphogenesis; IMP:MGI.
DR   GO; GO:0001889; P:liver development; IMP:MGI.
DR   GO; GO:0030324; P:lung development; IMP:MGI.
DR   GO; GO:0001893; P:maternal placenta development; IMP:MGI.
DR   GO; GO:0060137; P:maternal process involved in parturition; IMP:MGI.
DR   GO; GO:0048382; P:mesendoderm development; IMP:MGI.
DR   GO; GO:0001707; P:mesoderm formation; IMP:MGI.
DR   GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:MGI.
DR   GO; GO:0010721; P:negative regulation of cell development; IMP:MGI.
DR   GO; GO:0045596; P:negative regulation of cell differentiation; IDA:MGI.
DR   GO; GO:1901383; P:negative regulation of chorionic trophoblast cell proliferation; ISO:MGI.
DR   GO; GO:2000242; P:negative regulation of reproductive process; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:1901164; P:negative regulation of trophoblast cell migration; ISO:MGI.
DR   GO; GO:0007399; P:nervous system development; IMP:MGI.
DR   GO; GO:0001842; P:neural fold formation; IMP:MGI.
DR   GO; GO:0038092; P:nodal signaling pathway; IMP:UniProtKB.
DR   GO; GO:1900164; P:nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; IMP:BHF-UCL.
DR   GO; GO:0001890; P:placenta development; ISO:MGI.
DR   GO; GO:0010085; P:polarity specification of proximal/distal axis; IMP:MGI.
DR   GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; ISO:MGI.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR   GO; GO:0022409; P:positive regulation of cell-cell adhesion; ISO:MGI.
DR   GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR   GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR   GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI.
DR   GO; GO:0090009; P:primitive streak formation; IGI:MGI.
DR   GO; GO:0010470; P:regulation of gastrulation; IGI:MGI.
DR   GO; GO:0009966; P:regulation of signal transduction; IDA:MGI.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IDA:MGI.
DR   GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR   GO; GO:0019827; P:stem cell population maintenance; IGI:MGI.
DR   GO; GO:0048729; P:tissue morphogenesis; IMP:MGI.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISA:MGI.
DR   GO; GO:0090010; P:transforming growth factor beta receptor signaling pathway involved in primitive streak formation; IMP:MGI.
DR   GO; GO:0001829; P:trophectodermal cell differentiation; IDA:MGI.
DR   GO; GO:0001831; P:trophectodermal cellular morphogenesis; IMP:MGI.
DR   GO; GO:0001944; P:vasculature development; IMP:MGI.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   InterPro; IPR017948; TGFb_CS.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; SSF57501; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   2: Evidence at transcript level;
KW   Cleavage on pair of basic residues; Cytokine; Developmental protein;
KW   Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..244
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000034000"
FT   CHAIN           245..354
FT                   /note="Nodal"
FT                   /id="PRO_0000034001"
FT   CARBOHYD        73
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        254..320
FT                   /evidence="ECO:0000250"
FT   DISULFID        283..351
FT                   /evidence="ECO:0000250"
FT   DISULFID        287..353
FT                   /evidence="ECO:0000250"
FT   DISULFID        319
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        93..94
FT                   /note="EL -> DV (in Ref. 1; CAA49914)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   354 AA;  40476 MW;  40ECFC6785BB5826 CRC64;
     MSAHSLRILL LQACWALLHP RAPTAAALPL WTRGQPSSPS PLAYMLSLYR DPLPRADIIR
     SLQAQDVDVT GQNWTFTFDF SFLSQEEDLV WAELRLQLPG PMDIPTEGPL TIDIFHQAKG
     DPERDPADCL ERIWMETFTV IPSQVTFASG STVLEVTKPL SKWLKDPRAL EKQVSSRAEK
     CWHQPYTPPV PVASTNVLML YSNRPQEQRQ LGGATLLWEA ESSWRAQEGQ LSVERGGWGR
     RQRRHHLPDR SQLCRRVKFQ VDFNLIGWGS WIIYPKQYNA YRCEGECPNP VGEEFHPTNH
     AYIQSLLKRY QPHRVPSTCC APVKTKPLSM LYVDNGRVLL EHHKDMIVEE CGCL
 
 
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