ID   NOD3A_XENTR             Reviewed;         401 AA.
AC   Q800C0;
DT   10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=Nodal homolog 3-A;
DE   AltName: Full=Nodal-related protein 3-A;
DE   AltName: Full=Xtnr3-A;
DE   Flags: Precursor;
GN   Name=nodal3-A {ECO:0000250|UniProtKB:Q91620};
GN   Synonyms=nr3-A {ECO:0000312|EMBL:BAC75530.1};
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:BAC75530.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH BMP4, TISSUE
RP   SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   TISSUE=Gastrula {ECO:0000269|PubMed:14697360};
RX   PubMed=14697360; DOI=10.1016/j.ydbio.2003.09.015;
RA   Haramoto Y., Tanegashima K., Onuma Y., Takahashi S., Sekizaki H.,
RA   Asashima M.;
RT   "Xenopus tropicalis nodal-related gene 3 regulates BMP signaling: an
RT   essential role for the pro-region.";
RL   Dev. Biol. 265:155-168(2004).
RN   [2] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH BMP4, AND DOMAIN.
RX   PubMed=16762322; DOI=10.1016/j.bbrc.2006.05.121;
RA   Haramoto Y., Takahashi S., Asashima M.;
RT   "Two distinct domains in pro-region of Nodal-related 3 are essential for
RT   BMP inhibition.";
RL   Biochem. Biophys. Res. Commun. 346:470-478(2006).
RN   [3] {ECO:0000305}
RP   FUNCTION, MONOMER, AND MUTAGENESIS OF PHE-398 AND 398-PHE--ILE-401.
RX   PubMed=17089091; DOI=10.1007/s00427-006-0115-2;
RA   Haramoto Y., Takahashi S., Asashima M.;
RT   "Monomeric mature protein of Nodal-related 3 activates Xbra expression.";
RL   Dev. Genes Evol. 217:29-37(2007).
CC   -!- FUNCTION: Exhibits mesoderm-dorsalizing activity and neural-inducing
CC       activity, but lacks mesoderm-inducing activity. Regulates the
CC       expression of specific mesodermal and neural genes. Induces convergent
CC       extension movements at the embryonic midline by activating the fgf
CC       signaling pathway to induce t/bra expression in the organizer region.
CC       Acts with wnt11 to induce Spemann organizer cells and induce axis
CC       formation (By similarity). The unprocessed protein antagonizes bmp-
CC       signaling. {ECO:0000250|UniProtKB:Q91609, ECO:0000269|PubMed:14697360,
CC       ECO:0000269|PubMed:16762322, ECO:0000269|PubMed:17089091}.
CC   -!- SUBUNIT: Monomer. The propeptide region interacts with bmp4 in a non-
CC       covalent manner. {ECO:0000269|PubMed:14697360,
CC       ECO:0000269|PubMed:16762322}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q91620}.
CC   -!- TISSUE SPECIFICITY: Expressed in the dorsal marginal region of late
CC       blastula, becoming restricted to the Spemann organizer at the early
CC       gastrula stage. {ECO:0000269|PubMed:14697360}.
CC   -!- DEVELOPMENTAL STAGE: First detected at the blastula stage (stage 8).
CC       Expression peaks through the mid-blastula (stage 8.5) to early gastrula
CC       (stage 10) and then decreases during gastrulation.
CC       {ECO:0000269|PubMed:14697360}.
CC   -!- DOMAIN: The propeptide region and the N- and C-terminal thirds of the
CC       mature protein are necessary for neural induction activity. Although
CC       cleavage doesn't appear essential for activity, residues surrounding
CC       the cleavage site are necessary for activity (By similarity). The
CC       propeptide region is both necessary and sufficient for bmp-inhibitory
CC       activity. {ECO:0000250, ECO:0000269|PubMed:16762322}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
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DR   EMBL; AB093327; BAC75530.1; -; mRNA.
DR   RefSeq; NP_001297040.1; NM_001310111.1.
DR   AlphaFoldDB; Q800C0; -.
DR   PaxDb; Q800C0; -.
DR   GeneID; 101732995; -.
DR   KEGG; xtr:101732995; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   OrthoDB; 1518399at2759; -.
DR   Proteomes; UP000008143; Chromosome 3.
DR   Proteomes; UP000790000; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0070698; F:type I activin receptor binding; IBA:GO_Central.
DR   GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR   GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR   Gene3D; 2.10.90.10; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR001111; TGF-b_propeptide.
DR   InterPro; IPR015615; TGF-beta-rel.
DR   PANTHER; PTHR11848; PTHR11848; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; SSF57501; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Developmental protein; Disulfide bond;
KW   Gastrulation; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..274
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338454"
FT   CHAIN           275..401
FT                   /note="Nodal homolog 3-A"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000338455"
FT   CARBOHYD        168
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        299..365
FT                   /evidence="ECO:0000250|UniProtKB:P43021"
FT   DISULFID        328..396
FT                   /evidence="ECO:0000250|UniProtKB:P43021"
FT   MUTAGEN         398..401
FT                   /note="FKDI->CY: Still unable to dimerize."
FT                   /evidence="ECO:0000269|PubMed:17089091"
FT   MUTAGEN         398
FT                   /note="F->C: Still unable to dimerize."
FT                   /evidence="ECO:0000269|PubMed:17089091"
SQ   SEQUENCE   401 AA;  45802 MW;  4F05B296131ADD0C CRC64;
     MAFLSLFLCL VFSSPLMAMP PALQGRKAIS PASILKGPST DNGARDFHGR KFPHFMMQLY
     QNIISRRDKD LSNLEHPTLQ ESDTVQSFIA KSYTTVGNHW TLFFDMSSIS TSNELKLAEL
     RICLPSFGKS HSVTVEIYHT KDTKEKLFMG SFKTKISSAL DADCKVFNLT MVLHNYLIRG
     KRLIKDEYIQ AKGLLLRDLE KSAAEKGAEN VDTLKQDKYH VSDFAAERII LVVFAKERSQ
     AKPDPPSLGK QLFPLKYGMA DNANKVNGFR RLRRNKKEKT RIDVGTTPPK PVEEIKPKCR
     KVDMFVDFQK IGWGSWIVYP KAYNAYRCES ACAVPLNETD DATNYSYIKS LLPLSDTERR
     ECPSCVPVKM RSMSMLYYEN EDFVLRHHEE MIVEECGFKD I