NOD3A_XENLA
ID NOD3A_XENLA Reviewed; 401 AA.
AC Q91609;
DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Nodal homolog 3-A;
DE AltName: Full=Nodal-related protein 3-A;
DE AltName: Full=Xnr3;
DE AltName: Full=Xnr3-A;
DE Flags: Precursor;
GN Name=nodal3-a; Synonyms=nr3 {ECO:0000312|EMBL:AAA82755.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAA82755.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC TISSUE=Gastrula {ECO:0000269|PubMed:7606783};
RX PubMed=7606783; DOI=10.1016/0092-8674(95)90050-0;
RA Smith W.C., McKendry R., Ribisi S. Jr., Harland R.M.;
RT "A nodal-related gene defines a physical and functional domain within the
RT Spemann organizer.";
RL Cell 82:37-46(1995).
RN [2] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9025074; DOI=10.1016/s0925-4773(96)00624-7;
RA Glinka A., Delius H., Blumenstock C., Niehrs C.;
RT "Combinatorial signalling by Xwnt-11 and Xnr3 in the organizer
RT epithelium.";
RL Mech. Dev. 60:221-231(1996).
RN [3] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF CYS-299; CYS-328; CYS-365 AND
RP 398-PHE--MET-401.
RX PubMed=9053324; DOI=10.1242/dev.124.2.483;
RA Hansen C.S., Marion C.D., Steele K., George S., Smith W.C.;
RT "Direct neural induction and selective inhibition of mesoderm and epidermis
RT inducers by Xnr3.";
RL Development 124:483-492(1997).
RN [4] {ECO:0000305}
RP INDUCTION.
RX PubMed=9441678; DOI=10.1006/dbio.1997.8797;
RA McKendry R., Hsu S.-C., Harland R.M., Grosschedl R.;
RT "LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus
RT nodal-related 3 promoter.";
RL Dev. Biol. 192:420-431(1997).
RN [5] {ECO:0000305}
RP INDUCTION.
RX PubMed=9371792; DOI=10.1073/pnas.94.24.13017;
RA Kessler D.S.;
RT "Siamois is required for formation of Spemann's organizer.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13017-13022(1997).
RN [6] {ECO:0000305}
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 271-ARG--ARG-274 AND SER-330.
RX PubMed=10799488; DOI=10.1074/jbc.275.19.14124;
RA Ezal C.H., Marion C.D., Smith W.C.;
RT "Primary structure requirements for Xenopus nodal-related 3 and a
RT comparison with regions required by Xenopus nodal-related 2.";
RL J. Biol. Chem. 275:14124-14131(2000).
RN [7] {ECO:0000305}
RP INDUCTION.
RX PubMed=11934150;
RA Rex M., Hilton E., Old R.W.;
RT "Multiple interactions between maternally-activated signalling pathways
RT control Xenopus nodal-related genes.";
RL Int. J. Dev. Biol. 46:217-226(2002).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=12668633; DOI=10.1242/dev.00434;
RA Yokota C., Kofron M., Zuck M., Houston D.W., Isaacs H., Asashima M.,
RA Wylie C.C., Heasman J.;
RT "A novel role for a nodal-related protein; Xnr3 regulates convergent
RT extension movements via the FGF receptor.";
RL Development 130:2199-2212(2003).
RN [9] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH BMP4.
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).
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. The unprocessed protein antagonizes bmp-signaling.
CC {ECO:0000269|PubMed:10799488, ECO:0000269|PubMed:12668633,
CC ECO:0000269|PubMed:14697360, ECO:0000269|PubMed:7606783,
CC ECO:0000269|PubMed:9025074, ECO:0000269|PubMed:9053324}.
CC -!- SUBUNIT: Monomer (By similarity). The propeptide region interacts with
CC bmp4 in a non-covalent manner. {ECO:0000250,
CC ECO:0000269|PubMed:14697360}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q91620}.
CC -!- TISSUE SPECIFICITY: Expressed in the epithelial layer of the Spemann
CC organizer during gastrulation. {ECO:0000269|PubMed:7606783,
CC ECO:0000269|PubMed:9025074}.
CC -!- DEVELOPMENTAL STAGE: Expression increases from late blastula (stage 9)
CC through gastrulation, ending by the time of blastopore closure (stage
CC 13). {ECO:0000269|PubMed:7606783}.
CC -!- INDUCTION: By Li(+), siamois and wnt signaling, including wnt8 and
CC lef1. Induction by wnt8 is inhibited by vegt. Not induced by vegt or
CC activin. {ECO:0000269|PubMed:11934150, ECO:0000269|PubMed:7606783,
CC ECO:0000269|PubMed:9371792, ECO:0000269|PubMed:9441678}.
CC -!- DOMAIN: The propeptide region is both necessary and sufficient for bmp-
CC inhibitory activity (By similarity). The propeptide region and the
CC N- and C-terminal thirds of the mature protein are necessary for neural
CC induction activity. Although cleavage doesn't appear essential for
CC activity, residues surrounding the cleavage site are necessary for
CC activity. {ECO:0000250, ECO:0000269|PubMed:10799488}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U25993; AAA82755.1; -; mRNA.
DR RefSeq; NP_001079259.1; NM_001085790.1.
DR AlphaFoldDB; Q91609; -.
DR GeneID; 378537; -.
DR KEGG; xla:378537; -.
DR CTD; 378537; -.
DR Xenbase; XB-GENE-5964411; nodal3.1.L.
DR OrthoDB; 1518399at2759; -.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 378537; Expressed in gastrula and 1 other tissue.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
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_0000338450"
FT CHAIN 275..401
FT /note="Nodal homolog 3-A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000338451"
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 341
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 271..274
FT /note="RLRR->KLSS: Retains neural-inducing activity."
FT /evidence="ECO:0000269|PubMed:10799488"
FT MUTAGEN 299
FT /note="C->S: Retains neural-inducing activity but at
FT reduced potency."
FT /evidence="ECO:0000269|PubMed:9053324"
FT MUTAGEN 328
FT /note="C->S: Retains neural-inducing activity but at
FT reduced potency."
FT /evidence="ECO:0000269|PubMed:9053324"
FT MUTAGEN 330
FT /note="S->G: Retains neural-inducing activity."
FT /evidence="ECO:0000269|PubMed:10799488"
FT MUTAGEN 365
FT /note="C->S: Retains neural-inducing activity but at
FT reduced potency."
FT /evidence="ECO:0000269|PubMed:9053324"
FT MUTAGEN 398..401
FT /note="FKDM->CA: Retains neural-inducing activity."
FT /evidence="ECO:0000269|PubMed:9053324"
SQ SEQUENCE 401 AA; 46301 MW; 4850C81ECCABC0C2 CRC64;
MAFLNLFFCL VFISPLMAMP PVLQGRKSIS PDSILKDTST DIGAREFQGR KFPNFMMQLY
QNIIRGRDND LSNLEHPTLQ ESDTVQSFIA KSYTTVGNRW TLFFDMSSIS RSNELKLAEL
RICLPSFRKS HSVTVDIYHT NDGKEKLFMG SFKTKLSSAL DSDCKVFNLT ILLQNFLTRG
KRLIKDEYIQ AKGLHLKDLE KSATEKDTEN VDTMKQHQYH VSDFAAERIM LVVFAKEQSH
AKPDPPSLGQ KLFPSKYGID DNANKVNGFR RLRRNKKEKT QIHVSTVPPK PIEEIKPECK
KVDMFVDFQK IGWGSWIIYP KAYNAYRCES TCAVPQNETE NATNHSYIKS LLPLSDMERK
ECPSCVPMKM MSMSMLYYEN EDFILRHHEE MIVEECGFKD M
