NODAL_XENLA
ID NODAL_XENLA Reviewed; 406 AA.
AC Q91619; Q90XB4; Q90XB5;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Nodal homolog;
DE AltName: Full=Nodal-related protein 1;
DE AltName: Full=Xnr-1;
DE Short=Xnr1;
DE Short=nr-1;
DE Flags: Precursor;
GN Name=nodal {ECO:0000250|UniProtKB:P43021};
GN Synonyms=nr1 {ECO:0000303|PubMed:10683175};
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:AAA97392.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC TISSUE=Gastrula {ECO:0000269|PubMed:8582278};
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).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL05845.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-35 AND 56-126, AND 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 [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=9310324; DOI=10.1242/dev.124.17.3293;
RA Sampath K., Cheng A.M.S., Frisch A., Wright C.V.E.;
RT "Functional differences among Xenopus nodal-related genes in left-right
RT axis determination.";
RL Development 124:3293-3302(1997).
RN [4] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
RX PubMed=10375512; DOI=10.1242/dev.126.14.3229;
RA Osada S., Wright C.V.E.;
RT "Xenopus nodal-related signaling is essential for mesendodermal patterning
RT during early embryogenesis.";
RL Development 126:3229-3240(1999).
RN [5] {ECO:0000305}
RP INTERACTION WITH CER1.
RX PubMed=10067895; DOI=10.1038/17820;
RA Piccolo S., Agius E., Leyns L., Bhattacharyya S., Grunz H., Bouwmeester T.,
RA De Robertis E.M.;
RT "The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP
RT and Wnt signals.";
RL Nature 397:707-710(1999).
RN [6] {ECO:0000305}
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10683175; DOI=10.1242/dev.127.6.1221;
RA Hyde C.E., Old R.W.;
RT "Regulation of the early expression of the Xenopus nodal-related 1 gene,
RT Xnr1.";
RL Development 127:1221-1229(2000).
RN [7] {ECO:0000305}
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10804190; DOI=10.1242/dev.127.11.2503;
RA Osada S., Saijoh Y., Frisch A., Yeo C.-Y., Adachi H., Watanabe M.,
RA Whitman M., Hamada H., Wright C.V.E.;
RT "Activin/nodal responsiveness and asymmetric expression of a Xenopus nodal-
RT related gene converge on a FAST-regulated module in intron 1.";
RL Development 127:2503-2514(2000).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=12710967; DOI=10.1016/s0012-1606(03)00034-4;
RA Yamamoto S., Hikasa H., Ono H., Taira M.;
RT "Molecular link in the sequential induction of the Spemann organizer:
RT direct activation of the cerberus gene by Xlim-1, Xotx2, Mix.1, and
RT Siamois, immediately downstream from Nodal and Wnt signaling.";
RL Dev. Biol. 257:190-204(2003).
RN [9] {ECO:0000305}
RP INTERACTION WITH GDF10.
RX PubMed=12885561; DOI=10.1016/s0012-1606(03)00223-9;
RA Hino J., Nishimatsu S., Nagai T., Matsuo H., Kangawa K., Nohno T.;
RT "Coordination of BMP-3b and cerberus is required for head formation of
RT Xenopus embryos.";
RL Dev. Biol. 260:138-157(2003).
RN [10] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
RX PubMed=16281170; DOI=10.1387/ijdb.052008rt;
RA Toyoizumi R., Ogasawara T., Takeuchi S., Mogi K.;
RT "Xenopus nodal related-1 is indispensable only for left-right axis
RT determination.";
RL Int. J. Dev. Biol. 49:923-938(2005).
RN [11] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16959238; DOI=10.1016/j.ydbio.2006.08.021;
RA Ohi Y., Wright C.V.E.;
RT "Anteriorward shifting of asymmetric Xnr1 expression and contralateral
RT communication in left-right specification in Xenopus.";
RL Dev. Biol. 301:447-463(2007).
RN [12] {ECO:0000305}
RP FUNCTION.
RX PubMed=17123501; DOI=10.1016/j.ydbio.2006.10.033;
RA Foley A.C., Korol O., Timmer A.M., Mercola M.;
RT "Multiple functions of Cerberus cooperate to induce heart downstream of
RT Nodal.";
RL Dev. Biol. 303:57-65(2007).
CC -!- FUNCTION: Cooperation and regulatory loops of multiple nodals are
CC essential for mesendoderm patterning in early embryos. Essential for
CC mesoderm formation and axial patterning during embryonic development.
CC Activates the activin-like signaling pathway to induce dorsal and
CC ventral mesoderm in animal cap ectoderm. In addition, also dorsalizes
CC ventral marginal zone (VMZ) tissues during gastrulation. Acts in a
CC downstream signaling cascade via cripto and cer1 to mediate
CC cardiogenesis in embryonic mesoderm. Directs the orientation of the
CC left-right axis by driving the left-specific gene cascade in the left
CC lateral plate mesoderm. {ECO:0000269|PubMed:10375512,
CC ECO:0000269|PubMed:12710967, ECO:0000269|PubMed:16281170,
CC ECO:0000269|PubMed:16959238, ECO:0000269|PubMed:17123501,
CC ECO:0000269|PubMed:8582278, ECO:0000269|PubMed:9310324}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with,
CC and is inhibited by cer1 and gdf10/bmp3b.
CC {ECO:0000250|UniProtKB:P43021, ECO:0000269|PubMed:10067895,
CC ECO:0000269|PubMed:12885561}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the first phase of expression, localized to the
CC vegetal region of the blastula. During gastrulation (stage 10.5), this
CC expression disappears and instead becomes localized to the dorsal
CC marginal zone, with enrichment in the organizer. During the second
CC phase of expression in neurulae and tailbud embryos, expression
CC restarts firstly in two symmetric patches near the posterior end of the
CC notochord, and then in a large asymmetrical domain in the left lateral
CC plate mesoderm. {ECO:0000269|PubMed:10683175,
CC ECO:0000269|PubMed:10804190, ECO:0000269|PubMed:16959238,
CC ECO:0000269|PubMed:8582278}.
CC -!- DEVELOPMENTAL STAGE: Has two phases of temporal expression during
CC embryogenesis; first expressed at late blastula (stage 9) with
CC expression peaking at early gastrula. Expression then disappears before
CC restarting in a second phase in late neurulae (stage 17).
CC {ECO:0000269|PubMed:8582278}.
CC -!- INDUCTION: By dorsal mesoderm-inducing signals including smad2-smad4,
CC activin and other nodal-related proteins including nodal2/nr-2 and
CC nodal4/nr-4. Shows autoinduction by nodal/nr-1. Induced by vegt, acting
CC in an autoregulatory loop. Beta-catenin potentiates the response to
CC activin. Not induced by wnt8 alone, but wnt8 potentiates the response
CC to activin. Suppressed by ventral inducers such as bmp4.
CC {ECO:0000269|PubMed:10375512, ECO:0000269|PubMed:10683175,
CC ECO:0000269|PubMed:10804190, ECO:0000269|PubMed:11934150,
CC ECO:0000269|PubMed:16281170, ECO:0000269|PubMed:16959238,
CC ECO:0000269|PubMed:8582278}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
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DR EMBL; U29447; AAA97392.1; -; mRNA.
DR EMBL; AF410903; AAL05845.1; -; Genomic_DNA.
DR EMBL; AF410904; AAL05846.1; -; Genomic_DNA.
DR RefSeq; NP_001079265.1; NM_001085796.1.
DR AlphaFoldDB; Q91619; -.
DR GeneID; 378543; -.
DR KEGG; xla:378543; -.
DR CTD; 378543; -.
DR Xenbase; XB-GENE-865681; nodal1.L.
DR OMA; ATITIYH; -.
DR OrthoDB; 1518399at2759; -.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 378543; Expressed in gastrula and 2 other tissues.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0016015; F:morphogen activity; IMP:BHF-UCL.
DR GO; GO:0048318; P:axial mesoderm development; IMP:UniProtKB.
DR GO; GO:0048320; P:axial mesoderm formation; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0048339; P:paraxial mesoderm development; IEP:BHF-UCL.
DR GO; GO:1900224; P:positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; IMP:BHF-UCL.
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 InterPro; IPR017948; TGFb_CS.
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; 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; Cytokine; Developmental protein;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..281
FT /evidence="ECO:0000255"
FT /id="PRO_0000273274"
FT CHAIN 282..406
FT /note="Nodal homolog"
FT /evidence="ECO:0000255"
FT /id="PRO_0000273275"
FT REGION 195..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
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 306..372
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 335..403
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 339..405
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 369
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P43021"
SQ SEQUENCE 406 AA; 46332 MW; 3AFB1D98BCDEAE70 CRC64;
MAFLTAVLYL GFACISQGLP TWPDRVESRN PLFGSRVALN LPSLLDGNRH HRDMRYPLYM
MQLYQNLVTG NDTGLANRPN TATKEYDTVL SLFAKKCTES ENRWTLSFDM SAVSRSNELK
LAELRILLPH TEPSHNITMD MYHSRDGEDN LYLGSFNANP PSTKGSPWKV FNVTKILQPY
FKERRDIDSE HLKAKERAER GSGMSNAEFI DAPGPSQQYN PHQTSVPTYL NTKGVMLVLF
TKVKSSANHI GFPSLIKTAE SSKYVDIEKA SRVPGIRRHR RNRNENHHLS IGSIPSRHVE
NGKPLCRRVD MIVDFEDIGW SSWIVYPKKY NAYRCEGACP IPLNETFKPT NHAYMKSVVK
LYQPERVECP LCVPVKMSPL SMLYYEGDEV VLRHHQEMIV EECGCS
