NOD2A_XENLA
ID NOD2A_XENLA Reviewed; 405 AA.
AC Q91620;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Nodal homolog 2-A;
DE AltName: Full=Nodal-related protein 2-A;
DE AltName: Full=Xnr-2-A;
DE Short=Xnr2-A;
DE Short=nr-2;
DE Flags: Precursor;
GN Name=nodal2-a;
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:AAA97393.1}
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}
RP FUNCTION.
RX PubMed=8939607; DOI=10.1016/s0960-9822(96)00751-8;
RA Jones C.M., Armes N., Smith J.C.;
RT "Signalling by TGF-beta family members: short-range effects of Xnr-2 and
RT BMP-4 contrast with the long-range effects of activin.";
RL Curr. Biol. 6:1468-1475(1996).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF CYS-334.
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 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 [5] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 278-ARG--ARG-282; CYS-334 AND CYS-368.
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 [6]
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 346-PHE--PRO-348.
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]
RP FUNCTION, AND INDUCTION.
RX PubMed=11784097; DOI=10.1006/dbio.2001.0493;
RA Onuma Y., Takahashi S., Yokota C., Asashima M.;
RT "Multiple nodal-related genes act coordinately in Xenopus embryogenesis.";
RL Dev. Biol. 241:94-105(2002).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DERRIERE, AND MUTAGENESIS
RP OF 209-ARG--ARG-212 AND 278-ARG--ARG-282.
RX PubMed=12070085; DOI=10.1242/dev.129.13.3089;
RA Eimon P.M., Harland R.M.;
RT "Effects of heterodimerization and proteolytic processing on Derriere and
RT Nodal activity: implications for mesoderm induction in Xenopus.";
RL Development 129:3089-3103(2002).
RN [9] {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 [10] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15530392; DOI=10.1016/j.cub.2004.10.020;
RA Williams P.H., Hagemann A., Gonzalez-Gaitan M., Smith J.C.;
RT "Visualizing long-range movement of the morphogen Xnr2 in the Xenopus
RT embryo.";
RL Curr. Biol. 14:1916-1923(2004).
RN [11] {ECO:0000305}
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF 278-ARG--ARG-282.
RX PubMed=16193491; DOI=10.1002/dvdy.20574;
RA Onuma Y., Takahashi S., Haramoto Y., Tanegashima K., Yokota C., Whitman M.,
RA Asashima M.;
RT "Xnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of
RT dishevelled.";
RL Dev. Dyn. 234:900-910(2005).
RN [12]
RP INTERACTION WITH TSKU.
RX PubMed=17925852; DOI=10.1371/journal.pone.0001004;
RA Morris S.A., Almeida A.D., Tanaka H., Ohta K., Ohnuma S.;
RT "Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ
RT layer formation.";
RL PLoS ONE 2:e1004-e1004(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. Induces muscle
CC actin. Appears to act as both a short-range and long-range morphogen.
CC The unprocessed protein inhibits bmp- and wnt-signaling.
CC {ECO:0000269|PubMed:10375512, ECO:0000269|PubMed:10799488,
CC ECO:0000269|PubMed:11784097, ECO:0000269|PubMed:12070085,
CC ECO:0000269|PubMed:15530392, ECO:0000269|PubMed:16193491,
CC ECO:0000269|PubMed:8582278, ECO:0000269|PubMed:8939607,
CC ECO:0000269|PubMed:9053324, ECO:0000269|PubMed:9310324}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Forms
CC heterodimers with the TGF-beta family member derriere
CC (PubMed:12070085). Interacts with tsku; enhances nodal2 activity
CC (PubMed:17925852). {ECO:0000250|UniProtKB:P43021,
CC ECO:0000269|PubMed:12070085, ECO:0000269|PubMed:17925852}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12070085,
CC ECO:0000269|PubMed:15530392}.
CC -!- TISSUE SPECIFICITY: First localized to the vegetal region of the
CC blastula. Just prior to gastrulation (stage 10), this expression
CC disappears and instead becomes localized to the dorsal marginal zone,
CC with enrichment in the organizer. {ECO:0000269|PubMed:8582278}.
CC -!- DEVELOPMENTAL STAGE: First expressed at late blastula (stage 9) with
CC expression peaking at early gastrula. Expression then disappears and
CC does not return. {ECO:0000269|PubMed:8582278}.
CC -!- INDUCTION: By dorsal mesoderm-inducing signals including activin and
CC other nodal-related proteins. {ECO:0000269|PubMed:11784097,
CC ECO:0000269|PubMed:11934150, ECO:0000269|PubMed:8582278}.
CC -!- DOMAIN: The pro-region is necessary but not sufficient for wnt-
CC inhibitory activity. The central region is required for muscle
CC induction activity. {ECO:0000269|PubMed:10799488,
CC ECO:0000269|PubMed:16193491}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
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DR EMBL; U29448; AAA97393.1; -; mRNA.
DR RefSeq; NP_001081436.1; NM_001087967.1.
DR AlphaFoldDB; Q91620; -.
DR GeneID; 397835; -.
DR KEGG; xla:397835; -.
DR CTD; 397835; -.
DR Xenbase; XB-GENE-865706; nodal2.L.
DR OMA; TIVMNTI; -.
DR OrthoDB; 1518399at2759; -.
DR Proteomes; UP000186698; Chromosome 3L.
DR Bgee; 397835; Expressed in gastrula and 1 other tissue.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0019838; F:growth factor binding; IPI:UniProtKB.
DR GO; GO:0016015; F:morphogen activity; IMP:UniProtKB.
DR GO; GO:0048320; P:axial mesoderm formation; IMP:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IMP:UniProtKB.
DR GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:UniProtKB.
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; Developmental protein; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..282
FT /evidence="ECO:0000255"
FT /id="PRO_0000274253"
FT CHAIN 283..405
FT /note="Nodal homolog 2-A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000274254"
FT CARBOHYD 71
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 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 305..371
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 334..402
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 338..404
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT DISULFID 368
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P43021"
FT MUTAGEN 209..212
FT /note="RGVR->ALDA: Cleavage mutant which disrupts nodal
FT signaling in a dominant negative-like manner when
FT overexpressed. Remains secreted, retains some signaling
FT activity and able to induce some mesoderm; when associated
FT with 278-G--G-282."
FT /evidence="ECO:0000269|PubMed:12070085"
FT MUTAGEN 278..282
FT /note="RRPRR->GVDGG: Cleavage mutant which disrupts nodal
FT signaling in a dominant negative-like manner when
FT overexpressed. Remains secreted, retains some signaling
FT activity and able to induce some mesoderm; when associated
FT with 209-A--A-212."
FT /evidence="ECO:0000269|PubMed:10375512,
FT ECO:0000269|PubMed:12070085, ECO:0000269|PubMed:16193491"
FT MUTAGEN 334
FT /note="C->S: Fails to induce mesoderm."
FT /evidence="ECO:0000269|PubMed:10375512,
FT ECO:0000269|PubMed:9053324"
FT MUTAGEN 346..348
FT /note="FKP->ENA: Greatly reduces muscle actin inducing
FT activity."
FT /evidence="ECO:0000269|PubMed:10799488"
FT MUTAGEN 368
FT /note="C->S: No effect on mesoderm-inducing activities."
FT /evidence="ECO:0000269|PubMed:10375512"
SQ SEQUENCE 405 AA; 46067 MW; 8D852DF28AF23C88 CRC64;
MASLGVILFF VIASLIHGKP IHSERKAAKI PLEGSNLGYK KPNNIYGSRL SQGMRYPPSM
MQLYQTLILG NDTDLSILEY PVLQESDAVL SLIAKSCVVV GNRWTLSFDM SSISSSNELK
LAELRIRLPS FERSQDVTVE IYHTKEGQEN LFMGSFKTNP SVAMGSSWKI FNLTRMLQYY
LHQGEPFTNV EYIEVKNMHE RAKPHVIKRG VRAEVEEGLQ RNKDNTPASS FPTERVVLVV
FTRDKPTASH FGSPSLIHTV ESSKYVMSEN TVRVTDTRRP RRNQKTKNTI VMNTIPSRSV
GKTLCRRVDM IVDFEKIEWG DRIVYPKRFN AYRCEGACPI PLNETFKPTN HAYIKSLVKL
YDQEKVECSS CVPVKMSPLS MLLYEDGEVV LKHHEDMIVD ECGCN
