CER1_XENLA
ID CER1_XENLA Reviewed; 270 AA.
AC P70041; Q66IN4;
DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Cerberus;
DE Short=Cer;
DE AltName: Full=Xcer;
DE Contains:
DE RecName: Full=Cerberus long;
DE Short=Cer-L;
DE Contains:
DE RecName: Full=Cerberus short;
DE Short=Cer-S;
DE Flags: Precursor;
GN Name=cer1 {ECO:0000250|UniProtKB:O55233};
GN Synonyms=cer {ECO:0000312|EMBL:AAC60012.1};
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:AAC60012.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Dorsal lip {ECO:0000269|PubMed:8757128};
RX PubMed=8757128; DOI=10.1038/382595a0;
RA Bouwmeester T., Kim S.-H., Sasai Y., Lu B., De Robertis E.M.;
RT "Cerberus is a head-inducing secreted factor expressed in the anterior
RT endoderm of Spemann's organizer.";
RL Nature 382:595-601(1996).
RN [2] {ECO:0000305, ECO:0000312|EMBL:BAC54274.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
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 [3] {ECO:0000312|EMBL:AAH81277.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH81277.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH BMP4; NODAL AND WNT8.
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 [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=12952900; DOI=10.1242/dev.00705;
RA Silva A.C., Filipe M., Kuerner K.M., Steinbeisser H., Belo J.A.;
RT "Endogenous Cerberus activity is required for anterior head specification
RT in Xenopus.";
RL Development 130:4943-4953(2003).
RN [6] {ECO:0000305}
RP FUNCTION.
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 [7] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15138495; DOI=10.1371/journal.pbio.0020092;
RA Kuroda H., Wessely O., De Robertis E.M.;
RT "Neural induction in Xenopus: requirement for ectodermal and endomesodermal
RT signals via Chordin, Noggin, beta-Catenin, and Cerberus.";
RL PLoS Biol. 2:623-634(2004).
RN [8] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
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: Inhibits wnt, nodal/nr-1 and bmp signaling in the embryo to
CC promote head formation and anterior neural induction. Within the
CC endoderm, acts as an essential mediator of nodal/nr-1-induced
CC cardiogenesis in the overlying mesoderm. {ECO:0000269|PubMed:10067895,
CC ECO:0000269|PubMed:12885561, ECO:0000269|PubMed:12952900,
CC ECO:0000269|PubMed:15138495, ECO:0000269|PubMed:17123501,
CC ECO:0000269|PubMed:8757128}.
CC -!- SUBUNIT: The long chain interacts with nodal/nr-1, bmp4 and wnt8,
CC thereby inhibiting their function. The short chain interacts with
CC nodal/nr-1 but not bmp4 or wnt8. {ECO:0000269|PubMed:10067895}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8757128}.
CC -!- TISSUE SPECIFICITY: A component of the Nieuwkoop signaling center in
CC the blastula. Expressed transiently in a broad anterior domain of the
CC gastrula, including the anterior endoderm of the Spemann's organizer
CC and more laterally the cardiac primordia. Expression is excluded from
CC the prospective prechordal plate region and the ring of cells that give
CC rise to the trunk-tail mesoderm. {ECO:0000269|PubMed:15138495,
CC ECO:0000269|PubMed:8757128}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Zygotic
CC expression increases at stage 10 (early gastrula), continues during
CC gastrula and early neurula stages before rapidly declining during
CC neurulation. {ECO:0000269|PubMed:8757128}.
CC -!- INDUCTION: By nodal/nr-1 signaling and wnt8 signaling including the
CC downstream effectors mix-A/mix.1 and siamois acting synergistically
CC with either lhx1/lim1 or otx2. Also by acvr1b/alk4.
CC {ECO:0000269|PubMed:12710967, ECO:0000269|PubMed:17123501}.
CC -!- MISCELLANEOUS: Microinjection of cer1 into blastomeres results in the
CC formation of ectopic heads that contain cyclopic eyes as well as
CC duplicated internal organs such as liver and heart. The heart beats at
CC a rhythm different to that of the primary heart. Based on this
CC phenotype the name 'cerberus' was chosen after a mythological guardian
CC dog with multiple heads. {ECO:0000269|PubMed:8757128}.
CC -!- SIMILARITY: Belongs to the DAN family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH81277.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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; U64831; AAC60012.1; -; mRNA.
DR EMBL; AB086394; BAC54274.1; -; Genomic_DNA.
DR EMBL; BC081277; AAH81277.1; ALT_INIT; mRNA.
DR PIR; S71793; S71793.
DR RefSeq; NP_001081800.1; NM_001088331.2.
DR AlphaFoldDB; P70041; -.
DR SMR; P70041; -.
DR DNASU; 398060; -.
DR GeneID; 398060; -.
DR KEGG; xla:398060; -.
DR CTD; 398060; -.
DR Xenbase; XB-GENE-865019; cer1.S.
DR OrthoDB; 1134947at2759; -.
DR Proteomes; UP000186698; Chromosome 1S.
DR Bgee; 398060; Expressed in gastrula and 5 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; NAS:UniProtKB.
DR GO; GO:0036122; F:BMP binding; IPI:UniProtKB.
DR GO; GO:0038100; F:nodal binding; IPI:UniProtKB.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IGI:UniProtKB.
DR GO; GO:0048263; P:determination of dorsal identity; ISS:BHF-UCL.
DR GO; GO:1900116; P:extracellular negative regulation of signal transduction; IGI:UniProtKB.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0032926; P:negative regulation of activin receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:2000381; P:negative regulation of mesoderm development; ISS:BHF-UCL.
DR GO; GO:1900108; P:negative regulation of nodal signaling pathway; IGI:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR016860; Cerberus.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR004133; DAN.
DR PANTHER; PTHR15273; PTHR15273; 2.
DR Pfam; PF03045; DAN; 1.
DR SMART; SM00041; CT; 1.
DR PROSITE; PS01225; CTCK_2; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Developmental protein; Differentiation;
KW Disulfide bond; Gastrulation; Glycoprotein; Neurogenesis;
KW Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..270
FT /note="Cerberus long"
FT /id="PRO_0000273281"
FT CHAIN 110..270
FT /note="Cerberus short"
FT /id="PRO_0000273282"
FT DOMAIN 169..253
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 169..215
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 183..229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 193..245
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 197..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
SQ SEQUENCE 270 AA; 30723 MW; ADBB9159F500399F CRC64;
MLLNVLRICI IVCLVNDGAG KHSEGRERTK TYSLNSRGYF RKERGARRSK ILLVNTKGLD
EPHIGHGDFG LVAELFDSTR THTNRKEPDM NKVKLFSTVA HGNKSARRKA YNGSRRNIFS
RRSFDKRNTE VTEKPGAKMF WNNFLVKMNG APQNTSHGSK AQEIMKEACK TLPFTQNIVH
ENCDRMVIQN NLCFGKCISL HVPNQQDRRN TCSHCLPSKF TLNHLTLNCT GSKNVVKVVM
MVEECTCEAH KSNFHQTAQF NMDTSTTLHH
