GDF11_MOUSE
ID GDF11_MOUSE Reviewed; 405 AA.
AC Q9Z1W4; Q9QX55; Q9R221;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Growth/differentiation factor 11;
DE Short=GDF-11;
DE AltName: Full=Bone morphogenetic protein 11;
DE Short=BMP-11;
DE Flags: Precursor;
GN Name=Gdf11; Synonyms=Bmp11;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RX PubMed=10075854; DOI=10.1006/dbio.1998.9191;
RA Gamer L.W., Wolfman N.M., Celeste A.J., Hattersley G., Hewick R., Rosen V.;
RT "A novel BMP expressed in developing mouse limb, spinal cord, and tail bud
RT is a potent mesoderm inducer in Xenopus embryos.";
RL Dev. Biol. 208:222-232(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=129/SvJ;
RX PubMed=10391213; DOI=10.1038/10320;
RA McPherron A.C., Lawler A.M., Lee S.-J.;
RT "Regulation of anterior/posterior patterning of the axial skeleton by
RT growth/differentiation factor 11.";
RL Nat. Genet. 22:260-264(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-405.
RX PubMed=10072786; DOI=10.1016/s0925-4773(98)00205-6;
RA Nakashima M., Toyono T., Akamine A., Joyner A.;
RT "Expression of growth/differentiation factor 11, a new member of the
RT BMP/TGFbeta superfamily during mouse embryogenesis.";
RL Mech. Dev. 80:185-189(1999).
RN [4]
RP PROTEIN SEQUENCE OF 120-125, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF
RP ASP-120.
RX PubMed=15988002; DOI=10.1128/mcb.25.14.5846-5858.2005;
RA Ge G., Hopkins D.R., Ho W.B., Greenspan D.S.;
RT "GDF11 forms a bone morphogenetic protein 1-activated latent complex that
RT can modulate nerve growth factor-induced differentiation of PC12 cells.";
RL Mol. Cell. Biol. 25:5846-5858(2005).
RN [5]
RP FUNCTION, AND INTERACTION WITH ACVR2A AND ACVR2B.
RX PubMed=12414726; DOI=10.1101/gad.1021802;
RA Oh S.P., Yeo C.Y., Lee Y., Schrewe H., Whitman M., Li E.;
RT "Activin type IIA and IIB receptors mediate Gdf11 signaling in axial
RT vertebral patterning.";
RL Genes Dev. 16:2749-2754(2002).
RN [6]
RP FUNCTION, AND INTERACTION WITH ACVR2B.
RX PubMed=16845371; DOI=10.1038/sj.embor.7400752;
RA Andersson O., Reissmann E., Ibanez C.F.;
RT "Growth differentiation factor 11 signals through the transforming growth
RT factor-beta receptor ALK5 to regionalize the anterior-posterior axis.";
RL EMBO Rep. 7:831-837(2006).
CC -!- FUNCTION: Secreted signal that acts globally to regulate
CC anterior/posterior axial patterning during development
CC (PubMed:10391213). May play critical roles in patterning both
CC mesodermal and neural tissues (PubMed:10391213). It is required for
CC proper vertebral patterning and orofacial development (By similarity).
CC Signals through activin receptors type-2, ACVR2A and ACVR2B, and
CC activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the
CC phosphorylation of SMAD2 and SMAD3 (PubMed:16845371, PubMed:12414726).
CC {ECO:0000250|UniProtKB:O95390, ECO:0000269|PubMed:10391213,
CC ECO:0000269|PubMed:12414726, ECO:0000269|PubMed:16845371}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts
CC directly with ACVR2B (PubMed:16845371, PubMed:12414726). Interacts
CC directly with ACVR2A (PubMed:12414726). Interacts with ACVR1B, TGFBR1
CC and ACVR1C in an ACVR2B-dependent manner (PubMed:16845371). Interacts
CC with FST isoform 2/FS288 (By similarity).
CC {ECO:0000250|UniProtKB:O95390, ECO:0000269|PubMed:12414726,
CC ECO:0000269|PubMed:16845371}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the developing limb bud,
CC initially detected in the distal mesenchyme, and later localizing to
CC regions around the developing bones. Is also expressed in adult dental
CC pulp and brain.
CC -!- DEVELOPMENTAL STAGE: First strongly expressed in restricted domains at
CC 8.5 dpc where it is highest in the tail bud. At 10.5 dpc, expressed in
CC the branchial arches, limb bud, tail bud and posterior dorsal neural
CC tube. Later, expressed in terminally-differentiated odontoblasts, the
CC nasal epithelium, retina and specific regions of the brain.
CC {ECO:0000269|PubMed:10075854, ECO:0000269|PubMed:10391213}.
CC -!- PTM: Synthesized as large precursor molecule that undergoes proteolytic
CC cleavage by furin-like proteases (By similarity). This produces an
CC inactive form consisting of the mature C-terminal portion non-
CC covalently bound to its cleaved N-terminal propeptide. Activation of
CC the mature form requires additional cleavage of the propeptide by a
CC tolloid-like metalloproteinase. {ECO:0000250|UniProtKB:O95390,
CC ECO:0000269|PubMed:15988002}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice die neonatally showing altered
CC patterning of the axial skeleton and impaired renal, palate, stomach,
CC spleen and pancreatic development. {ECO:0000269|PubMed:10391213}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AF100906; AAC72853.1; -; Genomic_DNA.
DR EMBL; AF100904; AAC72853.1; JOINED; Genomic_DNA.
DR EMBL; AF100905; AAC72853.1; JOINED; Genomic_DNA.
DR EMBL; AF028337; AAF21633.1; -; Genomic_DNA.
DR EMBL; AF028335; AAF21633.1; JOINED; Genomic_DNA.
DR EMBL; AF028336; AAF21633.1; JOINED; Genomic_DNA.
DR EMBL; AF092734; AAD05267.1; -; mRNA.
DR CCDS; CCDS24296.1; -.
DR RefSeq; NP_034402.1; NM_010272.2.
DR AlphaFoldDB; Q9Z1W4; -.
DR SMR; Q9Z1W4; -.
DR BioGRID; 199886; 3.
DR DIP; DIP-29907N; -.
DR IntAct; Q9Z1W4; 5.
DR MINT; Q9Z1W4; -.
DR STRING; 10090.ENSMUSP00000026408; -.
DR GlyGen; Q9Z1W4; 1 site.
DR iPTMnet; Q9Z1W4; -.
DR PhosphoSitePlus; Q9Z1W4; -.
DR PaxDb; Q9Z1W4; -.
DR PeptideAtlas; Q9Z1W4; -.
DR PRIDE; Q9Z1W4; -.
DR ProteomicsDB; 265739; -.
DR Antibodypedia; 27725; 287 antibodies from 33 providers.
DR DNASU; 14561; -.
DR Ensembl; ENSMUST00000026408; ENSMUSP00000026408; ENSMUSG00000025352.
DR GeneID; 14561; -.
DR KEGG; mmu:14561; -.
DR UCSC; uc007hot.1; mouse.
DR CTD; 10220; -.
DR MGI; MGI:1338027; Gdf11.
DR VEuPathDB; HostDB:ENSMUSG00000025352; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000161052; -.
DR HOGENOM; CLU_020515_6_1_1; -.
DR InParanoid; Q9Z1W4; -.
DR OMA; NSRAGHW; -.
DR OrthoDB; 892873at2759; -.
DR PhylomeDB; Q9Z1W4; -.
DR TreeFam; TF318514; -.
DR BioGRID-ORCS; 14561; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9Z1W4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9Z1W4; protein.
DR Bgee; ENSMUSG00000025352; Expressed in dorsal root ganglion and 108 other tissues.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0035881; P:amacrine cell differentiation; IDA:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0001656; P:metanephros development; IDA:MGI.
DR GO; GO:1902870; P:negative regulation of amacrine cell differentiation; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; IGI:MGI.
DR GO; GO:0001501; P:skeletal system development; IGI:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0021512; P:spinal cord anterior/posterior patterning; IMP:MGI.
DR GO; GO:0072560; P:type B pancreatic cell maturation; IMP:MGI.
DR GO; GO:0001657; P:ureteric bud development; IMP:MGI.
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; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..296
FT /evidence="ECO:0000250"
FT /id="PRO_0000033988"
FT CHAIN 297..405
FT /note="Growth/differentiation factor 11"
FT /id="PRO_0000033989"
FT SITE 119..120
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:15988002"
FT SITE 296
FT /note="Cleavage; by FURIN"
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 302..312
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT DISULFID 311..370
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT DISULFID 339..402
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT DISULFID 343..404
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT DISULFID 369
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O95390"
FT MUTAGEN 120
FT /note="D->A: Inhibits processing of prodomain."
FT /evidence="ECO:0000269|PubMed:15988002"
FT CONFLICT 75
FT /note="E -> G (in Ref. 3; AAD05267)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="T -> N (in Ref. 2; AAF21633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 44947 MW; A74E382710A14781 CRC64;
MVLAAPLLLG FLLLALELRP RGEAAEGPAA AAAAAAAAAG VGGERSSRPA PSAPPEPDGC
PVCVWRQHSR ELRLESIKSQ ILSKLRLKEA PNISREVVKQ LLPKAPPLQQ ILDLHDFQGD
ALQPEDFLEE DEYHATTETV ISMAQETDPA VQTDGSPLCC HFHFSPKVMF TKVLKAQLWV
YLRPVPRPAT VYLQILRLKP LTGEGTAGGG GGGRRHIRIR SLKIELHSRS GHWQSIDFKQ
VLHSWFRQPQ SNWGIEINAF DPSGTDLAVT SLGPGAEGLH PFMELRVLEN TKRSRRNLGL
DCDEHSSESR CCRYPLTVDF EAFGWDWIIA PKRYKANYCS GQCEYMFMQK YPHTHLVQQA
NPRGSAGPCC TPTKMSPINM LYFNDKQQII YGKIPGMVVD RCGCS
