GDF5_MOUSE
ID GDF5_MOUSE Reviewed; 495 AA.
AC P43027; A2ARK2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Growth/differentiation factor 5;
DE Short=GDF-5;
DE AltName: Full=Bone morphogenetic protein 14;
DE Short=BMP-14;
DE Flags: Precursor;
GN Name=Gdf5; Synonyms=Bmp14, Bp, Gdf-5;
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 [MRNA], AND VARIANT SER-98.
RC STRAIN=CD-1; TISSUE=Embryo;
RX PubMed=8145850; DOI=10.1038/368639a0;
RA Storm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M.,
RA Lee S.-J.;
RT "Limb alterations in brachypodism mice due to mutations in a new member of
RT the TGF beta-superfamily.";
RL Nature 368:639-643(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-98.
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH HTRA3.
RX PubMed=15206957; DOI=10.1111/j.1440-169x.2004.00743.x;
RA Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.;
RT "Developmentally regulated expression of mouse HtrA3 and its role as an
RT inhibitor of TGF-beta signaling.";
RL Dev. Growth Differ. 46:257-274(2004).
RN [6]
RP INTERACTION WITH HTRA1.
RX PubMed=14973287; DOI=10.1242/dev.00999;
RA Oka C., Tsujimoto R., Kajikawa M., Koshiba-Takeuchi K., Ina J., Yano M.,
RA Tsuchiya A., Ueta Y., Soma A., Kanda H., Matsumoto M., Kawaichi M.;
RT "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family
RT proteins.";
RL Development 131:1041-1053(2004).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=24076600; DOI=10.1038/ng.2772;
RA Sartori R., Schirwis E., Blaauw B., Bortolanza S., Zhao J., Enzo E.,
RA Stantzou A., Mouisel E., Toniolo L., Ferry A., Stricker S., Goldberg A.L.,
RA Dupont S., Piccolo S., Amthor H., Sandri M.;
RT "BMP signaling controls muscle mass.";
RL Nat. Genet. 45:1309-1318(2013).
CC -!- FUNCTION: Growth factor involved in bone and cartilage formation.
CC During cartilage development regulates differentiation of chondrogenic
CC tissue through two pathways. Firstly, positively regulates
CC differentiation of chondrogenic tissue through its binding of high
CC affinity with BMPR1B and of less affinity with BMPR1A, leading to
CC induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD
CC protein signaling transduction (By similarity). Secondly, negatively
CC regulates chondrogenic differentiation through its interaction with NOG
CC (By similarity). Required to prevent excessive muscle loss upon
CC denervation. This function requires SMAD4 and is mediated by
CC phosphorylated SMAD1/5/8 (PubMed:24076600). Binds bacterial
CC lipopolysaccharide (LPS) and mediates LPS-induced inflammatory
CC response, including TNF secretion by monocytes (By similarity).
CC {ECO:0000250|UniProtKB:P43026, ECO:0000269|PubMed:24076600}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287).
CC Following LPS binding, may form a complex with CXCR4, HSP90AA1 and
CC HSPA8 (By similarity). Interacts with high affinity with NOG; inhibits
CC chondrogenesis (By similarity). Interacts with high affinity with
CC BMPR1B and lower affinity with BMPR1A; positively regulates chondrocyte
CC differentiation and induces SMAD-dependent signaling. Interacts with
CC FBN1 (via N-terminal domain) and FBN2 (By similarity).
CC {ECO:0000250|UniProtKB:P43026, ECO:0000269|PubMed:14973287,
CC ECO:0000269|PubMed:15206957}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P43026}. Cell
CC membrane {ECO:0000250|UniProtKB:P43026}.
CC -!- INDUCTION: Induced over 300-fold in tibialis anterior muscles 3 days
CC following denervation. High expression is maintained at least until 10
CC days after denervation. {ECO:0000269|PubMed:24076600}.
CC -!- DISEASE: Note=Defects in Gdf5 are the cause of brachypodism (bp) which
CC alters the length and numbers of bones in the limbs but spares the
CC axial skeleton. {ECO:0000269|PubMed:8145850}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; U08337; AAA18778.1; -; mRNA.
DR EMBL; AL845445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06156.1; -; Genomic_DNA.
DR EMBL; BC034546; AAH34546.1; -; mRNA.
DR CCDS; CCDS16958.1; -.
DR PIR; S43294; S43294.
DR RefSeq; NP_032135.2; NM_008109.3.
DR AlphaFoldDB; P43027; -.
DR SMR; P43027; -.
DR BioGRID; 199888; 2.
DR STRING; 10090.ENSMUSP00000048079; -.
DR GlyGen; P43027; 1 site.
DR iPTMnet; P43027; -.
DR PhosphoSitePlus; P43027; -.
DR PaxDb; P43027; -.
DR PRIDE; P43027; -.
DR Antibodypedia; 2854; 410 antibodies from 31 providers.
DR DNASU; 14563; -.
DR Ensembl; ENSMUST00000040162; ENSMUSP00000048079; ENSMUSG00000038259.
DR GeneID; 14563; -.
DR KEGG; mmu:14563; -.
DR UCSC; uc012chg.1; mouse.
DR CTD; 8200; -.
DR MGI; MGI:95688; Gdf5.
DR VEuPathDB; HostDB:ENSMUSG00000038259; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160455; -.
DR HOGENOM; CLU_020515_0_0_1; -.
DR InParanoid; P43027; -.
DR OMA; QGKRPTK; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; P43027; -.
DR TreeFam; TF316134; -.
DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
DR BioGRID-ORCS; 14563; 3 hits in 73 CRISPR screens.
DR PRO; PR:P43027; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P43027; protein.
DR Bgee; ENSMUSG00000038259; Expressed in manual digit and 107 other tissues.
DR Genevisible; P43027; MM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0036122; F:BMP binding; 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:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0060591; P:chondroblast differentiation; ISO:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR GO; GO:0035136; P:forelimb morphogenesis; IMP:MGI.
DR GO; GO:0035137; P:hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISO:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0043932; P:ossification involved in bone remodeling; IEA:Ensembl.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:MGI.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; ISO:MGI.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISO:MGI.
DR GO; GO:0007178; P:transmembrane receptor protein serine/threonine kinase signaling pathway; IGI: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 Cell membrane; Chondrogenesis; Cleavage on pair of basic residues;
KW Cytokine; Disulfide bond; Glycoprotein; Growth factor; Membrane;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT PROPEP 28..375
FT /evidence="ECO:0000255"
FT /id="PRO_0000033914"
FT CHAIN 376..495
FT /note="Growth/differentiation factor 5"
FT /id="PRO_0000033915"
FT REGION 30..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 80..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 394..460
FT /evidence="ECO:0000250"
FT DISULFID 423..492
FT /evidence="ECO:0000250"
FT DISULFID 427..494
FT /evidence="ECO:0000250"
FT DISULFID 459
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VARIANT 98
FT /note="P -> S"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8145850"
SQ SEQUENCE 495 AA; 54895 MW; 8FAECD5A9C996D6E CRC64;
MRLPKLLTLL LWHLAWLDLE LICTVLGAPD LGQRTPGAKP GLTKAEAKER PPLARNVFRP
GGHIYGVGAT NARAKGSSGQ TQAKKDEPRK MPPRSGGPET KPGPSSQTRQ AAARTVTPKG
QLPGGKASSK AGSAPSSFLL KKTREPGTPR EPKEPFRPPP ITPHEYMLSL YRTLSDADRK
GGNSSVKLEA GLANTITSFI DKGQDDRGPA VRKQRYVFDI SALEKDGLLG AELRILRKKP
LDVAKPAVPS SGRVAQLKLS SCPSGRQPAA LLDVRSVPGL DGSGWEVFDI WKLFRNFKNS
AQLCLELEAW ERGRAVDLRG LGFERTARQV HEKALFLVFG RTKKRDLFFN EIKARSGQDD
KTVYEYLFSQ RRKRRAPLAN RQGKRPSKNL KARCSRKALH VNFKDMGWDD WIIAPLEYEA
FHCEGLCEFP LRSHLEPTNH AVIQTLMNSM DPESTPPTCC VPTRLSPISI LFIDSANNVV
YKQYEDMVVE SCGCR
