BMP6_MOUSE
ID BMP6_MOUSE Reviewed; 510 AA.
AC P20722; B2RRV6;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Bone morphogenetic protein 6;
DE Short=BMP-6;
DE AltName: Full=VG-1-related protein;
DE Short=VGR-1;
DE Flags: Precursor;
GN Name=Bmp6; Synonyms=Bmp-6, Vgr1;
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].
RC TISSUE=Embryo;
RX PubMed=8089189; DOI=10.1083/jcb.126.6.1595;
RA Gitelman S.E., Kobrin M.S., Ye J.Q., Lopez A.R., Lee A., Derynck R.;
RT "Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral
RT bone formation in vivo.";
RL J. Cell Biol. 126:1595-1609(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9069123; DOI=10.1007/s003359900391;
RA Gitelman S.E., Kobrin M.S., Lee A., Fet V., Lyons K., Hogan B.L.M.,
RA Derynck R.;
RT "Structure and sequence of the mouse Bmp6 gene.";
RL Mamm. Genome 8:212-214(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-510.
RX PubMed=2734307; DOI=10.1073/pnas.86.12.4554;
RA Lyons K., Graycar J.L., Lee A., Hashmi S., Lindquist P.B., Chen E.Y.,
RA Hogan B.L.M., Derynck R.;
RT "Vgr-1, a mammalian gene related to Xenopus Vg-1, is a member of the
RT transforming growth factor beta gene superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4554-4558(1989).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=9664685;
RX DOI=10.1002/(sici)1520-6408(1998)22:4<321::aid-dvg3>3.0.co;2-8;
RA Solloway M.J., Dudley A.T., Bikoff E.K., Lyons K.M., Hogan B.L.,
RA Robertson E.J.;
RT "Mice lacking Bmp6 function.";
RL Dev. Genet. 22:321-339(1998).
RN [6]
RP INTERACTION WITH SOSTDC1.
RX PubMed=14623234; DOI=10.1016/j.ydbio.2003.08.011;
RA Laurikkala J., Kassai Y., Pakkasjaervi L., Thesleff I., Itoh N.;
RT "Identification of a secreted BMP antagonist, ectodin, integrating BMP,
RT FGF, and SHH signals from the tooth enamel knot.";
RL Dev. Biol. 264:91-105(2003).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH HEMOJUVELIN/HJV.
RX PubMed=19252486; DOI=10.1038/ng.335;
RA Andriopoulos B. Jr., Corradini E., Xia Y., Faasse S.A., Chen S.,
RA Grgurevic L., Knutson M.D., Pietrangelo A., Vukicevic S., Lin H.Y.,
RA Babitt J.L.;
RT "BMP6 is a key endogenous regulator of hepcidin expression and iron
RT metabolism.";
RL Nat. Genet. 41:482-487(2009).
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC essential roles in many developmental processes including cartilage and
CC bone formation (By similarity). Also plays an important role in the
CC regulation of iron metabolism by acting as a ligand for hemojuvelin/HJV
CC (PubMed:19252486). Initiates the canonical BMP signaling cascade by
CC associating with type I receptor ACVR1 and type II receptor ACVR2B. In
CC turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel
CC to the nucleus and act as activators and repressors of transcription of
CC target. Can also signal through non-canonical pathway such as TAZ-Hippo
CC signaling cascade to modulate VEGF signaling by regulating VEGFR2
CC expression (By similarity). {ECO:0000250|UniProtKB:P22004,
CC ECO:0000269|PubMed:19252486}.
CC -!- SUBUNIT: Interacts with SOSTDC1 (PubMed:14623234). Interacts (when
CC glycosylated) with type I receptor ACVR1. Interacts with type II
CC receptor ACVR2B (By similarity). Interacts with Hemojuvelin/HJV
CC (PubMed:19252486). {ECO:0000250|UniProtKB:P22004,
CC ECO:0000269|PubMed:14623234, ECO:0000269|PubMed:19252486}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the lung. Low levels seen in the
CC kidney.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile without
CC displaying overt effects in tissues known to express BMP6, suggesting a
CC functional redundancy among the factors of this subgroup
CC (PubMed:9664685). However, these mice show a significant increased
CC liver iron content (PubMed:19252486). {ECO:0000269|PubMed:19252486,
CC ECO:0000269|PubMed:9664685}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; X80992; CAA56917.1; -; mRNA.
DR EMBL; U73520; AAB18235.1; -; Genomic_DNA.
DR EMBL; U73515; AAB18235.1; JOINED; Genomic_DNA.
DR EMBL; U73516; AAB18235.1; JOINED; Genomic_DNA.
DR EMBL; U73517; AAB18235.1; JOINED; Genomic_DNA.
DR EMBL; U73518; AAB18235.1; JOINED; Genomic_DNA.
DR EMBL; U73519; AAB18235.1; JOINED; Genomic_DNA.
DR EMBL; BC138593; AAI38594.1; -; mRNA.
DR EMBL; BC138595; AAI38596.1; -; mRNA.
DR EMBL; J04566; AAA40548.1; -; mRNA.
DR CCDS; CCDS26462.1; -.
DR PIR; A54798; A54798.
DR RefSeq; NP_031582.1; NM_007556.3.
DR AlphaFoldDB; P20722; -.
DR SMR; P20722; -.
DR BioGRID; 198366; 1.
DR STRING; 10090.ENSMUSP00000126999; -.
DR GlyGen; P20722; 5 sites.
DR iPTMnet; P20722; -.
DR PhosphoSitePlus; P20722; -.
DR MaxQB; P20722; -.
DR PaxDb; P20722; -.
DR PRIDE; P20722; -.
DR ProteomicsDB; 273558; -.
DR Antibodypedia; 3456; 448 antibodies from 37 providers.
DR DNASU; 12161; -.
DR Ensembl; ENSMUST00000171970; ENSMUSP00000126999; ENSMUSG00000039004.
DR GeneID; 12161; -.
DR KEGG; mmu:12161; -.
DR UCSC; uc007qdp.1; mouse.
DR CTD; 654; -.
DR MGI; MGI:88182; Bmp6.
DR VEuPathDB; HostDB:ENSMUSG00000039004; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000158768; -.
DR HOGENOM; CLU_020515_4_1_1; -.
DR InParanoid; P20722; -.
DR OMA; ERQQPWP; -.
DR OrthoDB; 1063560at2759; -.
DR PhylomeDB; P20722; -.
DR TreeFam; TF316134; -.
DR BioGRID-ORCS; 12161; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Bmp6; mouse.
DR PRO; PR:P20722; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P20722; protein.
DR Bgee; ENSMUSG00000039004; Expressed in choroid plexus of fourth ventricle and 248 other tissues.
DR ExpressionAtlas; P20722; baseline and differential.
DR Genevisible; P20722; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0070700; F:BMP receptor binding; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; TAS:BHF-UCL.
DR GO; GO:0071281; P:cellular response to iron ion; IMP:BHF-UCL.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0001654; P:eye development; IGI:UniProtKB.
DR GO; GO:0006955; P:immune response; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEP:UniProtKB.
DR GO; GO:0001822; P:kidney development; IGI:UniProtKB.
DR GO; GO:0030539; P:male genitalia development; IGI:MGI.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; IMP:BHF-UCL.
DR GO; GO:1903392; P:negative regulation of adherens junction organization; ISO:MGI.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0001503; P:ossification; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IGI:MGI.
DR GO; GO:0032349; P:positive regulation of aldosterone biosynthetic process; ISO:MGI.
DR GO; GO:2000860; P:positive regulation of aldosterone secretion; ISO:MGI.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:MGI.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; ISO:MGI.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IDA:DFLAT.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:DFLAT.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:MGI.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IMP:BHF-UCL.
DR GO; GO:0003323; P:type B pancreatic cell development; ISO: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 Chondrogenesis; Cleavage on pair of basic residues; Cytokine;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Growth factor; Osteogenesis; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..371
FT /evidence="ECO:0000255"
FT /id="PRO_0000033872"
FT CHAIN 372..510
FT /note="Bone morphogenetic protein 6"
FT /id="PRO_0000033873"
FT REGION 87..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..178
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 379..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 238
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 409..475
FT /evidence="ECO:0000250"
FT DISULFID 438..507
FT /evidence="ECO:0000250"
FT DISULFID 442..509
FT /evidence="ECO:0000250"
FT DISULFID 474
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 73
FT /note="K -> M (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="E -> K (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="L -> P (in Ref. 4; AAA40548)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 510 AA; 56432 MW; 910B68531289FCD2 CRC64;
MPGLGRRAQW LCWWWGLLCS CGPPPLRPPL PVAAAAAGGQ LLGAGGSPVR AEQPPPQSSS
SGFLYRRLKT HEKREMQKEI LSVLGLPHRP RPLHGLQQPQ PPVLPPQQQQ QQQQQQTARE
EPPPGRLKSA PLFMLDLYNA LSNDDEEDGA SEGVGQEPGS HGGASSSQLR QPSPGAAHSL
NRKSLLAPGP GGGASPLTSA QDSAFLNDAD MVMSFVNLVE YDKEFSPHQR HHKEFKFNLS
QIPEGEAVTA AEFRVYKDCV VGSFKNQTFL ISIYQVLQEH QHRDSDLFLL DTRVVWASEE
GWLEFDITAT SNLWVVTPQH NMGLQLSVVT RDGLHVNPRA AGLVGRDGPY DKQPFMVAFF
KVSEVHVRTT RSASSRRRQQ SRNRSTQSQD VSRGSGSSDY NGSELKTACK KHELYVSFQD
LGWQDWIIAP KGYAANYCDG ECSFPLNAHM NATNHAIVQT LVHLMNPEYV PKPCCAPTKL
NAISVLYFDD NSNVILKKYR NMVVRACGCH
