BMP6_RAT
ID BMP6_RAT Reviewed; 506 AA.
AC Q04906; Q811S4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 144.
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, Vgr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Li H., Li J., Pittman D.D., Amalfitano A., Hankins G.R., Helm G.A.;
RT "An immunological study of BMP6 adenoviral gene therapy.";
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 300-506.
RC STRAIN=Lewis; TISSUE=Brain;
RX PubMed=1453478; DOI=10.1002/jnr.490330118;
RA Sauermann U., Meyermann R., Schluesener H.J.;
RT "Cloning of a novel TGF-beta related cytokine, the vgr, from rat brain:
RT cloning of and comparison to homologous human cytokines.";
RL J. Neurosci. Res. 33:142-147(1992).
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 (By similarity). 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:P20722,
CC ECO:0000250|UniProtKB:P22004}.
CC -!- SUBUNIT: Interacts with SOSTDC1 (By similarity). Interacts (when
CC glycosylated) with type I receptor ACVR1. Interacts with type II
CC receptor ACVR2B (By similarity). Interacts with Hemojuvelin/HJV (By
CC similarity). {ECO:0000250|UniProtKB:P20722,
CC ECO:0000250|UniProtKB:P22004}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {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; AY184240; AAO25744.1; -; mRNA.
DR EMBL; X58830; CAA41634.1; -; mRNA.
DR PIR; S37618; S37618.
DR RefSeq; NP_037239.1; NM_013107.1.
DR AlphaFoldDB; Q04906; -.
DR SMR; Q04906; -.
DR STRING; 10116.ENSRNOP00000018359; -.
DR GlyGen; Q04906; 5 sites.
DR iPTMnet; Q04906; -.
DR PhosphoSitePlus; Q04906; -.
DR PaxDb; Q04906; -.
DR Ensembl; ENSRNOT00000018359; ENSRNOP00000018359; ENSRNOG00000013717.
DR GeneID; 25644; -.
DR KEGG; rno:25644; -.
DR UCSC; RGD:2214; rat.
DR CTD; 654; -.
DR RGD; 2214; Bmp6.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000158768; -.
DR HOGENOM; CLU_020515_4_1_1; -.
DR InParanoid; Q04906; -.
DR OMA; ERQQPWP; -.
DR OrthoDB; 1063560at2759; -.
DR PhylomeDB; Q04906; -.
DR PRO; PR:Q04906; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000013717; Expressed in lung and 20 other tissues.
DR Genevisible; Q04906; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0070700; F:BMP receptor binding; ISO:RGD.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IDA:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:RGD.
DR GO; GO:0071281; P:cellular response to iron ion; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0001654; P:eye development; ISO:RGD.
DR GO; GO:0006955; P:immune response; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0001822; P:kidney development; ISO:RGD.
DR GO; GO:0030539; P:male genitalia development; ISO:RGD.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISO:RGD.
DR GO; GO:1903392; P:negative regulation of adherens junction organization; ISO:RGD.
DR GO; GO:2000048; P:negative regulation of cell-cell adhesion mediated by cadherin; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0001503; P:ossification; IDA:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:RGD.
DR GO; GO:0032349; P:positive regulation of aldosterone biosynthetic process; ISO:RGD.
DR GO; GO:2000860; P:positive regulation of aldosterone secretion; IDA:RGD.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:RGD.
DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:RGD.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:RGD.
DR GO; GO:0045595; P:regulation of cell differentiation; TAS:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0032026; P:response to magnesium ion; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0003323; P:type B pancreatic cell development; ISO:RGD.
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 2: Evidence at transcript 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..367
FT /evidence="ECO:0000255"
FT /id="PRO_0000033874"
FT CHAIN 368..506
FT /note="Bone morphogenetic protein 6"
FT /id="PRO_0000033875"
FT REGION 44..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..116
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..174
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 262
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 397
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 405..471
FT /evidence="ECO:0000250"
FT DISULFID 434..503
FT /evidence="ECO:0000250"
FT DISULFID 438..505
FT /evidence="ECO:0000250"
FT DISULFID 470
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 506 AA; 56223 MW; 703D077D7E94416C CRC64;
MPGLGRRAQW LCWWWGLLCS CGPPPLRPPL PVAAAAAGGQ LLGAGGSPVR AEQPPPQSSS
SGFLYRRLKT HEKREMQKEI LSVLGLPHRP RPLHGLQQPQ SPVLPQQQQS QQTAREEPPP
GRLKSAPLFM LDLYNSLSKD DEEDGVSEGE GLEPESHGRA SSSQLKQPSP GAAHSLNRKS
LLAPGPGGSA SPLTSAQDSA FLNDADMVMS FVNLVEYDKE FSPRQRHHKE FKFNLSQIPE
GEAVTAAEFR VYKDCVVGSF KNQTFLISIY QVLQEHQHRD SDLFLLDTRV VWASEEGWLE
FDITATSNLW VVTPQHNMGL QLSVVTRDGL HINPRAAGLV GRDGPYDKQP FMVAFFKVSE
VHVRTTRSAS SRRRQQSRNR STQSQDVSRG SSASDYNSSE LKTACKKHEL YVSFQDLGWQ
DWIIAPKGYA ANYCDGECSF PLNAHMNATN HAIVQTLVHL MNPEYVPKPC CAPTKLNAIS
VLYFDDNSNV ILKKYRNMVV RACGCH
