Bone morphogenetic protein 6

BMP6

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2QCW, 2R52, 2R53

Identifiers

Aliases

BMP6, VGR, VGR1, bone morphogenetic protein 6

External IDs

OMIM: 112266 MGI: 88182 HomoloGene: 1300 GeneCards: BMP6

Genetically Related Diseases

myopia, orofacial cleft^[1]

Gene ontology
Molecular function	• cytokine activity • BMP receptor binding • protein heterodimerization activity • transforming growth factor beta receptor binding • growth factor activity
Cellular component	• cytoplasm • extracellular space • extracellular region • membrane-bounded vesicle
Biological process	• eye development • regulation of apoptotic process • skeletal system development • cell differentiation • cellular response to iron ion • male genitalia development • positive regulation of aldosterone secretion • positive regulation of endothelial cell differentiation • regulation of MAPK cascade • positive regulation of endothelial cell proliferation • SMAD protein signal transduction • positive regulation of aldosterone biosynthetic process • response to retinoic acid • ossification • kidney development • positive regulation of bone mineralization • positive regulation of epithelial cell proliferation • positive regulation of pathway-restricted SMAD protein phosphorylation • cellular response to BMP stimulus • response to magnesium ion • response to glucocorticoid • negative regulation of transcription from RNA polymerase II promoter • endochondral ossification • positive regulation of DNA-dependent DNA replication • response to activity • BMP signaling pathway • response to iron ion • positive regulation of lipopolysaccharide-mediated signaling pathway • growth • multicellular organismal iron ion homeostasis • multicellular organism development • cellular response to mechanical stimulus • cartilage development • positive regulation of osteoblast differentiation • positive regulation of chondrocyte differentiation • osteoblast differentiation • immune response • positive regulation of neuron differentiation • positive regulation of protein secretion • inflammatory response • type B pancreatic cell development • positive regulation of transcription from RNA polymerase II promoter • positive regulation of SMAD protein import into nucleus • cellular iron ion homeostasis
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


654


12161

Ensembl


ENSG00000153162


ENSMUSG00000039004

UniProt


P22004


P20722

RefSeq (mRNA)


NM_001718


NM_007556

RefSeq (protein)


NP_001709.1


NP_031582.1

Location (UCSC)

Chr 6: 7.73 – 7.88 Mb

Chr 13: 38.35 – 38.5 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Bone morphogenetic protein 6 is a protein that in humans is encoded by the BMP6 gene.^[4]^[5]^[6]

The protein encoded by this gene is a member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce the growth of bone and cartilage. BMP6 is able to induce all osteogenic markers in mesenchymal stem cells.

The bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules that can induce ectopic bone growth. BMPs are part of the transforming growth factor-beta (TGFB) superfamily. BMPs were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. Based on its expression early in embryogenesis, the BMP encoded by this gene has a proposed role in early development. In addition, the fact that this BMP is closely related to BMP5 and BMP7 has led to speculation of possible bone inductive activity. As of April 2009, an additional function of BMP6 has been identified as described in Nature Genetics April; 41 [4]:386-8. BMP6 is the key regulator of hepcidin, the small peptide secreted by the liver which is the major regulator of iron metabolism in mammals.

^[6]

References

↑ "Diseases that are genetically associated with BMP6 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Hahn GV, Cohen RB, Wozney JM, Levitz CL, Shore EM, Zasloff MA, Kaplan FS (Dec 1992). "A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7". Genomics. 14 (3): 759–62. doi:10.1016/S0888-7543(05)80181-8. PMID 1427904.
↑ Sauermann U, Meyermann R, Schluesener HJ (Jan 1993). "Cloning of a novel TGF-beta related cytokine, the vgr, from rat brain: cloning of and comparison to homologous human cytokines". J Neurosci Res. 33 (1): 142–7. doi:10.1002/jnr.490330118. PMID 1453478.
1 2 "Entrez Gene: BMP6 bone morphogenetic protein 6".

Celeste AJ, Iannazzi JA, Taylor RC, et al. (1991). "Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone". Proc. Natl. Acad. Sci. U.S.A. 87 (24): 9843–7. doi:10.1073/pnas.87.24.9843. PMC 55270. PMID 2263636.
Schluesener HJ, Meyermann R (1995). "Immunolocalization of BMP-6, a novel TGF-beta-related cytokine, in normal and atherosclerotic smooth muscle cells". Atherosclerosis. 113 (2): 153–6. doi:10.1016/0021-9150(94)05438-O. PMID 7605353.
Gitelman SE, Kobrin MS, Ye JQ, et al. (1994). "Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo". J. Cell Biol. 126 (6): 1595–609. doi:10.1083/jcb.126.6.1595. PMC 2290953. PMID 8089189.
Barnes J, Anthony CT, Wall N, Steiner MS (1997). "Bone morphogenetic protein-6 expression in normal and malignant prostate". World Journal of Urology. 13 (6): 337–43. PMID 9116752.
Hamdy FC, Autzen P, Robinson MC, et al. (1997). "Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue". Cancer Res. 57 (19): 4427–31. PMID 9331107.
Olavesen MG, Bentley E, Mason RV, et al. (1998). "Fine mapping of 39 ESTs on human chromosome 6p23-p25". Genomics. 46 (2): 303–6. doi:10.1006/geno.1997.5032. PMID 9417921.
Rickard DJ, Hofbauer LC, Bonde SK, et al. (1998). "Bone morphogenetic protein-6 production in human osteoblastic cell lines. Selective regulation by estrogen". J. Clin. Invest. 101 (2): 413–22. doi:10.1172/JCI119880. PMC 508581. PMID 9435314.
Tamada H, Kitazawa R, Gohji K, et al. (1998). "Molecular cloning and analysis of the 5'-flanking region of the human bone morphogenetic protein-6 (BMP-6)". Biochim. Biophys. Acta. 1395 (3): 247–51. doi:10.1016/S0167-4781(97)00191-7. PMID 9512655.
Ebisawa T, Tada K, Kitajima I, et al. (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci. 112 (20): 3519–27. PMID 10504300.
Heikinheimo KA, Laine MA, Ritvos OV, et al. (1999). "Bone morphogenetic protein-6 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland". Cancer Res. 59 (22): 5815–21. PMID 10582704.
Ahmed N, Sammons J, Carson RJ, et al. (2001). "Effect of bone morphogenetic protein-6 on haemopoietic stem cells and cytokine production in normal human bone marrow stroma". Cell Biol. Int. 25 (5): 429–35. doi:10.1006/cbir.2000.0662. PMID 11401330.
Shimizu M, Higuchi K, Kasai S, et al. (2003). "A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density". Mamm. Genome. 13 (7): 335–40. doi:10.1007/s00335-001-2129-4. PMID 12140680.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Moser M, Binder O, Wu Y, et al. (2003). "BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation". Mol. Cell. Biol. 23 (16): 5664–79. doi:10.1128/MCB.23.16.5664-5679.2003. PMC 166349. PMID 12897139.
Bobacz K, Gruber R, Soleiman A, et al. (2003). "Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro". Arthritis Rheum. 48 (9): 2501–8. doi:10.1002/art.11248. PMID 13130469.
Lories RJ, Derese I, Ceuppens JL, Luyten FP (2003). "Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proinflammatory cytokines and differentially modulate fibroblast-like synoviocyte apoptosis". Arthritis Rheum. 48 (10): 2807–18. doi:10.1002/art.11389. PMID 14558086.
Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. doi:10.1038/nature02055. PMID 14574404.
Laurikkala J, Kassai Y, Pakkasjärvi L, et al. (2004). "Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot". Dev. Biol. 264 (1): 91–105. doi:10.1016/j.ydbio.2003.08.011. PMID 14623234.

Cell signaling: TGFβ signaling pathway

TGF beta superfamily of ligands

TGF beta family	TGF-β1 TGF-β2 TGF-β3

Bone morphogenetic proteins	BMP2 BMP3 BMP4 BMP5 BMP6 BMP7 BMP8a BMP8b BMP10 BMP15

Growth differentiation factors	GDF1 GDF2 GDF3 GDF5 GDF6 GDF7 Myostatin/GDF8 GDF9 GDF10 GDF11 GDF15

Other	Activin and inhibin Anti-müllerian hormone Nodal

TGF beta receptors
(Activin, BMP)

TGFBR1:	Activin type 1 receptors ACVR1 ACVR1B ACVR1C ACVRL1 BMPR1 BMPR1A BMPR1B

TGFBR2:	Activin type 2 receptors ACVR2A ACVR2B AMHR2 BMPR2

TGFBR3:	betaglycan

Transducers/SMAD

Ligand inhibitors

Coreceptors

BAMBI
Cripto

Other

SARA

TGFβ receptor superfamily modulators

Type I

ALK1 (ACVRL1)	Agonists: Activin (A, B, AB) Avotermin BMP (10) Cetermin GDF (2 (BMP9)) TGFβ (1, 2, 3) Antibodies: Ascrinvacumab Kinase inhibitors: K-02288 ML-347 (LDN-193719, VU0469381) Decoy receptors: Dalantercept Other inhibitors: Disitertide

ALK2 (ACVR1A)	Agonists: Activin (A, B, AB) AMH (MIS) Avotermin BMP (5, 6, 7, 8A, 8B) Eptotermin alfa TGFβ (1, 2, 3) Kinase inhibitors: DMH-1 DMH-2 Dorsomorphin (BML-275) K-02288 ML-347 (LDN-193719, VU0469381)

ALK3 (BMPR1A)	Agonists: AMH (MIS) BMP (2, 4, 5, 6, 7, 8A, 8B) Dibotermin alfa Eptotermin alfa Kinase inhibitors: DMH-2 Dorsomorphin (BML-275) K-02288

ALK4 (ACVR1B)	Agonists: Activin (A, B, AB) GDF (1, 3, 11 (BMP11)) Myostatin (GDF8) Nodal Antagonists: Inhibin (A, B) Lefty (1, 2) Kinase inhibitors: A 83-01 SB-431542 SB-505124

ALK5 (TGFβR1)	Agonists: Avotermin GDF (10 (BMP3B), 11 (BMP11)) TGFβ (1, 2, 3) Antibodies: Fresolimumab Lerdelimumab Metelimumab Kinase inhibitors: A 83-01 D-4476 GW-788388 LY-364947 LY-2109761 Galunisertib (LY-2157299) R-268712 RepSox (E-616452, SJN-2511) SB-431542 SB-505124 SB-525334 SD-208

ALK6 (BMPR1B)	Agonists: BMP (2, 4, 5, 6, 7, 8A, 8B, 15 (GDF9B)) Dibotermin alfa Eptotermin alfa GDF (5 (BMP14), 6 (BMP13), 7 (BMP12), 9, 15) Radotermin Kinase inhibitors: DMH-2 Dorsomorphin (BML-275) K-02288

ALK7 (ACVR1C)	Agonists: GDF (1, 3, 11 (BMP11)) Nodal Antagonists: Lefty (1, 2) Kinase inhibitors: A 83-01 SB-431542 SB-505124

Type II

TGFβR2	Agonists: Avotermin GDF (10 (BMP3B)) TGFβ (1, 2, 3) Antibodies: Fresolimumab Lerdelimumab Metelimumab Kinase inhibitors: DMH-2 LY-364947

BMPR2	Agonists: BMP (2, 4, 6, 7, 10) Dibotermin alfa Eptotermin alfa GDF (2 (BMP9), 5 (BMP14), 6 (BMP13), 7 (BMP12)) Radotermin Antagonists: Inhibin (A, B)

ACVR2A (ACVR2)	Agonists: Activin (A, B, AB) BMP (2, 4, 5, 6, 7, 8A, 8B, 15 (GDF9B)) Dibotermin alfa Eptotermin alfa GDF (1, 3, 5 (BMP14), 6 (BMP13), 7 (BMP12), 9, 11 (BMP11), 15) Myostatin (GDF8) Nodal Radotermin Antagonists: Inhibin (A, B) Lefty (1, 2) Decoy receptors: Sotatercept

ACVR2B	Agonists: Activin (A, B, AB) BMP (2, 4, 6, 7) Dibotermin alfa Eptotermin alfa GDF (1, 3, 5 (BMP14), 6 (BMP13), 7 (BMP12)) Myostatin (GDF8) Nodal Osteogenin (BMP3, BMP3A) Radotermin Antagonists: Inhibin (A, B) Lefty (1, 2) Decoy receptors: Ramatercept

AMHR2 (AMHR)	Agonists: AMH (MIS)

Type III

TGFβR3 (β-glycan)	Ligands: Avotermin Inhibin (A, B) TGFβ (1, 2, 3)

Unsorted

Endogenous antagonists/inhibitors: BAMBI
Cerberus (CER1)
Chordin
DAN (PARN)
Decorin
Follistatin
Gremlin (Drm)
LTBP1
Noggin
TGIF
Thrombospondin 1 (THBS1)
Tomoregulin 1

Antibodies: Stamulumab (against myostatin)
TRC105 (against endoglin)

Others: Endoglin

See also: Growth factor receptor modulators
Cytokine receptor modulators
Peptide receptor modulators

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia - version of the 5/29/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

Bone morphogenetic protein 6

References

Further reading