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Bone morphogenetic protein receptor

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Group of three receptors to bone morphogenetic proteins

Protein family

TKL Ser/Thr protein kinase family
Identifiers
Symbol	TKL
Membranome	1216

Bone morphogenetic protein receptors areserine-threonine kinase receptors.Transforming growth factor beta family proteins bind to these receptors.^[1] There are four bone morphogenetic protein receptors:^[2]

Structure

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Both type 1 and 2 bone morphogenetic protein receptors have a single transmembrane segment. Additionally, both types have a cysteine-rich extracellular domain and a cytoplasmic serine threonine kinase domain.^[3] Type 1 contains a glycine-serine-rich domain to be phosphorylated by type 2 kinase domain, initiating the signaling transduction pathway of theSMAD signaling cascade.^[3] The wrist epitope motif onBMP-2 has a high-affinity binding site for BMPR-IA. The knuckle epitope motif on BMP-2 has a low-affinity binding site for BMPR-II.^[4]

References

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^Miyazono K, Kamiya Y, Morikawa M (January 2010)."Bone morphogenetic protein receptors and signal transduction".Journal of Biochemistry.147 (1):35–51.doi:10.1093/jb/mvp148.PMID 19762341.
^Pasche B (December 2008). "The TGF Family. Cold Spring Harbor Monograph Series, Volume 50. Edited by Rik Derynck, Kohei Miyazono. Cold Spring Harbor (New York): Cold Spring Harbor Laboratory Press. xiv-1114 p.; ill.; index. 9780879697525. 2008".The Quarterly Review of Biology.83 (4): 405.doi:10.1086/596254.
^^a ^bMace PD, Cutfield JF, Cutfield SM (December 2006). "High resolution structures of the bone morphogenetic protein type II receptor in two crystal forms: implications for ligand binding".Biochemical and Biophysical Research Communications.351 (4):831–8.Bibcode:2006BBRC..351..831M.doi:10.1016/j.bbrc.2006.10.109.PMID 17094948.
^Miyazono K, Shimanuki T (January 2008). "Chapter 55: Bone morphogenetic protein receptors and actions.". In Bilezikian JP, Raisz LG, Martin TJ (eds.).Principles of bone biology (Third ed.). San Diego: Academic Press. pp. 1177–1196.doi:10.1016/B978-0-12-373884-4.00069-0.ISBN 978-0-12-373884-4.

External links

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Bone+Morphogenetic+Protein+Receptors at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

Receptors:growth factor receptors

Type I cytokine receptor

Receptor protein serine/threonine kinase

Receptor tyrosine kinase

Fibroblast growth factor 1 2 3 4
Nerve growth factors:high affinityTrk TrkA TrkB TrkC
Hepatocyte growth factor
Somatomedin Insulin-like growth factor 1
ErbB/Epidermal growth factor
VEGF 1 2 3

Tumor necrosis factor receptor

Nerve growth factors:Low affinity/p75

Ig superfamily

Other/ungrouped

Somatomedin
- Insulin-like growth factor 2

Cell signaling:TGFβ signaling pathway

TGF beta superfamily of ligands

Ligand ofACVR orTGFBR	TGF beta family TGF-β1 TGF-β2 TGF-β3 Activin and inhibin INHA INHBA INHBB INHBC Nodal
Ligand ofBMPR	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 Anti-müllerian hormone

TGF beta receptors
(Activin,BMP,family)

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

Other

SARA

Kinases:Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1
Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3 PDK4
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4
Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase Aurora C kinase
Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-
IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP
cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY
cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1
Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3
Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase
Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2
G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6
Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1
Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4
Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2
Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19
Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4
Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1
Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14
MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14
Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-
Tropomyosin kinase (EC 2.7.11.28)	-
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-
Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1Oxidoreductases (list) EC2Transferases (list) EC3Hydrolases (list) EC4Lyases (list) EC5Isomerases (list) EC6Ligases (list) EC7Translocases (list)

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)