Bone morphogenetic protein receptor type-1A

Details

Name
Bone morphogenetic protein receptor type-1A
Kind
protein
Synonyms
  • 2.7.11.30
  • Activin receptor-like kinase 3
  • ACVRLK3
  • ALK-3
  • ALK3
  • BMP type-1A receptor
  • BMPR-1A
  • Serine/threonine-protein kinase receptor R5
  • SKR5
Gene Name
BMPR1A
UniProtKB Entry
P36894Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0051546|Bone morphogenetic protein receptor type-1A
MPQLYIYIRLLGAYLFIISRVQGQNLDSMLHGTGMKSDSDQKKSENGVTLAPEDTLPFLK
CYCSGHCPDDAINNTCITNGHCFAIIEEDDQGETTLASGCMKYEGSDFQCKDSPKAQLRR
TIECCRTNLCNQYLQPTLPPVVIGPFFDGSIRWLVLLISMAVCIIAMIIFSSCFCYKHYC
KSISSRRRYNRDLEQDEAFIPVGESLKDLIDQSQSSGSGSGLPLLVQRTIAKQIQMVRQV
GKGRYGEVWMGKWRGEKVAVKVFFTTEEASWFRETEIYQTVLMRHENILGFIAADIKGTG
SWTQLYLITDYHENGSLYDFLKCATLDTRALLKLAYSAACGLCHLHTEIYGTQGKPAIAH
RDLKSKNILIKKNGSCCIADLGLAVKFNSDTNEVDVPLNTRVGTKRYMAPEVLDESLNKN
HFQPYIMADIYSFGLIIWEMARRCITGGIVEEYQLPYYNMVPSDPSYEDMREVVCVKRLR
PIVSNRWNSDECLRAVLKLMSECWAHNPASRLTALRIKKTLAKMVESQDVKI
Number of residues
532
Molecular Weight
60196.915
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / BMP receptor activity / metal ion binding / protein homodimerization activity / protein serine/threonine kinase activity / SMAD binding / transmembrane receptor protein serine/threonine kinase activity
Processes
BMP signaling pathway / cardiac conduction system development / cardiac right ventricle morphogenesis / cellular response to BMP stimulus / chondrocyte differentiation / developmental growth / dorsal aorta morphogenesis / dorsal/ventral axis specification / ectoderm development / embryonic digit morphogenesis / embryonic organ development / endocardial cushion formation / endocardial cushion morphogenesis / fibrous ring of heart morphogenesis / heart formation / hindlimb morphogenesis / immune response / in utero embryonic development / lateral mesoderm development / lung development / mesendoderm development / mesoderm formation / mitral valve morphogenesis / Mullerian duct regression / negative regulation of neurogenesis / negative regulation of smooth muscle cell migration / neural crest cell development / neural plate mediolateral regionalization / odontogenesis of dentin-containing tooth / outflow tract morphogenesis / outflow tract septum morphogenesis / paraxial mesoderm structural organization / pharyngeal arch artery morphogenesis / pituitary gland development / positive regulation of bone mineralization / positive regulation of cardiac muscle cell proliferation / positive regulation of cardiac ventricle development / positive regulation of epithelial cell proliferation / positive regulation of mesenchymal cell proliferation / positive regulation of osteoblast differentiation / regulation of cardiac muscle cell proliferation / regulation of cellular senescence / regulation of lateral mesodermal cell fate specification / somitogenesis / transforming growth factor beta receptor signaling pathway / tricuspid valve morphogenesis / ventricular compact myocardium morphogenesis / ventricular trabecula myocardium morphogenesis
Components
dendrite / external side of plasma membrane / HFE-transferrin receptor complex / neuronal cell body / plasma membrane
General Function
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6. May promote the expression of HAMP, potentially via its interaction with BMP2 (By similarity)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
1-23
Transmembrane Regions
153-176
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051547|Bone morphogenetic protein receptor type-1A (BMPR1A)
ATGCCTCAGCTATACATTTACATCAGATTATTGGGAGCCTATTTGTTCATCATTTCTCGT
GTTCAAGGACAGAATCTGGATAGTATGCTTCATGGCACTGGGATGAAATCAGACTCCGAC
CAGAAAAAGTCAGAAAATGGAGTAACCTTAGCACCAGAGGATACCTTGCCTTTTTTAAAG
TGCTATTGCTCAGGGCACTGTCCAGATGATGCTATTAATAACACATGCATAACTAATGGA
CATTGCTTTGCCATCATAGAAGAAGATGACCAGGGAGAAACCACATTAGCTTCAGGGTGT
ATGAAATATGAAGGATCTGATTTTCAGTGCAAAGATTCTCCAAAAGCCCAGCTACGCCGG
ACAATAGAATGTTGTCGGACCAATTTATGTAACCAGTATTTGCAACCCACACTGCCCCCT
GTTGTCATAGGTCCGTTTTTTGATGGCAGCATTCGATGGCTGGTTTTGCTCATTTCTATG
GCTGTCTGCATAATTGCTATGATCATCTTCTCCAGCTGCTTTTGTTACAAACATTATTGC
AAGAGCATCTCAAGCAGACGTCGTTACAATCGTGATTTGGAACAGGATGAAGCATTTATT
CCAGTTGGAGAATCACTAAAAGACCTTATTGACCAGTCACAAAGTTCTGGTAGTGGGTCT
GGACTACCTTTATTGGTTCAGCGAACTATTGCCAAACAGATTCAGATGGTCCGGCAAGTT
GGTAAAGGCCGATATGGAGAAGTATGGATGGGCAAATGGCGTGGCGAAAAAGTGGCGGTG
AAAGTATTCTTTACCACTGAAGAAGCCAGCTGGTTTCGAGAAACAGAAATCTACCAAACT
GTGCTAATGCGCCATGAAAACATACTTGGTTTCATAGCGGCAGACATTAAAGGTACAGGT
TCCTGGACTCAGCTCTATTTGATTACTGATTACCATGAAAATGGATCTCTCTATGACTTC
CTGAAATGTGCTACACTGGACACCAGAGCCCTGCTTAAATTGGCTTATTCAGCTGCCTGT
GGTCTGTGCCACCTGCACACAGAAATTTATGGCACCCAAGGAAAGCCCGCAATTGCTCAT
CGAGACCTAAAGAGCAAAAACATCCTCATCAAGAAAAATGGGAGTTGCTGCATTGCTGAC
CTGGGCCTTGCTGTTAAATTCAACAGTGACACAAATGAAGTTGATGTGCCCTTGAATACC
AGGGTGGGCACCAAACGCTACATGGCTCCCGAAGTGCTGGACGAAAGCCTGAACAAAAAC
CACTTCCAGCCCTACATCATGGCTGACATCTACAGCTTCGGCCTAATCATTTGGGAGATG
GCTCGTCGTTGTATCACAGGAGGGATCGTGGAAGAATACCAATTGCCATATTACAACATG
GTACCGAGTGATCCGTCATACGAAGATATGCGTGAGGTTGTGTGTGTCAAACGTTTGCGG
CCAATTGTGTCTAATCGGTGGAACAGTGATGAATGTCTACGAGCAGTTTTGAAGCTAATG
TCAGAATGCTGGGCCCACAATCCAGCCTCCAGACTCACAGCATTGAGAATTAAGAAGACG
CTTGCCAAGATGGTTGAATCCCAAGATGTAAAAATCTGA
Chromosome Location
10
Locus
10q23.2
External Identifiers
ResourceLink
UniProtKB IDP36894
UniProtKB Entry NameBMR1A_HUMAN
GeneCard IDBMPR1A
HGNC IDHGNC:1076
PDB ID(s)1ES7, 1REW, 2GOO, 2H62, 2H64, 2K3G, 2QJ9, 2QJA, 2QJB, 3NH7, 3QB4
KEGG IDhsa:657
IUPHAR/Guide To Pharmacology ID1786
NCBI Gene ID657
General References
  1. ten Dijke P, Ichijo H, Franzen P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K: Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity. Oncogene. 1993 Oct;8(10):2879-87. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  4. Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP: Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. [Article]
  5. Degenkolbe E, Konig J, Zimmer J, Walther M, Reissner C, Nickel J, Ploger F, Raspopovic J, Sharpe J, Dathe K, Hecht JT, Mundlos S, Doelken SC, Seemann P: A GDF5 point mutation strikes twice--causing BDA1 and SYNS2. PLoS Genet. 2013;9(10):e1003846. doi: 10.1371/journal.pgen.1003846. Epub 2013 Oct 3. [Article]
  6. Kirsch T, Sebald W, Dreyer MK: Crystal structure of the BMP-2-BRIA ectodomain complex. Nat Struct Biol. 2000 Jun;7(6):492-6. [Article]
  7. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B: Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet. 2001 Jun;28(2):184-7. [Article]
  8. Klages J, Kotzsch A, Coles M, Sebald W, Nickel J, Muller T, Kessler H: The solution structure of BMPR-IA reveals a local disorder-to-order transition upon BMP-2 binding. Biochemistry. 2008 Nov 18;47(46):11930-9. doi: 10.1021/bi801059j. Epub 2008 Oct 21. [Article]
  9. Zhou XP, Woodford-Richens K, Lehtonen R, Kurose K, Aldred M, Hampel H, Launonen V, Virta S, Pilarski R, Salovaara R, Bodmer WF, Conrad BA, Dunlop M, Hodgson SV, Iwama T, Jarvinen H, Kellokumpu I, Kim JC, Leggett B, Markie D, Mecklin JP, Neale K, Phillips R, Piris J, Rozen P, Houlston RS, Aaltonen LA, Tomlinson IP, Eng C: Germline mutations in BMPR1A/ALK3 cause a subset of cases of juvenile polyposis syndrome and of Cowden and Bannayan-Riley-Ruvalcaba syndromes. Am J Hum Genet. 2001 Oct;69(4):704-11. Epub 2001 Aug 30. [Article]
  10. Sayed MG, Ahmed AF, Ringold JR, Anderson ME, Bair JL, Mitros FA, Lynch HT, Tinley ST, Petersen GM, Giardiello FM, Vogelstein B, Howe JR: Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol. 2002 Nov;9(9):901-6. [Article]
  11. Friedl W, Uhlhaas S, Schulmann K, Stolte M, Loff S, Back W, Mangold E, Stern M, Knaebel HP, Sutter C, Weber RG, Pistorius S, Burger B, Propping P: Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum Genet. 2002 Jul;111(1):108-11. Epub 2002 Jun 13. [Article]
  12. Kim IJ, Park JH, Kang HC, Kim KH, Kim JH, Ku JL, Kang SB, Park SY, Lee JS, Park JG: Identification of a novel BMPR1A germline mutation in a Korean juvenile polyposis patient without SMAD4 mutation. Clin Genet. 2003 Feb;63(2):126-30. [Article]
  13. Delnatte C, Sanlaville D, Mougenot JF, Vermeesch JR, Houdayer C, Blois MC, Genevieve D, Goulet O, Fryns JP, Jaubert F, Vekemans M, Lyonnet S, Romana S, Eng C, Stoppa-Lyonnet D: Contiguous gene deletion within chromosome arm 10q is associated with juvenile polyposis of infancy, reflecting cooperation between the BMPR1A and PTEN tumor-suppressor genes. Am J Hum Genet. 2006 Jun;78(6):1066-74. Epub 2006 Apr 14. [Article]
  14. Cao X, Eu KW, Kumarasinghe MP, Li HH, Loi C, Cheah PY: Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high-density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function. J Med Genet. 2006 Mar;43(3):e13. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Dibotermin alfaapproved, investigationalyestargetligandDetails