Endoglin

Details

Name
Endoglin
Synonyms
  • END
Gene Name
ENG
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006766|Endoglin
MDRGTLPLAVALLLASCSLSPTSLAETVHCDLQPVGPERGEVTYTTSQVSKGCVAQAPNA
ILEVHVLFLEFPTGPSQLELTLQASKQNGTWPREVLLVLSVNSSVFLHLQALGIPLHLAY
NSSLVTFQEPPGVNTTELPSFPKTQILEWAAERGPITSAAELNDPQSILLRLGQAQGSLS
FCMLEASQDMGRTLEWRPRTPALVRGCHLEGVAGHKEAHILRVLPGHSAGPRTVTVKVEL
SCAPGDLDAVLILQGPPYVSWLIDANHNMQIWTTGEYSFKIFPEKNIRGFKLPDTPQGLL
GEARMLNASIVASFVELPLASIVSLHASSCGGRLQTSPAPIQTTPPKDTCSPELLMSLIQ
TKCADDAMTLVLKKELVAHLKCTITGLTFWDPSCEAEDRGDKFVLRSAYSSCGMQVSASM
ISNEAVVNILSSSSPQRKKVHCLNMDSLSFQLGLYLSPHFLQASNTIEPGQQSFVQVRVS
PSVSEFLLQLDSCHLDLGPEGGTVELIQGRAAKGNCVSLLSPSPEGDPRFSFLLHFYTVP
IPKTGTLSCTVALRPKTGSQDQEVHRTVFMRLNIISPDLSGCTSKGLVLPAVLGITFGAF
LIGALLTAALWYIYSHTRSPSKREPVVAVAAPASSESSSTNHSIGSTQSTPCSTSSMA
Number of residues
658
Molecular Weight
70577.325
Theoretical pI
6.59
GO Classification
Functions
activin binding / galactose binding / glycosaminoglycan binding / protein homodimerization activity / transforming growth factor beta binding / transforming growth factor beta receptor, cytoplasmic mediator activity / transforming growth factor beta-activated receptor activity / transmembrane signaling receptor activity / type I transforming growth factor beta receptor binding / type II transforming growth factor beta receptor binding
Processes
artery morphogenesis / BMP signaling pathway / cell adhesion / cell chemotaxis / cell migration / cell migration involved in endocardial cushion formation / cell motility / central nervous system vasculogenesis / chronological cell aging / detection of hypoxia / extracellular matrix disassembly / heart looping / intracellular signal transduction / negative regulation of cell migration / negative regulation of endothelial cell proliferation / negative regulation of nitric-oxide synthase activity / negative regulation of pathway-restricted SMAD protein phosphorylation / negative regulation of protein autophosphorylation / negative regulation of transcription from RNA polymerase II promoter / negative regulation of transforming growth factor beta receptor signaling pathway / patterning of blood vessels / positive regulation of BMP signaling pathway / positive regulation of pathway-restricted SMAD protein phosphorylation / positive regulation of protein phosphorylation / positive regulation of systemic arterial blood pressure / positive regulation of transcription from RNA polymerase II promoter / regulation of cell adhesion / regulation of cell proliferation / regulation of phosphorylation / regulation of transcription, DNA-templated / regulation of transforming growth factor beta receptor signaling pathway / response to hypoxia / smooth muscle tissue development / transforming growth factor beta receptor signaling pathway / vasculogenesis / venous blood vessel morphogenesis / wound healing
Components
cell surface / cytoplasm / endothelial microparticle / external side of plasma membrane / extracellular space / focal adhesion / nucleoplasm / receptor complex / transforming growth factor beta receptor homodimeric complex
General Function
Type ii transforming growth factor beta receptor binding
Specific Function
Major glycoprotein of vascular endothelium. Involved in the regulation of angiogenesis. May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors. Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade. Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGF-beta1 signaling through SMAD3.
Pfam Domain Function
Transmembrane Regions
587-611
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0021690|Endoglin (ENG)
ATGGACCGCGGCACGCTCCCTCTGGCTGTTGCCCTGCTGCTGGCCAGCTGCAGCCTCAGC
CCCACAAGTCTTGCAGAAACAGTCCATTGTGACCTTCAGCCTGTGGGCCCCGAGAGGGGC
GAGGTGACATATACCACTAGCCAGGTCTCGAAGGGCTGCGTGGCTCAGGCCCCCAATGCC
ATCCTTGAAGTCCATGTCCTCTTCCTGGAGTTCCCAACGGGCCCGTCACAGCTGGAGCTG
ACTCTCCAGGCATCCAAGCAAAATGGCACCTGGCCCCGAGAGGTGCTTCTGGTCCTCAGT
GTAAACAGCAGTGTCTTCCTGCATCTCCAGGCCCTGGGAATCCCACTGCACTTGGCCTAC
AATTCCAGCCTGGTCACCTTCCAAGAGCCCCCGGGGGTCAACACCACAGAGCTGCCATCC
TTCCCCAAGACCCAGATCCTTGAGTGGGCAGCTGAGAGGGGCCCCATCACCTCTGCTGCT
GAGCTGAATGACCCCCAGAGCATCCTCCTCCGACTGGGCCAAGCCCAGGGGTCACTGTCC
TTCTGCATGCTGGAAGCCAGCCAGGACATGGGCCGCACGCTCGAGTGGCGGCCGCGTACT
CCAGCCTTGGTCCGGGGCTGCCACTTGGAAGGCGTGGCCGGCCACAAGGAGGCGCACATC
CTGAGGGTCCTGCCGGGCCACTCGGCCGGGCCCCGGACGGTGACGGTGAAGGTGGAACTG
AGCTGCGCACCCGGGGATCTCGATGCCGTCCTCATCCTGCAGGGTCCCCCCTACGTGTCC
TGGCTCATCGACGCCAACCACAACATGCAGATCTGGACCACTGGAGAATACTCCTTCAAG
ATCTTTCCAGAGAAAAACATTCGTGGCTTCAAGCTCCCAGACACACCTCAAGGCCTCCTG
GGGGAGGCCCGGATGCTCAATGCCAGCATTGTGGCATCCTTCGTGGAGCTACCGCTGGCC
AGCATTGTCTCACTTCATGCCTCCAGCTGCGGTGGTAGGCTGCAGACCTCACCCGCACCG
ATCCAGACCACTCCTCCCAAGGACACTTGTAGCCCGGAGCTGCTCATGTCCTTGATCCAG
ACAAAGTGTGCCGACGACGCCATGACCCTGGTACTAAAGAAAGAGCTTGTTGCGCATTTG
AAGTGCACCATCACGGGCCTGACCTTCTGGGACCCCAGCTGTGAGGCAGAGGACAGGGGT
GACAAGTTTGTCTTGCGCAGTGCTTACTCCAGCTGTGGCATGCAGGTGTCAGCAAGTATG
ATCAGCAATGAGGCGGTGGTCAATATCCTGTCGAGCTCATCACCACAGCGGAAAAAGGTG
CACTGCCTCAACATGGACAGCCTCTCTTTCCAGCTGGGCCTCTACCTCAGCCCACACTTC
CTCCAGGCCTCCAACACCATCGAGCCGGGGCAGCAGAGCTTTGTGCAGGTCAGAGTGTCC
CCATCCGTCTCCGAGTTCCTGCTCCAGTTAGACAGCTGCCACCTGGACTTGGGGCCTGAG
GGAGGCACCGTGGAACTCATCCAGGGCCGGGCGGCCAAGGGCAACTGTGTGAGCCTGCTG
TCCCCAAGCCCCGAGGGTGACCCGCGCTTCAGCTTCCTCCTCCACTTCTACACAGTACCC
ATACCCAAAACCGGCACCCTCAGCTGCACGGTAGCCCTGCGTCCCAAGACCGGGTCTCAA
GACCAGGAAGTCCATAGGACTGTCTTCATGCGCTTGAACATCATCAGCCCTGACCTGTCT
GGTTGCACAAGCAAAGGCCTCGTCCTGCCCGCCGTGCTGGGCATCACCTTTGGTGCCTTC
CTCATCGGGGCCCTGCTCACTGCTGCACTCTGGTACATCTACTCGCACACGCGTGAGTAC
CCCAGGCCCCCACAGTGA
Chromosome Location
9
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP17813
UniProtKB Entry NameEGLN_HUMAN
GenBank Gene IDU37439
GenAtlas IDENG
HGNC IDHGNC:3349
General References
  1. Bellon T, Corbi A, Lastres P, Cales C, Cebrian M, Vera S, Cheifetz S, Massague J, Letarte M, Bernabeu C: Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions. Eur J Immunol. 1993 Sep;23(9):2340-5. [Article]
  2. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  3. Gougos A, Letarte M: Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem. 1990 May 25;265(15):8361-4. [Article]
  4. McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, et al.: Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994 Dec;8(4):345-51. [Article]
  5. Meng Q, Lux A, Holloschi A, Li J, Hughes JM, Foerg T, McCarthy JE, Heagerty AM, Kioschis P, Hafner M, Garland JM: Identification of Tctex2beta, a novel dynein light chain family member that interacts with different transforming growth factor-beta receptors. J Biol Chem. 2006 Dec 1;281(48):37069-80. Epub 2006 Sep 18. [Article]
  6. Lee NY, Blobe GC: The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells. J Biol Chem. 2007 Jul 20;282(29):21507-17. Epub 2007 May 31. [Article]
  7. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
  8. Castonguay R, Werner ED, Matthews RG, Presman E, Mulivor AW, Solban N, Sako D, Pearsall RS, Underwood KW, Seehra J, Kumar R, Grinberg AV: Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem. 2011 Aug 26;286(34):30034-46. doi: 10.1074/jbc.M111.260133. Epub 2011 Jul 7. [Article]
  9. Alt A, Miguel-Romero L, Donderis J, Aristorena M, Blanco FJ, Round A, Rubio V, Bernabeu C, Marina A: Structural and functional insights into endoglin ligand recognition and binding. PLoS One. 2012;7(2):e29948. doi: 10.1371/journal.pone.0029948. Epub 2012 Feb 8. [Article]
  10. Nolan-Stevaux O, Zhong W, Culp S, Shaffer K, Hoover J, Wickramasinghe D, Ruefli-Brasse A: Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies. PLoS One. 2012;7(12):e50920. doi: 10.1371/journal.pone.0050920. Epub 2012 Dec 27. [Article]
  11. Shovlin CL, Hughes JM, Scott J, Seidman CE, Seidman JG: Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am J Hum Genet. 1997 Jul;61(1):68-79. [Article]
  12. Yamaguchi H, Azuma H, Shigekiyo T, Inoue H, Saito S: A novel missense mutation in the endoglin gene in hereditary hemorrhagic telangiectasia. Thromb Haemost. 1997 Feb;77(2):243-7. [Article]
  13. Gallione CJ, Klaus DJ, Yeh EY, Stenzel TT, Xue Y, Anthony KB, McAllister KA, Baldwin MA, Berg JN, Lux A, Smith JD, Vary CP, Craigen WJ, Westermann CJ, Warner ML, Miller YE, Jackson CE, Guttmacher AE, Marchuk DA: Mutation and expression analysis of the endoglin gene in hereditary hemorrhagic telangiectasia reveals null alleles. Hum Mutat. 1998;11(4):286-94. [Article]
  14. Pece-Barbara N, Cymerman U, Vera S, Marchuk DA, Letarte M: Expression analysis of four endoglin missense mutations suggests that haploinsufficiency is the predominant mechanism for hereditary hemorrhagic telangiectasia type 1. Hum Mol Genet. 1999 Nov;8(12):2171-81. [Article]
  15. Gallione CJ, Scheessele EA, Reinhardt D, Duits AJ, Berg JN, Westermann CJ, Marchuk DA: Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect. Hum Genet. 2000 Jul;107(1):40-4. [Article]
  16. Cymerman U, Vera S, Pece-Barbara N, Bourdeau A, White RI Jr, Dunn J, Letarte M: Identification of hereditary hemorrhagic telangiectasia type 1 in newborns by protein expression and mutation analysis of endoglin. Pediatr Res. 2000 Jan;47(1):24-35. [Article]
  17. Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S: Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. [Article]
  18. Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M: Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat. 2005 Mar;25(3):320. [Article]
  19. Bossler AD, Richards J, George C, Godmilow L, Ganguly A: Novel mutations in ENG and ACVRL1 identified in a series of 200 individuals undergoing clinical genetic testing for hereditary hemorrhagic telangiectasia (HHT): correlation of genotype with phenotype. Hum Mutat. 2006 Jul;27(7):667-75. [Article]
  20. Argyriou L, Twelkemeyer S, Panchulidze I, Wehner LE, Teske U, Engel W, Nayernia K: Novel mutations in the ENG and ACVRL1 genes causing hereditary hemorrhagic teleangiectasia. Int J Mol Med. 2006 Apr;17(4):655-9. [Article]
  21. Richards-Yutz J, Grant K, Chao EC, Walther SE, Ganguly A: Update on molecular diagnosis of hereditary hemorrhagic telangiectasia. Hum Genet. 2010 Jul;128(1):61-77. doi: 10.1007/s00439-010-0825-4. Epub 2010 Apr 23. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06322CarotuximabinvestigationalunknownDetails