Key residues involved in calcium-binding motifs in EGF-like domains

Penny A HandfordG G Brownlee


Many extracellular proteins with diverse functions contain domains similar to epidermal growth factor (EGF), a number of which have a consensus Asp/Asn, Asp/Asn, Asp*/Asn*, Tyr/Phe (where the asterisk denotes a beta-hydroxylated residue). These include the coagulation factors IX and X, proteins with two EGF-like domains, the first of which contains the consensus residues. The first EGF-like domain of human factor IX contains a calcium-binding site, which is believed to be responsible for one of the high-affinity sites detected in this protein. Similar results have been obtained for bovine factor X. We have now used protein engineering and 1H-NMR techniques to investigate the importance of individual consensus residues for ligand binding. Measurement of a calcium-dependent Tyr 69 shift in the isolated first EGF-like domain from human factor IX demonstrates that Asp 47, Asp 49, and Asp 64 are directly involved in this binding. Gln 50, whose importance has previously been overlooked, is also involved in this binding. Two mutations in this domain, Asp 47----Glu, and Asp 64----Asn, present in patients with haemophilia B, reduce calcium binding to the domain greater than 4-fold and greater than 1,000-fold, respectively. Furthermore, ...Continue Reading


Jul 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L VilliersM G Colomb
May 20, 1988·Cell·B Furie, B C Furie
May 3, 1987·Nature·R M CookeB Sheard
Jan 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·T A Kunkel


Jun 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·S MatsuhashiK Hori
Jan 1, 1992·Protein Science : a Publication of the Protein Society·Martin BaronI D Campbell
Sep 29, 2005·Springer Seminars in Immunopathology·Rikke SørensenJens C Jensenius
Jul 27, 2001·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·E Pidcock, G R Moore
Mar 7, 2008·Molecular Biotechnology·Hisataka KitanoShinichiro Kokubun
Mar 1, 1993·Mechanisms of Development·S Baumgartner, R Chiquet-Ehrismann
Mar 1, 1994·Matrix Biology : Journal of the International Society for Matrix Biology·Cay M KieltyC Adrian Shuttleworth
Mar 1, 1995·Trends in Cardiovascular Medicine·F J Castellino
Aug 1, 1995·The International Journal of Biochemistry & Cell Biology·Cay M Kielty, C Adrian Shuttleworth
Jun 20, 2003·International Journal for Parasitology·David M WitcombeNicholas C Smith
Jun 20, 2003·Progress in Lipid Research·Barry R Lentz
Jun 20, 2003·Veterinary Immunology and Immunopathology·José M Pérez de la LastraDiego Llanes
Mar 1, 1997·Matrix Biology : Journal of the International Society for Matrix Biology·P Maurer, E Hohenester
Oct 1, 1996·Current Opinion in Cell Biology·P MaurerJ Engel
Jun 6, 2000·Trends in Biochemical Sciences·M StaceyA J McKnight
Jul 17, 1998·Current Opinion in Chemical Biology·J EvenäsS Forsén
Jun 1, 1993·Immunology and Cell Biology·V M AveryD L Gordon
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nicholas J WangRaymond J Cho
Feb 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S FukuokaG A Scheele
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T HiroseK A Hasty
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·D ZhongS P Bajaj
Nov 7, 2012·The Journal of Biological Chemistry·Rebecca K DoneganRaquel L Lieberman
Sep 26, 2006·The Cerebellum·Shin-Ya Saito, Hiroshi Takeshima
Mar 1, 1994·The Journal of Cell Biology·Cay M Kielty, C Adrian Shuttleworth
May 9, 2006·Antioxidants & Redox Signaling·Pat WhitemanPenny A Handford
Jan 1, 1997·Nucleic Acids Research·F GiannelliG G Brownlee
Apr 2, 2010·Biology of Reproduction·Elizabeth Canty-LairdStéphane Fabre
Mar 31, 2006·Journal of Medical Genetics·P N RobinsonMaurice Godfrey
Jan 14, 2000·Journal of Medical Genetics·P N Robinson, Maurice Godfrey
Jan 26, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S L DallasL F Bonewald
Mar 23, 2012·PloS One·Adam Piha-GossackDieter P Reinhardt
Nov 5, 1999·Biochemical and Biophysical Research Communications·S KurodaK Ting
Jul 12, 2012·Cellular and Molecular Life Sciences : CMLS·Robert J Huber, Danton H O'Day
Dec 27, 1993·FEBS Letters·Cay M Kielty, C Adrian Shuttleworth
Mar 14, 1994·FEBS Letters·M MayhewG G Brownlee
Jan 31, 2016·Protein Expression and Purification·Richard G DiScipioIngrid U Schraufstatter
Jun 10, 2005·FEBS Letters·R WagenerM Paulsson
Oct 10, 2015·Journal of Cell Communication and Signaling·Karina A Zeyer, Dieter P Reinhardt
Sep 24, 2009·Ageing Research Reviews·Ling-Gen GaoXian-Liang Zhou
Oct 2, 2004·Human Mutation·Anneke I den HollanderFrans P M Cremers
May 27, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Michael J FitchHeidi Stuhlmann
Sep 1, 2005·Journal of Thrombosis and Haemostasis : JTH·K Hansson, Johan Stenflo
Jan 2, 2007·Biochemical and Biophysical Research Communications·Eun Mi HwangJae-Yong Park
Mar 1, 1994·Blood Reviews·M Hertzberg
Jun 1, 1996·Baillière's Clinical Haematology·F Giannelli, P M Green
Jul 19, 2005·Molecular and Biochemical Parasitology·Javier PerizFiona M Tomley
Mar 26, 1999·American Journal of Human Genetics·T RantamäkiL Peltonen
Apr 14, 2016·Scientific Reports·Fumitaka IshiwariTakanori Fukushima
Aug 19, 2015·Mutation Research. Reviews in Mutation Research·Karina A Zeyer, Dieter P Reinhardt
Aug 25, 2012·Biochimica Et Biophysica Acta·Carolina N Perdigoto, Allison J Bardin
Apr 27, 2000·Mechanisms of Development·S KuriyamaT Kinoshita
Apr 23, 2002·Current Biology : CB·Kim S Midwood, Jean E Schwarzbauer
Dec 8, 2000·Biochimica Et Biophysica Acta·Penny A Handford
Jun 26, 2012·Journal of Molecular Biology·Yingnan ZhangDaniel Kirchhofer
Nov 26, 2009·Biochemical and Biophysical Research Communications·Dong-Gyu KimJae-Yong Park
Dec 5, 1998·American Journal of Human Genetics·R A MontgomeryH C Dietz
Feb 20, 1999·Journal of Molecular Biology·R SmallridgeA Kristina Downing
Mar 15, 1994·Structure·W I Weis
Jun 14, 1996·The Journal of Biological Chemistry·C H Bu, T Pourmotabbed
Mar 24, 1995·The Journal of Biological Chemistry·Penny A HandfordCay M Kielty
Dec 1, 1996·Circulation·D M MilewiczA Biddinger
Oct 3, 1991·Nature·Penny A HandfordG G Brownlee
Apr 15, 1993·Nature
Feb 21, 2006·The Journal of Biological Chemistry·Elizabeth G CantyKarl E Kadler
Nov 13, 1998·The Journal of Biological Chemistry·S AcharyaJ G Hollyfield
Nov 15, 2001·The Journal of Biological Chemistry·Arvind SrivastavaBarry R Lentz
Sep 25, 2002·The Journal of Biological Chemistry·Ruey-Bing YangJames N Topper
Mar 14, 1997·The Journal of Biological Chemistry·Dieter P ReinhardtH P Bächinger
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandor CsehNicole M Thielens
Nov 14, 1998·The American Journal of Physiology·Y S KanwarD R Peterson
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·I CaminschiM D Wright
Jan 27, 2007·The Journal of Biological Chemistry·Ehab El-HallousDieter P Reinhardt
Feb 28, 2008·The Journal of Biological Chemistry·Cheng-Fen TuRuey-Bing Yang
Jun 23, 2019·European Journal of Human Genetics : EJHG·Linnea M BaudhuinSusan A Lagerstedt
Oct 6, 2020·Frontiers in Genetics·Dimitra PeirasmakiStaffan G Svärd

Related Concepts

Calcium-Binding Proteins
Carboxylic Acids
Hemophilia B
Epidermal Growth Factor
In Vivo NMR Spectroscopy
Protein Conformation

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.