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PDBsum entry 1edm

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protein metals Protein-protein interface(s) links
Coagulation factor PDB id
1edm
Jmol
Contents
Protein chains
39 a.a. *
Metals
_CA ×3
Waters ×131
* Residue conservation analysis
PDB id:
1edm
Name: Coagulation factor
Title: Epidermal growth factor-like domain from human factor ix
Structure: Factor ix. Chain: b, c. Fragment: epidermal growth factor-like domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Strain: rz1032, xl1-blue, mc1061. Gene: human factor ix. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.50Å     R-factor:   0.157    
Authors: Z.Rao,P.Handford,M.Mayhew,V.Knott,G.G.Brownlee,D.Stuart
Key ref: Z.Rao et al. (1995). The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions. Cell, 82, 131-141. PubMed id: 7606779 DOI: 10.1016/0092-8674(95)90059-4
Date:
21-Mar-96     Release date:   14-Oct-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00740  (FA9_HUMAN) -  Coagulation factor IX
Seq:
Struc:
461 a.a.
39 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.3.4.21.22  - Coagulation factor IXa.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolyzes one Arg-|-Ile bond in factor X to form factor Xa.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium ion binding     1 term  

 

 
DOI no: 10.1016/0092-8674(95)90059-4 Cell 82:131-141 (1995)
PubMed id: 7606779  
 
 
The structure of a Ca(2+)-binding epidermal growth factor-like domain: its role in protein-protein interactions.
Z.Rao, P.Handford, M.Mayhew, V.Knott, G.G.Brownlee, D.Stuart.
 
  ABSTRACT  
 
Various diverse extracellular proteins possess Ca(2+)-binding epidermal growth factor (EGF)-like domains, the function of which remains uncertain. We have determined, at high resolution (1.5 A), the crystal structure of such a domain, from human clotting factor IX, as a complex with Ca2+. The Ca2+ ligands form a classic pentagonal bipyramid with six ligands contributed by one polypeptide chain and the seventh supplied by a neighboring EGF-like domain. The crystal structure identifies the role of Ca2+ in maintaining the conformation of the N-terminal region of the domain, but more importantly demonstrates that Ca2+ can directly mediate protein-protein contacts. The observed crystal packing of the domains provides a plausible model for the association of multiple tandemly linked EGF-like domains in proteins such as fibrillin-1, Notch, and protein S. This model is consistent with the known functional data and suggests a general biological role for these domains.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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PDB code: 2w86
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PDB code: 3bps
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PDB codes: 2vj2 2vj3
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PDB codes: 2bo2 2bou 2box
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Delta/notch-like epidermal growth factor (EGF)-related receptor, a novel EGF-like repeat-containing protein targeted to dendrites of developing and adult central nervous system neurons.
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Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation.
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PDB code: 1l3y
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  Hum Mutat, 19, 39-48.  
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Identification of a novel family of cell-surface proteins expressed in human vascular endothelium.
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  J Cell Biol, 154, 447-458.  
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Mutations in calcium-binding epidermal growth factor modules render fibrillin-1 susceptible to proteolysis. A potential disease-causing mechanism in Marfan syndrome.
  J Biol Chem, 275, 12339-12345.  
10956026 D.Tolkatchev, A.Ng, B.Zhu, and F.Ni (2000).
Identification of a thrombin-binding region in the sixth epidermal growth factor-like repeat of human thrombomodulin.
  Biochemistry, 39, 10365-10372.  
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Self-association of human protein S.
  Biochemistry, 39, 5468-5473.  
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Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.
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PDB code: 1oig
11058898 M.L.Heritage, J.C.MacMillan, R.P.Colliton, A.Genin, N.B.Spinner, and G.J.Anderson (2000).
Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome population.
  Hum Mutat, 16, 408-416.  
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Six novel mutations of the fibrillin-1 gene in Korean patients with Marfan syndrome.
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Fibrillin-1, a calcium binding protein of extracellular matrix.
  Biochim Biophys Acta, 1498, 84-90.  
10617609 P.H.Celie, P.J.Lenting, and K.Mertens (2000).
Hydrophobic contact between the two epidermal growth factor-like domains of blood coagulation factor IX contributes to enzymatic activity.
  J Biol Chem, 275, 229-234.  
10633129 P.N.Robinson, and M.Godfrey (2000).
The molecular genetics of Marfan syndrome and related microfibrillopathies.
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Protease and EGF1 domains of factor IXa play distinct roles in binding to factor VIIIa. Importance of helix 330 (helix 162 in chymotrypsin) of protease domain of factor IXa in its interaction with factor VIIIa.
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The epidermal growth factor precursor. A calcium-binding, beta-hydroxyasparagine containing modular protein present on the surface of platelets.
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Marfan syndrome: new clues to genotype-phenotype correlations.
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Grafting an RGD motif onto an epidermal growth factor-like module: chemical synthesis and functional characterization of the chimeric molecule.
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Factor VIIa's first epidermal growth factor-like domain's role in catalytic activity.
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The effect of O-fucosylation on the first EGF-like domain from human blood coagulation factor VII.
  Biochemistry, 38, 7097-7110.
PDB codes: 1f7e 1f7m 1ff7 1ffm
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Solution structure of the N-terminal EGF-like domain from human factor VII.
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PDB code: 1bf9
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Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
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PDB code: 1apq
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Recombinant latent transforming growth factor beta-binding protein 2 assembles to fibroblast extracellular matrix and is susceptible to proteolytic processing and release.
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Blood coagulation factor IX residues Glu78 and Arg94 provide a link between both epidermal growth factor-like domains that is crucial in the interaction with factor VIII light chain.
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A Gly --> Ser change causes defective folding in vitro of calcium-binding epidermal growth factor-like domains from factor IX and fibrillin-1.
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Phorbol ester-induced juxtamembrane cleavage of angiotensin-converting enzyme is not inhibited by a stalk containing intrachain disulfides.
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Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+ binding site, proteolysis in the autolysis loop, phospholipid, and factor X.
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  9461348 C.H.Cheng, J.P.Geng, and F.J.Castellino (1997).
The functions of the first epidermal growth factor homology region of human protein C as revealed by a charge-to-alanine scanning mutagenesis investigation.
  Biol Chem, 378, 1491-1500.  
9211891 C.R.Kelly, C.D.Dickinson, and W.Ruf (1997).
Ca2+ binding to the first epidermal growth factor module of coagulation factor VIIa is important for cofactor interaction and proteolytic function.
  J Biol Chem, 272, 17467-17472.  
8995426 D.P.Reinhardt, R.N.Ono, and L.Y.Sakai (1997).
Calcium stabilizes fibrillin-1 against proteolytic degradation.
  J Biol Chem, 272, 1231-1236.  
9233787 E.Hohenester, P.Maurer, and R.Timpl (1997).
Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40.
  EMBO J, 16, 3778-3786.
PDB code: 1bmo
9242658 E.Persson, O.H.Olsen, A.Ostergaard, and L.S.Nielsen (1997).
Ca2+ binding to the first epidermal growth factor-like domain of factor VIIa increases amidolytic activity and tissue factor affinity.
  J Biol Chem, 272, 19919-19924.  
9659904 G.V.Louie, W.Yang, M.E.Bowman, and S.Choe (1997).
Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor.
  Mol Cell, 1, 67-78.
PDB code: 1xdt
9278415 H.Tran, W.J.VanDusen, and W.S.Argraves (1997).
The self-association and fibronectin-binding sites of fibulin-1 map to calcium-binding epidermal growth factor-like domains.
  J Biol Chem, 272, 22600-22606.  
9389452 J.M.Arnold, R.Eri, B.M.Degnan, and M.F.Lavin (1997).
Novel gene containing multiple epidermal growth factor-like motifs transiently expressed in the papillae of the ascidian tadpole larvae.
  Dev Dyn, 210, 264-273.  
  9336830 M.D.Rand, A.Lindblom, J.Carlson, B.O.Villoutreix, and J.Stenflo (1997).
Calcium binding to tandem repeats of EGF-like modules. Expression and characterization of the EGF-like modules of human Notch-1 implicated in receptor-ligand interactions.
  Protein Sci, 6, 2059-2071.  
9287338 P.McCloskey, Y.W.Fridell, E.Attar, J.Villa, Y.Jin, B.Varnum, and E.T.Liu (1997).
GAS6 mediates adhesion of cells expressing the receptor tyrosine kinase Axl.
  J Biol Chem, 272, 23285-23291.  
  9007991 S.Gillis, B.C.Furie, B.Furie, H.Patel, M.C.Huberty, M.Switzer, W.B.Foster, H.A.Scoble, and M.D.Bond (1997).
gamma-Carboxyglutamic acids 36 and 40 do not contribute to human factor IX function.
  Protein Sci, 6, 185-196.  
  9032278 X.Fu, and M.P.Kamps (1997).
E2a-Pbx1 induces aberrant expression of tissue-specific and developmentally regulated genes when expressed in NIH 3T3 fibroblasts.
  Mol Cell Biol, 17, 1503-1512.  
9362480 X.Yuan, A.K.Downing, V.Knott, and P.A.Handford (1997).
Solution structure of the transforming growth factor beta-binding protein-like module, a domain associated with matrix fibrils.
  EMBO J, 16, 6659-6666.
PDB code: 1apj
9008713 Y.Nakajima, K.Miyazono, M.Kato, M.Takase, T.Yamagishi, and H.Nakamura (1997).
Extracellular fibrillar structure of latent TGF beta binding protein-1: role in TGF beta-dependent endothelial-mesenchymal transformation during endocardial cushion tissue formation in mouse embryonic heart.
  J Cell Biol, 136, 193-204.  
9310374 Y.Stenberg, K.Julenius, I.Dahlqvist, T.Drakenberg, and J.Stenflo (1997).
Calcium-binding properties of the third and fourth epidermal-growth-factor-like modules in vitamin-K-dependent protein S.
  Eur J Biochem, 248, 163-170.  
9405406 Z.C.Xiao, U.Bartsch, R.K.Margolis, G.Rougon, D.Montag, and M.Schachner (1997).
Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan.
  J Biol Chem, 272, 32092-32101.  
8653794 A.K.Downing, V.Knott, J.M.Werner, C.M.Cardy, I.D.Campbell, and P.A.Handford (1996).
Solution structure of a pair of calcium-binding epidermal growth factor-like domains: implications for the Marfan syndrome and other genetic disorders.
  Cell, 85, 597-605.
PDB codes: 1emn 1emo
8663282 B.M.Revelle, D.Scott, and P.J.Beck (1996).
Single amino acid residues in the E- and P-selectin epidermal growth factor domains can determine carbohydrate binding specificity.
  J Biol Chem, 271, 16160-16170.  
8962059 C.D.Dickinson, C.R.Kelly, and W.Ruf (1996).
Identification of surface residues mediating tissue factor binding and catalytic function of the serine protease factor VIIa.
  Proc Natl Acad Sci U S A, 93, 14379-14384.  
8548457 E.Hohenester, P.Maurer, C.Hohenadl, R.Timpl, J.N.Jansonius, and J.Engel (1996).
Structure of a novel extracellular Ca(2+)-binding module in BM-40.
  Nat Struct Biol, 3, 67-73.
PDB code: 1sra
8791520 F.Ramirez (1996).
Fibrillln mutations in Marfan syndrome and related phenotypes.
  Curr Opin Genet Dev, 6, 309-315.  
8666666 G.W.Moy, L.M.Mendoza, J.R.Schulz, W.J.Swanson, C.G.Glabe, and V.D.Vacquier (1996).
The sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1.
  J Cell Biol, 133, 809-817.  
9064337 J.Hamann, B.Vogel, G.M.van Schijndel, and R.A.van Lier (1996).
The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF).
  J Exp Med, 184, 1185-1189.  
  8763990 M.C.Ruiz, A.Charpilienne, F.Liprandi, R.Gajardo, F.Michelangeli, and J.Cohen (1996).
The concentration of Ca2+ that solubilizes outer capsid proteins from rotavirus particles is dependent on the strain.
  J Virol, 70, 4877-4883.  
8794734 M.Sunnerhagen, G.A.Olah, J.Stenflo, S.Forsén, T.Drakenberg, and J.Trewhella (1996).
The relative orientation of Gla and EGF domains in coagulation factor X is altered by Ca2+ binding to the first EGF domain. A combined NMR-small angle X-ray scattering study.
  Biochemistry, 35, 11547-11559.
PDB codes: 1whe 1whf
8870072 P.Bork, A.K.Downing, B.Kieffer, and I.D.Campbell (1996).
Structure and distribution of modules in extracellular proteins.
  Q Rev Biophys, 29, 119-167.  
8810297 P.J.Lenting, O.D.Christophe, H.Maat, D.J.Rees, and K.Mertens (1996).
Ca2+ binding to the first epidermal growth factor-like domain of human blood coagulation factor IX promotes enzyme activity and factor VIII light chain binding.
  J Biol Chem, 271, 25332-25337.  
8939653 P.Maurer, E.Hohenester, and J.Engel (1996).
Extracellular calcium-binding proteins.
  Curr Opin Cell Biol, 8, 609-617.  
8784348 S.C.Blacklow, and P.S.Kim (1996).
Protein folding and calcium binding defects arising from familial hypercholesterolemia mutations of the LDL receptor.
  Nat Struct Biol, 3, 758-762.  
8901515 S.J.Freedman, D.G.Sanford, W.W.Bachovchin, B.C.Furie, J.D.Baleja, and B.Furie (1996).
Structure and function of the epidermal growth factor domain of P-selectin.
  Biochemistry, 35, 13733-13744.
PDB code: 1fsb
8702686 Z.H.He, M.Fujiki, and B.D.Kohorn (1996).
A cell wall-associated, receptor-like protein kinase.
  J Biol Chem, 271, 19789-19793.  
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