Human Blood Plasma Proteins gives an overview of the proteins found in human blood plasma, with special emphasis on their structure and function and relationship to pathological states and disease. Topics covered include:

• introduction to blood components and blood plasma proteins
• blood plasma protein domains, motifs and repeats
• blood plasma protein families and posttranslational modifications
• blood coagulation and fibrinolysis
• the complement system
• the immune system
• enzymes
• inhibitors
• lipoproteins
• hormones
• cytokines and growth factors
• transport and storage

The information of each protein discussed in this book in some detail is summarised at the end of each chapter in a Data Sheet, where one can find the most important data of each protein at one glance. Full cross-referencing to protein databases is given and many of the proteins discussed are accompanied by their 3D structure.

Attractively presented in full colour, Human Blood Plasma Proteins is an essential atlas of this proteome for anyone working in biochemistry, protein chemistry and proteomics, structural biology, and medicine.

Johann Schaller and Simon Gerber are the authors of Human Blood Plasma Proteins: Structure and Function, published by Wiley.

• introduction to blood components and blood plasma proteins
• blood plasma protein domains, motifs and repeats
• blood plasma protein families and posttranslational modifications
• blood coagulation and fibrinolysis
• the complement system
• the immune system
• enzymes
• inhibitors
• lipoproteins
• hormones
• cytokines and growth factors
• transport and storage

The information of each protein discussed in this book in some detail is summarised at the end of each chapter in a Data Sheet, where one can find the most important data of each protein at one glance. Full cross-referencing to protein databases is given and many of the proteins discussed are accompanied by their 3D structure.

Attractively presented in full colour, Human Blood Plasma Proteins is an essential atlas of this proteome for anyone working in biochemistry, protein chemistry and proteomics, structural biology, and medicine.

Preface xi

1 Introduction 1

References 3

Part I 5

2 Blood Components 7

2.1 Introduction 7

2.2 Short History 7

2.3 Blood Components 8

2.3.1 Blood cells 8

2.3.2 Blood plasma 12

2.3.3 The blood group system 13

References 15

Data Sheet 16

3 Blood Plasma Proteins 17

3.1 Introduction 17

3.2 Short History 17

3.3 Classification of Blood Plasma Proteins 17

References 20

Part II 21

4 Domains, Motifs and Repeats 23

4.1 Introduction 23

4.2 The Epidermal Growth Factor (EGF)-Like Domain 24

4.3 The Kringle Domain 26

4.4 The g-Carboxyglutamic Acid-Rich (Gla) Domain 27

4.5 The PAN/Apple Domain 28

4.6 The Sushi/CCP/SCR Domain 30

4.7 The Fibronectin Type I, the Fibronectin Type II Collagen-Binding and the Fibronectin Type III Domains 31

4.8 The Coagulation Factors 5/8 Type C Domain (FA58C) 32

4.9 The Thrombospondin Type I Repeat (TSP1) 34

4.10 The VWFA, VWFC and VWFD Domains 35

4.11 The Cystatin-Like Domain 36

4.12 The LDL-Receptor Class A (LDLRA) and Class B (LDLRB) Domains 36

4.13 The C-Terminal Cystine Knot (CTCK) Structure 38

4.14 The Anaphylatoxin Domain 40

4.15 The CUB Domain 40

4.16 The NTR Domain 41

4.17 The C-Type Lectin (CTL) Domain 42

4.18 The Ig-Like Domain 43

References 44

5 Protein Families 47

5.1 Introduction 47

5.2 Serine Proteases: The Trypsin Family 47

5.3 Serine Protease Inhibitors (Serpins) 48

5.4 The a2-Macroglobulin Family 50

5.5 The Serum Albumin Family 52

5.6 The Pancreatic Trypsin Inhibitor (Kunitz) Family Signature 52

5.7 The Kazal Serine Protease Inhibitors Family Signature 53

5.8 The Multicopper Oxidase Family 54

5.9 The Lipocalin Family 54

5.10 The Globin Family 55

5.11 The Glucagon/Gastric Inhibitory Polypeptide (GIP)/Secretin/ Vasoactive Intestinal Peptide (VIP) Family 56

5.12 The Glycoprotein Hormone Family 58

5.13 Membrane Attack Complex Components/Perforin Signature (The Complement C6/C7/C8/C9 Family) 59

5.14 The Lipase Family 60

5.15 Hormone Families and Signatures 61

5.15.1 The erythropoietin/thrombopoietin signature 61

5.15.2 The corticotropin-releasing factor family 61

5.15.3 The gonadotropin-releasing hormone signature 62

5.15.4 The calcitonin/CGRP/IAPP family 62

5.15.5 The gastrin/cholecystokinin family 62

5.15.6 The insulin family 62

5.16 Growth Factor Families 64

5.16.1 The platelet-derived growth factor family 64

5.16.2 The transforming growth factor-b family 64

5.17 Cytokine Families 65

5.17.1 The tumor necrosis factor family 65

5.17.2 The interferon a, b and d family 66

5.18 Interleukin Families and Signatures 66

5.18.1 The interleukin-1 signature 66

5.18.2 The interleukin-2 signature 67

5.18.3 The interleukin-4/-13 signature 68

5.18.4 The interleukin-6/granulocyte colony-stimulating factor/myelomonocytic growth factor family 68

5.18.5 The interleukin-7 and -9 signature 69

5.18.6 Interleukin-10 family 69

5.19 The Small Cytokine (Intercrine/Chemokine) Family and Signature 70

References 72

6 Posttranslational Modifications 75

6.1 Introduction 75

6.2 Databases for Posttranslational Modifications (PTMs) 75

6.3 Disulfide Bridges 75

6.4 Glycosylation 77

6.5 Phosphorylation 79

6.5.1 Ser/Thr phosphorylation sites 80

6.5.2 Tyr phosphorylation site 81

6.6 Hydroxylation 81

6.6.1 Aspartic acid and asparagine hydroxylation site 81

6.7 Sulfation 82

6.8 Acylation and Alkylation 84

6.9 Amidation 84

6.10 Carboxylation 84

6.11 Crosslinks 85

6.11.1 The isoglutamyl cysteine thioester bond 85

6.11.2 The isopeptide bond 85

References 86

Part III 89

7 Blood Coagulation and Fibrinolysis 91

7.1 Introduction 91

7.1.1 Definition of haemostasis 91

7.2 Primary Haemostasis 92

7.3 The Coagulation Cascade 95

7.4 The Fibrinolytic System 109

7.5 The Regulation of Blood Coagulation and Fibrinolysis 114

7.6 The Kinin and Angiotensin/Renin Systems 116

References 119

Data Sheets 121

8 The Complement System 151

8.1 Introduction 151

8.1.1 Nomenclature 152

8.2 The Classical Pathway 152

8.2.1 The anaphylatoxins C3a, C4a and C5a 160

8.3 The Alternative Pathway 160

8.4 The Terminal Components of the Complement System 162

8.5 Components of Complement Activation 165

8.6 Regulation of the Complement System 167

References 171

Data Sheets 172

9 The Immune System 195

9.1 Introduction 195

9.2 Immunoglobulins 196

9.3 Antibody Diversity 203

9.4 Major Histocompatibility Complex (MHC) Proteins 205

9.5 Innate Immune System 209

9.6 Other Proteins 213

References 214…