Table 1 Function and dysfunction of human serpins

SERPINA1

Antitrypsin

Extracellular; inhibition of neutrophil elastase

Deficiency results in emphysema: polymerization and retention in the ER results in cirrhosis [14,64,65]

SERPINA2

Antitrypsin-related protein

Not characterized, probable pseudogene

SERPINA3

Antichymotrypsin

Extracellular; inhibition of cathepsin G

Deficiency results in emphysema (see [61] for a review)

SERPINA4

Kallistatin (PI4)

Extracellular, inhibition of kallikrein [68]

SERPINA5

Protein C inhibitor (PAI-3)

Extracellular; inhibition of active protein C (see [69] for a review)

Angioedema

SERPINA6

Corticosteroid-binding globulin

Extracellular; non-inhibitory; cortisol binding

Deficiency linked to chronic fatigue [83,84]

SERPINA7

Thyroxine-binding globulin

Extracellular; non-inhibitory, thyroxine binding

Deficiency results in hypothyroidism [85]

SERPINA8

Angiotensinogen

Extracellular; non-inhibitory; amino-terminal cleavage by the protease renin results in release of the decapeptide angiotensin I

Certain variants linked to essential hypertension [86]

SERPINA9

Centerin

Extracellular; maintenance of naive B cells [70]

SERPINA10

Protein Z-dependent proteinase inhibitor

Extracellular; inhibition of activated factor Z and XI

Deficiency linked to venous thromboembolic disease [87]

SERPINA11

XP_170754.3

Not characterized

SERPINA12

Vaspin

Extracellular; insulin-sensitizing adipocytokine [71]

SERPINA13

XM_370772

Not characterized

SERPINB1

Monocyte neutrophil elastase inhibitor

Intracellular; inhibition of neutrophil elastase [72]

SERPINB2

Plasminogen activator inhibitor-2 (PAI2)

Intracellular; inhibition of uPA (see [73] for a review)

SERPINB3

Squamous cell carcinoma antigen-1

Intracellular; cross-class inhibition of cathepsins L and V [6]

SERPINB4

Squamous cell carcinoma antigen-2

Intracellular; cross-class inhibition of cathepsin G and chymase [74]

SERPINB5

Maspin

Intracellular; non-inhibitory; inhibition of metastasis through uncharacterized mechanism

Downregulation and/or intracellular location linked to tumor progression and overall prognosis [10]

SERPINB6

Proteinase inhibitor-6 (PI6)

Intracellular, inhibition of cathepsin G [75]

SERPINB7

Megsin

Intracellular; megakaryocyte maturation [76]

IgA nephropathy

SERPINB8

Cytoplasmic antiproteinase 8 (PI8)

Intracellular; inhibition of furin [77]

SERPINB9

Cytoplasmic antiproteinase 9 (PI9)

Intracellular, inhibition of granzyme B [78]

SERPINB10

Bomapin (PI10)

Intracellular; inhibition of thrombin and trypsin [79]

SERPINB11

Epipin

Intracellular

SERPINB12

Yukopin

Intracellular; inhibition of trypsin [80]

SERPINB13

Headpin (PI13)

Intracellular; inhibition of cathepsins L and K

SERPINC1

Antithrombin

Extracellular; thrombin and factor Xa inhibitor

Deficiency results in thrombosis (see [88] for review)

SERPIND1

Heparin cofactor II

Extracellular; thrombin inhibitor

May contribute to thrombotic risk when combined with other deficiencies [89]

SERPINE1

Plasminogen activator inhibitor I (PAI1)

Extracellular; inhibitor of thrombin, uPA, tPA and plasmin

Abnormal bleeding [90]

SERPINE2

Protease nexin I (PI7)

Extracellular; inhibition of uPA and tPA

SERPINE3

Hs.512272

Not characterized

SERPINF1

Pigment epithelium derived factor

Non-inhibitory; potent anti-angiogenic molecule [81]

SERPINF2

Alpha-2-antiplasmin

Extracellular; plasmin inhibitor

Unrestrained fibrinolytic activity, bleeding [91]

SERPING1

C1 inhibitor

C1 esterase inhibitor

Angioedema [92]

SERPINH1

47kDa heat-shock protein

Non-inhibitory molecular Chaperone for collagens [9]

SERPINI1

Neuroserpin (PI12)

Extracellular; inhibitor of tPA, uPA and plasmin

Polymerization results in dementia [17]

SERPINI2

Myoepithelium-derived serine proteinase inhibitor (PI14)

Extracellular; inhibition of cancer metastasis [82]