SERine Proteinase INhibitors (serpin) family; SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSkiggEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19567   33 MSVSSALAMVYMGAKGNTAAQMSQALCLS----GNGDVHRGFQSLLAEVNKTGTQYLLRTANRLFGEKTCDFLPTFKESC 108

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  81 GKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19567  109 QKFYQAGLEELSFAEDTEECRKHINDWVSEKTEGK 143

serpin family B member 8, cytoplasmic antiproteinase 2; Cytoplasmic antiproteinase 2 (CAP-2 or peptidase inhibitor 8/PI-8) is a member of the ovalbumin family of serpins (ov-serpins). Serpin B8 is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. Diseases associated with SERPINB8 include Peeling Skin Syndrome 5 and Exfoliative Ichthyosis. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF). The ov-serpins are a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSkiggEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19567   33 MSVSSALAMVYMGAKGNTAAQMSQALCLS----GNGDVHRGFQSLLAEVNKTGTQYLLRTANRLFGEKTCDFLPTFKESC 108

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  81 GKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19567  109 QKFYQAGLEELSFAEDTEECRKHINDWVSEKTEGK 143

Serpin (serine protease inhibitor); Structure is a multi-domain fold containing a bundle of helices and a beta sandwich.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521    1 MSISSALAMVFMGAKGNTAAQMSQALCFSkiGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:pfam00079  28 LSISSALAMLYLGAKGETAEQLLEALGFN--ELDEEDVHQGFQKLLQSLNKPDKGYELKLANALFVEKGLKLKPDFLQLA 105

                          90       100       110
                  ....*....|....*....|....*....|....
gi 183074521   81 GKFYQATIKQLDFVNDTEkSTTRVNSWVADKTKG 114
Cdd:pfam00079 106 KKYYGAEVESVDFSDPSE-ARKKINSWVEKKTNG 138

serpin family B member 8, cytoplasmic antiproteinase 2; Cytoplasmic antiproteinase 2 (CAP-2 or peptidase inhibitor 8/PI-8) is a member of the ovalbumin family of serpins (ov-serpins). Serpin B8 is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. Diseases associated with SERPINB8 include Peeling Skin Syndrome 5 and Exfoliative Ichthyosis. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF). The ov-serpins are a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSkiggEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19567   33 MSVSSALAMVYMGAKGNTAAQMSQALCLS----GNGDVHRGFQSLLAEVNKTGTQYLLRTANRLFGEKTCDFLPTFKESC 108

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  81 GKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19567  109 QKFYQAGLEELSFAEDTEECRKHINDWVSEKTEGK 143

serpin family B member 6, cytoplasmic antiproteinase; Cytoplasmic antiproteinase (CAP, also called proteinase inhibitor 6/PI6 or placental thrombin inhibitor/PTI) is thought to be involved in the regulation of serine proteinases present in the brain or extravasated from the blood. It may play an important role in the inner ear in the protection against leakage of lysosomal content during stress; loss of this protection results in cell death and sensorineural hearing loss. It is an inhibitor of cathepsin G, kallikrein-8 and thrombin. The ovalbumin family of serpins (ov-serpins) is a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19565   32 MSISSALAMVYMGAKGNTAAQMAQTLSLNKSSGGGGDIHQGFQSLLTEVNKTGTQYLLRTANRLFGEKTCDFLSSFKDSC 111

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  81 GKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19565  112 QKFYQAEMEELDFISATEKSRKHINTWVAEKTEGK 146

SERine Proteinase INhibitors;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521     1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:smart00093  21 VSISSALAMLSLGAKGSTATQILEVLGFNLTETSEADIHQGFQHLLHLLNRPDSQLELKTANALFVDKSLKLKDSFLEDI 100

                           90       100       110
                   ....*....|....*....|....*....|....
gi 183074521    81 GKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKG 114
Cdd:smart00093 101 KKLYGAEVQSVDFSDKAEEAKKQINDWVEKKTQG 134

serpin thermopin and similar proteins; Thermopin, the serpin from Thermobifida fusca, functions as an irreversible proteinase inhibitor with resistance to polymerization at high temperatures. The crystal structure of the cleaved thermopin was found to adopt the canonical serpin fold, supporting its inclusion as a classical inhibitory member of the serpin superfamily. A detailed structural comparison revealed unique features, including charge-stabilizing interactions, a deleted element of secondary structure (the G helix), and a C-terminal "tail" that interacts with the top of the A beta sheet and plays an important role in the folding/unfolding of the molecule. These unique features provide structural and biophysical evidence as to how this unusual serpin member has adapted to remain functional in an extreme environment. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSkigGEDGDIHRGFQSLLVAINRTD--TEYVLRTANGLFGEKSYDFLTGFTDS 79
Cdd:cd19590   27 SISSALAMTYAGARGETAAEMAAVLHFP---LPQDDLHAAFNALDLALNSRDgpDPPELAVANALWGQKGYPFLPEFLDT 103

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  80 CGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKG 114
Cdd:cd19590  104 LAEYYGAGVRTVDFAGDPEGARKTINAWVAEQTNG 138

Serine protease inhibitor [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALcfsKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:COG4826   74 SISSALAMTYNGARGETAEEMAKVL---GFGLDLEELNAAFAALLAALNNDDPKVELSIANSLWAREGFTFKPDFLDTLA 150

                         90       100       110
                 ....*....|....*....|....*....|...
gi 183074521  82 KFYQATIKQLDFVNDtEKSTTRVNSWVADKTKG 114
Cdd:COG4826  151 DYYGAGVTSLDFSND-EAARDTINKWVSEKTNG 182

SERine Proteinase INhibitors (serpin) family; SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIggEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd00172   27 LSISTALSMLYLGARGETREELKKVLGLDSL--DEEDLHSAFKELLSSLKSSNENYTLKLANRIFVDKGFELKEDFKDAL 104

                         90       100       110
                 ....*....|....*....|....*....|....
gi 183074521  81 GKFYQATIKQLDFvNDTEKSTTRVNSWVADKTKG 114
Cdd:cd00172  105 KKYYGAEVESVDF-SNPEEARKEINKWVEEKTNG 137

serpin family B member 13, headpin; Headpin (also known as hurpin or proteinase inhibitor 13/P113) maps to chromosome 18q21.3 and is expressed in normal squamous epithelium of the oral mucosa, skin, and cervix. Inhibitory serpins are known to play an important role in tumor invasion, metastasis, tumor suppression and apoptosis. Headpin belongs to the ovalbumin family of serpins (ov-serpins), a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCF------SKIGGEDG-------DIHRGFQSLLVAINRTDTEYVLRTANGLFGE 67
Cdd:cd19572   32 VGISTAIGMLLLGTRGATASQLQKVFYSekdtesSRIKAEEKeviekteEIHHQFQKFLTEISKPTNDYELNIANRLFGE 111

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 183074521  68 KSYDFLTGFTDSCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKgENILLFYFDNILNSFI 130
Cdd:cd19572  112 KTYLFLQKYLDYVEKYYHASLEPVDFVNAADESRKKINSWVESQTN-EKIKDLFPDGSLSSST 173

serpin family B member 2, plasminogen activator inhibitor 2; Plasminogen activator inhibitor-2 (PAI-2/PLANH2, also called placental PAI, monocyte arg-serpin, or urokinase inhibitor) is a serine protease inhibitor that belongs to the ovalbumin family of serpins (ov-serpins). It is an effective inhibitor of urinary plasminogen activator (urokinase or uPA) and is involved in cell differentiation, tissue growth and regeneration. Ov-serpins are a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSKIGGED---------------------------------GDIHRGFQSLLVA 48
Cdd:cd19562   33 SISSTMAMVYMGSRGSTEDQMAKVLQFNEVGAYDltpgnpenftgcdfaqqiqrdnypdailqaqaaDKIHSSFRSLSSA 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 183074521  49 INRTDTEYVLRTANGLFGEKSYDFLTGFTDSCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19562  113 INASTGNYLLESVNKLFGEKSASFREEYIRLCQKYYSSEPQAVDFLECAEEARKKINSWVKTQTKGK 179

serpin miropin and similar proteins; Miropin, the serpin from Tannerella forsythia, is thought to contribute to the virulence of periodontal pathogens by inhibiting neutrophil serine proteases. Miropin broadly inhibits serine endopeptidases (SEPs) including trypsin, neutrophil elastase, pancreatic elastase, subtilisin, and cathepsin G and cysteine endopeptidases (CEPs) including papain, calpain-like peptidase Tpr, and gingipain K through various reactive-site bonds. This is achieved by offering several target bonds of the RCL for cleavage within a bait region, instead of a single RSB as found in canonical serpins. In addition, promiscuous inhibition is facilitated by the capacity to insert strands deviating from the canonical length into the central sheet A, while keeping the prey peptidase bound and inactivated. The structural adaptation of miropin to provide a relaxed inhibitory specificity, which allows for formation of inhibitory complexes using different sites, is unique among serpins. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSkiGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19588   34 SISMALGMTYNGAAGETKEEMAKVLGLE--GLSLEEINEAYKSLLELLPSLDPKVELSIANSIWYRKGFPVKPDFLDTNK 111

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 183074521  82 KFYQATIKQLDFVNDteKSTTRVNSWVADKTKG--ENIL 118
Cdd:cd19588  112 DYYDAEVEELDFSDP--AAVDTINNWVSEKTNGkiPKIL 148

serpin family A; The clade A of the serpin superfamily includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19957   28 SISTALAMLSLGAKSTTRTQILEGLGFNLTETPEAEIHEGFQHLLQTLNQPKKELQLKIGNALFVDKQLKLLKKFLEDAK 107

                         90       100       110
                 ....*....|....*....|....*....|...
gi 183074521  82 KFYQATIKQLDFvNDTEKSTTRVNSWVADKTKG 114
Cdd:cd19957  108 KLYNAEVFPTNF-SDPEEAKKQINDYVKKKTHG 139

serpin family B member 7, megsin; Megsin is named as such due to its primary expression in the mesangium, a structure associated with the capillaries in the glomerulus of the kidney. Megsin is thought to play a role in the regulation of a wide variety of processes in mesangial cells, such as matrix metabolism, cell proliferation, and apoptosis. Identification of the exact biological functions and target proteases of megsin will lead to the development of novel therapeutic approaches to glomerular diseases. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Megsin belongs to the ovalbumin family of serpins (ov-serpins), a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIG--GEDGDIHRGFQS----LLVAINRTDTEYVLRTANGLFGEKSYDFLT 74
Cdd:cd19566   33 LSIFTALALIRLGAQGDSASQIDKLLHVNTASryGNSSNNQPGLQSqlkrVLADINSSHKDYELSIANGLFAEKVYDFHK 112

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 183074521  75 GFTDSCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19566  113 NYIECAEKLYNAKVERVDFTNHVEDTRRKINKWIENETHGK 153

serpin family proteins from platyhelminthes; This group includes a variety of serpins from platyhelminthes (lung fluke, tapeworm, flatworm). SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKiGGEDGDIHRGFQSLL--VAINRTDTEYVLrtANGLFGEKSYDFLTGFTD 78
Cdd:cd19603   34 LSIYTALLMTLAGSDGNTKQELRSVLHLPD-CLEADEVHSSIGSLLqeFFKSSEGVELSL--ANRLFILQPITIKEEYKQ 110

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 183074521  79 SCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKG 114
Cdd:cd19603  111 ILKKYYKADTESVTFMPDNEAKRRHINQWVSENTKG 146

serpin family L, serpin family proteins from nematodes; The role of nematode serpins remains largely elusive. The only nematode serpin for which experimental evidence indicates an evasive function is Brugia malayi SPN-2 which specifically inhibits two human neutrophil-derived serine proteinases, cathepsin G and elastase. Less is known of Brugia malayi SPN-1, which is present at all stages of the parasite life cycle and could exist to inhibit a cognate proteinase endogenous to the parasite. Schistosoma serpins are hypothesized to play a role in both the physiological control of elastase within the schistosomes, and protection of the parasite from activated neutrophils during inflammation. Caenorhabditis elegans serpins are thought to regulate endogenous serine proteinases as well as inhibit proteinases produced by pathogenic microorganisms. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALcfSKiGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19581   25 SIALALALVHAGAKGETRTEIRNAL--LK-GATDEQIINHFSNLSKELSNATNGVEVNIANRIFVNKGFTIKKAFLDTVR 101

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 183074521  82 KFYQATIKQLDFVnDTEKSTTRVNSWVADKTKG--ENILLFYFDNILNSFIVSSL 134
Cdd:cd19581  102 KKYNAEAESLDFS-KTEETAKTINDFVREKTKGkiKNIITPESSKDAVALLINAI 155

serpin family B member 12, yukopin; Yukopin, encoded by the SERPINB12 gene, is a member of the serpin superfamily of serine protease inhibitors. It inhibits trypsin and plasmin, but not thrombin, coagulation factor Xa, or urokinase-type plasminogen activator. An important paralog of this gene is SERPINB4. The ovalbumin family of serpins (ov-serpins) is a family of closely related proteins, whose members can be secreted (ovalbumin), cytosolic (leukocyte elastase inhibitor, LEI), or targeted to both compartments (plasminogen activator inhibitor 2, PAI-2). It also characterized by N- and C-terminal extensions, the absence of a signal peptide, and a Ser rather than an Asn residue at the penultimate position. The ov-serpins corresponds to clade B of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIG--------------------------------------GEDGDIHRGF 42
Cdd:cd19571   33 LSISAAFGMVRLGARSDSAHQIDEVLHFNELSqneskepdpcskskkqevvagspfrqtgapdlqagsskDESELLSCYF 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521  43 QSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKGENILLFYF 122
Cdd:cd19571  113 GKLLSKLDRIKADYTLSIANRLYGEQEFPICPEYSDGVTQFYHTTIESVDFRKDTEKSRQEINFWVESQSQGKIKELFSK 192

                 ....*.
gi 183074521 123 DNILNS 128
Cdd:cd19571  193 DAITNA 198

serpin tengpin and similar proteins; Tengpin is an unusual prokaryotic serpin from the extremophile Thermoanaerobacter tengcongensis. In addition to the serpin domain, tengpin contains an N-terminal region that functions to trap the serpin domain in the native metastable state and prevent the spontaneous transition to the latent conformation. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCfskiGGEDGDIHRGFQSLLVAINrTDTEYVLRTANGLF--GEKSYDFLTGFTD 78
Cdd:cd19589   29 LSVYLALAMTANGAKGETKAELEKVLG----GSDLEELNAYLYAYLNSLN-NSEDTKLKIANSIWlnEDGSLTVKKDFLQ 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 183074521  79 SCGKFYQATIKQLDFvnDTEKSTTRVNSWVADKTKG--ENIL 118
Cdd:cd19589  104 TNADYYDAEVYSADF--DDDSTVKDINKWVSEKTNGmiPKIL 143

serpin family A member 6, corticosteroid-binding globulin; Corticosteroid-binding globulin (CBG, also known as transcortin) is encoded by the SERPINA6 gene in humans which encodes an alpha-globulin with corticosteroid-binding properties. It is produced in the liver. CBG binds several steroid hormones at high rates including cortisol, cortisone, deoxycorticosterone (DOC), corticosterone, aldosterone, progesterone, and 17a-hydroxyprogesterone. This family belongs to the clade A of the serpin superfamily, which includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19554   37 SISMALAMLSLGACGHTRTQLLQGLGFNLTEISEAEIHQGFQHLHHLLRESDTSLEMTMGNALFLDQSLELLESFSADIK 116

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 183074521  82 KFYQATIKQLDFvNDTEKSTTRVNSWVADKTKGENILLF 120
Cdd:cd19554  117 HYYESEALATDF-QDWATASRQINEYVKNKTQGKIVDLF 154

serpin family proteins from bacteria and crustaceans; This group includes a variety of serpin family proteins from various bacteria and crustaceans including sea louse and salmon louse. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLlvaiNRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19593   32 SISSALSMTSAGARGNTLEEMKEALNLPLDVEDLKSAYSSFTAL----NKSDENITLETANKLFPANALVLTEDFVSEAF 107

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 183074521  82 KFYQATIKQLDFVnDTEKSTTRVNSWVADKTKGeNILLF 120
Cdd:cd19593  108 KIFGLKVQYLAEI-FTEAALETINQWVRKKTEG-KIEFI 144

serpin family A member 2, protease inhibitor 1-like; Protease inhibitor 1-like (also called serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2, ARGS, protease inhibitor 1 (alpha-1-antitrypsin)-like)/PIL, and alpha-1-antitrypsin-related protein/ATR) belongs to the serpin superfamily and is encoded by the SERPINA2 gene in humans. SERPINA2 was once thought to be a pseudogene, but recent evidence shows that it produces an active transcript. It is very similar in structure and function to SERPINA1. This family belongs to the clade A of the serpin superfamily, which includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   2 SISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSCG 81
Cdd:cd19550   28 SIAAAFAMLSLGTKGDTHTQILEGLRFNLKETPEAEIHKCFQQLLNTLHQPDNQLQLTTGSSLFIDKNLKPVDKFLEGVK 107

                         90       100       110
                 ....*....|....*....|....*....|....
gi 183074521  82 KFYQATIKQLDFvNDTEKSTTRVNSWVADKTKGE 115
Cdd:cd19550  108 KLYHSEAIPINF-RDTEEAKKQINNYVEKETQRK 140

serpin family A member 9, centerin; Centerin, also known as germinal center B-cell-expressed transcript 1/GCET1, is a serpin whose expression is restricted to germinal center B-cells and lymphoid malignancies with germinal center B-cell maturation. Expression of centerin, together with bcl-6 and GCET2, constitutes a germinal center B-cell signature, which is associated with a good prognosis in diffuse large B-cell lymphomas. Centerin is thought to function in vivo in the germinal centre as an efficient inhibitor of a trypsin-like protease. It also inhibits the trypsin-like serine proteases trypsin, thrombin and plasmin and is able to bind heparin and DNA. The centerin gene maps to the A clade serpin cluster on chromosome 14q32.1, which also contains a1-antitrypsin and a1-antichymotrypsin together with seven other serpins. The clade A of the serpin superfamily includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19556   44 VSVSTSLAMLSLGAHSVTKTQILQGLGFNLTHTPESAIHQGFQHLVHSLTVPSKDLTLKMGSALFVKKELQLQANFLGNV 123

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 183074521  81 GKFYQATIKQLDFVNDTeKSTTRVNSWVADKTKGE 115
Cdd:cd19556  124 KRLYEAEVFSTDFSNPS-IAQARINSHVKKKTQGK 157

serpin family A member, alpha-1-antitrypsin and similar proteins; This group contains proteins similar to alpha-1-antitrypsin (also called A1AT, A1A, AAT, alpha1-proteinase inhibitor/A1PI, alpha1-antiproteinase/A1AP, and serum trypsin inhibitor), a protease inhibitor that belongs to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. When the blood contains inadequate amounts of A1AT or functionally defective A1AT (such as in alpha-1 antitrypsin deficiency), neutrophil elastase is excessively free to break down elastin, degrading the elasticity of the lungs, which results in respiratory complications, such as chronic obstructive pulmonary disease. Normally, A1AT leaves its site of origin, the liver, and joins the systemic circulation; defective A1AT can fail to do so, building up in the liver, which results in cirrhosis. This group belongs to the clade A of the serpin superfamily, which includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTdTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19549   29 LSVSVALAALSLGARGETHQQLFSGLGFNSSQVTQAQVNEAFEHLLHMLGHS-EELDLSAGNAVFIDDTFKPNPEFLKDL 107

                         90       100       110
                 ....*....|....*....|....*....|....
gi 183074521  81 GKFYQATIKQLDFVNDTEKSTTrVNSWVADKTKG 114
Cdd:cd19549  108 KHYYLSEGFTVDFTKTTEAADT-INKYVAKKTHG 140

serpin family P, plant serpins; Plant SERine Proteinase INhibitors (serpins) are potent inhibitors of a range of mammalian serine proteases in vitro, and at least seven serpin genes are expressed in Arabidopsis. Serpins from plants display a wide range of functions including protection of storage protein degradation by exogenous proteases and seed survival within the herbivore digestive tract. Comparison between Arabidopsis AtSerpin1 and other serpins reveals several distinguishing features including a plant-specific insertion between s2B and s3B, with a plant-specific motif YXXGXDXRXF and the presence of a beta-bulge in strand s2C. The conserved Asp-230 and Arg-232 in the motif form a network of hydrogen bonds stabilize a loop region, which is otherwise disordered in many other serpin structures. AtSerpin1 is targeted to the secretory pathway and was shown to interact with cysteine protease RD21 (RESPONSIVE TO DESICCATION-21). RD21 accepts peptides and ligates them to the N termini of acceptor proteins so it has been proposed that AtSerpin1 functions to curb this activity. This subgroup corresponds to clade P of the serpin superfamily. In general, serpins exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALcfskiGGEDGDIHRGFQSLLVAINRTDTEY----VLRTANGLFGEKSYDFLTGF 76
Cdd:cd02043   29 LSIHAALSLIAAGSKGPTLDQLLSFL-----GSESIDDLNSLASQLVSSVLADGSSsggpRLSFANGVWVDKSLSLKPSF 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 183074521  77 TDSCGKFYQATIKQLDFVNDTEKSTTRVNSWVADKTKG--ENIL 118
Cdd:cd02043  104 KELAANVYKAEARSVDFQTKAEEVRKEVNSWVEKATNGliKEIL 147

serpin family A member 11; Serpin A11, in rats also called liver regeneration-related protein LRRG023, is a serpin encoded by the gene SERPINA11. It maps on chromosome 14, at 14q32.13 and is strongly expressed in the human liver. The function of this protein is unknown. It belongs to the clade A of the serpin superfamily, which includes the classical serine proteinase inhibitors, alpha-1-antitrypsin and alpha-1-antichymotrypsin, protein C inhibitor, kallistatin, and non-inhibitory serpins, like corticosteroid and thyroxin binding globulins. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19557   29 VSLSSTLALLSLGAHADTQAQILESLGFNLTETPAADIHRGFQSLLHTLDLPSPKLELKLGHSLFLDRQLKPQQRFLDSA 108

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 183074521  81 GKFYQATIKQLDFvndTEKSTT--RVNSWVADKTKGE 115
Cdd:cd19557  109 KELYGALAFSANF---TEAAATgqQINDLVRKQTYGQ 142

insect serpins similar to Drosophila melanogaster Serpin 77Ba; Serpins in insects function within development, wound healing and immunity. Drosophila melanogaster Serpin 77Ba plays an essential role in regulating the tracheal melanization immune response to bacterial and fungal infection. Insect serpins from pine beetle, diamondback moth, red flour beetle, mosquito, silkworm, and fruit fly are included in this subfamily. SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants have been associated with blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALcfsKIGGEDGDIHRGFQSLLVAINRTDTEYVLRTANGLFGEKSYDFLTGFTDSC 80
Cdd:cd19598   31 FSVWSLLSLLSEGASGETLKELRKVL---RLPVDNKCLRNFYRALSNLLNVKTSGVELESLNAIFTDKNFPVKPDFRSVV 107

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 183074521  81 GKFYQATIKQLDFvNDTEKSTTRVNSWVADKTKG--ENILlfYFDNILNS--FIVSSL 134
Cdd:cd19598  108 QKTYDVKVVPVDF-SNSTKTANIINEYISNATHGriKNAV--KPDDLENArmLLLSAL 162

serpin family C member 1, antithrombin III; Antithrombin III (AT3/ATIII) is a non-vitamin K-dependent serine protease that inhibits coagulation by neutralizing the enzymatic activity of thrombin (factors IIa, IXa, Xa). It is the most important anticoagulant molecule in mammalian circulation systems, controlled by its interaction with the cofactor, heparin, which accelerates its interaction with target proteases. This subgroup corresponds to clade C of the serpin superfamily. In general, SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate blood coagulation cascades. Non-inhibitory serpins perform many diverse functions such as chaperoning proteins or transporting hormones. Serpins are of medical interest because mutants can cause blood clotting disorders, emphysema, cirrhosis, and dementia. A classification based on evolutionary relatedness has resulted in the assignment of serpins to 16 clades designated A-P along with some orphans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 183074521   1 MSISSALAMVFMGAKGNTAAQMSQALCFSKIGGEDGD-IHRGFQSLLVAINRT---DTEYVlrTANGLFGEKSYDFLTGF 76
Cdd:cd02045   44 LSISTAFAMTKLGACNDTLQQLMEVFKFDTISEKTSDqIHFFFAKLNCRLYRKankSSELV--SANRLFGDKSLTFNETY 121