Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually a serine protease inhibitor. Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure. Certain family members are similar to the tick anticoagulant peptide (TAP). This is a highly selective inhibitor of factor Xa in the blood coagulation pathways. TAP molecules are highly dipolar, and are arranged to form a twisted two- stranded antiparallel beta-sheet followed by an alpha helix.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 392920101   35 ICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQCK 87
Cdd:pfam00014   1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 392920101  199 DIDECRGYKAVCDRNAWCVNEIGSYKCECMA 229
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPD 31

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 392920101   323 NSCLDKFDHDYkdtCGNenWRPHFFFNHQTRMCEQFWYDGCRGrSRNIFSEYDTCTTMC 381
Cdd:smart00131   1 DVCLLPPDTGP---CGG--SIPRYYYDPETGTCEPFTYGGCGG-NANNFESLEECERTC 53

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 392920101   408 GQWQQRYYFDHASLTCRQFWFDGCRsDSRNIFDDELTCQWLC 449
Cdd:smart00131  13 GGSIPRYYYDPETGTCEPFTYGGCG-GNANNFESLEECERTC 53

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 392920101 550 DTCLAKNPCKNNGTCIfvWKKDTHYCKCQPGFHGNNC 586
Cdd:cd00054    3 DECASGNPCQNGGTCV--NTVGSYRCSCPPGYTGRNC 37

Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually a serine protease inhibitor. Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure. Certain family members are similar to the tick anticoagulant peptide (TAP). This is a highly selective inhibitor of factor Xa in the blood coagulation pathways. TAP molecules are highly dipolar, and are arranged to form a twisted two- stranded antiparallel beta-sheet followed by an alpha helix.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 392920101   35 ICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQCK 87
Cdd:pfam00014   1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392920101    34 DICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:smart00131   1 DVCLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 392920101    98 DLCLLDADQGHCGderNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:smart00131   1 DVCLLPPDTGPCG---GSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53

Calcium-binding EGF domain;

                          10        20        30
                  ....*....|....*....|....*....|.
gi 392920101  199 DIDECRGYKAVCDRNAWCVNEIGSYKCECMA 229
Cdd:pfam07645   1 DVDECATGTHNCPANTVCVNTIGSFECRCPD 31

Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually a serine protease inhibitor. Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure. Certain family members are similar to the tick anticoagulant peptide (TAP). This is a highly selective inhibitor of factor Xa in the blood coagulation pathways. TAP molecules are highly dipolar, and are arranged to form a twisted two- stranded antiparallel beta-sheet followed by an alpha helix.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101  460 CLEDFDEGLkkeCNGGRWRhqWYFDKGSKKCFSFWYDGCKGaNENIFQDELSCLHTC 516
Cdd:pfam00014   2 CSLPPDSGP---CKASIPR--WYYNPTTGTCEPFTYGGCGG-NANNFESLEECESTC 52

Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in human and mouse papilin, and similar proteins. Papilin is an extracellular matrix glycoprotein that has been found in many organisms to be involved in thin matrix layers during gastrulation, matrix associated with wandering, phagocytic hemocytes, basement membranes and space-filling matrix during Drosophila development. It is a multidomain protein that primarily occurs in basement membranes. Papilins interact with several extracellular matrix components and ADAMTS enzymes, influences cell rearrangements and may modulate metalloproteinases during organogenesis. Papilins exist in mammals and invertebrates as a set of related, though not necessarily identical proteins. Mammalian papilin contains a single Kunitz domain, while other papilins such as that from Caenorhabditis elegans, contains multiple Kunitz domains. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101 460 CLEDFDEGLKkeCngGRWRHQWYFDKGSKKCFSFWYDGCKGaNENIFQDELSCLHTC 516
Cdd:cd22635    1 CLLDKDAGTV--C--GDYVQRWYYDPATGACNRFWYGGCGG-NANRFATEAECLRTC 52

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 392920101   408 GQWQQRYYFDHASLTCRQFWFDGCRsDSRNIFDDELTCQWLC 449
Cdd:smart00131  13 GGSIPRYYYDPETGTCEPFTYGGCG-GNANNFESLEECERTC 53

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 392920101   199 DIDECRGyKAVCDRNAWCVNEIGSYKCECMASYRgDGKHCT 239
Cdd:smart00179   1 DIDECAS-GNPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF-like domain;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 392920101   279 DVNECLRrPEMCNKNAECINREGSFICTCLEGYAgNGYNCT 319
Cdd:smart00179   1 DIDECAS-GNPCQNGGTCVNTVGSYRCECPPGYT-DGRNCE 39

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 392920101 199 DIDECRGYkAVCDRNAWCVNEIGSYKCECMASYRgdGKHCT 239
Cdd:cd00054    1 DIDECASG-NPCQNGGTCVNTVGSYRCSCPPGYT--GRNCE 38

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 392920101 550 DTCLAKNPCKNNGTCIfvWKKDTHYCKCQPGFHGNNC 586
Cdd:cd00054    3 DECASGNPCQNGGTCV--NTVGSYRCSCPPGYTGRNC 37

EGF domain; This family includes a variety of EGF-like domain homologs. This family includes the C-terminal domain of the malaria parasite MSP1 protein.

                          10        20        30
                  ....*....|....*....|....*....|
gi 392920101  252 DCSMHATCMNG----VCQCKEGYEGDGFNC 277
Cdd:pfam12947   7 GCHPNATCTNTggsfTCTCNDGYTGDGVTC 36

Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the N-terminus of particular EGF-like domains; calcium-binding may be crucial for numerous protein-protein interactions. Six conserved core cysteines form three disulfide bridges as in non calcium-binding EGF domains, whose structures are very similar. EGF_CA can be found in tandem repeat arrangements.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 392920101 639 CES-NPCLNNGTCRTTKGysTYFCECANGFGGKNC 672
Cdd:cd00054    5 CASgNPCQNGGTCVNTVG--SYRCSCPPGYTGRNC 37

Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually a serine protease inhibitor. Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure. Certain family members are similar to the tick anticoagulant peptide (TAP). This is a highly selective inhibitor of factor Xa in the blood coagulation pathways. TAP molecules are highly dipolar, and are arranged to form a twisted two- stranded antiparallel beta-sheet followed by an alpha helix.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 392920101   35 ICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQCK 87
Cdd:pfam00014   1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53

BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392920101    34 DICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:smart00131   1 DVCLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53

Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz domain which is a common structural fold found in a family of reversible serine protease inhibitors. This domain is thought to have evolved over 500 million years and is ubiquitous in all kingdoms of life and has been incorporated into many different genes. In general, each domain is encoded by a single exon. Some genes encode proteins with a single Kunitz domain, e.g. bovine pancreatic trypsin inhibitor (BPTI), trophoblast Kunitz domain protein (TKDP), amyloid beta-protein precursor (ABPP), as well as Kunitz-type venom peptides such as dendrotoxin. Genes that encode multiple Kunitz domains include hepatocyte growth factor activator inhibitors HAI1 and HAI2 (two domains), tissue factor pathway inhibitor TFPI1 and TFPI2 (three domains) and Caenorhabditis elegans papilin (eleven domains). In addition, the Kunitz domain has been integrated into multi-domain proteins, e.g. the collagen alpha3(VI), alpha1(VII) and alpha1(XXVIII) chains, WFIKKN1 (containing WAP, Follistatin/Kazal, Immunoglobulin, two Kunitz and NTR domains) and papilin. Furthermore, each domain within a multi-Kunitz domain protein may exhibit different protease activity, such as for the three tandemly repeated domains within both tissue factor pathway inhibitors 1 and 2. The Kunitz domain is a representative of alpha/beta proteins with irregular secondary structure stabilized by three disulfide bonds and presenting three peptide loops that can be varied without introducing much destabilization to the scaffold. Protease inhibitors meet the scaffold criteria in that they are small, stable and capable of evolving the binding activity of exposed peptide loops through targeted randomization to construct combinatorial libraries. Kunitz domain-based scaffolds have been successfully utilized to construct and select a library of protease inhibitors with the potential for therapeutic application.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 392920101  36 CLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd00109    1 CLLPPDPGPCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51

Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz domain which is a common structural fold found in a family of reversible serine protease inhibitors. This domain is thought to have evolved over 500 million years and is ubiquitous in all kingdoms of life and has been incorporated into many different genes. In general, each domain is encoded by a single exon. Some genes encode proteins with a single Kunitz domain, e.g. bovine pancreatic trypsin inhibitor (BPTI), trophoblast Kunitz domain protein (TKDP), amyloid beta-protein precursor (ABPP), as well as Kunitz-type venom peptides such as dendrotoxin. Genes that encode multiple Kunitz domains include hepatocyte growth factor activator inhibitors HAI1 and HAI2 (two domains), tissue factor pathway inhibitor TFPI1 and TFPI2 (three domains) and Caenorhabditis elegans papilin (eleven domains). In addition, the Kunitz domain has been integrated into multi-domain proteins, e.g. the collagen alpha3(VI), alpha1(VII) and alpha1(XXVIII) chains, WFIKKN1 (containing WAP, Follistatin/Kazal, Immunoglobulin, two Kunitz and NTR domains) and papilin. Furthermore, each domain within a multi-Kunitz domain protein may exhibit different protease activity, such as for the three tandemly repeated domains within both tissue factor pathway inhibitors 1 and 2. The Kunitz domain is a representative of alpha/beta proteins with irregular secondary structure stabilized by three disulfide bonds and presenting three peptide loops that can be varied without introducing much destabilization to the scaffold. Protease inhibitors meet the scaffold criteria in that they are small, stable and capable of evolving the binding activity of exposed peptide loops through targeted randomization to construct combinatorial libraries. Kunitz domain-based scaffolds have been successfully utilized to construct and select a library of protease inhibitors with the potential for therapeutic application.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd00109    1 CLLPPDPGPC---RAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51

Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in human and mouse papilin, and similar proteins. Papilin is an extracellular matrix glycoprotein that has been found in many organisms to be involved in thin matrix layers during gastrulation, matrix associated with wandering, phagocytic hemocytes, basement membranes and space-filling matrix during Drosophila development. It is a multidomain protein that primarily occurs in basement membranes. Papilins interact with several extracellular matrix components and ADAMTS enzymes, influences cell rearrangements and may modulate metalloproteinases during organogenesis. Papilins exist in mammals and invertebrates as a set of related, though not necessarily identical proteins. Mammalian papilin contains a single Kunitz domain, while other papilins such as that from Caenorhabditis elegans, contains multiple Kunitz domains. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 392920101  36 CLEDVDPG-PCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22635    1 CLLDKDAGtVCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52

Kunitz-type domain from the alpha1 chain of type VII collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha1 chain of type VII collagen (collagen alpha-1(VII) chain also called long-chain collagen or LC collagen) and similar proteins. LC collagen, encoded by the COL7A1 gene, is a stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen. So far, over 800 COL7A1 mutations have been reported, including missense, nonsense, splicing, insertion, and deletion mutations which to varying degrees leads to deficiency of type VII collagen. Epidermolysis bullosa acquisita (EBA) is an autoimmune acquired blistering skin disease resulting from autoantibodies to type VII collagen. The COL7A1 protein contains a Kunitz domain, the deactivation of which induces tumorigenesis. This domain is similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 392920101  34 DICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22627    1 DPCLLPMDEGSCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53

early lactation protein (ELP), colostrum trypsin inhibitor (CTI), and similar proteins; This model includes the Kunitz-type proteins, colostrum trypsin inhibitor (CTI, also called colostrum BPI) and early lactation protein (ELP). In marsupials, the ELP gene is expressed in the mammary gland and the protein is secreted into milk during early lactation. Mature ELP shares approximately 55.4% similarity with the colostrum-specific bovine CTI protein. Marsupial ELP and eutherian CTI both have a single Kunitz domain and are secreted only during the early lactation phases, suggesting that this protein may have an important role in the immunologically immature young of these species. These proteins are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101  97 PDLCLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22632    1 PSLCQLPPARGPC---RSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTC 54

Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of papilin, and similar domains; This model includes Kunitz domains from papilins with multiple Kunitz domains, such as Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of papilin, among others. Papilins are essential for embryonic development. D. melanogaster papilin is an essential extracellular matrix (ECM) protein that influences cell rearrangements. It may act by modulating metalloproteinases action during organogenesis and is able to non-competitively inhibit procollagen N-proteinase, an ADAMTS metalloproteinase. C. elegans papilin (also called abnormal cell migration protein 6) mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of distal tip cell (DTC) migration and both isoforms have an N-terminal papilin cassette, lagrin repeats and six C-terminal Kunitz-type serine proteinase inhibitory domains. It plays a role in embryogenesis, the second phase of distal cell tip migration and is required for distribution of the metalloproteinase, mig-17, during organogenesis. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 392920101  36 CLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22637    1 CDQPKDTGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51

Kunitz protease inhibitor (KPI) domain 2 (KPI-2 or K2) of tissue factor pathway inhibitor (TFPI); This model represents the second Kunitz-type domain (K2 or KPI-2) of tissue factor pathway inhibitor (TFPI or TFPI1), also known as extrinsic pathway inhibitor (EPI) or lipoprotein-associated coagulation inhibitor (LACI). TFPI down-regulates the extrinsic coagulation pathway via inhibition of activated factor X (FXa or Xa) and FVIIa (VIIa). It inhibits activated FXa via a "slow-tight binding mechanism", i.e. rapid formation of a loose FXa-TFPI complex that then slowly isomerizes to a tight FXa-TFPI* complex. Subsequent inhibition of FVIIa is facilitated by the presence of tissue factor (TF) and FXa, which together rapidly and efficiently form a quaternary FXa-TFPI-TF-FVIIa complex in which the activity of FXa and FVIIa are inhibited. TFPI consists of 3 Kunitz-type protease inhibitor (KPI) domains in a tandem arrangement; the K2 domain is exposed on functionally active TFPI pools in circulation in blood, in platelets, and attached to the endothelium. While the K1 (or KPI-1) domain of TFPI has been shown to bind and inhibit FVIIa, the K2 domain inhibits FXa by binding directly to the active site and forming a FXa:TFPI complex. A close interaction between the TFPI K2 domain and the FXa active site is essential for the FXa inhibitory action of TFPI and for the formation of an inactive TF/FVIIa/FXa/TFPI complex which then prevents FXa generation. Thus, blockage of K2 would prevent TFPI binding to both FXa and FVIIa/TF, and fully abolish TFPI inhibition of the coagulation cascade. The structure of the K2 domain is similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392920101  97 PDLCLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVCG 154
Cdd:cd22614    2 PDFCFLEEDPGIC---RGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTCE 56

Kunitz-type actitoxins such as Anemonia viridis U-actitoxin-Avd3l, and similar proteins; This model includes the Kunitz-type actitoxins such as Anemonia viridis U-actitoxin-Avd3l (also called U-AITX-Avd3l or AsKC9), Anthopleura elegantissima KappaPI-actitoxin-Ael3a (also called KappaPI-AITX-Ael3a or Kunitz-type serine protease inhibitor APEKTx1) and Anthopleura aff. xanthogrammica PI-actitoxin-Axm2b (also called PI-AITX-Axm2b or Kunitz-type proteinase inhibitor AXPI-II). U-AITX-Avd3l and KappaPI-AITX-Ael3a are dual-function toxins that inhibit both the serine protease trypsin and voltage-gated potassium channels Kv1.2/KCNA2. These proteins are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392920101  96 VPDLCLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22633    1 INSICLLPKDVGGC---RARFPRYYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55

Kunitz protease inhibitor (KPI) domain 3 (KPI-3 or K3) of tissue factor pathway inhibitor (TFPI) and TFPI2, and similar proteins; This model represents the third Kunitz-type domain (K3 or KPI-3) of tissue factor pathway inhibitor (TFPI or TFPI1), also known as extrinsic pathway inhibitor (EPI) or lipoprotein-associated coagulation inhibitor (LACI), and of TFPI2 (or TFPI-2). TFPI1 down-regulates the extrinsic coagulation pathway via inhibition of activated factor X (FXa or Xa) and FVIIa (VIIa). It inhibits activated FXa via a "slow-tight binding mechanism", i.e. rapid formation of a loose FXa-TFPI1 complex that then slowly isomerizes to a tight FXa-TFPI1* complex. Subsequent inhibition of FVIIa is facilitated by the presence of tissue factor (TF) and FXa, which together rapidly and efficiently form a quaternary FXa-TFPI1-TF-FVIIa complex in which the activity of FXa and FVIIa are inhibited. TFPI1 consists of 3 Kunitz-type protease inhibitor (KPI) domains in a tandem arrangement; while the K1 domain of TFPI has been shown to bind and inhibit FVIIa and the K2 domain similarly inhibits FXa, the K3 domain has no known inhibitory function. However, Protein S, which functions as a cofactor for TFPI to efficiently enhance TFPI inhibition of FXa and FXa activated TF-VIIa, is dependent on direct interactions with two important residues within K3, a Glutamate and an Arginine. This model also includes TFPI2 Kunitz domain 3 (KD3). TFPI2 exhibits inhibitory activity primarily toward trypsin, plasmin, and factor VIIa (FVIIa)/tissue factor (TF) via its KD1. It is believed to be the major inhibitor of plasmin in the extracellular matrix (ECM) but has little inhibitory activity toward urokinase-type plasminogen activator, tissue-type plasminogen activator, or thrombin. While TFPI2 specifically inhibits the proteases via the P1 arginine residue in KD1, domains KD2 and KD3 appear to have no discernible inhibitory activity and may serve to bind to nearby proteins to localize TFPI2 in the ECM. The structure of this domain is similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392920101  97 PDLCLLDADQGHC-GDERNghwwYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22615    1 PSFCLSPKDEGLCsASVTR----YYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54

Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr proteins; This model includes Drosophila melanogaster Kunitz domain 1 of papilin and Manduca sexta Kunitz domain 1 of lacunin, and similar proteins. D. melanogaster papilin is an essential extracellular matrix (ECM) protein that influences cell rearrangements. It may act by modulating metalloproteinase action during organogenesis and is able to non-competitively inhibit procollagen N-proteinase, an ADAMTS metalloproteinase. M. sexta lacunin is a large multidomain ECM containing several domains including several Kunitz-type protease inhibitors, thrombospondin type I, immunoglobulin-like and others. It exerts multiple effects on a variety of cell behaviors associated with the complex phenomenon of epithelial morphogenesis. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 392920101  36 CLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22639    1 CSLPKDRGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51

Kunitz domain of epididymal protease inhibitor eppin and similar proteins; This subfamily includes the Kunitz inhibitor domain protein eppin (also called Cancer/testis antigen 71 or CT71, epididymal protease inhibitor, protease inhibitor WAP7, serine protease inhibitor-like with Kunitz and WAP domains 1, or WAP four-disulfide core domain protein 7) as well as WAP four-disulfide core domain proteins 6A and 6B in mice, and similar proteins. Eppin is a serine protease inhibitor that plays an essential role in male reproduction and fertility. It modulates the hydrolysis of seminal fluid protein semenogelin 1 (SEMG1) by the serine protease kallikrein-related peptidase 3 (KLK3, PSA), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1, thereby inhibiting sperm motility. Thus, eppin could potentially be used as a target for male contraception. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 392920101  34 DICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQCKYK 89
Cdd:cd22611    1 DVCSLPKESGPCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNICKKK 56

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This model represents the Kunitz-type domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2 or TFPI-2) and similar proteins. TFPI2 exhibits inhibitory activity primarily toward trypsin, plasmin, and factor VIIa (FVIIa)/tissue factor (TF) via its KD1. It is believed to be the major inhibitor of plasmin in the extracellular matrix (ECM) but has little inhibitory activity toward urokinase-type plasminogen activator, tissue-type plasminogen activator, or thrombin. TFPI2 specifically inhibits the proteases via the P1 arginine residue in KD1. The TFPI2 domains KD2 and KD3 appear to have no discernible inhibitory activity and may serve to bind to nearby proteins to localize TFPI2 in the ECM. Structure studies of KD1 complexed with proteases may help in the development of specific and potent KD1 domain protein that may have a large pharmacologic impact in preventing tumor metastasis, retinal degeneration, and degradation of collagen in the ECM. The structure of this domain is similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 392920101  32 NEDICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22616    1 NAEICLLPPDEGPCRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTC 55

Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in human and mouse papilin, and similar proteins. Papilin is an extracellular matrix glycoprotein that has been found in many organisms to be involved in thin matrix layers during gastrulation, matrix associated with wandering, phagocytic hemocytes, basement membranes and space-filling matrix during Drosophila development. It is a multidomain protein that primarily occurs in basement membranes. Papilins interact with several extracellular matrix components and ADAMTS enzymes, influences cell rearrangements and may modulate metalloproteinases during organogenesis. Papilins exist in mammals and invertebrates as a set of related, though not necessarily identical proteins. Mammalian papilin contains a single Kunitz domain, while other papilins such as that from Caenorhabditis elegans, contains multiple Kunitz domains. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392920101 100 CLLDADQGH-CGDernghwW---YFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22635    1 CLLDKDAGTvCGD------YvqrWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52

Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually a serine protease inhibitor. Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure. Certain family members are similar to the tick anticoagulant peptide (TAP). This is a highly selective inhibitor of factor Xa in the blood coagulation pathways. TAP molecules are highly dipolar, and are arranged to form a twisted two- stranded antiparallel beta-sheet followed by an alpha helix.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101  460 CLEDFDEGLkkeCNGGRWRhqWYFDKGSKKCFSFWYDGCKGaNENIFQDELSCLHTC 516
Cdd:pfam00014   2 CSLPPDSGP---CKASIPR--WYYNPTTGTCEPFTYGGCGG-NANNFESLEECESTC 52

Kunitz-type domain from the alpha6 chain of fish type VI collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha6 chain of type VI collagen (collagen alpha 6(VI) chain) and similar proteins. Collagen VI is a widely expressed member of the triple helix-containing protein superfamily of collagens and forms beaded microfibrils that anchor large interstitial structures. Immediately after fibril formation, the Kunitz domain can be cleaved off. This domain is similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22631    1 CLLGQDAGSC---QNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51

Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration protein 6 or mig-6), Amblyomma hebraeum amblin domain 1, and similar proteins; This model includes Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration protein 6 or mig-6) and domain 1 of Amblyomma hebraeum amblin, and similar proteins. C. elegans papilin (also called abnormal cell migration protein 6) mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of distal tip cell (DTC) migration and both isoforms have an N-terminal papilin cassette, lagrin repeats and six C-terminal Kunitz-type serine proteinase inhibitory domains. It plays a role in embryogenesis, the second phase of distal cell tip migration and is required for distribution of the metalloproteinase, mig-17, during organogenesis. Amblin contains two Kunitz-like domains and specifically inhibits thrombin. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22638    1 CTLKPETGPC---RAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51

second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; This subfamily includes WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 (WFIKKN1, WFKN1), WFIKKN2 (WFKN2), and similar proteins. WFIKKN proteins are protease inhibitors that contain two distinct Kunitz-type protease inhibitor domains. They may have serine protease- and metalloprotease-inhibitor activity. This model represents the second Kunitz (KU2) domain, which has been shown to inhibit trypsin, but not chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator. However, the inhibition constant of this domain for bovine trypsin is about five orders of magnitudes lower than that of bovine pancreatic trypsin inhibitor (BPTI) for trypsin. This could be due to unfavorable side-chain conformation of a tryptophan at P2' site which is incompatible with a trypsin complex; typical trypsin inhibitors of the Kunitz family feature a tyrosine residue or other less bulky residues at this site. The structure of KU2 is similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 392920101  35 ICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQC 86
Cdd:cd22606    1 ICSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDAC 52

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This model represents the Kunitz-type domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2 or TFPI-2) and similar proteins. TFPI2 exhibits inhibitory activity primarily toward trypsin, plasmin, and factor VIIa (FVIIa)/tissue factor (TF) via its KD1. It is believed to be the major inhibitor of plasmin in the extracellular matrix (ECM) but has little inhibitory activity toward urokinase-type plasminogen activator, tissue-type plasminogen activator, or thrombin. TFPI2 specifically inhibits the proteases via the P1 arginine residue in KD1. The TFPI2 domains KD2 and KD3 appear to have no discernible inhibitory activity and may serve to bind to nearby proteins to localize TFPI2 in the ECM. Structure studies of KD1 complexed with proteases may help in the development of specific and potent KD1 domain protein that may have a large pharmacologic impact in preventing tumor metastasis, retinal degeneration, and degradation of collagen in the ECM. The structure of this domain is similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVCG 154
Cdd:cd22616    5 CLLPPDEGPC---RALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTCW 56

Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr proteins; This model includes Drosophila melanogaster Kunitz domain 1 of papilin and Manduca sexta Kunitz domain 1 of lacunin, and similar proteins. D. melanogaster papilin is an essential extracellular matrix (ECM) protein that influences cell rearrangements. It may act by modulating metalloproteinase action during organogenesis and is able to non-competitively inhibit procollagen N-proteinase, an ADAMTS metalloproteinase. M. sexta lacunin is a large multidomain ECM containing several domains including several Kunitz-type protease inhibitors, thrombospondin type I, immunoglobulin-like and others. It exerts multiple effects on a variety of cell behaviors associated with the complex phenomenon of epithelial morphogenesis. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22639    1 CSLPKDRGPC---RNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51

Kunitz protease inhibitor (KPI) domain 1 (KPI-1 or K1) of tissue factor pathway inhibitor (TFPI); This model represents the first Kunitz-type domain (K1 or KPI-1) of tissue factor pathway inhibitor (TFPI or TFPI1), also known as extrinsic pathway inhibitor (EPI) or lipoprotein-associated coagulation inhibitor (LACI). TFPI down-regulates the extrinsic coagulation pathway via inhibition of activated factor X (FXa or Xa) and FVIIa (VIIa). It inhibits activated FXa via a "slow-tight binding mechanism", i.e. rapid formation of a loose FXa-TFPI complex that then slowly isomerizes to a tight FXa-TFPI* complex. Subsequent inhibition of FVIIa is facilitated by the presence of tissue factor (TF) and FXa, which together rapidly and efficiently form a quaternary FXa-TFPI-TF-FVIIa complex in which the activity of FXa and FVIIa are inhibited. TFPI consists of 3 Kunitz-type protease inhibitor (KPI) domains in a tandem arrangement; The K1 domain of TFPI has been shown to bind and inhibit FVIIa while the K2 domain similarly inhibits FXa. Small peptide blocking inhibition of FXa and TF-FVIIa by TFPI shows that domain K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to the tight FXa-TFPI complex. The structure of the K1 domain is similar to those of other Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101 100 CLLDADQGHCgdeRNGHWWYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22613    4 CAFKADDGPC---KAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTC 54

venom Kunitz-type proteins such as textilinin, BF9 and PILP; This group includes toxins isolated from snake venoms, such as textilinin, vestiginin, spermatin, mulgin, venom basic protease inhibitor IX (BF9), and protease inhibitor-like protein (PILP), among others. Pseudonaja textilis textilinin-1 is a Kunitz-type serine protease inhibitor that binds to and blocks the activity of a range of serine proteases, including plasmin and trypsin. Ability of testilinin to inhibit plasmin, a protease involved in fibrinolysis, raises the possibility that it may be used as an alternative to aprotinin (Trasylol), which is a systemic antibleeding agent in surgery. Also included is the Bungarus fasciatus fraction IX (BF9), a chymotrypsin inhibitor that binds chymotrypsin but not trypsin. Protease inhibitor-like proteins PILP-1 and PILP-2 show weak binding and inhibition of matrix metalloproteinase-2 (MMP-2) and show an activity in inhibiting migration and invasion of neuroblastoma; they do not inhibit chymotrypsin or trypsin. The structures of these toxins are similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101  97 PDLCLLDADQGHCGDERNGhwwYFFNQESGECEKFFYYGCGGNDNKFYSLHMCRKVC 153
Cdd:cd22594    2 PKFCELPADPGPCNAYKPA---FYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTC 55

first Kunitz domain of bikunin and similar proteins; This subfamily includes the N-terminal domain of bikunin (also known as inter-alpha-trypsin inhibitor light chain (ITI-LC) or urinary trypsin inhibitor), a plasma protease inhibitor, that is associated with inflammation and stabilizes the extracellular matrix. It is encoded together with alpha-1-microglobulin (A1M) by an alpha-1-microglobulin/bikunin precursor (AMBP) gene that is tightly controlled by several hepatocyte-enriched nuclear (HEN) factors, and cleaved by a furin-like protease that releases the two mature molecules. Bikunin is a Kunitz-type serine protease inhibitor, found in vertebrate serum and urine, modified by a chondroitin sulfate (CS) chain. The structures of these toxins are similar to that of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor), showing an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds. Bikunin contains two Kunitz domains; this model represents the first repeat.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 392920101  34 DICLEDVDPGPCQYYQVQWFWDKQVEECKEFHYGGCMGTKNRFSSKQQCVKQCK 87
Cdd:cd22596    1 DSCKLPPDAGPCFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTCR 54

Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in human and mouse papilin, and similar proteins. Papilin is an extracellular matrix glycoprotein that has been found in many organisms to be involved in thin matrix layers during gastrulation, matrix associated with wandering, phagocytic hemocytes, basement membranes and space-filling matrix during Drosophila development. It is a multidomain protein that primarily occurs in basement membranes. Papilins interact with several extracellular matrix components and ADAMTS enzymes, influences cell rearrangements and may modulate metalloproteinases during organogenesis. Papilins exist in mammals and invertebrates as a set of related, though not necessarily identical proteins. Mammalian papilin contains a single Kunitz domain, while other papilins such as that from Caenorhabditis elegans, contains multiple Kunitz domains. These domains are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 392920101 460 CLEDFDEGLKkeCngGRWRHQWYFDKGSKKCFSFWYDGCKGaNENIFQDELSCLHTC 516
Cdd:cd22635    1 CLLDKDAGTV--C--GDYVQRWYYDPATGACNRFWYGGCGG-NANRFATEAECLRTC 52

EGF domain; This family includes a variety of EGF-like domain homologs. This family includes the C-terminal domain of the malaria parasite MSP1 protein.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 392920101  283 CLRRPEMCNKNAECINREGSFICTCLEGYAGNGYNC 318
Cdd:pfam12947   1 CSDNNGGCHPNATCTNTGGSFTCTCNDGYTGDGVTC 36

chymotrypsin inhibitor SCI-I_III-like; This model includes the Kunitz-type chymotrypsin inhibitors SCI-III and SCI-I, and similar proteins in insects. SCI-III and SCI-I inhibit chymotrypsin, avoiding the accidental chymotrypsin-mediated activation of prophenoloxidase. This enzyme is required by the insect immune system to produce melanin which is used to engulf foreign objects. This subfamily also includes Kunitz-type male accessory gland peptide with protease inhibitory activity, synthesized and secreted by male accessory glands of Drosophila funebris; it may play a role as an acrosin inhibitor involved in reproduction. These proteins are similar to Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor) that shows an alpha/beta fold with irregular secondary structure stabilized by three disulfide bonds.