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Conserved domains on  [gi|1020533973|ref|XP_016106176|]
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PREDICTED: kunitz-type protease inhibitor 1 [Sinocyclocheilus grahami]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Kunitz_HAI1_1-like cd22623
Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes ...
238-296 2.42e-41

Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1 (HAI1 or HAI-1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. KD1, the major inhibitory domain of HAI-1, is involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure; presence of the target protease causes changes in the HAI-1 structure to an extended conformation. HAI-1 has been shown to inhibit several serine proteases such as matripase, hepsin, trypsin, hepatocyte growth factor activator (HGFA), and prostasin. It is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structures of these domains 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.


:

Pssm-ID: 438666  Cd Length: 59  Bit Score: 141.91  E-value: 2.42e-41
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1020533973 238 QSERHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKNT 296
Cdd:cd22623     1 QSELYCLAPKKVGPCRGSFPRWHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSACRGV 59
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
369-429 2.09e-39

Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 1 (HAI-1 or HAI1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. While the Kunitz domain 1 (KD1) is the major inhibitory domain of HAI-1 and involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure, studies show that deletion of HAI-1 Kunitz domain 2 (KD2) and the extracellular region enhanced inhibition of matriptase. HAI-1 KD2 has been shown to have potent inhibitory activity against trypsin, but it cannot inhibit hepatocyte growth factor activator (HGFA), and matriptase. HAI-1 is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structure of KD2 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.


:

Pssm-ID: 438667  Cd Length: 61  Bit Score: 136.88  E-value: 2.09e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSGVTENDVF 429
Cdd:cd22624     1 RCTEPPVTGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETCSGVTEKDVF 61
MANEC pfam07502
MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the ...
36-124 1.34e-30

MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the N-terminal region of several membrane-associated and extracellular proteins. Although formerly called MANSC (for motif at N terminus with seven cysteines) it has now been renamed by MANEC (motif at N terminus with eight cysteines) by Richard Mitter and Stephen Fitzgerald after the discovery of an eighth conserved cysteine. It is postulated that this domain may play a role in the formation of protein complexes involving various protease activators and inhibitors.


:

Pssm-ID: 462186  Cd Length: 90  Bit Score: 113.94  E-value: 1.34e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  36 QCVQPFkSGRKDFVLDTEESIEDGAVFLSNPSVAHRNACIAACCRDPRCNLALIE-DGYEKGPNNSCFLFNCLYKQKYVC 114
Cdd:pfam07502   2 SCLEDF-TGVEDFIIDTEDSVKNGATFLSSPEVSSARDCVRACCSTPRCNLAVFEeRPGGEDAIPSCYLFNCLYPSRFVC 80
                          90
                  ....*....|
gi 1020533973 115 RFIQKKGFTN 124
Cdd:pfam07502  81 KFAPHKGYTS 90
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
315-349 1.88e-08

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure


:

Pssm-ID: 238060  Cd Length: 35  Bit Score: 49.90  E-value: 1.88e-08
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1020533973 315 CGEDQFKCSNGCCVKKELECDEQQQCSDGSDEENC 349
Cdd:cd00112     1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35
PKD_4 pfam18911
PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.
146-229 1.92e-07

PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.


:

Pssm-ID: 436824 [Multi-domain]  Cd Length: 85  Bit Score: 48.81  E-value: 1.92e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 146 PPIANAGRDVVVQPNEEVLLNGIESWD-DRNIISYEWSLisGDESLhiektdlPDQVKVSKL--VPGVYKFKLTVTDSAH 222
Cdd:pfam18911   3 APVADAGGDRIVAEGETVTFDASASDDpDGDILSYRWDF--GDGTT-------ATGANVSHTyaAPGTYTVTLTVTDDSG 73

                  ....*..
gi 1020533973 223 HSDSAQV 229
Cdd:pfam18911  74 ASNSTAT 80
 
Name Accession Description Interval E-value
Kunitz_HAI1_1-like cd22623
Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes ...
238-296 2.42e-41

Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1 (HAI1 or HAI-1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. KD1, the major inhibitory domain of HAI-1, is involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure; presence of the target protease causes changes in the HAI-1 structure to an extended conformation. HAI-1 has been shown to inhibit several serine proteases such as matripase, hepsin, trypsin, hepatocyte growth factor activator (HGFA), and prostasin. It is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structures of these domains 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.


Pssm-ID: 438666  Cd Length: 59  Bit Score: 141.91  E-value: 2.42e-41
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1020533973 238 QSERHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKNT 296
Cdd:cd22623     1 QSELYCLAPKKVGPCRGSFPRWHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSACRGV 59
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
369-429 2.09e-39

Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 1 (HAI-1 or HAI1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. While the Kunitz domain 1 (KD1) is the major inhibitory domain of HAI-1 and involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure, studies show that deletion of HAI-1 Kunitz domain 2 (KD2) and the extracellular region enhanced inhibition of matriptase. HAI-1 KD2 has been shown to have potent inhibitory activity against trypsin, but it cannot inhibit hepatocyte growth factor activator (HGFA), and matriptase. HAI-1 is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structure of KD2 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.


Pssm-ID: 438667  Cd Length: 61  Bit Score: 136.88  E-value: 2.09e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSGVTENDVF 429
Cdd:cd22624     1 RCTEPPVTGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETCSGVTEKDVF 61
MANEC pfam07502
MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the ...
36-124 1.34e-30

MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the N-terminal region of several membrane-associated and extracellular proteins. Although formerly called MANSC (for motif at N terminus with seven cysteines) it has now been renamed by MANEC (motif at N terminus with eight cysteines) by Richard Mitter and Stephen Fitzgerald after the discovery of an eighth conserved cysteine. It is postulated that this domain may play a role in the formation of protein complexes involving various protease activators and inhibitors.


Pssm-ID: 462186  Cd Length: 90  Bit Score: 113.94  E-value: 1.34e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  36 QCVQPFkSGRKDFVLDTEESIEDGAVFLSNPSVAHRNACIAACCRDPRCNLALIE-DGYEKGPNNSCFLFNCLYKQKYVC 114
Cdd:pfam07502   2 SCLEDF-TGVEDFIIDTEDSVKNGATFLSSPEVSSARDCVRACCSTPRCNLAVFEeRPGGEDAIPSCYLFNCLYPSRFVC 80
                          90
                  ....*....|
gi 1020533973 115 RFIQKKGFTN 124
Cdd:pfam07502  81 KFAPHKGYTS 90
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
370-420 2.58e-20

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.


Pssm-ID: 425421  Cd Length: 53  Bit Score: 84.23  E-value: 2.58e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:pfam00014   2 CSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
243-294 2.91e-19

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.


Pssm-ID: 425421  Cd Length: 53  Bit Score: 81.15  E-value: 2.91e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:pfam00014   2 CSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
370-420 8.42e-19

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.


Pssm-ID: 197529  Cd Length: 53  Bit Score: 80.00  E-value: 8.42e-19
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973  370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:smart00131   3 CLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
MANEC smart00765
The MANEC domain, formerly called MANSC; This domain, comprising 8 conserved cysteines, is ...
32-124 1.29e-17

The MANEC domain, formerly called MANSC; This domain, comprising 8 conserved cysteines, is found in the N terminus of higher multicellular animal membrane and extracellular proteins. It is postulated that this domain may play a role in the formation of protein complexes involving various protease activators and inhibitors. It is possible that some of the cysteine residues in the MANSC domain form structurally important disulfide bridges. All of the MANSC-containing proteins contain predicted transmembrane regions and signal peptides. It has been proposed that the MANSC domain in HAI-1 might function through binding with hepatocyte growth factor activator and matriptase.


Pssm-ID: 129004  Cd Length: 93  Bit Score: 77.88  E-value: 1.29e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973   32 SAQGQCVQPFkSGRKDFVLDTEESIEDGAVFLSNP-SVAHRNACIAACCRDPRCNLALIEDGYEKGPNNsCFLFNCLYKQ 110
Cdd:smart00765   1 SPGEDCLGRF-RVLENAIIRTEESLSAGARFLKSPiAVNTWEDCVRACCSTPNCNLAVFELRREDAEGN-CYLFNCTYPG 78
                           90
                   ....*....|....
gi 1020533973  111 KYVCRFIQKKGFTN 124
Cdd:smart00765  79 KEVCKFKPHEGYTS 92
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
243-293 1.49e-17

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.


Pssm-ID: 197529  Cd Length: 53  Bit Score: 76.15  E-value: 1.49e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973  243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:smart00131   3 CLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
315-349 1.88e-08

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure


Pssm-ID: 238060  Cd Length: 35  Bit Score: 49.90  E-value: 1.88e-08
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1020533973 315 CGEDQFKCSNGCCVKKELECDEQQQCSDGSDEENC 349
Cdd:cd00112     1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35
PKD_4 pfam18911
PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.
146-229 1.92e-07

PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.


Pssm-ID: 436824 [Multi-domain]  Cd Length: 85  Bit Score: 48.81  E-value: 1.92e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 146 PPIANAGRDVVVQPNEEVLLNGIESWD-DRNIISYEWSLisGDESLhiektdlPDQVKVSKL--VPGVYKFKLTVTDSAH 222
Cdd:pfam18911   3 APVADAGGDRIVAEGETVTFDASASDDpDGDILSYRWDF--GDGTT-------ATGANVSHTyaAPGTYTVTLTVTDDSG 73

                  ....*..
gi 1020533973 223 HSDSAQV 229
Cdd:pfam18911  74 ASNSTAT 80
LDLa smart00192
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
315-346 1.94e-07

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.


Pssm-ID: 197566  Cd Length: 33  Bit Score: 47.24  E-value: 1.94e-07
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1020533973  315 CGEDQFKCSNGCCVKKELECDEQQQCSDGSDE 346
Cdd:smart00192   2 CPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33
Ldl_recept_a pfam00057
Low-density lipoprotein receptor domain class A;
313-349 4.39e-07

Low-density lipoprotein receptor domain class A;


Pssm-ID: 395011  Cd Length: 37  Bit Score: 46.09  E-value: 4.39e-07
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1020533973 313 SSCGEDQFKCSNGCCVKKELECDEQQQCSDGSDEENC 349
Cdd:pfam00057   1 STCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37
PKD smart00089
Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 ...
156-233 7.37e-06

Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 protein contains 14 repeats, present elsewhere such as in microbial collagenases.


Pssm-ID: 214510 [Multi-domain]  Cd Length: 79  Bit Score: 43.98  E-value: 7.37e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1020533973  156 VVQPNEEVLLNGiESWDDRNIISYEWSLisGDESLHIEKTdlpdqVKVSKLVPGVYKFKLTVTDSAhHSDSAQVTLLV 233
Cdd:smart00089  10 VGVAGESVTFTA-TSSDDGSIVSYTWDF--GDGTSSTGPT-----VTHTYTKPGTYTVTLTVTNAV-GSASATVTVVV 78
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
146-238 7.41e-06

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 48.88  E-value: 7.41e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  146 PPIANAGRDVVVQPNEEVLLNGIESWD-DRNIISYEWSLISGDEslhIEKTDlPDQVKVSKLVPGVYK-----FKLTVTD 219
Cdd:NF038112  1187 RPVANAGPDQTVLERTTVTLNGSGSFDpDGDPLTYAWTQVSGPA---VTLTG-ADTATPSFTAPEVTAdtvltFQLVVSD 1262
                           90
                   ....*....|....*....
gi 1020533973  220 SAHHSDSAQVTLLVLTPDQ 238
Cdd:NF038112  1263 GTKTSAPDTVTVLVRNVNR 1281
PKD cd00146
polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an ...
147-233 2.60e-05

polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an IG-like fold; domain probably functions as a ligand binding site in protein-protein or protein-carbohydrate interactions; a single instance of the repeat is presented here. The domain is also found in microbial collagenases and chitinases.


Pssm-ID: 238084 [Multi-domain]  Cd Length: 81  Bit Score: 42.48  E-value: 2.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 147 PIANAGRDVVVQPNEEVLLNgIESWDDRNIISYEWSLisGDESlhiekTDLPDQVKVSK--LVPGVYKFKLTVTDSAHHS 224
Cdd:cd00146     1 PTASVSAPPVAELGASVTFS-ASDSSGGSIVSYKWDF--GDGE-----VSSSGEPTVTHtyTKPGTYTVTLTVTNAVGSS 72

                  ....*....
gi 1020533973 225 DSAQVTLLV 233
Cdd:cd00146    73 STKTTTVVV 81
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
144-233 2.78e-04

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 43.88  E-value: 2.78e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  144 DKPPIANAGRDVVVQPNEEVLLNGIESWDDRNIISYEWSLISG-DESLHIEKTDLPDQVKVSKLVPGVYKFKLTVTDSAH 222
Cdd:NF038112  1373 NRAPVANAGADQTVDERSTVTLSGSATDPDGDALTYAWTQTAGpTVTLTGADTATASFTAPEVAADTELTFQLTVSADGQ 1452
                           90
                   ....*....|.
gi 1020533973  223 HSDSAQVTLLV 233
Cdd:NF038112  1453 ASADVTVTVTV 1463
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
147-243 1.54e-03

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 41.57  E-value: 1.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  147 PIANAGRDVVVQPNEEVLLNGIESWDDRNIISYEWSLISGdESLHIEKTDLPdqvKVSKLVPGV-----YKFKLTVTDSA 221
Cdd:NF038112  1470 PVAHAGESITVDEGSTVTLDASATDPDGDTLTYAWTQVAG-PSVTLTGADSA---KLTFTAPEVsadttLTFSLTVTDGS 1545
                           90       100
                   ....*....|....*....|..
gi 1020533973  222 HHSDSAQVTLLVLTPDQSERHC 243
Cdd:NF038112  1546 GSSGPVVVTVTVKNVNRAPDGG 1567
 
Name Accession Description Interval E-value
Kunitz_HAI1_1-like cd22623
Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes ...
238-296 2.42e-41

Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1 (HAI1 or HAI-1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. KD1, the major inhibitory domain of HAI-1, is involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure; presence of the target protease causes changes in the HAI-1 structure to an extended conformation. HAI-1 has been shown to inhibit several serine proteases such as matripase, hepsin, trypsin, hepatocyte growth factor activator (HGFA), and prostasin. It is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structures of these domains 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.


Pssm-ID: 438666  Cd Length: 59  Bit Score: 141.91  E-value: 2.42e-41
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1020533973 238 QSERHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKNT 296
Cdd:cd22623     1 QSELYCLAPKKVGPCRGSFPRWHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSACRGV 59
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
369-429 2.09e-39

Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 1 (HAI-1 or HAI1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. While the Kunitz domain 1 (KD1) is the major inhibitory domain of HAI-1 and involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure, studies show that deletion of HAI-1 Kunitz domain 2 (KD2) and the extracellular region enhanced inhibition of matriptase. HAI-1 KD2 has been shown to have potent inhibitory activity against trypsin, but it cannot inhibit hepatocyte growth factor activator (HGFA), and matriptase. HAI-1 is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structure of KD2 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.


Pssm-ID: 438667  Cd Length: 61  Bit Score: 136.88  E-value: 2.09e-39
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSGVTENDVF 429
Cdd:cd22624     1 RCTEPPVTGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETCSGVTEKDVF 61
MANEC pfam07502
MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the ...
36-124 1.34e-30

MANEC domain; This region of similarity, comprising 8 conserved cysteines, is found in the N-terminal region of several membrane-associated and extracellular proteins. Although formerly called MANSC (for motif at N terminus with seven cysteines) it has now been renamed by MANEC (motif at N terminus with eight cysteines) by Richard Mitter and Stephen Fitzgerald after the discovery of an eighth conserved cysteine. It is postulated that this domain may play a role in the formation of protein complexes involving various protease activators and inhibitors.


Pssm-ID: 462186  Cd Length: 90  Bit Score: 113.94  E-value: 1.34e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  36 QCVQPFkSGRKDFVLDTEESIEDGAVFLSNPSVAHRNACIAACCRDPRCNLALIE-DGYEKGPNNSCFLFNCLYKQKYVC 114
Cdd:pfam07502   2 SCLEDF-TGVEDFIIDTEDSVKNGATFLSSPEVSSARDCVRACCSTPRCNLAVFEeRPGGEDAIPSCYLFNCLYPSRFVC 80
                          90
                  ....*....|
gi 1020533973 115 RFIQKKGFTN 124
Cdd:pfam07502  81 KFAPHKGYTS 90
Kunitz_HAI1_1-like cd22623
Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes ...
369-423 9.64e-24

Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 1 (HAI1 or HAI-1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. KD1, the major inhibitory domain of HAI-1, is involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure; presence of the target protease causes changes in the HAI-1 structure to an extended conformation. HAI-1 has been shown to inhibit several serine proteases such as matripase, hepsin, trypsin, hepatocyte growth factor activator (HGFA), and prostasin. It is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structures of these domains 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.


Pssm-ID: 438666  Cd Length: 59  Bit Score: 94.15  E-value: 9.64e-24
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSGV 423
Cdd:cd22623     5 YCLAPKKVGPCRGSFPRWHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSACRGV 59
Kunitz_HAI2_1-like cd22621
Kunitz-type domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
242-293 1.13e-23

Kunitz-type domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and similar proteins; This model includes the Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2 or HAI2, also known as placental bikunin or Kunitz-type protease inhibitor 2). HAI-2 is composed of two Kunitz domains that strongly inhibit many serine proteases with sub-nanomolar affinities. HAI-2 Kunitz domain 1 (KD1) has been found to be the domain responsible for inhibition of hepatocyte growth factor (HGF) activator; activated HGF/scatter factor (HGF/SF) binds to its receptor tyrosine kinase MET to induce dimerization and initiate phosphorylation cascades leading to comprehensive cellular changes that, in the deregulated context of cancer, drive malignant transformation and progression. HAI-2 has been found to be a natural tumor suppressor in renal cell carcinoma, breast cancer and prostate cancer; its loss leads to tumor growth and progression in part due to increased MET signaling. HAI-2 is also a specific substrate for mesotrypsin, which is up-regulated with progression in prostate cancers and shown to contribute to invasion and metastasis; these activities of mesotrypsin may in part be mediated through cleavage and inactivation of HAI-2, resulting in increases in HGF/SF activation and MET signaling. HAI-2 is a physiological inhibitor of hepsin and matriptase, two type II transmembrane serine proteases that, like HGF activator, can convert latent pro-HGF/SF into the two-chain active signaling heterodimer. The structures of these KD1 domains 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.


Pssm-ID: 438664  Cd Length: 53  Bit Score: 93.69  E-value: 1.13e-23
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22621     2 FCHLPKVVGRCRASFPRWWYNATSQSCQEFIFGGCKGNLNNFLSEQECLQKC 53
Kunitz_HAI2_2-like cd22622
Kunitz-type domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
369-420 5.97e-22

Kunitz-type domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and similar proteins; This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2 or HAI2, also known as placental bikunin or Kunitz-type protease inhibitor 2). HAI-2 is composed of two Kunitz domains that strongly inhibit many serine proteases with sub-nanomolar affinities. It has been found to be a natural tumor suppressor in renal cell carcinoma, breast cancer and prostate cancer, the loss of which leads to tumor growth and progression attributable at least in part to increased MET signaling. HAI-2 is a specific substrate of mesotrypsin which is up-regulated with progression in prostate cancers and shown to contribute to invasion and metastasis; these activities of mesotrypsin may in part be mediated through cleavage and inactivation of HAI-2, resulting in increases in hetatocyte growth factor/scatter factor (HGF/SF) activation and MET signaling. HAI-2 is a physiological inhibitor of hepsin and matriptase, two type II transmembrane serine proteases that, like HGF activator, can convert latent pro-HGF/SF into the two-chain active signaling heterodimer. KD2 is similar to KD1, whose structure 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.


Pssm-ID: 438665  Cd Length: 53  Bit Score: 88.95  E-value: 5.97e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22622     2 YCAAPRVTGPCRAAFPRWYYDPESQSCKEFIYGGCRGNKNNYLSEEECMDRC 53
Kunitz-type cd00109
Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz ...
370-420 4.35e-21

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.


Pssm-ID: 438633  Cd Length: 51  Bit Score: 86.45  E-value: 4.35e-21
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd00109     1 CLLPPDPGPCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51
Kunitz-type cd00109
Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz ...
243-293 2.36e-20

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.


Pssm-ID: 438633  Cd Length: 51  Bit Score: 84.14  E-value: 2.36e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd00109     1 CLLPPDPGPCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
370-420 2.58e-20

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.


Pssm-ID: 425421  Cd Length: 53  Bit Score: 84.23  E-value: 2.58e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:pfam00014   2 CSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
243-294 2.91e-19

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.


Pssm-ID: 425421  Cd Length: 53  Bit Score: 81.15  E-value: 2.91e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:pfam00014   2 CSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53
Kunitz_HAI2_2-like cd22622
Kunitz-type domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
242-293 5.34e-19

Kunitz-type domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and similar proteins; This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2 or HAI2, also known as placental bikunin or Kunitz-type protease inhibitor 2). HAI-2 is composed of two Kunitz domains that strongly inhibit many serine proteases with sub-nanomolar affinities. It has been found to be a natural tumor suppressor in renal cell carcinoma, breast cancer and prostate cancer, the loss of which leads to tumor growth and progression attributable at least in part to increased MET signaling. HAI-2 is a specific substrate of mesotrypsin which is up-regulated with progression in prostate cancers and shown to contribute to invasion and metastasis; these activities of mesotrypsin may in part be mediated through cleavage and inactivation of HAI-2, resulting in increases in hetatocyte growth factor/scatter factor (HGF/SF) activation and MET signaling. HAI-2 is a physiological inhibitor of hepsin and matriptase, two type II transmembrane serine proteases that, like HGF activator, can convert latent pro-HGF/SF into the two-chain active signaling heterodimer. KD2 is similar to KD1, whose structure 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.


Pssm-ID: 438665  Cd Length: 53  Bit Score: 80.48  E-value: 5.34e-19
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22622     2 YCAAPRVTGPCRAAFPRWYYDPESQSCKEFIYGGCRGNKNNYLSEEECMDRC 53
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
370-420 8.42e-19

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.


Pssm-ID: 197529  Cd Length: 53  Bit Score: 80.00  E-value: 8.42e-19
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973  370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:smart00131   3 CLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
Kunitz_PPTI-like cd22608
Pseudocerastes persicus trypsin inhibitor (PPTI), Kunitz-type serine protease inhibitor ...
369-420 2.45e-18

Pseudocerastes persicus trypsin inhibitor (PPTI), Kunitz-type serine protease inhibitor bitisilin, and similar proteins; This group contains Pseudocerastes persicus trypsin inhibitor (PPTI), Bitis gabonica Kunitz-type serine protease inhibitor bitisilin-1 (BG-11), -2 (BG-15) and -3 (two-Kunitz protease inhibitor), Oxyuranus scutellatus scutellatus taicatoxin, and serine protease inhibitor component (TSPI, also called venom protease inhibitor 1 or venom protease inhibitor 2), among others. PPTI from P. persicus venom shows inhibitory effect against trypsin proteolytic activity and has similarities to dendrotoxins (DTXs), with corresponding functionally important residues. Studies have shown the ability of PPTI to inhibit voltage-gated potassium channels, and consequently have dual functionality. Bitilisins 1, 2, and 3 are serine protease inhibitors expressed in snake venom glands; bitsilin-3 consists of two Kunitz protease inhibitor domains. Taicatoxin inhibits trypsin, tissue kallikrein, elastase, plasmin and factor Xa, and is also known to block the voltage-dependent L-type calcium channels from the heart, and the small conductance calcium-activated potassium channels (KCa) in chromaffin cells and in the brain. The structures of these Kunitz-type proteins are similar to 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.


Pssm-ID: 438651  Cd Length: 54  Bit Score: 78.49  E-value: 2.45e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22608     3 FCYLPADPGPCKAYIPRFYYNSASNKCQQFIYGGCKGNANNFETKDECRYTC 54
Kunitz_HAI2_1-like cd22621
Kunitz-type domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
369-420 2.48e-18

Kunitz-type domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and similar proteins; This model includes the Kunitz domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2 or HAI2, also known as placental bikunin or Kunitz-type protease inhibitor 2). HAI-2 is composed of two Kunitz domains that strongly inhibit many serine proteases with sub-nanomolar affinities. HAI-2 Kunitz domain 1 (KD1) has been found to be the domain responsible for inhibition of hepatocyte growth factor (HGF) activator; activated HGF/scatter factor (HGF/SF) binds to its receptor tyrosine kinase MET to induce dimerization and initiate phosphorylation cascades leading to comprehensive cellular changes that, in the deregulated context of cancer, drive malignant transformation and progression. HAI-2 has been found to be a natural tumor suppressor in renal cell carcinoma, breast cancer and prostate cancer; its loss leads to tumor growth and progression in part due to increased MET signaling. HAI-2 is also a specific substrate for mesotrypsin, which is up-regulated with progression in prostate cancers and shown to contribute to invasion and metastasis; these activities of mesotrypsin may in part be mediated through cleavage and inactivation of HAI-2, resulting in increases in HGF/SF activation and MET signaling. HAI-2 is a physiological inhibitor of hepsin and matriptase, two type II transmembrane serine proteases that, like HGF activator, can convert latent pro-HGF/SF into the two-chain active signaling heterodimer. The structures of these KD1 domains 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.


Pssm-ID: 438664  Cd Length: 53  Bit Score: 78.67  E-value: 2.48e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22621     2 FCHLPKVVGRCRASFPRWWYNATSQSCQEFIFGGCKGNLNNFLSEQECLQKC 53
Kunitz_WFIKKN_2-like cd22606
second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
370-420 4.09e-18

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.


Pssm-ID: 438649  Cd Length: 53  Bit Score: 77.78  E-value: 4.09e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22606     2 CSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDAC 52
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
242-297 1.08e-17

Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes Kunitz domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 1 (HAI-1 or HAI1, also known as Kunitz-type protease inhibitor 1), a membrane-bound multidomain protein essential to the integrity of the basement membrane during placental development. HAI-1 contains an extracellular region and several internal domains that include two Kunitz domains separated in sequence but spatially closed to each other, and their interdomain interactions have evolved to stimulate the inhibitory activity of an integrated Kunitz. While the Kunitz domain 1 (KD1) is the major inhibitory domain of HAI-1 and involved in auto-inhibition of the extracellular region via steric blockage of its active site in the HAI-1 compact tertiary structure, studies show that deletion of HAI-1 Kunitz domain 2 (KD2) and the extracellular region enhanced inhibition of matriptase. HAI-1 KD2 has been shown to have potent inhibitory activity against trypsin, but it cannot inhibit hepatocyte growth factor activator (HGFA), and matriptase. HAI-1 is also important in maintaining postnatal homeostasis in many tissues, including keratinization of the epidermis, hair development, colonic epithelium integrity, proliferation and cell fate of neural progenitor cells, and tissue injury and repair. The interaction between HAI-1 and matriptase is critical for tissue morphogenesis and cellular biology. HAI-1:matriptase ratio imbalance results in tumorigenesis; slight overexpression of matriptase relative to HAI-1 causes spontaneous squamous cell carcinoma, a phenotype that can be effectively reversed back to wild type by additional expression of HAI-1, indicating the need for a tight functional relationship between the two to maintain homeostasis. The structure of KD2 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.


Pssm-ID: 438667  Cd Length: 61  Bit Score: 76.79  E-value: 1.08e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKNTT 297
Cdd:cd22624     1 RCTEPPVTGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETCSGVT 56
MANEC smart00765
The MANEC domain, formerly called MANSC; This domain, comprising 8 conserved cysteines, is ...
32-124 1.29e-17

The MANEC domain, formerly called MANSC; This domain, comprising 8 conserved cysteines, is found in the N terminus of higher multicellular animal membrane and extracellular proteins. It is postulated that this domain may play a role in the formation of protein complexes involving various protease activators and inhibitors. It is possible that some of the cysteine residues in the MANSC domain form structurally important disulfide bridges. All of the MANSC-containing proteins contain predicted transmembrane regions and signal peptides. It has been proposed that the MANSC domain in HAI-1 might function through binding with hepatocyte growth factor activator and matriptase.


Pssm-ID: 129004  Cd Length: 93  Bit Score: 77.88  E-value: 1.29e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973   32 SAQGQCVQPFkSGRKDFVLDTEESIEDGAVFLSNP-SVAHRNACIAACCRDPRCNLALIEDGYEKGPNNsCFLFNCLYKQ 110
Cdd:smart00765   1 SPGEDCLGRF-RVLENAIIRTEESLSAGARFLKSPiAVNTWEDCVRACCSTPNCNLAVFELRREDAEGN-CYLFNCTYPG 78
                           90
                   ....*....|....
gi 1020533973  111 KYVCRFIQKKGFTN 124
Cdd:smart00765  79 KEVCKFKPHEGYTS 92
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
243-293 1.49e-17

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.


Pssm-ID: 197529  Cd Length: 53  Bit Score: 76.15  E-value: 1.49e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973  243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:smart00131   3 CLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
Kunitz_TFPI2_1-like cd22616
Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
370-421 2.12e-17

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.


Pssm-ID: 438659  Cd Length: 57  Bit Score: 76.12  E-value: 2.12e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCS 421
Cdd:cd22616     5 CLLPPDEGPCRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTCW 56
Kunitz_SmCI_3-like cd22603
third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
242-293 2.94e-17

third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), Bombyx mori cocoon shell-associated trypsin inhibitor (CSTI), Bombus terrestris Kunitz-type serine protease inhibitor Bt-KTI, and similar domains. SmCI is a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. CSTI and Bt-KTI are single Kunitz domain proteins that inhibit trypsin; in addition, Bt-KTI also inhibits plasmin. This model contains the third Kunitz domain of SmCI which has a structure 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.


Pssm-ID: 438646  Cd Length: 53  Bit Score: 75.54  E-value: 2.94e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22603     2 DCLLPSETGPCKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53
Kunitz_SmCI_3-like cd22603
third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
369-420 3.58e-17

third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), Bombyx mori cocoon shell-associated trypsin inhibitor (CSTI), Bombus terrestris Kunitz-type serine protease inhibitor Bt-KTI, and similar domains. SmCI is a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. CSTI and Bt-KTI are single Kunitz domain proteins that inhibit trypsin; in addition, Bt-KTI also inhibits plasmin. This model contains the third Kunitz domain of SmCI which has a structure 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.


Pssm-ID: 438646  Cd Length: 53  Bit Score: 75.16  E-value: 3.58e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22603     2 DCLLPSETGPCKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53
Kunitz_amblin-like cd22638
Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration ...
370-420 4.22e-17

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.


Pssm-ID: 438680  Cd Length: 51  Bit Score: 75.12  E-value: 4.22e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22638     1 CTLKPETGPCRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51
Kunitz_ABPP-like cd22607
Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily ...
370-420 4.43e-17

Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily includes the amyloid-beta precursor protein (ABPP, also called APP, APPI, Alzheimer disease amyloid protein, amyloid-beta A4 protein, cerebral vascular amyloid peptide (CVAP), protease nexin II (PN2)), as well as amyloid-like protein 2 (APLP2, also called amyloid protein homolog or APPH), among others. ABPP/APPI is an inhibitor of serine proteases such as anionic and cationic trypsins. For example, APPI-4M is a variant that specifically inhibits Kallikrein (KLK)-related peptidase 6 (KLK6), which is highly upregulated in several types of cancer where its increased activity promotes cancer invasion and metastasis. Amyloid-like protein 2 (APLP2) inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein, and may play a role in the regulation of hemostasis. Proteins in this subfamily contain a single Kunitz domain, with a structure 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.


Pssm-ID: 438650  Cd Length: 52  Bit Score: 75.15  E-value: 4.43e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22607     2 CSEQAETGPCRAMMPRWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52
Kunitz_BPTI cd22592
bovine pancreatic trypsin inhibitor; This model contains bovine pancreatic trypsin inhibitor ...
243-293 1.07e-16

bovine pancreatic trypsin inhibitor; This model contains bovine pancreatic trypsin inhibitor (BPTI, also known as pancreatic Kunitz inhibitor, aprotinin, or trypsin-kallikrein inhibitor), a small protein that inhibits the action of the trypsin, and is thus a member of the serine protease family of inhibitors. This class of enzymes contains conserved cysteine residues that form 3 disulfide bonds to stabilize the three-dimensional structure. BPTI has a relatively broad specificity, inhibiting trypsin as well as chymotrypsin, and elastase-like serine (pro)enzymes capable of very different primary specificity. It reacts rapidly with serine proteases to form stable complexes, but the enzyme:inhibitor complex formation may involve several intermediates corresponding to discrete reaction steps. Furthermore, BPTI inhibits the nitric oxide synthase type-I and -II action, and impairs K+ transport by Ca2+-activated K+ channels. Clinically, BPTI is used in certain surgical interventions, such as cardiopulmonary surgery and orthotopic liver transplantation since it significantly reduces hemorrhagic complications.


Pssm-ID: 438635  Cd Length: 52  Bit Score: 73.83  E-value: 1.07e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22592     2 CLEPPYTGPCKARIIRYFYNAKSGLCETFVYGGCRAKRNNFLSAEDCMRTC 52
Kunitz_actitoxin-like cd22633
Kunitz-type actitoxins such as Anemonia viridis U-actitoxin-Avd3l, and similar proteins; This ...
243-293 3.50e-16

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.


Pssm-ID: 438676  Cd Length: 55  Bit Score: 72.57  E-value: 3.50e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22633     5 CLLPKDVGGCRARFPRYYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55
Kunitz_TFPI2_1-like cd22616
Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
243-293 6.00e-16

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.


Pssm-ID: 438659  Cd Length: 57  Bit Score: 71.89  E-value: 6.00e-16
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22616     5 CLLPPDEGPCRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTC 55
Kunitz_eppin cd22611
Kunitz domain of epididymal protease inhibitor eppin and similar proteins; This subfamily ...
370-420 2.58e-15

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.


Pssm-ID: 438654  Cd Length: 57  Bit Score: 70.13  E-value: 2.58e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22611     3 CSLPKESGPCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNIC 53
Kunitz_eppin cd22611
Kunitz domain of epididymal protease inhibitor eppin and similar proteins; This subfamily ...
243-295 3.07e-15

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.


Pssm-ID: 438654  Cd Length: 57  Bit Score: 69.74  E-value: 3.07e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKN 295
Cdd:cd22611     3 CSLPKESGPCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNICKK 55
Kunitz_bikunin_1-like cd22596
first Kunitz domain of bikunin and similar proteins; This subfamily includes the N-terminal ...
243-294 3.82e-15

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.


Pssm-ID: 438639  Cd Length: 54  Bit Score: 69.59  E-value: 3.82e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:cd22596     3 CKLPPDAGPCFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTCR 54
Kunitz_SmCI_1-like cd22601
first Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
370-420 3.99e-15

first Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. This model contains the first Kunitz domain of SmCI, which has a structure 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.


Pssm-ID: 438644  Cd Length: 55  Bit Score: 69.45  E-value: 3.99e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22601     4 CDLPADRGPCTAYIPRWFYNKTTKKCEKFVYGGCQGNKNRFETKDDCLANC 54
Kunitz_PPTI-like cd22608
Pseudocerastes persicus trypsin inhibitor (PPTI), Kunitz-type serine protease inhibitor ...
241-293 4.32e-15

Pseudocerastes persicus trypsin inhibitor (PPTI), Kunitz-type serine protease inhibitor bitisilin, and similar proteins; This group contains Pseudocerastes persicus trypsin inhibitor (PPTI), Bitis gabonica Kunitz-type serine protease inhibitor bitisilin-1 (BG-11), -2 (BG-15) and -3 (two-Kunitz protease inhibitor), Oxyuranus scutellatus scutellatus taicatoxin, and serine protease inhibitor component (TSPI, also called venom protease inhibitor 1 or venom protease inhibitor 2), among others. PPTI from P. persicus venom shows inhibitory effect against trypsin proteolytic activity and has similarities to dendrotoxins (DTXs), with corresponding functionally important residues. Studies have shown the ability of PPTI to inhibit voltage-gated potassium channels, and consequently have dual functionality. Bitilisins 1, 2, and 3 are serine protease inhibitors expressed in snake venom glands; bitsilin-3 consists of two Kunitz protease inhibitor domains. Taicatoxin inhibits trypsin, tissue kallikrein, elastase, plasmin and factor Xa, and is also known to block the voltage-dependent L-type calcium channels from the heart, and the small conductance calcium-activated potassium channels (KCa) in chromaffin cells and in the brain. The structures of these Kunitz-type proteins are similar to 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.


Pssm-ID: 438651  Cd Length: 54  Bit Score: 69.25  E-value: 4.32e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 241 RHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22608     2 KFCYLPADPGPCKAYIPRFYYNSASNKCQQFIYGGCKGNANNFETKDECRYTC 54
Kunitz_BmTI-like cd22604
Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group ...
239-293 5.02e-15

Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group includes Kunitz-type serine protease inhibitors 6 (BmTI-6) and A (BmTI-A), both of which inhibit bovine trypsin, bovine chymotrypsin, human plasmin, human plasma kallikrein and human neutrophil elastase, but not bovine thrombin, human factor Xa or porcine pancreatic kallikrein. They may play a role in blocking blood coagulation during the larvae fixation on cattle. This subfamily also includes Rhipicephalus microplus protease inhibitor carrapatin. 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.


Pssm-ID: 438647 [Multi-domain]  Cd Length: 56  Bit Score: 69.40  E-value: 5.02e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1020533973 239 SERHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22604     2 FEKQCSPTADSGPCFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56
Kunitz_actitoxin-like cd22633
Kunitz-type actitoxins such as Anemonia viridis U-actitoxin-Avd3l, and similar proteins; This ...
370-420 6.43e-15

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.


Pssm-ID: 438676  Cd Length: 55  Bit Score: 69.10  E-value: 6.43e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22633     5 CLLPKDVGGCRARFPRYYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55
Kunitz_TFPI1_TFPI2_3-like cd22615
Kunitz protease inhibitor (KPI) domain 3 (KPI-3 or K3) of tissue factor pathway inhibitor ...
370-420 8.19e-15

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.


Pssm-ID: 438658  Cd Length: 54  Bit Score: 68.47  E-value: 8.19e-15
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22615     4 CLSPKDEGLCSASVTRYYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54
Kunitz_BPTI cd22592
bovine pancreatic trypsin inhibitor; This model contains bovine pancreatic trypsin inhibitor ...
370-420 1.11e-14

bovine pancreatic trypsin inhibitor; This model contains bovine pancreatic trypsin inhibitor (BPTI, also known as pancreatic Kunitz inhibitor, aprotinin, or trypsin-kallikrein inhibitor), a small protein that inhibits the action of the trypsin, and is thus a member of the serine protease family of inhibitors. This class of enzymes contains conserved cysteine residues that form 3 disulfide bonds to stabilize the three-dimensional structure. BPTI has a relatively broad specificity, inhibiting trypsin as well as chymotrypsin, and elastase-like serine (pro)enzymes capable of very different primary specificity. It reacts rapidly with serine proteases to form stable complexes, but the enzyme:inhibitor complex formation may involve several intermediates corresponding to discrete reaction steps. Furthermore, BPTI inhibits the nitric oxide synthase type-I and -II action, and impairs K+ transport by Ca2+-activated K+ channels. Clinically, BPTI is used in certain surgical interventions, such as cardiopulmonary surgery and orthotopic liver transplantation since it significantly reduces hemorrhagic complications.


Pssm-ID: 438635  Cd Length: 52  Bit Score: 68.05  E-value: 1.11e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22592     2 CLEPPYTGPCKARIIRYFYNAKSGLCETFVYGGCRAKRNNFLSAEDCMRTC 52
Kunitz_SHPI cd22618
Stichodactyla helianthus Kunitz inhibitor protein ShPI-1, Heteractis crispa protease inhibitor ...
370-420 1.70e-14

Stichodactyla helianthus Kunitz inhibitor protein ShPI-1, Heteractis crispa protease inhibitor stichotoxin-Hcr2e, and similar proteins; This model includes Kunitz inhibitor protein ShPI-1, the major protease inhibitor from the sea anemone Stichodactyla helianthus, as well as protease inhibitor stichotoxin-Hcr2e (also called PI- stichotoxin-Hcr2e, PI-SHTX-Hcr2e, or Kunitz-type serine protease inhibitor InhVJ) and HCRG1 from Heteractis crispa. ShPI-1 has an unusually broad specificity toward several serine proteases, including trypsin, chymotrypsin, human neutrophil elastase, kallikrein and plasmin, and can also bind aspartic and cysteine proteases, such as pepsin and papain, respectively. PI-SHTX-Hcr2e and HCRG1 inhibit trypsin and chymotrypsin, but do not inhibit the serine proteases plasmin, thrombin, kallikrein, the cysteine proteinase papain, and the aspartic protease pepsin. The structures of these domains 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.


Pssm-ID: 438661  Cd Length: 53  Bit Score: 67.56  E-value: 1.70e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22618     2 CSEPKVVGPCKAYFPRFYFDSETGKCTPFIYGGCGGNGNNFETLHACRAIC 52
Kunitz_BmTI-like cd22604
Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group ...
370-420 3.47e-14

Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group includes Kunitz-type serine protease inhibitors 6 (BmTI-6) and A (BmTI-A), both of which inhibit bovine trypsin, bovine chymotrypsin, human plasmin, human plasma kallikrein and human neutrophil elastase, but not bovine thrombin, human factor Xa or porcine pancreatic kallikrein. They may play a role in blocking blood coagulation during the larvae fixation on cattle. This subfamily also includes Rhipicephalus microplus protease inhibitor carrapatin. 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.


Pssm-ID: 438647 [Multi-domain]  Cd Length: 56  Bit Score: 67.09  E-value: 3.47e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22604     6 CSPTADSGPCFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56
Kunitz_TFPI1_TFPI2_3-like cd22615
Kunitz protease inhibitor (KPI) domain 3 (KPI-3 or K3) of tissue factor pathway inhibitor ...
243-293 3.61e-14

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.


Pssm-ID: 438658  Cd Length: 54  Bit Score: 66.93  E-value: 3.61e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22615     4 CLSPKDEGLCSASVTRYYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54
Kunitz_SmCI_2-like cd22602
second Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
370-420 4.43e-14

second Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. This model contains the second Kunitz domain of SmCI, which has a structure 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.


Pssm-ID: 438645  Cd Length: 51  Bit Score: 66.41  E-value: 4.43e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22602     1 CSLPSKVGPCRVSARRWFHNPETEKCEVFIYGGCHGNANRFATETECQEVC 51
Kunitz_TFPI2_2-like cd22617
Kunitz domain 2 (KD2) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
243-293 6.98e-14

Kunitz domain 2 (KD2) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This model represents the Kunitz-type domain 2 (KD2) 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. 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. 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.


Pssm-ID: 438660  Cd Length: 54  Bit Score: 65.87  E-value: 6.98e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22617     4 CREVPDEGPCRALITRYFYNMTSMRCEEFTYGGCYGNGNNFRDKSSCISAC 54
Kunitz_TFPI2_2-like cd22617
Kunitz domain 2 (KD2) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
370-420 8.24e-14

Kunitz domain 2 (KD2) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This model represents the Kunitz-type domain 2 (KD2) 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. 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. 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.


Pssm-ID: 438660  Cd Length: 54  Bit Score: 65.87  E-value: 8.24e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22617     4 CREVPDEGPCRALITRYFYNMTSMRCEEFTYGGCYGNGNNFRDKSSCISAC 54
Kunitz_textilinin-like cd22594
venom Kunitz-type proteins such as textilinin, BF9 and PILP; This group includes toxins ...
370-421 8.39e-14

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.


Pssm-ID: 438637  Cd Length: 56  Bit Score: 65.80  E-value: 8.39e-14
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCS 421
Cdd:cd22594     5 CELPADPGPCNAYKPAFYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTCA 56
Kunitz_papilin cd22635
Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in ...
377-420 2.34e-13

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.


Pssm-ID: 438678  Cd Length: 52  Bit Score: 64.59  E-value: 2.34e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1020533973 377 GPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22635     9 TVCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52
Kunitz_collagen_alpha3_VI cd22629
Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This ...
370-420 2.47e-13

Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha3 chain of type VI collagen (collagen alpha 3(VI) chain), encoded by COL6A3 gene. 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. Mutations in the alpha1, alpha2, and alpha3 chains of collagen VI cause myopathies ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, including intermediate forms. Early onset isolated dystonia, a neurological disease, has been shown to be caused by mutations in the alpha3 chain. Findings also indicated potential associations between COL6A3 polymorphisms and lung cancer risk. 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.


Pssm-ID: 438672  Cd Length: 53  Bit Score: 64.31  E-value: 2.47e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22629     3 CKLPKDEGTCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53
Kunitz_TKDP-like cd22609
trophoblast Kunitz domain protein (TKDP) and similar proteins; This model contains the ...
370-420 2.73e-13

trophoblast Kunitz domain protein (TKDP) and similar proteins; This model contains the trophoblast Kunitz domain protein 1 (TKDP-1) and splice variant TKDP-4, among others, which are Kunitz inhibitor domain proteins. TKDP-1 is expressed in the trophectoderm which forms the outer epithelial layer of the trophoblast, and may play a role in mediating maternal-conceptus interactions in the immediate preimplantation period. However, it does not appear to have proteinase inhibitory activity. These domains are similar to those 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.


Pssm-ID: 438652  Cd Length: 52  Bit Score: 64.39  E-value: 2.73e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22609     2 CLEPKVVGVCKASMTRYFYNAQTGHCEQFVYGGCGGNRNNFLTLEDCMKTC 52
Kunitz_ELP-like cd22632
early lactation protein (ELP), colostrum trypsin inhibitor (CTI), and similar proteins; This ...
370-420 3.21e-13

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.


Pssm-ID: 438675  Cd Length: 55  Bit Score: 63.99  E-value: 3.21e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22632     4 CQLPPARGPCRSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTC 54
Kunitz_boophilin_2-like cd22600
second Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
243-295 4.50e-13

second Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group includes venom serine protease inhibitors such as Rhipicephalus microplus and Ixodes scapularis boofilin, among others. Boophilin prevents blood clot formation to allow successful feeding and digestion through its inhibition activity of thrombin and other host anticoagulating factors like kallikrein, coagulation factor VII, or plasmin; it interacts with the host thrombin and trypsin. The structures of these domains 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. Rhipicephalus microplus boophilin contains two Kunitz domains; this model represents the second repeat.


Pssm-ID: 438643  Cd Length: 54  Bit Score: 63.60  E-value: 4.50e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKN 295
Cdd:cd22600     2 CKPAAESGLCAAYLERWFFNVTTGACETFVYGGCGGNANNYKSQEECELACLR 54
Kunitz_amblin-like cd22638
Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration ...
243-293 4.79e-13

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.


Pssm-ID: 438680  Cd Length: 51  Bit Score: 63.56  E-value: 4.79e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22638     1 CTLKPETGPCRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51
Kunitz_TKDP-like cd22609
trophoblast Kunitz domain protein (TKDP) and similar proteins; This model contains the ...
243-293 4.95e-13

trophoblast Kunitz domain protein (TKDP) and similar proteins; This model contains the trophoblast Kunitz domain protein 1 (TKDP-1) and splice variant TKDP-4, among others, which are Kunitz inhibitor domain proteins. TKDP-1 is expressed in the trophectoderm which forms the outer epithelial layer of the trophoblast, and may play a role in mediating maternal-conceptus interactions in the immediate preimplantation period. However, it does not appear to have proteinase inhibitory activity. These domains are similar to those 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.


Pssm-ID: 438652  Cd Length: 52  Bit Score: 63.62  E-value: 4.95e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22609     2 CLEPKVVGVCKASMTRYFYNAQTGHCEQFVYGGCGGNRNNFLTLEDCMKTC 52
Kunitz_SHPI cd22618
Stichodactyla helianthus Kunitz inhibitor protein ShPI-1, Heteractis crispa protease inhibitor ...
243-294 4.95e-13

Stichodactyla helianthus Kunitz inhibitor protein ShPI-1, Heteractis crispa protease inhibitor stichotoxin-Hcr2e, and similar proteins; This model includes Kunitz inhibitor protein ShPI-1, the major protease inhibitor from the sea anemone Stichodactyla helianthus, as well as protease inhibitor stichotoxin-Hcr2e (also called PI- stichotoxin-Hcr2e, PI-SHTX-Hcr2e, or Kunitz-type serine protease inhibitor InhVJ) and HCRG1 from Heteractis crispa. ShPI-1 has an unusually broad specificity toward several serine proteases, including trypsin, chymotrypsin, human neutrophil elastase, kallikrein and plasmin, and can also bind aspartic and cysteine proteases, such as pepsin and papain, respectively. PI-SHTX-Hcr2e and HCRG1 inhibit trypsin and chymotrypsin, but do not inhibit the serine proteases plasmin, thrombin, kallikrein, the cysteine proteinase papain, and the aspartic protease pepsin. The structures of these domains 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.


Pssm-ID: 438661  Cd Length: 53  Bit Score: 63.71  E-value: 4.95e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:cd22618     2 CSEPKVVGPCKAYFPRFYFDSETGKCTPFIYGGCGGNGNNFETLHACRAICR 53
Kunitz_ELP-like cd22632
early lactation protein (ELP), colostrum trypsin inhibitor (CTI), and similar proteins; This ...
243-294 5.54e-13

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.


Pssm-ID: 438675  Cd Length: 55  Bit Score: 63.60  E-value: 5.54e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:cd22632     4 CQLPPARGPCRSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTCK 55
Kunitz_papilin cd22635
Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in ...
243-293 7.92e-13

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.


Pssm-ID: 438678  Cd Length: 52  Bit Score: 63.05  E-value: 7.92e-13
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVG-PCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22635     1 CLLDKDAGtVCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52
Kunitz_collagen_alpha1_XXVIII cd22628
Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This ...
370-420 1.12e-12

Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha1 chain of type XXVIII collagen (collagen alpha-1(XXVIII) chain) and similar proteins. The zebrafish has four collagen XXVIII genes all of which are differentially expressed in the liver, thymus, muscle, intestine and skin; only the alpha1 chain contains the Kunitz domain which is often proteolytically processed. Mammals only contain the alpha1 collagen chain, expressed mostly in dorsal root ganglia and peripheral nerves. The Kunitz domain is found at the C-terminus, and is most related to Kunitz domains of papilin and alpha3(VI) collagen. 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.


Pssm-ID: 438671  Cd Length: 51  Bit Score: 62.30  E-value: 1.12e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22628     1 CLEPLDPGPCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51
Kunitz_boophilin_1-like cd22599
first Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
370-422 1.15e-12

first Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group includes venom serine protease inhibitors such as Rhipicephalus microplus and Ixodes scapularis boofilin, among others. Boophilin prevents blood clot formation to allow successful feeding and digestion through its inhibition activity of thrombin and other host anticoagulating factors like kallikrein, coagulation factor VII, or plasmin; it interacts with the host thrombin and trypsin. The structures of these domains 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. Rhipicephalus microplus boophilin contains two Kunitz domains; this model represents the first repeat.


Pssm-ID: 438642  Cd Length: 61  Bit Score: 62.88  E-value: 1.15e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSG 422
Cdd:cd22599     6 CRLPADEGICRALIPRFYFNTETGQCTEFIYGGCGGNENNFETIEECEKACGA 58
Kunitz_WFIKKN_2-like cd22606
second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
243-293 1.17e-12

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.


Pssm-ID: 438649  Cd Length: 53  Bit Score: 62.37  E-value: 1.17e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22606     2 CSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDAC 52
Kunitz_boophilin_2-like cd22600
second Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
370-420 1.17e-12

second Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group includes venom serine protease inhibitors such as Rhipicephalus microplus and Ixodes scapularis boofilin, among others. Boophilin prevents blood clot formation to allow successful feeding and digestion through its inhibition activity of thrombin and other host anticoagulating factors like kallikrein, coagulation factor VII, or plasmin; it interacts with the host thrombin and trypsin. The structures of these domains 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. Rhipicephalus microplus boophilin contains two Kunitz domains; this model represents the second repeat.


Pssm-ID: 438643  Cd Length: 54  Bit Score: 62.45  E-value: 1.17e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22600     2 CKPAAESGLCAAYLERWFFNVTTGACETFVYGGCGGNANNYKSQEECELAC 52
Kunitz_TFPI1_1-like cd22613
Kunitz protease inhibitor (KPI) domain 1 (KPI-1 or K1) of tissue factor pathway inhibitor ...
377-420 1.91e-12

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.


Pssm-ID: 438656  Cd Length: 55  Bit Score: 61.99  E-value: 1.91e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1020533973 377 GPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22613    11 GPCKAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTC 54
Kunitz_ABPP-like cd22607
Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily ...
243-293 2.01e-12

Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily includes the amyloid-beta precursor protein (ABPP, also called APP, APPI, Alzheimer disease amyloid protein, amyloid-beta A4 protein, cerebral vascular amyloid peptide (CVAP), protease nexin II (PN2)), as well as amyloid-like protein 2 (APLP2, also called amyloid protein homolog or APPH), among others. ABPP/APPI is an inhibitor of serine proteases such as anionic and cationic trypsins. For example, APPI-4M is a variant that specifically inhibits Kallikrein (KLK)-related peptidase 6 (KLK6), which is highly upregulated in several types of cancer where its increased activity promotes cancer invasion and metastasis. Amyloid-like protein 2 (APLP2) inhibits trypsin, chymotrypsin, plasmin, factor XIA, and plasma and glandular kallikrein, and may play a role in the regulation of hemostasis. Proteins in this subfamily contain a single Kunitz domain, with a structure 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.


Pssm-ID: 438650  Cd Length: 52  Bit Score: 61.67  E-value: 2.01e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22607     2 CSEQAETGPCRAMMPRWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52
Kunitz_TFPI1_2-like cd22614
Kunitz protease inhibitor (KPI) domain 2 (KPI-2 or K2) of tissue factor pathway inhibitor ...
376-421 2.33e-12

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.


Pssm-ID: 438657  Cd Length: 56  Bit Score: 61.56  E-value: 2.33e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1020533973 376 VGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCS 421
Cdd:cd22614    11 PGICRGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTCE 56
Kunitz_conkunitzin cd22593
conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 ...
370-420 3.09e-12

conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 (Cs1) and -S2 (Cs2). Conkunitzins are pore-modulating toxins that block voltage-dependent potassium channels (Kvs) by exploiting inherent slow inactivation to block K+ channels. Cs1 binds to the channel turrets and disrupts the structural water hydrogen-bonding network, exposing the peripheral water pockets of ion channels and triggering an asymmetric collapse of the pore. Conus bullatus conkunitzin-B1, expressed in the venom duct, specifically blocks voltage-activated potassium channels (Kv) of the Shaker family. Members of this subfamily contain 2 disulfide bonds instead of the 3 present in most Kunitz domain proteins.


Pssm-ID: 438636  Cd Length: 51  Bit Score: 61.08  E-value: 3.09e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22593     1 CSLPLDEGSGNSSLTRWYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51
Kunitz_dendrotoxin cd22595
dendrotoxins I, K, B and similar proteins; This group includes toxins isolated from snake ...
370-422 3.76e-12

dendrotoxins I, K, B and similar proteins; This group includes toxins isolated from snake venoms, such as dendrotoxins (DTXs) I, K and B, mambaquaretin-1 (MQ-1) and calcicludine. The dendrotoxins have little or no anti-protease activity but have been shown to block certain subtypes of voltage dependent potassium channels in neurons. Dendroaspis angusticeps (green mamba) alpha-dendrotoxin is a neurotoxin that enhances acetylcholine release at neuromuscular junctions. Studies with cloned K(+) channels show that this toxin blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range, whereas Dendroaspis polylepis (black mamba) dendrotoxin K preferentially blocks Kv1.1 channels. Also, structural analogs of dendrotoxins have facilitated defining the molecular recognition properties of different types of K(+) channels, and therefore, dendrotoxins are widely used as probes for studying the function of K(+) channels in physiology and pathophysiology. 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.


Pssm-ID: 438638  Cd Length: 56  Bit Score: 61.30  E-value: 3.76e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSG 422
Cdd:cd22595     4 CKLPVRPGPCKAFISAFYYNWKAKKCHPFTYSGCGGNANRFKTIEECRRTCVG 56
Kunitz_TFPI1_2-like cd22614
Kunitz protease inhibitor (KPI) domain 2 (KPI-2 or K2) of tissue factor pathway inhibitor ...
243-293 4.76e-12

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.


Pssm-ID: 438657  Cd Length: 56  Bit Score: 60.79  E-value: 4.76e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22614     5 CFLEEDPGICRGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTC 55
Kunitz_textilinin-like cd22594
venom Kunitz-type proteins such as textilinin, BF9 and PILP; This group includes toxins ...
241-293 4.98e-12

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.


Pssm-ID: 438637  Cd Length: 56  Bit Score: 60.79  E-value: 4.98e-12
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 241 RHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22594     3 KFCELPADPGPCNAYKPAFYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTC 55
Kunitz_papilin_mig6-like cd22637
Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of ...
370-420 1.15e-11

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.


Pssm-ID: 438679  Cd Length: 51  Bit Score: 59.68  E-value: 1.15e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22637     1 CDQPKDTGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51
Kunitz_SmCI_1-like cd22601
first Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
243-293 3.42e-11

first Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. This model contains the first Kunitz domain of SmCI, which has a structure 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.


Pssm-ID: 438644  Cd Length: 55  Bit Score: 58.28  E-value: 3.42e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22601     4 CDLPADRGPCTAYIPRWFYNKTTKKCEKFVYGGCQGNKNRFETKDDCLANC 54
Kunitz_boophilin_1-like cd22599
first Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
243-295 5.60e-11

first Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group includes venom serine protease inhibitors such as Rhipicephalus microplus and Ixodes scapularis boofilin, among others. Boophilin prevents blood clot formation to allow successful feeding and digestion through its inhibition activity of thrombin and other host anticoagulating factors like kallikrein, coagulation factor VII, or plasmin; it interacts with the host thrombin and trypsin. The structures of these domains 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. Rhipicephalus microplus boophilin contains two Kunitz domains; this model represents the first repeat.


Pssm-ID: 438642  Cd Length: 61  Bit Score: 57.87  E-value: 5.60e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACKN 295
Cdd:cd22599     6 CRLPADEGICRALIPRFYFNTETGQCTEFIYGGCGGNENNFETIEECEKACGA 58
Kunitz_SmCI_2-like cd22602
second Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
243-293 5.77e-11

second Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group includes Sabellastarte magnifica carboxypeptidase inhibitor (SmCI), a tri-domain BPTI-Kunitz inhibitor capable of inhibiting serine proteases and A-like metallocarboxypeptidases. While the BPTI-Kunitz family of proteins includes voltage gated channel blockers and inhibitors of serine proteases, SmCI is the only BPTI-Kunitz protein capable of inhibiting metallocarboxypeptidases. Binding studies show that SmCI is able to bind three trypsin molecules under saturating conditions, but only one elastase interacts with the inhibitor. Additionally, SmCI can bind serine proteases and carboxypeptidases at the same time (at least in the ratio 1:1:1), thus becoming the first protease inhibitor that simultaneously blocks these two mechanistic classes of enzymes. This model contains the second Kunitz domain of SmCI, which has a structure 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.


Pssm-ID: 438645  Cd Length: 51  Bit Score: 57.55  E-value: 5.77e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22602     1 CSLPSKVGPCRVSARRWFHNPETEKCEVFIYGGCHGNANRFATETECQEVC 51
Kunitz_ixolaris_2 cd22626
Kunitz-type domain 2 (K2) of Ixolaris, and similar proteins; This model includes the second ...
370-420 7.06e-11

Kunitz-type domain 2 (K2) of Ixolaris, and similar proteins; This model includes the second Kunitz-type domain (K2) of ixolaris from the venomous organism Conus striatus. Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, and forms a quaternary tissue factor (TF)/FVIIa/FX(a)/Ixolaris inhibitory complex. It blocks TF-induced coagulation and PAR2 (proteinase-activated receptor 2) signaling, and prevents thrombosis, tumor growth, and immune activation. Ixolaris consists of 2 Kunitz domains (K1 and K2), both of which recognize the heparin-binding (pro)exosite (HBE) on FX. This model contains K2, an extraordinarily dynamic domain that encompasses several residues involved in FX binding. Its backbone plasticity is critical for ixolaris biological activity. This domain contains 2 disulfide bonds instead of the 3 typical of Kunitz domain proteins.


Pssm-ID: 438669  Cd Length: 51  Bit Score: 57.47  E-value: 7.06e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22626     1 CSLELDYGVGKAYIPRWYFNTSNARCEMFIFGGIGGNKNNFETLEECKKTC 51
Kunitz_ixolaris_2 cd22626
Kunitz-type domain 2 (K2) of Ixolaris, and similar proteins; This model includes the second ...
243-293 7.56e-11

Kunitz-type domain 2 (K2) of Ixolaris, and similar proteins; This model includes the second Kunitz-type domain (K2) of ixolaris from the venomous organism Conus striatus. Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, and forms a quaternary tissue factor (TF)/FVIIa/FX(a)/Ixolaris inhibitory complex. It blocks TF-induced coagulation and PAR2 (proteinase-activated receptor 2) signaling, and prevents thrombosis, tumor growth, and immune activation. Ixolaris consists of 2 Kunitz domains (K1 and K2), both of which recognize the heparin-binding (pro)exosite (HBE) on FX. This model contains K2, an extraordinarily dynamic domain that encompasses several residues involved in FX binding. Its backbone plasticity is critical for ixolaris biological activity. This domain contains 2 disulfide bonds instead of the 3 typical of Kunitz domain proteins.


Pssm-ID: 438669  Cd Length: 51  Bit Score: 57.47  E-value: 7.56e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22626     1 CSLELDYGVGKAYIPRWYFNTSNARCEMFIFGGIGGNKNNFETLEECKKTC 51
Kunitz_TFPI1_1-like cd22613
Kunitz protease inhibitor (KPI) domain 1 (KPI-1 or K1) of tissue factor pathway inhibitor ...
250-293 8.29e-11

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.


Pssm-ID: 438656  Cd Length: 55  Bit Score: 57.36  E-value: 8.29e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1020533973 250 GPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22613    11 GPCKAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTC 54
Kunitz_SCI-I-like cd22634
chymotrypsin inhibitor SCI-I_III-like; This model includes the Kunitz-type chymotrypsin ...
377-420 1.21e-10

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.


Pssm-ID: 438677  Cd Length: 57  Bit Score: 56.75  E-value: 1.21e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1020533973 377 GPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22634    14 ISCFAYIPSWSYNPDKNECEEFIYGGCGGNDNRFSTKAECEQKC 57
Kunitz_bikunin_2-like cd22597
second Kunitz domain of bikunin and similar proteins; This subfamily includes the C-terminal ...
368-420 1.34e-10

second Kunitz domain of bikunin and similar proteins; This subfamily includes the C-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. Bikunin 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 second repeat.


Pssm-ID: 438640  Cd Length: 55  Bit Score: 56.62  E-value: 1.34e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 368 AHCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22597     2 AACRLPIVPGPCKGFVDLWAFDAVQGKCVPFSYGGCQGNGNKFYSEKECEEYC 54
Kunitz_collagen_alpha3_VI cd22629
Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This ...
243-293 2.14e-10

Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha3 chain of type VI collagen (collagen alpha 3(VI) chain), encoded by COL6A3 gene. 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. Mutations in the alpha1, alpha2, and alpha3 chains of collagen VI cause myopathies ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, including intermediate forms. Early onset isolated dystonia, a neurological disease, has been shown to be caused by mutations in the alpha3 chain. Findings also indicated potential associations between COL6A3 polymorphisms and lung cancer risk. 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.


Pssm-ID: 438672  Cd Length: 53  Bit Score: 56.22  E-value: 2.14e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22629     3 CKLPKDEGTCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53
Kunitz_collagen_alpha1_XXVIII cd22628
Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This ...
243-293 2.32e-10

Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This model includes the Kunitz-type domain from the alpha1 chain of type XXVIII collagen (collagen alpha-1(XXVIII) chain) and similar proteins. The zebrafish has four collagen XXVIII genes all of which are differentially expressed in the liver, thymus, muscle, intestine and skin; only the alpha1 chain contains the Kunitz domain which is often proteolytically processed. Mammals only contain the alpha1 collagen chain, expressed mostly in dorsal root ganglia and peripheral nerves. The Kunitz domain is found at the C-terminus, and is most related to Kunitz domains of papilin and alpha3(VI) collagen. 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.


Pssm-ID: 438671  Cd Length: 51  Bit Score: 55.75  E-value: 2.32e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22628     1 CLEPLDPGPCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51
Kunitz_WFIKKN_1-like cd22605
first Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
385-420 2.46e-10

first 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 first Kunitz domain that is 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.


Pssm-ID: 438648  Cd Length: 52  Bit Score: 55.83  E-value: 2.46e-10
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1020533973 385 RWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22605    17 RWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52
Kunitz_KTT cd22620
scorpion venom Kunitz-type toxin (KTT) such as LmKTT-1a, BmKTT-1, and BmKTT-2; This model ...
243-294 2.47e-10

scorpion venom Kunitz-type toxin (KTT) such as LmKTT-1a, BmKTT-1, and BmKTT-2; This model includes scorpion Kunitz-type toxin (KTT) such as Lychas mucronatus LmKTT-1a (also called Delta-KTx 2.1 or SdPII), Mesobuthus martensii BmKTT-1 (also called Delta-KTx 2.4) and BmKTT-2 (also called Delta-KTx 3.1), all expressed by the venom gland. LmKTT-1a, BmKTT-1 and BmKTT-2 are all dual-function toxins that completely inhibit trypsin activity but have no effect on chymotrypsin or elastase. They also inhibit mKv1.3/KCNA3 potassium channel currents. The structures of these domains are similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor); however, they lack the conserved CysII-CysIV disulfide bond but contains 2 cysteine residues at the C-terminus that generate a new disulfide bond.


Pssm-ID: 438663  Cd Length: 58  Bit Score: 56.04  E-value: 2.47e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNACK 294
Cdd:cd22620     3 CQLPSDTGRGKASFTRYYYNEESGKCETFIYGGVGGNSNNFLTKEDCCKECA 54
Kunitz_bikunin_2-like cd22597
second Kunitz domain of bikunin and similar proteins; This subfamily includes the C-terminal ...
243-293 3.59e-10

second Kunitz domain of bikunin and similar proteins; This subfamily includes the C-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. Bikunin 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 second repeat.


Pssm-ID: 438640  Cd Length: 55  Bit Score: 55.47  E-value: 3.59e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22597     4 CRLPIVPGPCKGFVDLWAFDAVQGKCVPFSYGGCQGNGNKFYSEKECEEYC 54
Kunitz_huwentoxin cd22598
Kunitz-type toxin huwentoxin-XI; This model contains Kunitz-type serine protease inhibitor ...
370-421 3.61e-10

Kunitz-type toxin huwentoxin-XI; This model contains Kunitz-type serine protease inhibitor huwentoxin-XI, including U15-theraphotoxin-Hs1g (also called U15-TRTX-Hs1g or Huwentoxin HW11c39), and kappaPI-theraphotoxin-Hs1a (also called KappaPI-TRTX-Hs1a or Huwentoxin-HW11g8). Huwentoxin-XI is a bifunctional toxin that inhibits both serine proteases (trypsin) and voltage-gated potassium channels (Kv) via surfaces displayed on opposite faces of the toxin. The structures of these domains 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.


Pssm-ID: 438641  Cd Length: 53  Bit Score: 55.38  E-value: 3.61e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDplNEKCHRFTYGGCDGNENNFETSDKCMDNCS 421
Cdd:cd22598     3 CRLPSDRGRCKASFERWYFN--GRTCAKFIYGGCGGNDNKFPTQEACMKRCA 52
Kunitz_SCI-I-like cd22634
chymotrypsin inhibitor SCI-I_III-like; This model includes the Kunitz-type chymotrypsin ...
242-293 3.63e-10

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.


Pssm-ID: 438677  Cd Length: 57  Bit Score: 55.60  E-value: 3.63e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22634     6 HSLGGGDGISCFAYIPSWSYNPDKNECEEFIYGGCGGNDNRFSTKAECEQKC 57
Kunitz_collagen_alpha6_VI cd22630
Kunitz-type domain from the alpha6 chain of human type VI collagen, and similar proteins; This ...
369-420 3.88e-10

Kunitz-type domain from the alpha6 chain of human 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), encoded by COL6A6 gene, 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.


Pssm-ID: 438673  Cd Length: 55  Bit Score: 55.30  E-value: 3.88e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 369 HCTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22630     2 ACSLDQDEGECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALC 53
Kunitz_papilin_lacunin-like cd22639
Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr ...
370-420 5.33e-10

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.


Pssm-ID: 438681  Cd Length: 52  Bit Score: 54.89  E-value: 5.33e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22639     1 CSLPKDRGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51
Kunitz_KTT cd22620
scorpion venom Kunitz-type toxin (KTT) such as LmKTT-1a, BmKTT-1, and BmKTT-2; This model ...
370-421 8.38e-10

scorpion venom Kunitz-type toxin (KTT) such as LmKTT-1a, BmKTT-1, and BmKTT-2; This model includes scorpion Kunitz-type toxin (KTT) such as Lychas mucronatus LmKTT-1a (also called Delta-KTx 2.1 or SdPII), Mesobuthus martensii BmKTT-1 (also called Delta-KTx 2.4) and BmKTT-2 (also called Delta-KTx 3.1), all expressed by the venom gland. LmKTT-1a, BmKTT-1 and BmKTT-2 are all dual-function toxins that completely inhibit trypsin activity but have no effect on chymotrypsin or elastase. They also inhibit mKv1.3/KCNA3 potassium channel currents. The structures of these domains are similar to those of Kunitz-type proteinase inhibitors such as BPTI (bovine pancreatic trypsin inhibitor); however, they lack the conserved CysII-CysIV disulfide bond but contains 2 cysteine residues at the C-terminus that generate a new disulfide bond.


Pssm-ID: 438663  Cd Length: 58  Bit Score: 54.50  E-value: 8.38e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCS 421
Cdd:cd22620     3 CQLPSDTGRGKASFTRYYYNEESGKCETFIYGGVGGNSNNFLTKEDCCKECA 54
Kunitz_conkunitzin cd22593
conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 ...
243-293 2.00e-09

conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 (Cs1) and -S2 (Cs2). Conkunitzins are pore-modulating toxins that block voltage-dependent potassium channels (Kvs) by exploiting inherent slow inactivation to block K+ channels. Cs1 binds to the channel turrets and disrupts the structural water hydrogen-bonding network, exposing the peripheral water pockets of ion channels and triggering an asymmetric collapse of the pore. Conus bullatus conkunitzin-B1, expressed in the venom duct, specifically blocks voltage-activated potassium channels (Kv) of the Shaker family. Members of this subfamily contain 2 disulfide bonds instead of the 3 present in most Kunitz domain proteins.


Pssm-ID: 438636  Cd Length: 51  Bit Score: 53.38  E-value: 2.00e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22593     1 CSLPLDEGSGNSSLTRWYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51
Kunitz_papilin_mig6-like cd22637
Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of ...
243-293 2.07e-09

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.


Pssm-ID: 438679  Cd Length: 51  Bit Score: 53.13  E-value: 2.07e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22637     1 CDQPKDTGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51
Kunitz_bikunin_1-like cd22596
first Kunitz domain of bikunin and similar proteins; This subfamily includes the N-terminal ...
370-420 3.54e-09

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.


Pssm-ID: 438639  Cd Length: 54  Bit Score: 52.64  E-value: 3.54e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22596     3 CKLPPDAGPCFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTC 53
Kunitz_dendrotoxin cd22595
dendrotoxins I, K, B and similar proteins; This group includes toxins isolated from snake ...
241-293 8.11e-09

dendrotoxins I, K, B and similar proteins; This group includes toxins isolated from snake venoms, such as dendrotoxins (DTXs) I, K and B, mambaquaretin-1 (MQ-1) and calcicludine. The dendrotoxins have little or no anti-protease activity but have been shown to block certain subtypes of voltage dependent potassium channels in neurons. Dendroaspis angusticeps (green mamba) alpha-dendrotoxin is a neurotoxin that enhances acetylcholine release at neuromuscular junctions. Studies with cloned K(+) channels show that this toxin blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range, whereas Dendroaspis polylepis (black mamba) dendrotoxin K preferentially blocks Kv1.1 channels. Also, structural analogs of dendrotoxins have facilitated defining the molecular recognition properties of different types of K(+) channels, and therefore, dendrotoxins are widely used as probes for studying the function of K(+) channels in physiology and pathophysiology. 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.


Pssm-ID: 438638  Cd Length: 56  Bit Score: 51.67  E-value: 8.11e-09
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1020533973 241 RHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22595     2 KFCKLPVRPGPCKAFISAFYYNWKAKKCHPFTYSGCGGNANRFKTIEECRRTC 54
Kunitz_collagen_alpha6_VI-like cd22631
Kunitz-type domain from the alpha6 chain of fish type VI collagen, and similar proteins; This ...
370-420 1.27e-08

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.


Pssm-ID: 438674 [Multi-domain]  Cd Length: 51  Bit Score: 51.07  E-value: 1.27e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22631     1 CLLGQDAGSCQNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51
LDLa cd00112
Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central ...
315-349 1.88e-08

Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein; other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement; the binding of calcium is required for in vitro formation of the native disulfide isomer and is necessary in establishing and maintaining the modular structure


Pssm-ID: 238060  Cd Length: 35  Bit Score: 49.90  E-value: 1.88e-08
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1020533973 315 CGEDQFKCSNGCCVKKELECDEQQQCSDGSDEENC 349
Cdd:cd00112     1 CPPNEFRCANGRCIPSSWVCDGEDDCGDGSDEENC 35
Kunitz_papilin_lacunin-like cd22639
Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr ...
243-293 3.25e-08

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.


Pssm-ID: 438681  Cd Length: 52  Bit Score: 49.88  E-value: 3.25e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22639     1 CSLPKDRGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51
Kunitz_B2B cd22619
Kunitz-type serine protease inhibitor subunit of beta 2-bungarotoxin, and similar proteins; ...
370-420 1.40e-07

Kunitz-type serine protease inhibitor subunit of beta 2-bungarotoxin, and similar proteins; This model includes the Kunitz inhibitor subunit of beta 2-bungarotoxin, a presynaptic neurotoxin of the Bungarus multicinctus venom. Beta-bungarotoxin is a heterodimeric neurotoxin consisting of a phospholipase subunit linked by a disulfide bond to the Kunitz protease inhibitor subunit; the latter subunit is homologous to venom basic protease inhibitors but has no protease inhibitor activity and is non-toxic. The beta-bungarotoxin Kunitz subunit serves to guide the toxin to its site of action on the presynaptic membrane by virtue of a high-affinity interaction with a specific subclass of voltage-sensitive potassium channels. This subfamily also includes Kunitz-type serine protease inhibitor homolog beta-bungarotoxin B1 chain and protease inhibitor-like protein 1 (PILP-1). The B1 chain also has no protease inhibitor activity but blocks voltage-gated potassium channels, while PILP-1 inhibits trypsin. The structures of these domains 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.


Pssm-ID: 438662  Cd Length: 58  Bit Score: 48.32  E-value: 1.40e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22619     7 CDKPPDTKRCKRVVRAFYYNPSAKTCLQFVYGGCNGNGNHFKSKALCRCHC 57
Kunitz_collagen_alpha1_VII cd22627
Kunitz-type domain from the alpha1 chain of type VII collagen, and similar proteins; This ...
370-420 1.53e-07

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.


Pssm-ID: 438670  Cd Length: 53  Bit Score: 48.01  E-value: 1.53e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 370 CTDPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22627     3 CLLPMDEGSCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53
PKD_4 pfam18911
PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.
146-229 1.92e-07

PKD domain; This entry is composed of PKD domains found in bacterial surface proteins.


Pssm-ID: 436824 [Multi-domain]  Cd Length: 85  Bit Score: 48.81  E-value: 1.92e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 146 PPIANAGRDVVVQPNEEVLLNGIESWD-DRNIISYEWSLisGDESLhiektdlPDQVKVSKL--VPGVYKFKLTVTDSAH 222
Cdd:pfam18911   3 APVADAGGDRIVAEGETVTFDASASDDpDGDILSYRWDF--GDGTT-------ATGANVSHTyaAPGTYTVTLTVTDDSG 73

                  ....*..
gi 1020533973 223 HSDSAQV 229
Cdd:pfam18911  74 ASNSTAT 80
LDLa smart00192
Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density ...
315-346 1.94e-07

Low-density lipoprotein receptor domain class A; Cysteine-rich repeat in the low-density lipoprotein (LDL) receptor that plays a central role in mammalian cholesterol metabolism. The N-terminal type A repeats in LDL receptor bind the lipoproteins. Other homologous domains occur in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/alpha 2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. Mutations in the LDL receptor gene cause familial hypercholesterolemia.


Pssm-ID: 197566  Cd Length: 33  Bit Score: 47.24  E-value: 1.94e-07
                           10        20        30
                   ....*....|....*....|....*....|..
gi 1020533973  315 CGEDQFKCSNGCCVKKELECDEQQQCSDGSDE 346
Cdd:smart00192   2 CPPGEFQCDNGRCIPSSWVCDGVDDCGDGSDE 33
Kunitz_collagen_alpha1_VII cd22627
Kunitz-type domain from the alpha1 chain of type VII collagen, and similar proteins; This ...
243-293 2.08e-07

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.


Pssm-ID: 438670  Cd Length: 53  Bit Score: 47.63  E-value: 2.08e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22627     3 CLLPMDEGSCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53
Ldl_recept_a pfam00057
Low-density lipoprotein receptor domain class A;
313-349 4.39e-07

Low-density lipoprotein receptor domain class A;


Pssm-ID: 395011  Cd Length: 37  Bit Score: 46.09  E-value: 4.39e-07
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1020533973 313 SSCGEDQFKCSNGCCVKKELECDEQQQCSDGSDEENC 349
Cdd:pfam00057   1 STCSPNEFQCGSGECIPRSWVCDGDPDCGDGSDEENC 37
Kunitz_huwentoxin cd22598
Kunitz-type toxin huwentoxin-XI; This model contains Kunitz-type serine protease inhibitor ...
243-293 5.08e-07

Kunitz-type toxin huwentoxin-XI; This model contains Kunitz-type serine protease inhibitor huwentoxin-XI, including U15-theraphotoxin-Hs1g (also called U15-TRTX-Hs1g or Huwentoxin HW11c39), and kappaPI-theraphotoxin-Hs1a (also called KappaPI-TRTX-Hs1a or Huwentoxin-HW11g8). Huwentoxin-XI is a bifunctional toxin that inhibits both serine proteases (trypsin) and voltage-gated potassium channels (Kv) via surfaces displayed on opposite faces of the toxin. The structures of these domains 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.


Pssm-ID: 438641  Cd Length: 53  Bit Score: 46.52  E-value: 5.08e-07
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASskCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22598     3 CRLPSDRGRCKASFERWYFNGRT--CAKFIYGGCGGNDNKFPTQEACMKRC 51
Kunitz_collagen_alpha6_VI-like cd22631
Kunitz-type domain from the alpha6 chain of fish type VI collagen, and similar proteins; This ...
243-293 1.09e-06

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.


Pssm-ID: 438674 [Multi-domain]  Cd Length: 51  Bit Score: 45.30  E-value: 1.09e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22631     1 CLLGQDAGSCQNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51
Kunitz_collagen_alpha6_VI cd22630
Kunitz-type domain from the alpha6 chain of human type VI collagen, and similar proteins; This ...
242-293 6.08e-06

Kunitz-type domain from the alpha6 chain of human 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), encoded by COL6A6 gene, 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.


Pssm-ID: 438673  Cd Length: 55  Bit Score: 43.36  E-value: 6.08e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1020533973 242 HCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22630     2 ACSLDQDEGECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALC 53
PKD smart00089
Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 ...
156-233 7.37e-06

Repeats in polycystic kidney disease 1 (PKD1) and other proteins; Polycystic kidney disease 1 protein contains 14 repeats, present elsewhere such as in microbial collagenases.


Pssm-ID: 214510 [Multi-domain]  Cd Length: 79  Bit Score: 43.98  E-value: 7.37e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1020533973  156 VVQPNEEVLLNGiESWDDRNIISYEWSLisGDESLHIEKTdlpdqVKVSKLVPGVYKFKLTVTDSAhHSDSAQVTLLV 233
Cdd:smart00089  10 VGVAGESVTFTA-TSSDDGSIVSYTWDF--GDGTSSTGPT-----VTHTYTKPGTYTVTLTVTNAV-GSASATVTVVV 78
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
146-238 7.41e-06

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 48.88  E-value: 7.41e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  146 PPIANAGRDVVVQPNEEVLLNGIESWD-DRNIISYEWSLISGDEslhIEKTDlPDQVKVSKLVPGVYK-----FKLTVTD 219
Cdd:NF038112  1187 RPVANAGPDQTVLERTTVTLNGSGSFDpDGDPLTYAWTQVSGPA---VTLTG-ADTATPSFTAPEVTAdtvltFQLVVSD 1262
                           90
                   ....*....|....*....
gi 1020533973  220 SAHHSDSAQVTLLVLTPDQ 238
Cdd:NF038112  1263 GTKTSAPDTVTVLVRNVNR 1281
Kunitz_B2B cd22619
Kunitz-type serine protease inhibitor subunit of beta 2-bungarotoxin, and similar proteins; ...
238-293 8.54e-06

Kunitz-type serine protease inhibitor subunit of beta 2-bungarotoxin, and similar proteins; This model includes the Kunitz inhibitor subunit of beta 2-bungarotoxin, a presynaptic neurotoxin of the Bungarus multicinctus venom. Beta-bungarotoxin is a heterodimeric neurotoxin consisting of a phospholipase subunit linked by a disulfide bond to the Kunitz protease inhibitor subunit; the latter subunit is homologous to venom basic protease inhibitors but has no protease inhibitor activity and is non-toxic. The beta-bungarotoxin Kunitz subunit serves to guide the toxin to its site of action on the presynaptic membrane by virtue of a high-affinity interaction with a specific subclass of voltage-sensitive potassium channels. This subfamily also includes Kunitz-type serine protease inhibitor homolog beta-bungarotoxin B1 chain and protease inhibitor-like protein 1 (PILP-1). The B1 chain also has no protease inhibitor activity but blocks voltage-gated potassium channels, while PILP-1 inhibits trypsin. The structures of these domains 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.


Pssm-ID: 438662  Cd Length: 58  Bit Score: 43.32  E-value: 8.54e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1020533973 238 QSERHCLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22619     2 KRHPDCDKPPDTKRCKRVVRAFYYNPSAKTCLQFVYGGCNGNGNHFKSKALCRCHC 57
Kunitz_WFIKKN_1-like cd22605
first Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
243-293 1.85e-05

first 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 first Kunitz domain that is 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.


Pssm-ID: 438648  Cd Length: 52  Bit Score: 41.96  E-value: 1.85e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 243 CLTPKKVGPCRGSFPRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22605     2 CLKEPDREDCGEEQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52
PKD cd00146
polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an ...
147-233 2.60e-05

polycystic kidney disease I (PKD) domain; similar to other cell-surface modules, with an IG-like fold; domain probably functions as a ligand binding site in protein-protein or protein-carbohydrate interactions; a single instance of the repeat is presented here. The domain is also found in microbial collagenases and chitinases.


Pssm-ID: 238084 [Multi-domain]  Cd Length: 81  Bit Score: 42.48  E-value: 2.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 147 PIANAGRDVVVQPNEEVLLNgIESWDDRNIISYEWSLisGDESlhiekTDLPDQVKVSK--LVPGVYKFKLTVTDSAHHS 224
Cdd:cd00146     1 PTASVSAPPVAELGASVTFS-ASDSSGGSIVSYKWDF--GDGE-----VSSSGEPTVTHtyTKPGTYTVTLTVTNAVGSS 72

                  ....*....
gi 1020533973 225 DSAQVTLLV 233
Cdd:cd00146    73 STKTTTVVV 81
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
144-233 2.78e-04

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 43.88  E-value: 2.78e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  144 DKPPIANAGRDVVVQPNEEVLLNGIESWDDRNIISYEWSLISG-DESLHIEKTDLPDQVKVSKLVPGVYKFKLTVTDSAH 222
Cdd:NF038112  1373 NRAPVANAGADQTVDERSTVTLSGSATDPDGDALTYAWTQTAGpTVTLTGADTATASFTAPEVAADTELTFQLTVSADGQ 1452
                           90
                   ....*....|.
gi 1020533973  223 HSDSAQVTLLV 233
Cdd:NF038112  1453 ASADVTVTVTV 1463
Kunitz_ixolaris_1 cd22625
Kunitz-type domain 1 (K1) of Ixolaris, and similar proteins; This model includes the first ...
257-293 7.22e-04

Kunitz-type domain 1 (K1) of Ixolaris, and similar proteins; This model includes the first Kunitz-type domain (K1) of ixolaris from the venomous organism Conus striatus. Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, and forms a quaternary tissue factor (TF)/FVIIa/FX(a)/Ixolaris inhibitory complex. It blocks TF-induced coagulation and PAR2 (proteinase-activated receptor 2) signaling, and prevents thrombosis, tumor growth, and immune activation. Ixolaris consists of 2 Kunitz domains (K1 and K2), both of which recognize the heparin-binding (pro)exosite (HBE) on FX. While K2 is an extraordinarily dynamic domain that encompasses several residues involved in FX binding, K1 domain keeps as a rigid platform supporting the conformational dynamic of the K2 domain, forming a salt bridge with FXa. 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.


Pssm-ID: 438668  Cd Length: 53  Bit Score: 37.63  E-value: 7.22e-04
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1020533973 257 PRWHYNAASSKCEQFIFGGCKENNNNYLSEQECLNAC 293
Cdd:cd22625    17 KRYGYNKKTQQCEEFLGTECGGGGNSFEEAKECWSSC 53
myxo_dep_M36 NF038112
myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family ...
147-243 1.54e-03

myxosortase-dependent M36 family metallopeptidase; Members of this bacterial protein family have an M36 family metallopeptidase domain, like fungalysin (see PF02128), and a C-terminal MYXO-CTERM domain (see TIGR03901), suggesting processing and surface-anchoring by the still-unknown putative transpeptidase, myxosortase. Members of this family include MXAN_3564 (mepA), part of the effector cargo of outer membrane vesicles that the species produces in large numbers during predation on other microbes.


Pssm-ID: 468355 [Multi-domain]  Cd Length: 1597  Bit Score: 41.57  E-value: 1.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973  147 PIANAGRDVVVQPNEEVLLNGIESWDDRNIISYEWSLISGdESLHIEKTDLPdqvKVSKLVPGV-----YKFKLTVTDSA 221
Cdd:NF038112  1470 PVAHAGESITVDEGSTVTLDASATDPDGDTLTYAWTQVAG-PSVTLTGADSA---KLTFTAPEVsadttLTFSLTVTDGS 1545
                           90       100
                   ....*....|....*....|..
gi 1020533973  222 HHSDSAQVTLLVLTPDQSERHC 243
Cdd:NF038112  1546 GSSGPVVVTVTVKNVNRAPDGG 1567
REJ pfam02010
REJ domain; The REJ (Receptor for Egg Jelly) domain is found in PKD1, and the sperm receptor ...
147-235 1.71e-03

REJ domain; The REJ (Receptor for Egg Jelly) domain is found in PKD1, and the sperm receptor for egg jelly Swiss:Q26627. The function of this domain is unknown. The domain is 600 amino acids long so is probably composed of multiple structural domains. There are six completely conserved cysteine residues that may form disulphide bridges. This region contains tandem PKD-like domains.


Pssm-ID: 366875 [Multi-domain]  Cd Length: 448  Bit Score: 40.95  E-value: 1.71e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1020533973 147 PIANAGRDVVVQPNEEVLLNGIESWD------DRNIISYEWSLI---SGDESLHIEK-TDLPDQVKV------------- 203
Cdd:pfam02010  86 AVIDGGSSRVVGYNQDLTLDGSESYDpdvdpgSSSGLTYLWSCRrssSGDNPLLNNDpVCFSDQNEGtllqstsssltip 165
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1020533973 204 -SKLVPGV-YKFKLTVTDSAHHSDSAQVTLLVLT 235
Cdd:pfam02010 166 aSTLQANVtYTFKLTVSKGSRNSASTTQTILVVD 199
Kunitz_MitTx cd22610
Micrurus tener tener Kunitz-type neurotoxin MitTx-alpha; Micrurus tener tener Kunitz-type ...
372-422 3.11e-03

Micrurus tener tener Kunitz-type neurotoxin MitTx-alpha; Micrurus tener tener Kunitz-type neurotoxin MitTx-alpha is a subunit of the pain-inducing, heterodimeric polypeptide toxin that activates acid sensing ion channel a (ASIC1a) at nanomolar concentrations in a pH-independent manner. Acid sensing ion channels (ASICs) are sodium-selective, voltage-independent and amiloride-blockable ion channels that detect extracellular protons produced during inflammation or ischemic injury, and belong to the superfamily of degenerin/epithelial sodium channels. Subtype ASICa is expressed by primary afferent sensory neurons and is activated by MitTx. MitTx consists of two, non-covalently associated alpha and beta subunits that resemble Kunitz and phospholipase-A2 proteins, respectively, and together they function as a potent and selective ASIC1a agonist. The MitTx-alpha structures 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.


Pssm-ID: 438653  Cd Length: 59  Bit Score: 36.15  E-value: 3.11e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1020533973 372 DPAVVGPCRASFPRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNCSG 422
Cdd:cd22610     9 DPPFFQKCGAFVDSYYFNRSRITCVHFFYGQCDVNQNHFTTMSECNRVCHG 59
Kunitz_ixolaris_1 cd22625
Kunitz-type domain 1 (K1) of Ixolaris, and similar proteins; This model includes the first ...
384-420 8.66e-03

Kunitz-type domain 1 (K1) of Ixolaris, and similar proteins; This model includes the first Kunitz-type domain (K1) of ixolaris from the venomous organism Conus striatus. Ixolaris is a potent tick salivary anticoagulant that binds coagulation factor Xa (FXa) and zymogen FX, and forms a quaternary tissue factor (TF)/FVIIa/FX(a)/Ixolaris inhibitory complex. It blocks TF-induced coagulation and PAR2 (proteinase-activated receptor 2) signaling, and prevents thrombosis, tumor growth, and immune activation. Ixolaris consists of 2 Kunitz domains (K1 and K2), both of which recognize the heparin-binding (pro)exosite (HBE) on FX. While K2 is an extraordinarily dynamic domain that encompasses several residues involved in FX binding, K1 domain keeps as a rigid platform supporting the conformational dynamic of the K2 domain, forming a salt bridge with FXa. 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.


Pssm-ID: 438668  Cd Length: 53  Bit Score: 34.54  E-value: 8.66e-03
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1020533973 384 PRWYYDPLNEKCHRFTYGGCDGNENNFETSDKCMDNC 420
Cdd:cd22625    17 KRYGYNKKTQQCEEFLGTECGGGGNSFEEAKECWSSC 53
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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