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Conserved domains on  [gi|16751923|ref|NP_444514|]
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WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 1 precursor [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
NTR_WFIKKN cd03575
NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative ...
427-537 2.70e-64

NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative secreted proteins which may be multivalent protease inhibitors that act on serine proteases as well as metalloproteases. Human WFIKKN and a related protein sharing the same domain architecture were observed to have distinct tissue expression patterns. WFIKKN is also referred to as growth and differentiation factor-associated serum protein-1 (GASP-1). It inhibits the activity of mature myostatin, a specific regulator of skeletal muscle mass and a member of the TGFbeta superfamily.


:

Pssm-ID: 239630  Cd Length: 109  Bit Score: 204.96  E-value: 2.70e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 427 ALSLCRSDFAIVGRLTEVLEEPEaaGGIARVALEDVLKDDKMGLKFLGTKYLEVTLSGMDWACPCPNMTAGDGPLVIMGE 506
Cdd:cd03575   1 VPSLCRSDFAIVGRLTELTEELD--SGHARVTLEEVLKDEKMGLKFFGTEPLEVTLLNMDWSCPCPNITAGEGPLIIMGD 78
                        90       100       110
                ....*....|....*....|....*....|.
gi 16751923 507 VRDGVAVLDAGSYVRAASEKRVKKILELLEK 537
Cdd:cd03575  79 VHDGMAVLQPDSYVRASSERRVRKLREVLHK 109
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
186-280 8.43e-58

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


:

Pssm-ID: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 187.76  E-value: 8.43e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTA 265
Cdd:cd05765   1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80
                        90
                ....*....|....*
gi 16751923 266 RNAAGLLRADFPLSV 280
Cdd:cd05765  81 RNSGGLLRANFPLSV 95
Kunitz_WFIKKN_2-like cd22606
second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
358-410 3.22e-32

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: 117.84  E-value: 3.22e-32
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDACP 410
Cdd:cd22606   1 ICSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDACP 53
Kunitz-type super family cl00101
Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz ...
298-351 1.91e-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.


The actual alignment was detected with superfamily member cd22605:

Pssm-ID: 444694  Cd Length: 52  Bit Score: 84.72  E-value: 1.91e-20
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 16751923 298 ECLPDVQACTGPTspHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22605   1 ECLKEPDREDCGE--EQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
120-155 4.64e-06

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


:

Pssm-ID: 238052 [Multi-domain]  Cd Length: 41  Bit Score: 43.41  E-value: 4.64e-06
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 16751923 120 CEKEPSFTCASDGLTYYNRCYMDAEACLRGLHLHIV 155
Cdd:cd00104   1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVA 36
WAP pfam00095
WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or ...
29-78 6.73e-05

WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or elastase-specific inhibitors.


:

Pssm-ID: 459672 [Multi-domain]  Cd Length: 42  Bit Score: 40.49  E-value: 6.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 16751923    29 HPGVCPnqlspnlWVDAQSTCERECSRDQDCAAAEKCCINVCGlHSCVAA 78
Cdd:pfam00095   1 KPGCCP-------RLGARGCCRSCCSSDDDCPGRQKCCSNGCG-SVCVPP 42
 
Name Accession Description Interval E-value
NTR_WFIKKN cd03575
NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative ...
427-537 2.70e-64

NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative secreted proteins which may be multivalent protease inhibitors that act on serine proteases as well as metalloproteases. Human WFIKKN and a related protein sharing the same domain architecture were observed to have distinct tissue expression patterns. WFIKKN is also referred to as growth and differentiation factor-associated serum protein-1 (GASP-1). It inhibits the activity of mature myostatin, a specific regulator of skeletal muscle mass and a member of the TGFbeta superfamily.


Pssm-ID: 239630  Cd Length: 109  Bit Score: 204.96  E-value: 2.70e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 427 ALSLCRSDFAIVGRLTEVLEEPEaaGGIARVALEDVLKDDKMGLKFLGTKYLEVTLSGMDWACPCPNMTAGDGPLVIMGE 506
Cdd:cd03575   1 VPSLCRSDFAIVGRLTELTEELD--SGHARVTLEEVLKDEKMGLKFFGTEPLEVTLLNMDWSCPCPNITAGEGPLIIMGD 78
                        90       100       110
                ....*....|....*....|....*....|.
gi 16751923 507 VRDGVAVLDAGSYVRAASEKRVKKILELLEK 537
Cdd:cd03575  79 VHDGMAVLQPDSYVRASSERRVRKLREVLHK 109
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
186-280 8.43e-58

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 187.76  E-value: 8.43e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTA 265
Cdd:cd05765   1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80
                        90
                ....*....|....*
gi 16751923 266 RNAAGLLRADFPLSV 280
Cdd:cd05765  81 RNSGGLLRANFPLSV 95
Kunitz_WFIKKN_2-like cd22606
second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
358-410 3.22e-32

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: 117.84  E-value: 3.22e-32
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDACP 410
Cdd:cd22606   1 ICSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDACP 53
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
357-409 1.79e-20

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: 84.62  E-value: 1.79e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 16751923    357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:smart00131   1 DVCLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
Kunitz_WFIKKN_1-like cd22605
first Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
298-351 1.91e-20

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: 84.72  E-value: 1.91e-20
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 16751923 298 ECLPDVQACTGPTspHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22605   1 ECLKEPDREDCGE--EQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
358-409 2.10e-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: 84.62  E-value: 2.10e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 16751923   358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:pfam00014   1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
185-267 1.90e-17

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 76.84  E-value: 1.90e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVvvtsiGQLVLYNARPEDAGLYTCT 264
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-----STLTISNVTRSDAGTYTCV 75

                  ...
gi 16751923   265 ARN 267
Cdd:pfam13927  76 ASN 78
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
192-280 2.09e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 74.46  E-value: 2.09e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923    192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenLIMRPDQMYGnVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK---LLAESGRFSV-SRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76

                   ....*....
gi 16751923    272 LRADFPLSV 280
Cdd:smart00410  77 ASSGTTLTV 85
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
120-155 4.64e-06

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


Pssm-ID: 238052 [Multi-domain]  Cd Length: 41  Bit Score: 43.41  E-value: 4.64e-06
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 16751923 120 CEKEPSFTCASDGLTYYNRCYMDAEACLRGLHLHIV 155
Cdd:cd00104   1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVA 36
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
307-351 6.32e-06

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: 43.40  E-value: 6.32e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 16751923   307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:pfam00014   8 SGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
307-351 2.86e-05

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: 41.48  E-value: 2.86e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 16751923    307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:smart00131   9 TGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
WAP pfam00095
WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or ...
29-78 6.73e-05

WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or elastase-specific inhibitors.


Pssm-ID: 459672 [Multi-domain]  Cd Length: 42  Bit Score: 40.49  E-value: 6.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 16751923    29 HPGVCPnqlspnlWVDAQSTCERECSRDQDCAAAEKCCINVCGlHSCVAA 78
Cdd:pfam00095   1 KPGCCP-------RLGARGCCRSCCSSDDDCPGRQKCCSNGCG-SVCVPP 42
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
116-155 1.06e-03

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 36.89  E-value: 1.06e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 16751923    116 CRDRCEKEPSFTCASDGLTYYNRCYMDAEACLRGLHLHIV 155
Cdd:smart00280   2 CPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVK 41
 
Name Accession Description Interval E-value
NTR_WFIKKN cd03575
NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative ...
427-537 2.70e-64

NTR domain, WFIKKN subfamily; WFIKKN proteins contain a C-terminal NTR domain and are putative secreted proteins which may be multivalent protease inhibitors that act on serine proteases as well as metalloproteases. Human WFIKKN and a related protein sharing the same domain architecture were observed to have distinct tissue expression patterns. WFIKKN is also referred to as growth and differentiation factor-associated serum protein-1 (GASP-1). It inhibits the activity of mature myostatin, a specific regulator of skeletal muscle mass and a member of the TGFbeta superfamily.


Pssm-ID: 239630  Cd Length: 109  Bit Score: 204.96  E-value: 2.70e-64
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 427 ALSLCRSDFAIVGRLTEVLEEPEaaGGIARVALEDVLKDDKMGLKFLGTKYLEVTLSGMDWACPCPNMTAGDGPLVIMGE 506
Cdd:cd03575   1 VPSLCRSDFAIVGRLTELTEELD--SGHARVTLEEVLKDEKMGLKFFGTEPLEVTLLNMDWSCPCPNITAGEGPLIIMGD 78
                        90       100       110
                ....*....|....*....|....*....|.
gi 16751923 507 VRDGVAVLDAGSYVRAASEKRVKKILELLEK 537
Cdd:cd03575  79 VHDGMAVLQPDSYVRASSERRVRKLREVLHK 109
IgI_3_WFIKKN-like cd05765
Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz ...
186-280 8.43e-58

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409422 [Multi-domain]  Cd Length: 95  Bit Score: 187.76  E-value: 8.43e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTA 265
Cdd:cd05765   1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80
                        90
                ....*....|....*
gi 16751923 266 RNAAGLLRADFPLSV 280
Cdd:cd05765  81 RNSGGLLRANFPLSV 95
Kunitz_WFIKKN_2-like cd22606
second Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
358-410 3.22e-32

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: 117.84  E-value: 3.22e-32
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDACP 410
Cdd:cd22606   1 ICSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDACP 53
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
357-409 1.79e-20

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: 84.62  E-value: 1.79e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 16751923    357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:smart00131   1 DVCLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
Kunitz_WFIKKN_1-like cd22605
first Kunitz domain of WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing proteins; ...
298-351 1.91e-20

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: 84.72  E-value: 1.91e-20
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 16751923 298 ECLPDVQACTGPTspHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22605   1 ECLKEPDREDCGE--EQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
358-409 2.10e-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: 84.62  E-value: 2.10e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 16751923   358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:pfam00014   1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
359-409 1.92e-19

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: 82.18  E-value: 1.92e-19
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22624   2 CTEPPVTGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETC 52
Kunitz-type cd00109
Kunitz/Bovine pancreatic trypsin inhibitor (BPTI) domain; This family contains the Kunitz ...
359-409 2.18e-19

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: 81.44  E-value: 2.18e-19
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd00109   1 CLLPPDPGPCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51
Kunitz_TFPI2_1-like cd22616
Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
357-409 1.21e-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: 76.89  E-value: 1.21e-17
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22616   3 EICLLPPDEGPCRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTC 55
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
185-267 1.90e-17

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 76.84  E-value: 1.90e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVvvtsiGQLVLYNARPEDAGLYTCT 264
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-----STLTISNVTRSDAGTYTCV 75

                  ...
gi 16751923   265 ARN 267
Cdd:pfam13927  76 ASN 78
Kunitz_HAI1_1-like cd22623
Kunitz domain 1 of hepatocyte growth factor activator inhibitor-1 (HAI-1); This model includes ...
359-409 1.26e-16

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: 74.12  E-value: 1.26e-16
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22623   6 CLAPKKVGPCRGSFPRWHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSAC 56
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
192-280 2.09e-16

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 74.46  E-value: 2.09e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923    192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenLIMRPDQMYGnVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK---LLAESGRFSV-SRSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76

                   ....*....
gi 16751923    272 LRADFPLSV 280
Cdd:smart00410  77 ASSGTTLTV 85
I-set pfam07679
Immunoglobulin I-set domain;
192-280 2.73e-16

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 74.22  E-value: 2.73e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenliMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQP-----LRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGE 81

                  ....*....
gi 16751923   272 LRADFPLSV 280
Cdd:pfam07679  82 AEASAELTV 90
Kunitz_HAI2_1-like cd22621
Kunitz-type domain 1 (KD1) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
357-409 1.71e-15

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: 70.58  E-value: 1.71e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22621   1 DFCHLPKVVGRCRASFPRWWYNATSQSCQEFIFGGCKGNLNNFLSEQECLQKC 53
Kunitz_SmCI_3-like cd22603
third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
357-409 1.73e-15

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: 70.54  E-value: 1.73e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22603   1 EDCLLPSETGPCKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53
Kunitz_amblin-like cd22638
Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration ...
359-409 4.24e-15

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: 69.34  E-value: 4.24e-15
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22638   1 CTLKPETGPCRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51
Kunitz_actitoxin-like cd22633
Kunitz-type actitoxins such as Anemonia viridis U-actitoxin-Avd3l, and similar proteins; This ...
359-409 1.64e-14

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: 67.95  E-value: 1.64e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22633   5 CLLPKDVGGCRARFPRYYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55
Kunitz_PPTI-like cd22608
Pseudocerastes persicus trypsin inhibitor (PPTI), Kunitz-type serine protease inhibitor ...
359-409 2.48e-14

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: 67.32  E-value: 2.48e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22608   4 CYLPADPGPCKAYIPRFYYNSASNKCQQFIYGGCKGNANNFETKDECRYTC 54
Kunitz_bikunin_2-like cd22597
second Kunitz domain of bikunin and similar proteins; This subfamily includes the C-terminal ...
357-409 2.56e-14

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: 67.41  E-value: 2.56e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22597   2 AACRLPIVPGPCKGFVDLWAFDAVQGKCVPFSYGGCQGNGNKFYSEKECEEYC 54
Kunitz_TFPI2_2-like cd22617
Kunitz domain 2 (KD2) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
357-409 3.80e-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: 66.64  E-value: 3.80e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22617   2 KVCREVPDEGPCRALITRYFYNMTSMRCEEFTYGGCYGNGNNFRDKSSCISAC 54
Kunitz_collagen_alpha3_VI cd22629
Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This ...
357-409 4.21e-14

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: 66.62  E-value: 4.21e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22629   1 DICKLPKDEGTCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53
Kunitz_TFPI1_2-like cd22614
Kunitz protease inhibitor (KPI) domain 2 (KPI-2 or K2) of tissue factor pathway inhibitor ...
357-409 7.05e-14

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: 66.18  E-value: 7.05e-14
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22614   3 DFCFLEEDPGICRGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTC 55
Kunitz_SCI-I-like cd22634
chymotrypsin inhibitor SCI-I_III-like; This model includes the Kunitz-type chymotrypsin ...
347-409 9.21e-14

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: 66.00  E-value: 9.21e-14
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16751923 347 CQQACARGPGDAcvlpavqGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22634   2 CGQPHSLGGGDG-------ISCFAYIPSWSYNPDKNECEEFIYGGCGGNDNRFSTKAECEQKC 57
Kunitz_HAI2_2-like cd22622
Kunitz-type domain 2 (KD2) of hepatocyte growth factor activator inhibitor type 2 (HAI-2), and ...
357-409 1.20e-13

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: 65.46  E-value: 1.20e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22622   1 EYCAAPRVTGPCRAAFPRWYYDPESQSCKEFIYGGCRGNKNNYLSEEECMDRC 53
Kunitz_textilinin-like cd22594
venom Kunitz-type proteins such as textilinin, BF9 and PILP; This group includes toxins ...
359-409 1.61e-13

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: 65.03  E-value: 1.61e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22594   5 CELPADPGPCNAYKPAFYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTC 55
Ig cd00096
Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found ...
203-270 3.87e-13

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409353 [Multi-domain]  Cd Length: 70  Bit Score: 64.66  E-value: 3.87e-13
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 16751923 203 ASLHCDVSGRPPPAVTWEKQshqreNLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKN-----GKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63
IgI_4_Dscam cd20956
Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
185-270 4.09e-13

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409548 [Multi-domain]  Cd Length: 96  Bit Score: 65.27  E-value: 4.09e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWE------KQSHQRenlimrpdqMYGNvVVTSIGQLVLY----NAR 254
Cdd:cd20956   1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTldgfpiPESPRF---------RVGD-YVTSDGDVVSYvnisSVR 70
                        90
                ....*....|....*.
gi 16751923 255 PEDAGLYTCTARNAAG 270
Cdd:cd20956  71 VEDGGEYTCTATNDVG 86
Kunitz_eppin cd22611
Kunitz domain of epididymal protease inhibitor eppin and similar proteins; This subfamily ...
357-413 4.87e-13

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: 63.96  E-value: 4.87e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDACPVPR 413
Cdd:cd22611   1 DVCSLPKESGPCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNICKKKR 57
Kunitz_collagen_alpha1_VII cd22627
Kunitz-type domain from the alpha1 chain of type VII collagen, and similar proteins; This ...
357-409 8.75e-13

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: 63.04  E-value: 8.75e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22627   1 DPCLLPMDEGSCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53
Kunitz_BmTI-like cd22604
Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group ...
357-409 8.85e-13

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: 62.85  E-value: 8.85e-13
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22604   4 KQCSPTADSGPCFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56
Kunitz_boophilin_2-like cd22600
second Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
358-409 1.69e-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: 62.06  E-value: 1.69e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 16751923 358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22600   1 GCKPAAESGLCAAYLERWFFNVTTGACETFVYGGCGGNANNYKSQEECELAC 52
Kunitz_boophilin_1-like cd22599
first Kunitz domain of Rhipicephalus microplus boophilin and similar proteins; This group ...
359-413 2.38e-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: 62.11  E-value: 2.38e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDACPVPR 413
Cdd:cd22599   6 CRLPADEGICRALIPRFYFNTETGQCTEFIYGGCGGNENNFETIEECEKACGAPE 60
IgI_4_Robo cd05726
Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
192-280 4.75e-12

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409391 [Multi-domain]  Cd Length: 98  Bit Score: 62.28  E-value: 4.75e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd05726   6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGS 85

                ....*....
gi 16751923 272 LRADFPLSV 280
Cdd:cd05726  86 ILAKAQLEV 94
Kunitz_collagen_alpha6_VI cd22630
Kunitz-type domain from the alpha6 chain of human type VI collagen, and similar proteins; This ...
357-409 5.13e-12

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: 60.69  E-value: 5.13e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22630   1 DACSLDQDEGECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALC 53
Kunitz_papilin cd22635
Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in ...
359-409 5.79e-12

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: 60.74  E-value: 5.79e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 16751923 359 CVLPAVQG-PCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22635   1 CLLDKDAGtVCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52
Kunitz_TFPI1_1-like cd22613
Kunitz protease inhibitor (KPI) domain 1 (KPI-1 or K1) of tissue factor pathway inhibitor ...
359-409 5.90e-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: 60.45  E-value: 5.90e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22613   4 CAFKADDGPCKAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTC 54
Kunitz_conkunitzin cd22593
conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 ...
359-409 7.27e-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: 60.31  E-value: 7.27e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 359 CVLPAVQGpcRGWEP--RWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22593   1 CSLPLDEG--SGNSSltRWYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51
Kunitz_collagen_alpha1_XXVIII cd22628
Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This ...
359-409 9.93e-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: 59.99  E-value: 9.93e-12
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22628   1 CLEPLDPGPCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51
Kunitz_ELP-like cd22632
early lactation protein (ELP), colostrum trypsin inhibitor (CTI), and similar proteins; This ...
359-409 1.05e-11

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: 59.75  E-value: 1.05e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22632   4 CQLPPARGPCRSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTC 54
Kunitz_TFPI1_TFPI2_3-like cd22615
Kunitz protease inhibitor (KPI) domain 3 (KPI-3 or K3) of tissue factor pathway inhibitor ...
359-409 1.10e-11

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: 60.00  E-value: 1.10e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22615   4 CLSPKDEGLCSASVTRYYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54
IgI_LRIG1-like cd05763
Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like ...
192-281 1.53e-11

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.


Pssm-ID: 409420 [Multi-domain]  Cd Length: 91  Bit Score: 60.71  E-value: 1.53e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQ-------SHQRENLIMRPDQMYgnvvvtsigqlVLYNARPEDAGLYTCT 264
Cdd:cd05763   6 PHDITIRAGSTARLECAATGHPTPQIAWQKDggtdfpaARERRMHVMPEDDVF-----------FIVDVKIEDTGVYSCT 74
                        90
                ....*....|....*..
gi 16751923 265 ARNAAGLLRADFPLSVV 281
Cdd:cd05763  75 AQNSAGSISANATLTVL 91
Kunitz_SmCI_1-like cd22601
first Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
356-409 1.74e-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: 59.44  E-value: 1.74e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 16751923 356 GDACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22601   1 IDVCDLPADRGPCTAYIPRWFYNKTTKKCEKFVYGGCQGNKNRFETKDDCLANC 54
Kunitz_papilin_mig6-like cd22637
Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of ...
359-409 2.21e-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: 58.91  E-value: 2.21e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22637   1 CDQPKDTGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51
Kunitz_bikunin_1-like cd22596
first Kunitz domain of bikunin and similar proteins; This subfamily includes the N-terminal ...
357-409 5.26e-11

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: 58.03  E-value: 5.26e-11
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22596   1 DSCKLPPDAGPCFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTC 53
Kunitz_papilin_lacunin-like cd22639
Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr ...
359-409 1.30e-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: 56.81  E-value: 1.30e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22639   1 CSLPKDRGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51
Kunitz_SHPI cd22618
Stichodactyla helianthus Kunitz inhibitor protein ShPI-1, Heteractis crispa protease inhibitor ...
359-409 1.52e-10

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: 56.78  E-value: 1.52e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22618   2 CSEPKVVGPCKAYFPRFYFDSETGKCTPFIYGGCGGNGNNFETLHACRAIC 52
Kunitz_SmCI_2-like cd22602
second Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
359-409 1.65e-10

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: 56.39  E-value: 1.65e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22602   1 CSLPSKVGPCRVSARRWFHNPETEKCEVFIYGGCHGNANRFATETECQEVC 51
Kunitz_collagen_alpha6_VI-like cd22631
Kunitz-type domain from the alpha6 chain of fish type VI collagen, and similar proteins; This ...
359-409 3.25e-10

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: 55.70  E-value: 3.25e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22631   1 CLLGQDAGSCQNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51
Kunitz_ABPP-like cd22607
Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily ...
359-409 4.09e-10

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: 55.51  E-value: 4.09e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22607   2 CSEQAETGPCRAMMPRWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52
Kunitz_TKDP-like cd22609
trophoblast Kunitz domain protein (TKDP) and similar proteins; This model contains the ...
359-409 4.75e-10

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: 55.15  E-value: 4.75e-10
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22609   2 CLEPKVVGVCKASMTRYFYNAQTGHCEQFVYGGCGGNRNNFLTLEDCMKTC 52
IgI_Myotilin_C_like cd05744
Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of ...
186-270 8.09e-10

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409405 [Multi-domain]  Cd Length: 91  Bit Score: 55.58  E-value: 8.09e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWekqshQRENLIMRPDQMYGNVV-VTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd05744   1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFW-----QLNGKPVRPDSAHKMLVrENGRHSLIIEPVTKRDAGIYTCI 75

                ....*.
gi 16751923 265 ARNAAG 270
Cdd:cd05744  76 ARNRAG 81
Kunitz_ixolaris_2 cd22626
Kunitz-type domain 2 (K2) of Ixolaris, and similar proteins; This model includes the second ...
359-409 2.81e-09

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: 52.85  E-value: 2.81e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22626   1 CSLELDYGVGKAYIPRWYFNTSNARCEMFIFGGIGGNKNNFETLEECKKTC 51
IgI_2_Follistatin_like cd05736
Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; ...
186-273 3.41e-09

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.


Pssm-ID: 409399 [Multi-domain]  Cd Length: 93  Bit Score: 54.19  E-value: 3.41e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQshqreNLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTA 265
Cdd:cd05736   1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKN-----GMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIA 75

                ....*...
gi 16751923 266 RNAAGLLR 273
Cdd:cd05736  76 KNEGGVDE 83
IgI_1_MuSK cd20970
agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of ...
188-270 4.15e-09

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409562 [Multi-domain]  Cd Length: 92  Bit Score: 53.67  E-value: 4.15e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 188 LYSSPSPQA---VQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRpdqmygnVVVTSIGQ-LVLYNARPEDAGLYTC 263
Cdd:cd20970   2 VISTPQPSFtvtAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTR-------YIVRENGTtLTIRNIRRSDMGIYLC 74

                ....*..
gi 16751923 264 TARNAAG 270
Cdd:cd20970  75 IASNGVP 81
IgI_4_MYLK-like cd20976
Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a ...
185-280 4.18e-09

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409568 [Multi-domain]  Cd Length: 90  Bit Score: 53.79  E-value: 4.18e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenLIMRPDQMYGNVVVtsiGQLVLYNARPEDAGLYTCT 264
Cdd:cd20976   1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQP---LQYAADRSTCEAGV---GELHIQDVLPEDHGTYTCL 74
                        90
                ....*....|....*.
gi 16751923 265 ARNAAGLLRADFPLSV 280
Cdd:cd20976  75 AKNAAGQVSCSAWVTV 90
Ig_2 pfam13895
Immunoglobulin domain; This domain contains immunoglobulin-like domains.
191-280 5.78e-09

Immunoglobulin domain; This domain contains immunoglobulin-like domains.


Pssm-ID: 464026 [Multi-domain]  Cd Length: 79  Bit Score: 52.78  E-value: 5.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   191 SPSPQAVQVGGTASLHCDVSGRPPPAVTWEKqshqrenlimrpdqmyGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:pfam13895   5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYK----------------DGSAISSSPNFFTLSVSAEDSGTYTCVARNGRG 68
                          90
                  ....*....|.
gi 16751923   271 -LLRADFPLSV 280
Cdd:pfam13895  69 gKVSNPVELTV 79
Kunitz_dendrotoxin cd22595
dendrotoxins I, K, B and similar proteins; This group includes toxins isolated from snake ...
358-409 6.78e-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: 52.06  E-value: 6.78e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 16751923 358 ACVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22595   3 FCKLPVRPGPCKAFISAFYYNWKAKKCHPFTYSGCGGNANRFKTIEECRRTC 54
Kunitz_BPTI cd22592
bovine pancreatic trypsin inhibitor; This model contains bovine pancreatic trypsin inhibitor ...
359-409 6.84e-09

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: 51.87  E-value: 6.84e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22592   2 CLEPPYTGPCKARIIRYFYNAKSGLCETFVYGGCRAKRNNFLSAEDCMRTC 52
Kunitz_KTT cd22620
scorpion venom Kunitz-type toxin (KTT) such as LmKTT-1a, BmKTT-1, and BmKTT-2; This model ...
359-409 9.75e-09

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: 51.80  E-value: 9.75e-09
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22620   3 CQLPSDTGRGKASFTRYYYNEESGKCETFIYGGVGGNSNNFLTKEDCCKEC 53
IgI_4_hemolin-like cd20978
Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set ...
186-280 1.16e-08

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409570 [Multi-domain]  Cd Length: 88  Bit Score: 52.39  E-value: 1.16e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGG-TASLHCDVSGRPPPAVTWekqSHQRENLIMRPdqmyGNVVVTSiGQLVLYNARPEDAGLYTCT 264
Cdd:cd20978   1 PKFIQKPEKNVVVKGGqDVTLPCQVTGVPQPKITW---LHNGKPLQGPM----ERATVED-GTLTIINVQPEDTGYYGCV 72
                        90
                ....*....|....*.
gi 16751923 265 ARNAAGLLRADFPLSV 280
Cdd:cd20978  73 ATNEIGDIYTETLLHV 88
IgI_5_Robo cd20952
Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the ...
190-270 1.45e-08

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors


Pssm-ID: 409544 [Multi-domain]  Cd Length: 87  Bit Score: 52.11  E-value: 1.45e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 190 SSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenlIMRPDQmygNVVVTSIGQLVLYNARPEDAGLYTCTARNAA 269
Cdd:cd20952   4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVP----LLGKDE---RITTLENGSLQIKGAEKSDTGEYTCVALNLS 76

                .
gi 16751923 270 G 270
Cdd:cd20952  77 G 77
ig pfam00047
Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of ...
190-278 1.52e-08

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.


Pssm-ID: 395002  Cd Length: 86  Bit Score: 51.81  E-value: 1.52e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   190 SSPSPQAVQVGGTASLHCDVS-GRPPPAVTWEKQShQRENLIMRPDQMYGNvvvTSIGQLVLYNARPEDAGLYTCTARNA 268
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEG-GTLIESLKVKHDNGR---TTQSSLLISNVTKEDAGTYTCVVNNP 76
                          90
                  ....*....|
gi 16751923   269 AGLLRADFPL 278
Cdd:pfam00047  77 GGSATLSTSL 86
Ig_Titin_like cd05748
Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed ...
197-270 2.17e-08

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.


Pssm-ID: 409406 [Multi-domain]  Cd Length: 82  Bit Score: 51.44  E-value: 2.17e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 16751923 197 VQVGGTASLHCDVSGRPPPAVTWEKqshqrENLIMRPDQMYgNVVVTSI-GQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05748   4 VRAGESLRLDIPIKGRPTPTVTWSK-----DGQPLKETGRV-QIETTASsTSLVIKNAKRSDSGKYTLTLKNSAG 72
IgC2_3_Dscam cd20957
Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
191-267 2.43e-08

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.


Pssm-ID: 409549 [Multi-domain]  Cd Length: 88  Bit Score: 51.38  E-value: 2.43e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQShqrenlimRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARN 267
Cdd:cd20957   7 DPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG--------KPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75
NTR_like cd03523
NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in ...
429-521 2.64e-08

NTR_like domain; a beta barrel with an oligosaccharide/oligonucleotide-binding fold found in netrins, complement proteins, tissue inhibitors of metalloproteases (TIMP), and procollagen C-proteinase enhancers (PCOLCE), amongst others. In netrins, the domain plays a role in controlling axon branching in neural development, while the common function of these modules in TIMPs appears to be binding to metzincins. A subset of this family is also known as the C345C domain because it occurs as a C-terminal domain in complement C3, C4 and C5. In C5, the domain interacts with various partners during the formation of the membrane attack complex.


Pssm-ID: 239600  Cd Length: 105  Bit Score: 51.70  E-value: 2.64e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 429 SLCRSDFAIVGRLTEVLEEPEaaGGIARVALEDVLKD-----DKMGLKFLGTKylevtlsgmDWACPCPNMTAGDGPLVI 503
Cdd:cd03523   2 AFCKSDYVVRAKIKEIKEEND--DVKYEVKIIKIYKTgkakaDKADLRFYYTA---------PACCPCHPILNPGREYLI 70
                        90       100
                ....*....|....*....|
gi 16751923 504 MG--EVRDGVAVLDAGSYVR 521
Cdd:cd03523  71 MGkeEDSQGGLVLDPLSFVE 90
IgI_7_Dscam cd20954
Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar ...
185-270 3.42e-08

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409546 [Multi-domain]  Cd Length: 96  Bit Score: 51.16  E-value: 3.42e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEK----QSHQRENLIMRPD-QMYGNvvvtsiGQLVLYNARPEDAG 259
Cdd:cd20954   1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKatgsTPGEYKDLLYDPNvRILPN------GTLVFGHVQKENEG 74
                        90
                ....*....|.
gi 16751923 260 LYTCTARNAAG 270
Cdd:cd20954  75 HYLCEAKNGIG 85
IgI_3_Robo cd05725
Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
192-280 4.43e-08

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409390 [Multi-domain]  Cd Length: 83  Bit Score: 50.47  E-value: 4.43e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQ--RENLIMRPDQmygnvvvtsigQLVLYNARPEDAGLYTCTARNAA 269
Cdd:cd05725   4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGElpKGRYEILDDH-----------SLKIRKVTAGDMGSYTCVAENMV 72
                        90
                ....*....|.
gi 16751923 270 GLLRADFPLSV 280
Cdd:cd05725  73 GKIEASATLTV 83
Ig4_L1-CAM_like cd05867
Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members ...
200-281 6.23e-08

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409453 [Multi-domain]  Cd Length: 89  Bit Score: 50.28  E-value: 6.23e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEKQSHQRENLimRPDQMYGnvvvTSIGQLVLYNARPEDAGLYTCTARNAAGLLRADFPLS 279
Cdd:cd05867  14 GETARLDCQVEGIPTPNITWSINGAPIEGT--DPDPRRH----VSSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVH 87

                ..
gi 16751923 280 VV 281
Cdd:cd05867  88 VV 89
IgI_Myotilin_C cd05892
C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily ...
194-271 9.18e-08

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409473  Cd Length: 92  Bit Score: 49.77  E-value: 9.18e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 194 PQAVQV--GGTASLHCDVSGRPPPAVTWEKQShqrENLIMRPDQM------YGNVVvtsigqLVLYNARPEDAGLYTCTA 265
Cdd:cd05892   7 PQNKKVleGDPVRLECQISAIPPPQIFWKKNN---EMLQYNTDRIslyqdnCGRIC------LLIQNANKKDAGWYTVSA 77

                ....*.
gi 16751923 266 RNAAGL 271
Cdd:cd05892  78 VNEAGV 83
IgI_NCAM-1 cd05869
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members ...
196-270 3.41e-07

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 143277 [Multi-domain]  Cd Length: 97  Bit Score: 48.44  E-value: 3.41e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 16751923 196 AVQVGGTASLHCDVSGRPPPAVTWekqSHQRENLIMRPDQMYGNVVVTS---IGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05869  13 AMELEEQITLTCEASGDPIPSITW---RTSTRNISSEEKTLDGHIVVRSharVSSLTLKYIQYTDAGEYLCTASNTIG 87
IgI_2_Titin_Z1z2-like cd20972
Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and ...
185-270 4.82e-07

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409564 [Multi-domain]  Cd Length: 91  Bit Score: 47.96  E-value: 4.82e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENlimRPD-QMYGNVVVTSigqLVLYNARPEDAGLYTC 263
Cdd:cd20972   1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQN---SPDiQIHQEGDLHS---LIIAEAFEEDTGRYSC 74

                ....*..
gi 16751923 264 TARNAAG 270
Cdd:cd20972  75 LATNSVG 81
IgI_2_FGFRL1-like cd05856
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1 ...
199-280 5.67e-07

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409442  Cd Length: 92  Bit Score: 47.55  E-value: 5.67e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 199 VGGTASLHCDVSGRPPPAVTWEKQSHQrenlimrpdqmygnVVVTSIGQ-------LVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd05856  18 VGSSVRLKCVASGNPRPDITWLKDNKP--------------LTPPEIGEnkkkkwtLSLKNLKPEDSGKYTCHVSNRAGE 83

                ....*....
gi 16751923 272 LRADFPLSV 280
Cdd:cd05856  84 INATYKVDV 92
Ig4_L1-NrCAM_like cd04978
Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), ...
192-281 8.04e-07

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.


Pssm-ID: 409367 [Multi-domain]  Cd Length: 89  Bit Score: 47.06  E-value: 8.04e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLimrPDQMYGNVVVTSigqLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd04978   6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPA---PEDMRRTVDGRT---LIFSNLQPNDTAVYQCNASNVHGY 79
                        90
                ....*....|
gi 16751923 272 LRADFPLSVV 281
Cdd:cd04978  80 LLANAFLHVL 89
IgI_2_Palladin_C cd20990
Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig ...
186-281 8.83e-07

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409582  Cd Length: 91  Bit Score: 47.02  E-value: 8.83e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWekqshQRENLIMRPDQMYGNVVVTS-IGQLVLYNARPEDAGLYTCT 264
Cdd:cd20990   1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSW-----QLDGKPIRPDSAHKMLVRENgVHSLIIEPVTSRDAGIYTCI 75
                        90
                ....*....|....*..
gi 16751923 265 ARNAAGllRADFPLSVV 281
Cdd:cd20990  76 ATNRAG--QNSFNLELV 90
Kunitz_huwentoxin cd22598
Kunitz-type toxin huwentoxin-XI; This model contains Kunitz-type serine protease inhibitor ...
357-409 8.86e-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: 46.14  E-value: 8.86e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 357 DACVLPAVQGPCRGWEPRWAYSPllQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22598   1 DTCRLPSDRGRCKASFERWYFNG--RTCAKFIYGGCGGNDNKFPTQEACMKRC 51
IgI_titin_I1-like cd20951
Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of ...
186-270 1.05e-06

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409543 [Multi-domain]  Cd Length: 94  Bit Score: 47.03  E-value: 1.05e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMY---GNVVVtsigqLVLYNARPEDAGLYT 262
Cdd:cd20951   1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIeseYGVHV-----LHIRRVTVEDSAVYS 75

                ....*...
gi 16751923 263 CTARNAAG 270
Cdd:cd20951  76 AVAKNIHG 83
Ig5_Contactin cd04969
Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth ...
197-270 1.20e-06

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409358 [Multi-domain]  Cd Length: 89  Bit Score: 46.68  E-value: 1.20e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 16751923 197 VQVGGTASLHCDVSGRPPPAVTWEKQShqrENLIMRPDqmygnVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd04969  14 AAKGGDVIIECKPKASPKPTISWSKGT---ELLTNSSR-----ICILPDGSLKIKNVTKSDEGKYTCFAVNFFG 79
IgI_5_Dscam cd20958
Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; ...
200-280 3.28e-06

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409550 [Multi-domain]  Cd Length: 89  Bit Score: 45.25  E-value: 3.28e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEK------QSH-QRenlimrpdqmygnvvVTSIGQLVLYNA-RPEDAGLYTCTARNAAGL 271
Cdd:cd20958  15 GQTLRLHCPVAGYPISSITWEKdgrrlpLNHrQR---------------VFPNGTLVIENVqRSSDEGEYTCTARNQQGQ 79
                        90
                ....*....|
gi 16751923 272 L-RADFPLSV 280
Cdd:cd20958  80 SaSRSVFVKV 89
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
120-155 4.64e-06

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


Pssm-ID: 238052 [Multi-domain]  Cd Length: 41  Bit Score: 43.41  E-value: 4.64e-06
                        10        20        30
                ....*....|....*....|....*....|....*.
gi 16751923 120 CEKEPSFTCASDGLTYYNRCYMDAEACLRGLHLHIV 155
Cdd:cd00104   1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVA 36
IgI_3_FGFR2 cd05858
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member ...
192-271 4.91e-06

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409444  Cd Length: 105  Bit Score: 45.34  E-value: 4.91e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQsHQRENLIMRPDQM-YGNVVVTS--------IGQLVLYNARPEDAGLYT 262
Cdd:cd05858   8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKH-VEKNGSKYGPDGLpYVEVLKTAgvnttdkeIEVLYLRNVTFEDAGEYT 86

                ....*....
gi 16751923 263 CTARNAAGL 271
Cdd:cd05858  87 CLAGNSIGI 95
IgI_2_FGFR_like cd05729
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar ...
196-280 5.44e-06

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.


Pssm-ID: 409393 [Multi-domain]  Cd Length: 95  Bit Score: 44.90  E-value: 5.44e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 196 AVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenlIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGLLRAD 275
Cdd:cd05729  15 ALPAANKVRLECGAGGNPMPNITWLKDGKE----FKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHT 90

                ....*
gi 16751923 276 FPLSV 280
Cdd:cd05729  91 YDVDV 95
Kunitz_BPTI pfam00014
Kunitz/Bovine pancreatic trypsin inhibitor domain; Indicative of a protease inhibitor, usually ...
307-351 6.32e-06

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: 43.40  E-value: 6.32e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 16751923   307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:pfam00014   8 SGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52
Kunitz_collagen_alpha3_VI cd22629
Kunitz-type domain from the alpha3 chain of human type VI collagen, and similar proteins; This ...
307-351 6.64e-06

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: 43.51  E-value: 6.64e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22629   9 EGTCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53
IgI_2_MuSK cd20968
agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ...
200-270 9.61e-06

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409560 [Multi-domain]  Cd Length: 88  Bit Score: 44.16  E-value: 9.61e-06
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEK-QSHQRENlimrpdqmyGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd20968  14 GLKAVLPCTTMGNPKPSVSWIKgDDLIKEN---------NRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76
NTR_Sfrp1_like cd03580
NTR domain, Secreted frizzled-related protein (Sfrp) 1-like subfamily; composed of proteins ...
414-514 1.38e-05

NTR domain, Secreted frizzled-related protein (Sfrp) 1-like subfamily; composed of proteins similar to human Sfrp1, Sfrp2 and Sfrp5. Sfrps are soluble proteins containing an NTR domain C-terminal to a cysteine-rich Frizzled domain. They show diverse functions and are thought to work in Wnt signaling indirectly, as modulators or antagonists by binding Wnt ligands, and directly, via the Wnt receptor, Frizzled. They participate in regulating the patterning along the anteroposterior axis in vertebrates. Human Sfrp1 has been found frequently to be downregulated in breast cancer and is associated with disease progression and poor prognosis.


Pssm-ID: 239635  Cd Length: 126  Bit Score: 44.59  E-value: 1.38e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 414 TPPCRACRLRSKLA----LSLCRSDFAIVGRLTEVLEEpeaaGGIARVALEDVLKDDKMG-LKFLGTKYLEVTL-SGMDw 487
Cdd:cd03580   1 PKVCPPCENEEESAktllDNFCASDFALKVKIKEISYE----NGDRKVIGEKKKEILKQGpLKKKDLKKLVLWLkNGAN- 75
                        90       100
                ....*....|....*....|....*..
gi 16751923 488 aCPCPNMTAGDGPLVIMGEVRDGVAVL 514
Cdd:cd03580  76 -CPCPQLDNLNGVYLVMGRKVDGKLLL 101
IgI_Titin_like cd05747
Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the ...
184-279 1.46e-05

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 143224 [Multi-domain]  Cd Length: 92  Bit Score: 43.88  E-value: 1.46e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 184 VPPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQshqrenlimrpdqmyGNVVVTSIGQLVL---YNARPE---- 256
Cdd:cd05747   2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMRE---------------GQIIVSSQRHQITsteYKSTFEiskv 66
                        90       100
                ....*....|....*....|....*.
gi 16751923 257 ---DAGLYTCTARNAAGLLRADFPLS 279
Cdd:cd05747  67 qmsDEGNYTVVVENSEGKQEAQFTLT 92
IgI_2_FGFR cd05857
Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of ...
196-280 1.66e-05

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.


Pssm-ID: 409443 [Multi-domain]  Cd Length: 95  Bit Score: 43.69  E-value: 1.66e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 196 AVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenlIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGLLRAD 275
Cdd:cd05857  15 AVPAANTVKFRCPAAGNPTPTMRWLKNGKE----FKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHT 90

                ....*
gi 16751923 276 FPLSV 280
Cdd:cd05857  91 YHLDV 95
IgI_2_RPTP_IIa_LAR_like cd05738
Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; ...
192-270 1.90e-05

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.


Pssm-ID: 409400 [Multi-domain]  Cd Length: 91  Bit Score: 43.46  E-value: 1.90e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKqshqrENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05738   6 PQLKVVEKARTATMLCAASGNPDPEISWFK-----DFLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAG 79
Kunitz_papilin_lacunin-like cd22639
Drosophila melanogaster Kunitz domain 1, Manduca sexta lacunin Kunitz domain 1, and simialr ...
307-351 2.06e-05

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: 42.18  E-value: 2.06e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22639   7 RGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51
IgC_1_Robo cd07693
First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar ...
186-270 2.10e-05

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.


Pssm-ID: 409490 [Multi-domain]  Cd Length: 99  Bit Score: 43.31  E-value: 2.10e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQShqrENLIMRPDQMYGNVVVTSIGQL----VLYNARPE-DAGL 260
Cdd:cd07693   1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNG---QPLETDKDDPRSHRIVLPSGSLfflrVVHGRKGRsDEGV 77
                        90
                ....*....|
gi 16751923 261 YTCTARNAAG 270
Cdd:cd07693  78 YVCVAHNSLG 87
KU smart00131
BPTI/Kunitz family of serine protease inhibitors; Serine protease inhibitors. One member of ...
307-351 2.86e-05

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: 41.48  E-value: 2.86e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 16751923    307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:smart00131   9 TGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53
IgI_NCAM-1_like cd05732
Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar ...
200-270 2.89e-05

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.


Pssm-ID: 409395 [Multi-domain]  Cd Length: 96  Bit Score: 42.90  E-value: 2.89e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDqmyGNVVVTS---IGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05732  16 LEQITLTCEAEGDPIPEITWRRATRGISFEEGDLD---GRIVVRGharVSSLTLKDVQLTDAGRYDCEASNRIG 86
IgI_2_Robo cd05724
Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of ...
192-270 2.89e-05

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409389 [Multi-domain]  Cd Length: 87  Bit Score: 42.77  E-value: 2.89e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVS-GRPPPAVTWEKQSHQRENLIMRpdqmygnVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05724   4 PSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNER-------VRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76
Kunitz_B2B cd22619
Kunitz-type serine protease inhibitor subunit of beta 2-bungarotoxin, and similar proteins; ...
359-409 3.27e-05

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: 41.77  E-value: 3.27e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 16751923 359 CVLPAVQGPCRGWEPRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22619   7 CDKPPDTKRCKRVVRAFYYNPSAKTCLQFVYGGCNGNGNHFKSKALCRCHC 57
IgV cd00099
Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin ...
191-266 4.87e-05

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.


Pssm-ID: 409355 [Multi-domain]  Cd Length: 111  Bit Score: 42.71  E-value: 4.87e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPP-PAVTW--EKQSHQRENLI-----------MRPDQMYGNVVVTSIGQLVLYNARPE 256
Cdd:cd00099   4 SPRSLSVQEGESVTLSCEVSSSFSsTYIYWyrQKPGQGPEFLIylssskgktkgGVPGRFSGSRDGTSSFSLTISNLQPE 83
                        90
                ....*....|
gi 16751923 257 DAGLYTCTAR 266
Cdd:cd00099  84 DSGTYYCAVS 93
Ig_DSCAM cd05735
Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here ...
183-280 5.14e-05

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.


Pssm-ID: 409398  Cd Length: 101  Bit Score: 42.48  E-value: 5.14e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 183 PVPPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHqrenlIMRPDQMYGNVVVTS------IGQLVLYNARPE 256
Cdd:cd05735   1 KIPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDT-----IINPSEMSRYLVTTKevgdevISTLQILPTVRE 75
                        90       100
                ....*....|....*....|....
gi 16751923 257 DAGLYTCTARNAAGLLRADFPLSV 280
Cdd:cd05735  76 DSGFFSCHAINSYGEDRGIIQLTV 99
Ig4_Peroxidasin cd05746
Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
205-279 6.09e-05

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143223  Cd Length: 69  Bit Score: 41.40  E-value: 6.09e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 16751923 205 LHCDVSGRPPPAVTWEKQSHQRENlimrpdqmYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGLLRADFPLS 279
Cdd:cd05746   3 IPCSAQGDPEPTITWNKDGVQVTE--------SGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69
Ig_DSCAM cd05734
Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members ...
185-270 6.52e-05

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.


Pssm-ID: 409397 [Multi-domain]  Cd Length: 97  Bit Score: 42.09  E-value: 6.52e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd05734   1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCK 80

                ....*.
gi 16751923 265 ARNAAG 270
Cdd:cd05734  81 VSNDVG 86
WAP pfam00095
WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or ...
29-78 6.73e-05

WAP-type (Whey Acidic Protein) 'four-disulfide core'; WAP belongs to the group of Elafin or elastase-specific inhibitors.


Pssm-ID: 459672 [Multi-domain]  Cd Length: 42  Bit Score: 40.49  E-value: 6.73e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 16751923    29 HPGVCPnqlspnlWVDAQSTCERECSRDQDCAAAEKCCINVCGlHSCVAA 78
Cdd:pfam00095   1 KPGCCP-------RLGARGCCRSCCSSDDDCPGRQKCCSNGCG-SVCVPP 42
IgI_3_Contactin-1 cd05851
Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) ...
200-271 7.77e-05

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 143259  Cd Length: 88  Bit Score: 41.55  E-value: 7.77e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEKqshqrenlIMRPdqMYGNVVVTSIGQ-LVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd05851  16 GQNVTLECFALGNPVPVIRWRK--------ILEP--MPATAEISMSGAvLKIFNIQPEDEGTYECEAENIKGK 78
V-set pfam07686
Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 ...
191-281 8.88e-05

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.


Pssm-ID: 462230  Cd Length: 109  Bit Score: 42.06  E-value: 8.88e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923   191 SPSPQAVQVGGTASLHCDVSGR---PPPAVTWEKQS--HQRENLIMRPDQMYGNVVVT-----------SIGQLVLYNAR 254
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSmseASTSVYWYRQPpgKGPTFLIAYYSNGSEEGVKKgrfsgrgdpsnGDGSLTIQNLT 81
                          90       100
                  ....*....|....*....|....*...
gi 16751923   255 PEDAGLYTCTAR-NAAGLLRADFPLSVV 281
Cdd:pfam07686  82 LSDSGTYTCAVIpSGEGVFGKGTRLTVL 109
IgI_3_NCAM-1 cd05730
Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of ...
192-280 1.25e-04

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.


Pssm-ID: 143207 [Multi-domain]  Cd Length: 95  Bit Score: 41.07  E-value: 1.25e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQ--VGGTAS------LHCDVSGRPPPAVTWEKQSHQRENlimrPDQMYGNVVVTSigQLVLYNARPEDAGLYTC 263
Cdd:cd05730   2 PTIRARQseVNATANlgqsvtLACDADGFPEPTMTWTKDGEPIES----GEEKYSFNEDGS--EMTILDVDKLDEAEYTC 75
                        90
                ....*....|....*..
gi 16751923 264 TARNAAGLLRADFPLSV 280
Cdd:cd05730  76 IAENKAGEQEAEIHLKV 92
IgI_3_FGFR cd04974
Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of ...
192-271 1.37e-04

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409363  Cd Length: 102  Bit Score: 41.25  E-value: 1.37e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKqsHQREN-LIMRPDQM-YGNVV-------VTSIGQLVLYNARPEDAGLYT 262
Cdd:cd04974   8 PANQTVVLGSDVEFHCKVYSDAQPHIQWLK--HVEVNgSKYGPDGLpYVTVLkvagvntTGEENTLTISNVTFDDAGEYI 85

                ....*....
gi 16751923 263 CTARNAAGL 271
Cdd:cd04974  86 CLAGNSIGL 94
IgV_1_MRC-OX-2_like cd05846
First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; ...
193-263 1.39e-04

First immunoglobulin (Ig) variable (V) domain of rat MRC OX-2 antigen, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of rat MRC OX-2 antigen (also known as CD200) and similar proteins. MRC OX-2 is a membrane glycoprotein expressed in a variety of lymphoid and non-lymphoid cells in rats. It has a similar broad distribution pattern in humans. MRC OX-2 may regulate myeloid cell activity. The protein has an extracellular portion containing two Ig-like domains, a transmembrane portion, and a cytoplasmic portion.


Pssm-ID: 409433  Cd Length: 108  Bit Score: 41.18  E-value: 1.39e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 193 SPQAVQVGGTASLHCD-VSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSI-------------GQLVLYNARPEDA 258
Cdd:cd05846   6 GDTRAVLGGNATLSCNlTLPEEVLQVTWQKIKASSPENIVTYSKKYGVKIQPSYvrrisftssglnsTSITIWNVTLEDE 85

                ....*
gi 16751923 259 GLYTC 263
Cdd:cd05846  86 GCYKC 90
Ig3_L1-CAM cd05876
Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here ...
200-280 1.44e-04

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.


Pssm-ID: 409460 [Multi-domain]  Cd Length: 83  Bit Score: 40.66  E-value: 1.44e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEkqshqRENLIMRPDQM-YGNVVVTsigqLVLYNARPEDAGLYTCTARNAAGLLRADFPL 278
Cdd:cd05876  10 GQSLVLECIAEGLPTPTVKWL-----RPSGPLPPDRVkYQNHNKT----LQLLNVGESDDGEYVCLAENSLGSARHAYYV 80

                ..
gi 16751923 279 SV 280
Cdd:cd05876  81 TV 82
Ig_Perlecan_like cd05743
Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan ...
200-271 1.50e-04

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.


Pssm-ID: 143220  Cd Length: 78  Bit Score: 40.55  E-value: 1.50e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 16751923 200 GGTASLHCDVSGRPPPAVTWekqshqRENLIMRPDQmyGNVVVTS---IGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd05743   1 GETVEFTCVATGVPTPIINW------RLNWGHVPDS--ARVSITSeggYGTLTIRDVKESDQGAYTCEAINTRGM 67
IgI_1_Contactin cd04967
First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; ...
201-274 1.65e-04

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409356 [Multi-domain]  Cd Length: 96  Bit Score: 40.69  E-value: 1.65e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 16751923 201 GTASLHCDVSGRPPPAVTWEKQSHQrenLIMRPDQMYGNVVvtsiGQLVLYN-ARPEDAGLYTCTARNAAGLLRA 274
Cdd:cd04967  20 KKVALNCRARANPVPSYRWLMNGTE---IDLESDYRYSLVD----GTLVISNpSKAKDAGHYQCLATNTVGSVLS 87
NTR_PCOLCE cd03576
NTR domain, PCOLCE subfamily; Procollagen C-endopeptidase enhancers (PCOLCEs) are ...
412-540 1.82e-04

NTR domain, PCOLCE subfamily; Procollagen C-endopeptidase enhancers (PCOLCEs) are extracellular matrix proteins that enhance the activity of procollagen C-proteases, by binding to the procollagen I C-peptide. They contain a C-terminal NTR domain, which have been suggested to possess inhibitory functions towards specific serine proteases but not towards metzincins, which are inhibited by the related TIMPs.


Pssm-ID: 239631  Cd Length: 124  Bit Score: 41.22  E-value: 1.82e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 412 PRTPPC-RACRLRSKLALSLCRSDFAIVGRLTEVLEEPEAAggIARVALEDVLKDDKMGL----KFLGTKYLEVtlsgmd 486
Cdd:cd03576   1 PTAALCqQKCRRTGTLESNYCSSEFVITGTVISMTRGPGSL--HATVSIIKLYKEGRLAItqagKTMSVKITVV------ 72
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 16751923 487 waCP-CPNMTAGdGPLVIMGEV-RDGVAVLDAGSYVRAASEKRvKKILELLEKQAC 540
Cdd:cd03576  73 --CKqCPLLRRG-LNYILMGQVdEEGRGVIPPESFVMLYKTKH-QKLLAALSNKKC 124
IgI_Twitchin_like cd20949
C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, ...
192-271 1.90e-04

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.


Pssm-ID: 409541 [Multi-domain]  Cd Length: 89  Bit Score: 40.39  E-value: 1.90e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenliMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd20949   6 AYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQP-----ISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80
Kunitz_collagen_alpha1_XXVIII cd22628
Kunitz-type domain from the alpha1 chain of type XXVIII collagen, and similar proteins; This ...
308-351 2.38e-04

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: 38.80  E-value: 2.38e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 16751923 308 GPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22628   8 GPCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51
IgI_2_JAM1 cd20950
Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF ...
194-270 2.41e-04

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.


Pssm-ID: 409542  Cd Length: 97  Bit Score: 40.38  E-value: 2.41e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 194 PQAVQVGGTASLHC-DVSGRPPPAVTWEKqshqrENLIMRPD----QMYGN---VVVTSIGQLVLYNARPEDAGLYTCTA 265
Cdd:cd20950   6 PSSATIGNRAVLTCsEPDGSPPSEYTWFK-----DGVVMPTNpkstRAFSNssySLDPTTGELVFDPLSASDTGEYSCEA 80

                ....*
gi 16751923 266 RNAAG 270
Cdd:cd20950  81 RNGYG 85
Kunitz_BmTI-like cd22604
Kunitz-type serine protease inhibitor 6 (BmTI-6), A (BmTI-A), and similar proteins; This group ...
299-351 3.07e-04

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: 38.97  E-value: 3.07e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 299 CLPdvQACTGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22604   6 CSP--TADSGPCFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56
IgI_APEG-1_like cd20975
Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and ...
186-280 3.12e-04

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409567  Cd Length: 91  Bit Score: 39.76  E-value: 3.12e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 186 PALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWekqshQRENLIMRPDQ-MYGNVVVTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd20975   1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSW-----LRNRQPVRPDQrRFAEEAEGGLCRLRILAAERGDAGFYTCK 75
                        90
                ....*....|....*.
gi 16751923 265 ARNAAGLLRADFPLSV 280
Cdd:cd20975  76 AVNEYGARQCEARLEV 91
IgI_1_NCAM-1_like cd04977
First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar ...
191-270 3.40e-04

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-nonNCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves the Ig1, Ig2, and Ig3 domains. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409366  Cd Length: 95  Bit Score: 39.93  E-value: 3.40e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPPpAVTWekQSHQRENLIMRpdqmYGNVVVTSIG----QLVLYNARPEDAGLYTCTAR 266
Cdd:cd04977   6 IPSYAEISVGESKFFLCKVSGDAK-NINW--VSPNGEKVLTK----HGNLKVVNHGsvlsSLTIYNANINDAGIYKCVAT 78

                ....
gi 16751923 267 NAAG 270
Cdd:cd04977  79 NGKG 82
IgI_1_NCAM-2 cd05866
First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the ...
197-270 3.46e-04

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-2 (OCAM/mamFas II, RNCAM). NCAM-2 is organized similarly to NCAM-1, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409452  Cd Length: 93  Bit Score: 40.03  E-value: 3.46e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 16751923 197 VQVGGTASLHCDVSGRPppaVTWEKQSHQRENLIMRPDQMYGNVVVTSigQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd05866  12 LSVGESKFFTCTAIGEP---ESIDWYNPQGEKIVSSQRVVVQKEGVRS--RLTIYNANIEDAGIYRCQATDAKG 80
Ig0_BSG1 cd20940
Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are ...
191-267 3.54e-04

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.


Pssm-ID: 409534  Cd Length: 116  Bit Score: 40.33  E-value: 3.54e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRENLI------MRPDQMYGNVVVT--SIGQLVLYNARPEDAGLYT 262
Cdd:cd20940   6 SPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEICsqlwdgARLDRVHINATYHqhATSTISIDNLTEEDTGTYE 85

                ....*
gi 16751923 263 CTARN 267
Cdd:cd20940  86 CRASN 90
Kunitz_amblin-like cd22638
Caenorhabditis elegans Kunitz domain 11 of papilin (also called abnormal cell migration ...
307-351 3.77e-04

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: 38.52  E-value: 3.77e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22638   7 TGPCRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51
Kunitz_papilin cd22635
Kunitz domain of papilin, and similar proteins; This model includes the Kunitz domain found in ...
317-351 3.93e-04

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: 38.40  E-value: 3.93e-04
                        10        20        30
                ....*....|....*....|....*....|....*
gi 16751923 317 WHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22635  18 WYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52
Ig2_PTK7 cd05760
Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here ...
185-270 4.74e-04

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.


Pssm-ID: 409417  Cd Length: 95  Bit Score: 39.53  E-value: 4.74e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQRenlimrPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd05760   1 PVVLKHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPL------SDGQGNYSVSSKERTLTLRSAGPDDSGLYYCC 74

                ....*.
gi 16751923 265 ARNAAG 270
Cdd:cd05760  75 AHNAFG 80
IgI_3_Contactin cd04968
Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) ...
199-270 5.27e-04

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409357 [Multi-domain]  Cd Length: 88  Bit Score: 39.07  E-value: 5.27e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 16751923 199 VGGTASLHCDVSGRPPPAVTWekqshqRENLIMRPDQMygnVVVTSIGQLVLYNARPEDAGLYTCTARNAAG 270
Cdd:cd04968  15 KGQTVTLECFALGNPVPQIKW------RKVDGSPSSQW---EITTSEPVLEIPNVQFEDEGTYECEAENSRG 77
Kunitz_ixolaris_1 cd22625
Kunitz-type domain 1 (K1) of Ixolaris, and similar proteins; This model includes the first ...
359-409 7.13e-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: 7.13e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 16751923 359 CVLPAVQG-PCRGWE-PRWAYSPLLQQCHPFVYGGCEGNGNNFHSRESCEDAC 409
Cdd:cd22625   1 CTLPIQEItTCESQPtKRYGYNKKTQQCEEFLGTECGGGGNSFEEAKECWSSC 53
Kunitz_HAI1_2-like cd22624
Kunitz domain 2 of hepatocyte growth factor activator inhibitor-1 (HAI1); This model includes ...
307-351 7.73e-04

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: 37.88  E-value: 7.73e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22624   8 TGPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETC 52
IgI_8_hMLCK_like cd05762
Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar ...
185-283 8.86e-04

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.


Pssm-ID: 409419  Cd Length: 99  Bit Score: 38.78  E-value: 8.86e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQSHQrenliMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd05762   1 PPQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQ-----IQEGEGIKIENTENSSKLTITEGQQEHCGCYTLE 75
                        90
                ....*....|....*....
gi 16751923 265 ARNAAGLLRADFPLSVVQR 283
Cdd:cd05762  76 VENKLGSRQAQVNLTVVDK 94
Ig_Semaphorin_C cd04979
Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are ...
190-268 9.23e-04

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.


Pssm-ID: 409368  Cd Length: 88  Bit Score: 38.59  E-value: 9.23e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 16751923 190 SSPSPQAVQVGGTASLHCDVSGRPPPaVTWekqSHQRENLimrPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNA 268
Cdd:cd04979   1 TSFKQISVKEGDTVILSCSVKSNNAP-VTW---IHNGKKV---PRYRSPRLVLKTERGLLIRSAQEADAGVYECHSGER 72
Kunitz_SmCI_3-like cd22603
third Kunitz domain of Carboxypeptidase Inhibitor SmCI and similar domains; This group ...
307-351 9.60e-04

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: 37.41  E-value: 9.60e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22603   9 TGPCKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53
Ig6_Contactin cd04970
Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth ...
191-280 1.04e-03

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.


Pssm-ID: 409359  Cd Length: 102  Bit Score: 38.69  E-value: 1.04e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPPPAVT--WEKQSH----QRENLIMRpdQMYGnvvVTSIGQLVLYNARPEDAGLYTCT 264
Cdd:cd04970   8 APSNADITVGENATLQCHASHDPTLDLTftWSFNGVpidlEKIEGHYR--RRYG---KDSNGDLEIVNAQLKHAGRYTCT 82
                        90
                ....*....|....*.
gi 16751923 265 ARNAAGLLRADFPLSV 280
Cdd:cd04970  83 AQTVVDSDSASATLVV 98
Kunitz_conkunitzin cd22593
conkunitzin-S1 and -S2, and similar proteins; This model includes Kunitz-type conkunitzin-S1 ...
317-351 1.06e-03

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: 37.20  E-value: 1.06e-03
                        10        20        30
                ....*....|....*....|....*....|....*
gi 16751923 317 WHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22593  17 WYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
116-155 1.06e-03

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 36.89  E-value: 1.06e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 16751923    116 CRDRCEKEPSFTCASDGLTYYNRCYMDAEACLRGLHLHIV 155
Cdd:smart00280   2 CPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVK 41
Ig_C5_MyBP-C cd05894
C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here ...
191-270 1.10e-03

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.


Pssm-ID: 409475  Cd Length: 86  Bit Score: 38.28  E-value: 1.10e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 191 SPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQshqrENLIMRPDqmyGNVVVTS---IGQLVLYNARPEDAGLYTCTARN 267
Cdd:cd05894   1 AENTIVVVAGNKLRLDVPISGEPAPTVTWSRG----DKAFTATE---GRVRVESykdLSSFVIEGAEREDEGVYTITVTN 73

                ...
gi 16751923 268 AAG 270
Cdd:cd05894  74 PVG 76
Ig3_Peroxidasin cd05745
Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the ...
200-280 1.21e-03

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.


Pssm-ID: 143222 [Multi-domain]  Cd Length: 74  Bit Score: 37.61  E-value: 1.21e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 200 GGTASLHCDVSGRPPPAVTWEKQSHQrenliMRPDQMYgnvVVTSIGQLVLYNARPEDAGLYTCTARNAAGLLRADFPLS 279
Cdd:cd05745   2 GQTVDFLCEAQGYPQPVIAWTKGGSQ-----LSVDRRH---LVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLT 73

                .
gi 16751923 280 V 280
Cdd:cd05745  74 V 74
IgI_NrCAM cd05874
Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); ...
185-270 1.32e-03

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.


Pssm-ID: 409458  Cd Length: 95  Bit Score: 38.43  E-value: 1.32e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQAVQVGGTASLHCDVSGRPPPAVTWEKQ-SH----QRENLIMRPDQmyGNVVVTSIGqlvlyNARPED-A 258
Cdd:cd05874   1 PTITHQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNgTHfdidKDPKVTMKPNT--GTLVINIMN-----GEKAEAyE 73
                        90
                ....*....|..
gi 16751923 259 GLYTCTARNAAG 270
Cdd:cd05874  74 GVYQCTARNERG 85
IgI_Myomesin_like_C cd05737
C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of ...
192-280 1.36e-03

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.


Pssm-ID: 319300  Cd Length: 92  Bit Score: 37.96  E-value: 1.36e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQshqrENLIMRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARNAAGL 271
Cdd:cd05737   8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKN----DQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGS 83

                ....*....
gi 16751923 272 LRADFPLSV 280
Cdd:cd05737  84 ETSDVTVSV 92
Ig4_Contactin-2-like cd05728
Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The ...
192-280 1.51e-03

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.


Pssm-ID: 143205 [Multi-domain]  Cd Length: 85  Bit Score: 37.96  E-value: 1.51e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 192 PSPQAVQVGGTASLHCDVSGRPPPAVTWEKQShQRENLIMRPDQMYGNVVVTsigQLVLynarpEDAGLYTCTARNAAGL 271
Cdd:cd05728   6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNG-QPLASENRIEVEAGDLRIT---KLSL-----SDSGMYQCVAENKHGT 76

                ....*....
gi 16751923 272 LRADFPLSV 280
Cdd:cd05728  77 IYASAELAV 85
Kunitz_TFPI2_1-like cd22616
Kunitz domain 1 (KD1) of tissue factor pathway inhibitor 2 (TFPI2) and similar proteins; This ...
317-353 2.10e-03

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: 36.45  E-value: 2.10e-03
                        10        20        30
                ....*....|....*....|....*....|....*..
gi 16751923 317 WHYDPQRGGCMTFPARGCDGAARGFETYEACQQACAR 353
Cdd:cd22616  21 YYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTCWR 57
IgI_1_Contactin-1 cd05849
First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; ...
201-274 2.13e-03

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.


Pssm-ID: 409436 [Multi-domain]  Cd Length: 95  Bit Score: 37.63  E-value: 2.13e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 16751923 201 GTASLHCDVSGRPPPAVTWEKQSHQRENLIMRPDQMYGNVVVTSigqlvlyNARPEDAGLYTCTARNAAGLLRA 274
Cdd:cd05849  20 GKVSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINN-------PDKYKDAGRYVCIVSNIYGKVRS 86
Kunitz_ABPP-like cd22607
Kunitz domain found in the amyloid-beta precursor protein (ABPP) subfamily; This subfamily ...
304-351 2.26e-03

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: 36.25  E-value: 2.26e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 16751923 304 QACTGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22607   5 QAETGPCRAMMPRWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52
IgI_Lingo-1 cd20969
Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing ...
185-280 2.89e-03

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.


Pssm-ID: 409561  Cd Length: 92  Bit Score: 37.37  E-value: 2.89e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 185 PPALYSSPSPQA-VQVGGTASLHCDVSGRPPPAVTWekqSHQRENLIMRPDQmyGNVVVTSIGQLVLYNARPEDAGLYTC 263
Cdd:cd20969   1 RAAIRDRKAQQVfVDEGHTVQFVCRADGDPPPAILW---LSPRKHLVSAKSN--GRLTVFPDGTLEVRYAQVQDNGTYLC 75
                        90
                ....*....|....*..
gi 16751923 264 TARNAAGLLRADFPLSV 280
Cdd:cd20969  76 IAANAGGNDSMPAHLHV 92
IgI_L1-CAM_like cd05733
Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; ...
204-270 2.94e-03

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.


Pssm-ID: 409396 [Multi-domain]  Cd Length: 94  Bit Score: 37.00  E-value: 2.94e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16751923 204 SLHCDVSGRPPPAVTWEKQS-----HQRENLIMRPDQmyGNVVVTSigqlvlYNARPED-AGLYTCTARNAAG 270
Cdd:cd05733  20 TIKCEAKGNPQPTFRWTKDGkffdpAKDPRVSMRRRS--GTLVIDN------HNGGPEDyQGEYQCYASNELG 84
Kunitz_papilin_mig6-like cd22637
Drosophila melanogaster Kunitz domains 5, 6, 7, and Caenorhabditis elegans Kunitz domain 5 of ...
307-351 4.22e-03

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: 35.41  E-value: 4.22e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQAC 351
Cdd:cd22637   7 TGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51
IgI_M-protein_C cd05891
C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily ...
194-280 4.96e-03

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.


Pssm-ID: 143299  Cd Length: 92  Bit Score: 36.43  E-value: 4.96e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 194 PQAVQV--GGTASLHCDVSGRPPPAVTWEKQSHQREnlimrPDQMYgnVVVTSIGQ---LVLYNARPEDAGLYTCTARNA 268
Cdd:cd05891   8 PDVVTImeGKTLNLTCTVFGNPDPEVIWFKNDQDIE-----LSEHY--SVKLEQGKyasLTIKGVTSEDSGKYSINVKNK 80
                        90
                ....*....|..
gi 16751923 269 AGLLRADFPLSV 280
Cdd:cd05891  81 YGGETVDVTVSV 92
IgI_SALM5_like cd05764
Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; ...
200-280 7.78e-03

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.


Pssm-ID: 409421 [Multi-domain]  Cd Length: 88  Bit Score: 35.91  E-value: 7.78e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16751923 200 GGTASLHCDVSGRPPPAVTWekqshqrenlIMRPDQMYGNVVVTSI---GQLVLYNARPEDAGLYTCTARNAAGLLRADF 276
Cdd:cd05764  15 GQRATLRCKARGDPEPAIHW----------ISPEGKLISNSSRTLVydnGTLDILITTVKDTGAFTCIASNPAGEATARV 84

                ....
gi 16751923 277 PLSV 280
Cdd:cd05764  85 ELHI 88
Kunitz_collagen_alpha6_VI cd22630
Kunitz-type domain from the alpha6 chain of human type VI collagen, and similar proteins; This ...
307-353 8.23e-03

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: 34.89  E-value: 8.23e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 16751923 307 TGPTSPHLVLWHYDPQRGGCMTFPARGCDGAARGFETYEACQQACAR 353
Cdd:cd22630   9 EGECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALCVK 55
IgI_Perlecan_like cd05754
Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of ...
192-267 8.87e-03

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.


Pssm-ID: 409412  Cd Length: 85  Bit Score: 35.61  E-value: 8.87e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 16751923 192 PSPQAVQVGGTASLHCD-VSGRPPPAVTWEkqshqrenlimRPDQMYGNVVVTSIGQLVLYNARPEDAGLYTCTARN 267
Cdd:cd05754   8 PRSQEVRPGADVSFICRaKSKSPAYTLVWT-----------RVNGTLPSRAMDFNGILTIRNVQLSDAGTYVCTGSN 73
 
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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