NCBI Conserved Domain Search

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 231.35 E-value: 1.35e-69

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGGGTH 112
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  113 TGRGLDFMLRNHFVEASGSRAGqkVPQIAVVITDGKSQDTVESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPHSQHV 192
Cdd:cd01472    81 TGKALKYVRENLFTEASGSREG--VPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKELYV 158


                  ....*.
gi 657584104  193 YSVSDF 198
Cdd:cd01472   159 FNVADF 164

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 224.47 E-value: 3.77e-67

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGGGTH 112
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  113 TGRGLDFMLRNHFVEASGSRAGqkVPQIAVVITDGKSQDTVESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPHSQHV 192
Cdd:cd01482    81 TGKALTHVREKNFTPDAGARPG--VPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSETHV 158


                  ....*.
gi 657584104  193 YSVSDF 198
Cdd:cd01482   159 FNVADF 164

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 216.37 E-value: 3.96e-64

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    34 DIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGGGT-H 112
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRYLGGGTtN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   113 TGRGLDFMLRNHFVEASGSRAGqkVPQIAVVITDGKSQDT-VESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPHSQH 191
Cdd:pfam00092   81 TGKALKYALENLFSSAAGARPG--APKVVVLLTDGRSQDGdPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPGEGH 158

                          170
                   ....*....|....*
gi 657584104   192 VYSVSDFAALQGISQ 206
Cdd:pfam00092  159 VFTVSDFEALEDLQD 173

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 213.63 E-value: 1.97e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGGTE 315
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  316 TGEAIDFLMNQYFTEDAGSRAKqrVPQIAVVITDGDSTDDVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPPKRFM 395
Cdd:cd01472    81 TGKALKYVRENLFTEASGSREG--VPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKELYV 158


                  ....*
gi 657584104  396 FTIDN 400
Cdd:cd01472   159 FNVAD 163

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 211.38 E-value: 1.24e-62

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGGTE 315
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  316 TGEAIDFLMNQYFTEDAGSRAkqRVPQIAVVITDGDSTDDVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPPKRFM 395
Cdd:cd01482    81 TGKALTHVREKNFTPDAGARP--GVPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSETHV 158


                  ....*.
gi 657584104  396 FTIDNY 401
Cdd:cd01482   159 FNVADF 164

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 196.34 E-value: 3.76e-57

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   237 DIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGGT-E 315
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRYLGGGTtN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   316 TGEAIDFLMNQYFTEDAGSRAkqRVPQIAVVITDGDSTD-DVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPPKRF 394
Cdd:pfam00092   81 TGKALKYALENLFSSAAGARP--GAPKVVVLLTDGRSQDgDPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPGEGH 158

                          170
                   ....*....|....*
gi 657584104   395 MFTIDNYEALQRLTE 409
Cdd:pfam00092  159 VFTVSDFEALEDLQD 173

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 194.75 E-value: 9.17e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDrpaDQAQQVYLNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSD---DPRTEFYLNTYRSKDDVLEAVKNLRYIGG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 GTNTGAALKFARESVFIKERGSRKdkGVQQVAVVITDGESQDDVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASHPPN 781
Cdd:cd01472    78 GTNTGKALKYVRENLFTEASGSRE--GVPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKE 155


                  ....*....
gi 657584104  782 KHVFIVDSF 790
Cdd:cd01472   156 LYVFNVADF 164

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 196.45 E-value: 1.66e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGGGTH 112
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  113 TGRGLDFMLRNHFVEASGSRAG-QKVPQIAVVITDGKSQDTVESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPHSQH 191
Cdd:cd01475    83 TGLAIQYAMNNAFSEAEGARPGsERVPRVGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEPLADH 162

                         170       180
                  ....*....|....*....|....*..
gi 657584104  192 VYSVSDFAALQGISQSIVQTLCTTVEE 218
Cdd:cd01475   163 VFYVEDFSTIEELTKKFQGKICVVPDL 189

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 189.07 E-value: 8.90e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGG-GT 111
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRLRGGsQL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  112 HTGRGLDFMLRNHFVEASGSRAGQKVPQIAVVITDGKSQDTVESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPhsQH 191
Cdd:cd01481    81 NTGSALDYVVKNLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDP--SF 158


                  ....*..
gi 657584104  192 VYSVSDF 198
Cdd:cd01481   159 VFQVSDF 165

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 187.48 E-value: 3.81e-54

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDrpaDQAQQVYLNTFNNKDELLKFIKILPYHGGG 702
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSS---DVRTEFPLNDYSSKEELLSAVDNLRYLGGG 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   703 T-NTGAALKFARESVFIKERGSRkdKGVQQVAVVITDGESQD-DVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASHPP 780
Cdd:pfam00092   78 TtNTGKALKYALENLFSSAAGAR--PGAPKVVVLLTDGRSQDgDPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPG 155

                          170
                   ....*....|....*...
gi 657584104   781 NKHVFIVDSFAKLKSMEQ 798
Cdd:pfam00092  156 EGHVFTVSDFEALEDLQD 173

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 186.72 E-value: 6.31e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPAdqaQQVYLNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPR---TEFDLNAYTSKEDVLAAIKNLPYKGG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 GTNTGAALKFARESVFIKERGSRKdkGVQQVAVVITDGESQDDVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASHPPN 781
Cdd:cd01482    78 NTRTGKALTHVREKNFTPDAGARP--GVPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSE 155


                  ....*....
gi 657584104  782 KHVFIVDSF 790
Cdd:cd01482   156 THVFNVADF 164

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 184.42 E-value: 2.93e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGG-GT 111
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGgGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  112 HTGRGLDFMLRNHFveaSGSRAGQKVPQIAVVITDGKSQD--TVESHAEELRKRGIVLYAIGIKDADEDQLKEIANKPHS 189
Cdd:cd01450    81 NTGKALQYALEQLF---SESNARENVPKVIIVLTDGRSDDggDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSE 157


                  ....
gi 657584104  190 QHVY 193
Cdd:cd01450   158 RHVF 161

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 178.29 E-value: 5.85e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTG-GT 314
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRLRGGsQL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  315 ETGEAIDFLMNQYFTEDAGSRAKQRVPQIAVVITDGDSTDDVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPpkRF 394
Cdd:cd01481    81 NTGSALDYVVKNLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDP--SF 158


                  ....*..
gi 657584104  395 MFTIDNY 401
Cdd:cd01481   159 VFQVSDF 165

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 173.63 E-value: 1.63e-49

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTG-GT 314
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGgGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  315 ETGEAIDFLMNQYFTEdagSRAKQRVPQIAVVITDGDSTD--DVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPPK 392
Cdd:cd01450    81 NTGKALQYALEQLFSE---SNARENVPKVIIVLTDGRSDDggDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSE 157


                  ....
gi 657584104  393 RFMF 396
Cdd:cd01450   158 RHVF 161

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 173.25 E-value: 2.40e-49

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPADqaqQVYLNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRV---EFSLNDYKSKDDLLKAVKNLKYLGG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 -GTNTGAALKFARESVFIKergSRKDKGVQQVAVVITDGESQD--DVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASH 778
Cdd:cd01450    78 gGTNTGKALQYALEQLFSE---SNARENVPKVIIVLTDGRSDDggDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASC 154


                  ....*..
gi 657584104  779 PPNKHVF 785
Cdd:cd01450   155 PSERHVF 161

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 171.48 E-value: 1.61e-48

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104     34 DIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPY-MGGGTH 112
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSYkLGGGTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    113 TGRGLDFMLRNHFVEASGSRAGqkVPQIAVVITDGKSQDTVESH---AEELRKRGIVLYAIGIK-DADEDQLKEIANKPH 188
Cdd:smart00327   81 LGAALQYALENLFSKSAGSRRG--APKVVILITDGESNDGPKDLlkaAKELKRSGVKVFVVGVGnDVDEEELKKLASAPG 158

                           170
                    ....*....|....*..
gi 657584104    189 SQHVYSVSDFAALQGIS 205
Cdd:smart00327  159 GVYVFLPELLDLLIDLL 175

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 168.61 E-value: 1.49e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGGGT-H 1097
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRYLGGGTtN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1098 TGEAITDV-SQYFDSSRGGRPGLRQRLVVITDGEAQDV-VRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPD--RMY 1173
Cdd:pfam00092   81 TGKALKYAlENLFSSAAGARPGAPKVVVLLTDGRSQDGdPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPGegHVF 160

                          170
                   ....*....|....
gi 657584104  1174 AERDFDALKDLESQ 1187
Cdd:pfam00092  161 TVSDFEALEDLQDQ 174

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 167.84 E-value: 2.91e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1398 DLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGGGT-N 1476
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRYLGGGTtN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1477 IGLALDS-IREYFEASRGCRRsaGISQNLVLITDGESQD-DVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTP--ER 1552
Cdd:pfam00092   81 TGKALKYaLENLFSSAAGARP--GAPKVVVLLTDGRSQDgDPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPgeGH 158

                          170
                   ....*....|...
gi 657584104  1553 LFTVENFGSLEKI 1565
Cdd:pfam00092  159 VFTVSDFEALEDL 171

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 165.64 E-value: 9.51e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGGTE 315
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  316 TGEAIDFLMNQYFTEDAGSR-AKQRVPQIAVVITDGDSTDDVAAPALRLRQHGVIMFAIGVGKANPTELEAIANRPPKRF 394
Cdd:cd01475    83 TGLAIQYAMNNAFSEAEGARpGSERVPRVGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEPLADH 162

                         170       180
                  ....*....|....*....|..
gi 657584104  395 MFTIDNYEALQRLTEGLLQTVC 416
Cdd:cd01475   163 VFYVEDFSTIEELTKKFQGKIC 184

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 160.86 E-value: 6.86e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGGGTE 911
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  912 TGRALAFMSPHFDRAMTTRGHKVPEYLVVITDGKSSDKVKVPAEQLRAQGVIVYSIGVKSADMEELREISGDPKRT--FF 989
Cdd:cd01472    81 TGKALKYVRENLFTEASGSREGVPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKELyvFN 160


                  ....
gi 657584104  990 VNNF 993
Cdd:cd01472   161 VADF 164

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 160.90 E-value: 8.87e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1206 DIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLR-SPFGDTY 1284
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRyLGGGTTN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1285 TGKALAYSLQ-FFDAQHGGRAalQVPQILMVITDGDATDrNSLVAPSVALRDHGVSVFSIGVEGANMTQLEIMAGYDRSK 1363
Cdd:pfam00092   81 TGKALKYALEnLFSSAAGARP--GAPKVVVLLTDGRSQD-GDPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPGEG 157

                          170
                   ....*....|....*..
gi 657584104  1364 -VFYVDNFEALETLYKN 1379
Cdd:pfam00092  158 hVFTVSDFEALEDLQDQ 174

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 159.38 E-value: 1.98e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGG-GTH 1097
Cdd:cd01450     2 DIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGgGTN 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104 1098 TGEAITDVSQYFDSSRGGRPGLRQRLVVITDGEAQDV--VRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPDR 1171
Cdd:cd01450    82 TGKALQYALEQLFSESNARENVPKVIIVLTDGRSDDGgdPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSE 157

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 158.60 E-value: 3.65e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGGGTN 1476
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1477 IGLALDSIRE-YFEASRGCRRsaGISQNLVLITDGESQDDVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTPER--L 1553
Cdd:cd01482    81 TGKALTHVREkNFTPDAGARP--GVPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSEthV 158


                  ....*.
gi 657584104 1554 FTVENF 1559
Cdd:cd01482   159 FNVADF 164

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 167.39 E-value: 6.01e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1794 GHEGIRGSRGLPGSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPQGVQGCSGRRGVKGFRGLRGNRGEDGEDGLDGVDGE 1873
Cdd:NF038329  132 GEQGPRGDRGETGPAGPAGPPGPQGERGEKGPAGPQGEAGPQGPAGKDGEAGAKGPAGEKGPQGPRGETGPAGEQGPAGP 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1874 QGLTGADGGRGERGNPGNPGipgirgeaglKGQRGLRGDPGEPGADnnspgakGDSGNAGLPGLPGPDGRPGESGIVGNP 1953
Cdd:NF038329  212 AGPDGEAGPAGEDGPAGPAG----------DGQQGPDGDPGPTGED-------GPQGPDGPAGKDGPRGDRGEAGPDGPD 274

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1954 GQDGRRGSPgvkgaagepgaaglqGIPGASGPQGTRGVRGQPGPRgipglpgpqggpgsvggpgaagrrggnGQKGQPGD 2033
Cdd:NF038329  275 GKDGERGPV---------------GPAGKDGQNGKDGLPGKDGKD---------------------------GQNGKDGL 312

                         250       260
                  ....*....|....*....|...
gi 657584104 2034 PGDKGVPGPLGPRGMPGEDGRDG 2056
Cdd:NF038329  313 PGKDGKDGQPGKDGLPGKDGKDG 335

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 158.00 E-value: 9.35e-44

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPADqaqQVYLNTFNNKDELLKFIKILPYH-GG 701
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARV---LFPLNDSRSKDALLEALASLSYKlGG 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    702 GTNTGAALKFARESVFIKERGSRkdKGVQQVAVVITDGESQD---DVSQPAADLRRAGVTIYSVGVKNA-NKVQLVEMAS 777
Cdd:smart00327   78 GTNLGAALQYALENLFSKSAGSR--RGAPKVVILITDGESNDgpkDLLKAAKELKRSGVKVFVVGVGNDvDEEELKKLAS 155

                           170
                    ....*....|....*.
gi 657584104    778 HPPNKHVFIVDSFAKL 793
Cdd:smart00327  156 APGGVYVFLPELLDLL 171

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 156.46 E-value: 2.63e-43

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    237 DIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGG-TE 315
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSYKLGGgTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    316 TGEAIDFLMNQYFTEDAGSRAkqRVPQIAVVITDGDSTD---DVAAPALRLRQHGVIMFAIGVGKA-NPTELEAIANRPP 391
Cdd:smart00327   81 LGAALQYALENLFSKSAGSRR--GAPKVVILITDGESNDgpkDLLKAAKELKRSGVKVFVVGVGNDvDEEELKKLASAPG 158

                           170
                    ....*....|....*.
gi 657584104    392 KRFMFTIDNYEALQRL 407
Cdd:smart00327  159 GVYVFLPELLDLLIDL 174

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 165.46 E-value: 2.85e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1806 GSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPQGVQGCSGRRGVKGFRGLRGNRGEDGEDGLDGVDGEQGLTGADGGRGE 1885
Cdd:NF038329  117 GEKGEPGPAGPAGPAGEQGPRGDRGETGPAGPAGPPGPQGERGEKGPAGPQGEAGPQGPAGKDGEAGAKGPAGEKGPQGP 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1886 RGNPGNPGIPGIRGEAGLKGQRGLRGDPGEPGadnnsPGAKGDSGNAGLPGlpgPDGRPGESGIVGNPGQDGRRGSPGVk 1965
Cdd:NF038329  197 RGETGPAGEQGPAGPAGPDGEAGPAGEDGPAG-----PAGDGQQGPDGDPG---PTGEDGPQGPDGPAGKDGPRGDRGE- 267

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1966 gaagepgaaglqgiPGASGPqgtrgvRGQPGPRgipglpgpqggpgsvggpgaagrrggngqkgqpGDPGDKGVPGPLGP 2045
Cdd:NF038329  268 --------------AGPDGP------DGKDGER---------------------------------GPVGPAGKDGQNGK 294

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 657584104 2046 RGMPGEDGRDGY-GPAGRKGVKGDPGFPGYPGLLGEDGLQGPKGLP 2090
Cdd:NF038329  295 DGLPGKDGKDGQnGKDGLPGKDGKDGQPGKDGLPGKDGKDGQPGKP 340

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 155.46 E-value: 3.92e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGGGTN 1476
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1477 IGLALDSIRE-YFEASrgCRRSAGISQNLVLITDGESQDDVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTPERLFt 1555
Cdd:cd01472    81 TGKALKYVREnLFTEA--SGSREGVPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKELY- 157


                  ....*..
gi 657584104 1556 VENFGSL 1562
Cdd:cd01472   158 VFNVADF 164

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 157.16 E-value: 6.97e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYndrpADQAQQVY-LNTFNNKDELLKFIKILPYHG 700
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQY----SSTVKQEFpLGRFKSKADLKRAVRRMEYLE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  701 GGTNTGAALKFARESVFIKERGSRK-DKGVQQVAVVITDGESQDDVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASHP 779
Cdd:cd01475    79 TGTMTGLAIQYAMNNAFSEAEGARPgSERVPRVGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEP 158

                         170       180
                  ....*....|....*....|....*.
gi 657584104  780 PNKHVFIVDSFAKLKSMEQSLQKILC 805
Cdd:cd01475   159 LADHVFYVEDFSTIEELTKKFQGKIC 184

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 154.40 E-value: 1.03e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPAdqaQQVYLNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPR---PEFYLNTHSTKADVLGAVRRLRLRGG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 -GTNTGAALKFARESVFIKERGSRKDKGVQQVAVVITDGESQDDVSQPAADLRRAGVTIYSVGVKNANKVQLVEMASHPp 780
Cdd:cd01481    78 sQLNTGSALDYVVKNLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDP- 156

                         170
                  ....*....|
gi 657584104  781 nKHVFIVDSF 790
Cdd:cd01481   157 -SFVFQVSDF 165

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 152.04 E-value: 1.05e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   833 DIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGGGT-E 911
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRYLGGGTtN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   912 TGRALAF-MSPHFDRAMTTRGHkVPEYLVVITDGKSSDK-VKVPAEQLRAQGVIVYSIGVKSADMEELREISGDP--KRT 987
Cdd:pfam00092   81 TGKALKYaLENLFSSAAGARPG-APKVVVLLTDGRSQDGdPEEVARELKSAGVTVFAVGVGNADDEELRKIASEPgeGHV 159

                          170
                   ....*....|
gi 657584104   988 FFVNNFDALK 997
Cdd:pfam00092  160 FTVSDFEALE 169

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 153.31 E-value: 1.87e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGGGTN 1476
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1477 IGLALD-SIREYFEASRGCR-RSAGISQNLVLITDGESQDDVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTP--ER 1552
Cdd:cd01475    83 TGLAIQyAMNNAFSEAEGARpGSERVPRVGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEPlaDH 162

                         170       180       190
                  ....*....|....*....|....*....|...
gi 657584104 1553 LFTVENFGSLEKIKQKVINTICkskPIRDPSAC 1585
Cdd:cd01475   163 VFYVEDFSTIEELTKKFQGKIC---VVPDLCAT 192

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 150.46 E-value: 2.22e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGGGTHT 1098
Cdd:cd01472     2 DIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTNT 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104 1099 GEAITDVS-QYFDSSRGGRPGLRQRLVVITDGEAQDVVRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPDRMYAE 1175
Cdd:cd01472    82 GKALKYVReNLFTEASGSREGVPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKNADEEELKQIASDPKELYVF 159

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 150.52 E-value: 2.39e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRSPFGD-T 1283
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGGgT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1284 YTGKALAYSLQFFDAQHGGRaaLQVPQILMVITDGDATDRNSLVAPSVALRDHGVSVFSIGVEGANMTQLEIMAGYDRSK 1363
Cdd:cd01450    81 NTGKALQYALEQLFSESNAR--ENVPKVIIVLTDGRSDDGGDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSER 158


                  ...
gi 657584104 1364 VFY 1366
Cdd:cd01450   159 HVF 161

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 146.28 E-value: 8.35e-40

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGGGTE 911
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  912 TGRALAFMSPHFDRAMTTRGHKVPEYLVVITDGKSSDKVKVPAEQLRAQGVIVYSIGVKSADMEELREISGDPKRT--FF 989
Cdd:cd01482    81 TGKALTHVREKNFTPDAGARPGVPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSEThvFN 160


                  ....
gi 657584104  990 VNNF 993
Cdd:cd01482   161 VADF 164

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 145.90 E-value: 9.37e-40

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGG-GT 1475
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGgGT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 657584104 1476 NIGLALDSIREYFEASRGCRRsaGISQNLVLITDGESQD--DVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTPER 1552
Cdd:cd01450    81 NTGKALQYALEQLFSESNARE--NVPKVIIVLTDGRSDDggDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSE 157

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 144.13 E-value: 5.98e-39

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQI-GGGTH 1097
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSYKlGGGTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1098 TGEAITDVSQY-FDSSRGGRPGLRQRLVVITDGEAQDV---VRGPAAALRAKGVVVYAIGVV-DANTTQLLEISGSPDRM 1172
Cdd:smart00327   81 LGAALQYALENlFSKSAGSRRGAPKVVILITDGESNDGpkdLLKAAKELKRSGVKVFVVGVGnDVDEEELKKLASAPGGV 160

                           170
                    ....*....|.
gi 657584104   1173 YA--ERDFDAL 1181
Cdd:smart00327  161 YVflPELLDLL 171

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 142.88 E-value: 1.58e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   34 DIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYMGGGTHT 113
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  114 GRGLDFMLRNHFVEASGSRAGQKvpQIAVVITDGKSQDTVESHA--EELRKRGIVLYAIGIKDA-----DEDQLKEIANK 186
Cdd:cd01469    82 ATAIQYVVTELFSESNGARKDAT--KVLVVITDGESHDDPLLKDviPQAEREGIIRYAIGVGGHfqrenSREELKTIASK 159

                         170
                  ....*....|....*...
gi 657584104  187 PHSQHVYSVSDFAALQGI 204
Cdd:cd01469   160 PPEEHFFNVTDFAALKDI 177

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 142.43 E-value: 1.66e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGG-GT 910
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGgGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  911 ETGRALAFMSPHFDRAMTTRGhKVPEYLVVITDGKSSD--KVKVPAEQLRAQGVIVYSIGVKSADMEELREISGDPKRTF 988
Cdd:cd01450    81 NTGKALQYALEQLFSESNARE-NVPKVIIVLTDGRSDDggDPKEAAAKLKDEGIKVFVVGVGPADEEELREIASCPSERH 159


                  ..
gi 657584104  989 FV 990
Cdd:cd01450   160 VF 161

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 142.37 E-value: 1.91e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRSPFGDTY 1284
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGTN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1285 TGKALAYSLQFFdAQHGGRAALQVPQILMVITDGDATDRnsLVAPSVALRDHGVSVFSIGVEGANMTQLEIMAgyDRSKV 1364
Cdd:cd01472    81 TGKALKYVRENL-FTEASGSREGVPKVLVVITDGKSQDD--VEEPAVELKQAGIEVFAVGVKNADEEELKQIA--SDPKE 155


                  ....*....
gi 657584104 1365 FYVDNFEAL 1373
Cdd:cd01472   156 LYVFNVADF 164

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 139.90 E-value: 2.02e-37

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1398 DLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMR-QLGGGTN 1476
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSyKLGGGTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1477 IGLALDSIREY-FEASRGCRRsaGISQNLVLITDGESQD---DVEDAAERLRALGIEVFAIGIGNVHDLELL-QITGTPE 1551
Cdd:smart00327   81 LGAALQYALENlFSKSAGSRR--GAPKVVILITDGESNDgpkDLLKAAKELKRSGVKVFVVGVGNDVDEEELkKLASAPG 158

                           170
                    ....*....|....*.
gi 657584104   1552 RLFTVENFGSLEKIKQ 1567
Cdd:smart00327  159 GVYVFLPELLDLLIDL 174

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 138.61 E-value: 3.59e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGG-GT 1475
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRLRGGsQL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1476 NIGLALDSIRE-YFEASRGCRRSAGISQNLVLITDGESQDDVEDAAERLRALGIEVFAIGIGNVHDLELLQITGTPERLF 1554
Cdd:cd01481    81 NTGSALDYVVKnLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDPSFVF 160


                  ....*
gi 657584104 1555 TVENF 1559
Cdd:cd01481   161 QVSDF 165

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 137.59 E-value: 1.02e-36

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1206 DIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLR-SPFGDTY 1284
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSyKLGGGTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1285 TGKALAYSLQ-FFDAQHGGRAalQVPQILMVITDGDATDRNSLVAPSV-ALRDHGVSVFSIGVEGA-NMTQLEIMAG-YD 1360
Cdd:smart00327   81 LGAALQYALEnLFSKSAGSRR--GAPKVVILITDGESNDGPKDLLKAAkELKRSGVKVFVVGVGNDvDEEELKKLASaPG 158

                           170
                    ....*....|....*.
gi 657584104   1361 RSKVFYVDNFEALETL 1376
Cdd:smart00327  159 GVYVFLPELLDLLIDL 174

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 136.72 E-value: 2.46e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  237 DIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRTGGTET 316
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  317 GEAIDFLMNQYFTEDAGSRAKqrVPQIAVVITDGDSTDDVAAPAL--RLRQHGVIMFAIGVGKA--NPT---ELEAIANR 389
Cdd:cd01469    82 ATAIQYVVTELFSESNGARKD--ATKVLVVITDGESHDDPLLKDVipQAEREGIIRYAIGVGGHfqRENsreELKTIASK 159

                         170
                  ....*....|....*
gi 657584104  390 PPKRFMFTIDNYEAL 404
Cdd:cd01469   160 PPEEHFFNVTDFAAL 174

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 133.95 E-value: 1.28e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRSPFGDTY 1284
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1285 TGKALAYSLQ-FFDAQHGGRAalQVPQILMVITDGDATDrnSLVAPSVALRDHGVSVFSIGVEGANMTQLEIMAGY-DRS 1362
Cdd:cd01482    81 TGKALTHVREkNFTPDAGARP--GVPKVVILITDGKSQD--DVELPARVLRNLGVNVFAVGVKDADESELKMIASKpSET 156


                  ....*...
gi 657584104 1363 KVFYVDNF 1370
Cdd:cd01482   157 HVFNVADF 164

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 134.02 E-value: 2.23e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGGGTHT 1098
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1099 GEAI-TDVSQYFDSSRGGRPGLRQRLVVITDGEAQDVVRGPAA--ALRAKGVVVYAIGVVDA-NTTQLLE----ISGSPD 1170
Cdd:cd01469    82 ATAIqYVVTELFSESNGARKDATKVLVVITDGESHDDPLLKDVipQAEREGIIRYAIGVGGHfQRENSREelktIASKPP 161

                         170
                  ....*....|....*.
gi 657584104 1171 RMYAER--DFDALKDL 1184
Cdd:cd01469   162 EEHFFNvtDFAALKDI 177

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 133.60 E-value: 2.30e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVDS--GISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRqrrLQTN 508
Cdd:cd01481     1 KDIVFLIDGsdNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLR---LRGG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  509 EPRNLGSALQYASANFFTSEAGSRADQGYRQYLVVLSGKDSDDEVFRQSRLIKSEGVTVVGM-SLGASMNEIRVISTAP- 586
Cdd:cd01481    78 SQLNTGSALDYVVKNLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIgARNADLAELQQIAFDPs 157


                  ....
gi 657584104  587 YAYQ 590
Cdd:cd01481   158 FVFQ 161

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 132.19 E-value: 8.28e-35

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    833 DIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQI-GGGTE 911
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSYKlGGGTN 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    912 TGRALAF-MSPHFDRAMTTRGHkVPEYLVVITDGKSSDK---VKVPAEQLRAQGVIVYSIGVKSA-DMEELREISGDPKR 986
Cdd:smart00327   81 LGAALQYaLENLFSKSAGSRRG-APKVVILITDGESNDGpkdLLKAAKELKRSGVKVFVVGVGNDvDEEELKKLASAPGG 159

                           170
                    ....*....|....*
gi 657584104    987 TFFVNNFDALKPIKD 1001
Cdd:smart00327  160 VYVFLPELLDLLIDL 174

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 131.53 E-value: 9.01e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPY-MGGGT 111
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKKgLGGGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  112 HTGRGLDFMLRNHFVEASGSRagqkvPQIAVVITDGKSQD---TVESHAEELRKRGIVLYAIGIKD-ADEDQLKEIANKP 187
Cdd:cd00198    81 NIGAALRLALELLKSAKRPNA-----RRVIILLTDGEPNDgpeLLAEAARELRKLGITVYTIGIGDdANEDELKEIADKT 155


                  ....*.
gi 657584104  188 HSQHVY 193
Cdd:cd00198   156 TGGAVF 161

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: 127.34 E-value: 9.96e-35

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22631     1 CLLGQDAGSCQNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 130.48 E-value: 2.36e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGGGTHT 1098
Cdd:cd01482     2 DIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTRT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1099 GEAITDVSQ-YFDSSRGGRPGLRQRLVVITDGEAQDVVRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPDRMYAER- 1176
Cdd:cd01482    82 GKALTHVREkNFTPDAGARPGVPKVVILITDGKSQDDVELPARVLRNLGVNVFAVGVKDADESELKMIASKPSETHVFNv 161


                  ...
gi 657584104 1177 -DF 1178
Cdd:cd01482   162 aDF 164

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 131.35 E-value: 8.29e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1017 PGDLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGGGT 1096
Cdd:cd01475     2 PTDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1097 HTGEAIT---DVSqyFDSSRGGRPGlRQR----LVVITDGEAQDVVRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSP 1169
Cdd:cd01475    82 MTGLAIQyamNNA--FSEAEGARPG-SERvprvGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEP 158

                         170       180       190
                  ....*....|....*....|....*....|..
gi 657584104 1170 --DRMYAERDFDALKDLESQVALELCDPERDC 1199
Cdd:cd01475   159 laDHVFYVEDFSTIEELTKKFQGKICVVPDLC 190

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: 124.30 E-value: 1.26e-33

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22635     1 CLLDKDAGTVCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 129.04 E-value: 4.87e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGGGTE 911
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  912 TGRALAFMsphFDRAMT------TRGHKVPEYLVVITDGKSSDKVKVPAEQLRAQGVIVYSIGVKSADMEELREISGDP- 984
Cdd:cd01475    83 TGLAIQYA---MNNAFSeaegarPGSERVPRVGIVVTDGRPQDDVSEVAAKARALGIEMFAVGVGRADEEELREIASEPl 159

                         170       180
                  ....*....|....*....|....*...
gi 657584104  985 -KRTFFVNNFDALKPIKDDIITDICSTD 1011
Cdd:cd01475   160 aDHVFYVEDFSTIEELTKKFQGKICVVP 187

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 133.49 E-value: 1.65e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1882 GRGERGNPGNPGIPGIRGEAGLKGQRGLRGDPGEpgadnnspgaKGDSGNAGLPGLPGPDGRPGESGIVGNPGQDGRRGs 1961
Cdd:NF038329  115 GDGEKGEPGPAGPAGPAGEQGPRGDRGETGPAGP----------AGPPGPQGERGEKGPAGPQGEAGPQGPAGKDGEAG- 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1962 pgvkgaagepgaagLQGIPGASGPQGTRGVRGQPGPRgipglpgpqggpgsvggpgaagrrggngqkGQPGDPGDKGVPG 2041
Cdd:NF038329  184 --------------AKGPAGEKGPQGPRGETGPAGEQ------------------------------GPAGPAGPDGEAG 219

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2042 PLGPRGMPGEDGRDGYGPAGRKGVKGDPGFPGYPGLLGEDGLQGPKGLPgrkgnrgrggnsgrsgesGISGDPGYAGHRG 2121
Cdd:NF038329  220 PAGEDGPAGPAGDGQQGPDGDPGPTGEDGPQGPDGPAGKDGPRGDRGEA------------------GPDGPDGKDGERG 281


                  ....*.
gi 657584104 2122 PRGLPG 2127
Cdd:NF038329  282 PVGPAG 287

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 124.60 E-value: 2.64e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPadqAQQVYLNTFNNKDELLKFIK-ILPYHG 700
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNA---RVVLPLTTDTDKADLLEAIDaLKKGLG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  701 GGTNTGAALKFARESVFikergSRKDKGVQQVAVVITDGESQDD---VSQPAADLRRAGVTIYSVGVKN-ANKVQLVEMA 776
Cdd:cd00198    78 GGTNIGAALRLALELLK-----SAKRPNARRVIILLTDGEPNDGpelLAEAARELRKLGITVYTIGIGDdANEDELKEIA 152


                  ....*....
gi 657584104  777 SHPPNKHVF 785
Cdd:cd00198   153 DKTTGGAVF 161

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 124.36 E-value: 4.00e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRsPFGDT- 1283
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLR-LRGGSq 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1284 -YTGKALAY-SLQFFDAQHGGRAALQVPQILMVITDGDATDrnSLVAPSVALRDHGVSVFSIGVEGANMTQLEIMAgYDR 1361
Cdd:cd01481    80 lNTGSALDYvVKNLFTKSAGSRIEEGVPQFLVLITGGKSQD--DVERPAVALKRAGIVPFAIGARNADLAELQQIA-FDP 156


                  ....*....
gi 657584104 1362 SKVFYVDNF 1370
Cdd:cd01481   157 SFVFQVSDF 165

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 124.39 E-value: 4.23e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDRPadqaQQVY-LNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESF----RTEFtLNEYRTKEEPLSLVKHISQLLG 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 GTNTGAALKFARESVFIKERGSRKDkgVQQVAVVITDGESQDDVSQPAA--DLRRAGVTIYSVGV----KNANKVQ-LVE 774
Cdd:cd01469    78 LTNTATAIQYVVTELFSESNGARKD--ATKVLVVITDGESHDDPLLKDVipQAEREGIIRYAIGVgghfQRENSREeLKT 155

                         170       180
                  ....*....|....*....|.
gi 657584104  775 MASHPPNKHVFIVDSFAKLKS 795
Cdd:cd01469   156 IASKPPEEHFFNVTDFAALKD 176

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 123.20 E-value: 7.87e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGG-GT 910
Cdd:cd01481     1 KDIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRLRGGsQL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  911 ETGRALAF-MSPHFDRAMTTRGHK-VPEYLVVITDGKSSDKVKVPAEQLRAQGVIVYSIGVKSADMEELREISGDPKRTF 988
Cdd:cd01481    81 NTGSALDYvVKNLFTKSAGSRIEEgVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDPSFVF 160


                  ....*
gi 657584104  989 FVNNF 993
Cdd:cd01481   161 QVSDF 165

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: 116.16 E-value: 8.01e-31

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCL 2766
Cdd:cd22630     1 DACSLDQDEGECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALCV 54

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 118.27 E-value: 4.87e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQdYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTI--QKLEFPLNRFYSKGEMSKAIDDMQQIGGGT 1096
Cdd:cd01476     2 DLLFVLDSSGSVRGK-FEKYKKYIERIVEGLEIGPTATRVALITYSGRgrQRVRFNLPKHNDGEELLEKVDNLRFIGGTT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1097 HTGEAITDVSQYFDSSRGGRPGLRQRLVVITDGEAQDVVRGPAAALRA-KGVVVYAIGVVD---ANTTQLLEISGSPDRM 1172
Cdd:cd01476    81 ATGAAIEVALQQLDPSEGRREGIPKVVVVLTDGRSHDDPEKQARILRAvPNIETFAVGTGDpgtVDTEELHSITGNEDHI 160


                  .
gi 657584104 1173 Y 1173
Cdd:cd01476   161 F 161

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 118.05 E-value: 5.10e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIR-QIGGGT 910
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKkGLGGGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  911 ETGRALAFMSPHFDRAMTTRGHKVpeyLVVITDGKSSD---KVKVPAEQLRAQGVIVYSIGVKS-ADMEELREISGDPKR 986
Cdd:cd00198    81 NIGAALRLALELLKSAKRPNARRV---IILLTDGEPNDgpeLLAEAARELRKLGITVYTIGIGDdANEDELKEIADKTTG 157


                  ....
gi 657584104  987 TFFV 990
Cdd:cd00198   158 GAVF 161

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 118.05 E-value: 5.51e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQYRT-GGT 314
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKKGLgGGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  315 ETGEAIDFLMNQYFtedagSRAKQRVPQIAVVITDGDSTDD---VAAPALRLRQHGVIMFAIGVG-KANPTELEAIANRP 390
Cdd:cd00198    81 NIGAALRLALELLK-----SAKRPNARRVIILLTDGEPNDGpelLAEAARELRKLGITVYTIGIGdDANEDELKEIADKT 155


                  ....*.
gi 657584104  391 PKRFMF 396
Cdd:cd00198   156 TGGAVF 161

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 118.23 E-value: 6.02e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  833 DIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQIGGGTET 912
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  913 GRAL------AFmspHFDRAMTTRGHKVpeyLVVITDGKSSDKVKVPA--EQLRAQGVIVYSIGV-----KSADMEELRE 979
Cdd:cd01469    82 ATAIqyvvteLF---SESNGARKDATKV---LVVITDGESHDDPLLKDviPQAEREGIIRYAIGVgghfqRENSREELKT 155

                         170       180
                  ....*....|....*....|..
gi 657584104  980 ISGDPKRTFF--VNNFDALKPI 999
Cdd:cd01469   156 IASKPPEEHFfnVTDFAALKDI 177

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 115.79 E-value: 3.10e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVDS--GISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTn 508
Cdd:cd01472     1 ADIVFLVDGseSIGLSNFNLVKDFVKRVVERLDIGPDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRYIGGGT- 79

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 657584104  509 eprNLGSALQYASANFFTSEAGSRadQGYRQYLVVLSGKDSDDEVFRQSRLIKSEGVTVVGMSLG-ASMNEIRVISTAP 586
Cdd:cd01472    80 ---NTGKALKYVRENLFTEASGSR--EGVPKVLVVITDGKSQDDVEEPAVELKQAGIEVFAVGVKnADEEELKQIASDP 153

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 115.50 E-value: 4.35e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQIGG-GTH 1097
Cdd:cd01481     2 DIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGPDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRLRGGsQLN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1098 TGEAITDVSQ-YFDSSRGGR--PGLRQRLVVITDGEAQDVVRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPDRMYA 1174
Cdd:cd01481    82 TGSALDYVVKnLFTKSAGSRieEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARNADLAELQQIAFDPSFVFQ 161


                  ....
gi 657584104 1175 ERDF 1178
Cdd:cd01481   162 VSDF 165

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 116.72 E-value: 7.72e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRSPFGDTY 1284
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1285 TGKALAYSLQ--FFDAQhGGR-AALQVPQILMVITDGDATDRNSLVAPSValRDHGVSVFSIGVEGANMTQLEIMAGYDR 1361
Cdd:cd01475    83 TGLAIQYAMNnaFSEAE-GARpGSERVPRVGIVVTDGRPQDDVSEVAAKA--RALGIEMFAVGVGRADEEELREIASEPL 159

                         170       180
                  ....*....|....*....|....*
gi 657584104 1362 SK-VFYVDNFEALETLYKNITQVLC 1385
Cdd:cd01475   160 ADhVFYVEDFSTIEELTKKFQGKIC 184

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 113.91 E-value: 2.12e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   432 DIFFLVDS--GISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQrrlQTNE 509
Cdd:pfam00092    1 DIVFLLDGsgSIGGDNFEKVKEFLKKLVESLDIGPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRY---LGGG 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   510 PRNLGSALQYASANFFTSEAGSRAdqGYRQYLVVLS-GKDSDDEVFRQSRLIKSEGVTV--VGMSlGASMNEIRVISTAP 586
Cdd:pfam00092   78 TTNTGKALKYALENLFSSAAGARP--GAPKVVVLLTdGRSQDGDPEEVARELKSAGVTVfaVGVG-NADDEELRKIASEP 154

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 113.04 E-value: 2.67e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLR-SPFGDT 1283
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKkGLGGGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1284 YTGKALAYSLQFFDAQHGGRAalqvPQILMVITDGDATDRNSLVAPSVA-LRDHGVSVFSIGV-EGANMTQLEIMAGYDR 1361
Cdd:cd00198    81 NIGAALRLALELLKSAKRPNA----RRVIILLTDGEPNDGPELLAEAAReLRKLGITVYTIGIgDDANEDELKEIADKTT 156


                  ....*
gi 657584104 1362 SKVFY 1366
Cdd:cd00198   157 GGAVF 161

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 112.27 E-value: 4.81e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQ-QIGGGTH 1097
Cdd:cd00198     2 DIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKkGLGGGTN 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104 1098 TGEAITDVSQYFDSSRggRPGLRQRLVVITDGEAQDVVRGP---AAALRAKGVVVYAIGV-VDANTTQLLEISGSPDR 1171
Cdd:cd00198    82 IGAALRLALELLKSAK--RPNARRVIILLTDGEPNDGPELLaeaARELRKLGITVYTIGIgDDANEDELKEIADKTTG 157

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 112.45 E-value: 7.60e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1206 DIIFLVDGSTSITLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRSPFGDTYT 1285
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1286 GKALAYSL-QFFDAQHGGRAalQVPQILMVITDGDATD--RNSLVAPsvALRDHGVSVFSIGVEGA---NMTQLE---IM 1356
Cdd:cd01469    82 ATAIQYVVtELFSESNGARK--DATKVLVVITDGESHDdpLLKDVIP--QAEREGIIRYAIGVGGHfqrENSREElktIA 157

                         170       180
                  ....*....|....*....|
gi 657584104 1357 AGYDRSKVFYVDNFEALETL 1376
Cdd:cd01469   158 SKPPEEHFFNVTDFAALKDI 177

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 111.89 E-value: 7.66e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHI-FNMRQLGGGT 1475
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIdALKKGLGGGT 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 657584104 1476 NIGLALDSIREYFEAsrgcRRSAGISQNLVLITDGESQDD---VEDAAERLRALGIEVFAIGIGNVHDLELLQ 1545
Cdd:cd00198    81 NIGAALRLALELLKS----AKRPNARRVIILLTDGEPNDGpelLAEAARELRKLGITVYTIGIGDDANEDELK 149

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 109.80 E-value: 3.81e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGvANFQMVRTFLHSIISGLEISPTRVRVGIVMYNDrPADQAQQVYLNTFNNKDELLKFIKILPYHGG 701
Cdd:cd01476     1 LDLLFVLDSSGSVR-GKFEKYKKYIERIVEGLEIGPTATRVALITYSG-RGRQRVRFNLPKHNDGEELLEKVDNLRFIGG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  702 GTNTGAALKFAREsvfIKERGSRKDKGVQQVAVVITDGESQDDVSQPAADLRR-AGVTIYSVGVKNANKVQLVEMASHPP 780
Cdd:cd01476    79 TTATGAAIEVALQ---QLDPSEGRREGIPKVVVVLTDGRSHDDPEKQARILRAvPNIETFAVGTGDPGTVDTEELHSITG 155


                  ....*..
gi 657584104  781 N-KHVFI 786
Cdd:cd01476   156 NeDHIFT 162

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 108.26 E-value: 1.52e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTdYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQN--EFYLNQFYTEEAVSKHIFNMRQLGGG 1474
Cdd:cd01476     1 LDLLFVLDSSGSVRGK-FEKYKKYIERIVEGLEIGPTATRVALITYSGRGRQrvRFNLPKHNDGEELLEKVDNLRFIGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1475 TNIGLALDSIREYFEASRGCRRsaGISQNLVLITDGESQDDVEDAAERLRAL-GIEVFAIGIGN---VHDLELLQITGTP 1550
Cdd:cd01476    80 TATGAAIEVALQQLDPSEGRRE--GIPKVVVVLTDGRSHDDPEKQARILRAVpNIETFAVGTGDpgtVDTEELHSITGNE 157


                  ....*
gi 657584104 1551 ERLFT 1555
Cdd:cd01476   158 DHIFT 162

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: 103.42 E-value: 2.16e-26

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22639     1 CSLPKDRGPCRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVC 51

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: 103.60 E-value: 2.54e-26

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22629     1 DICKLPKDEGTCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 113.85 E-value: 5.94e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1903 LKGQRGLRGDpGEPGadnnSPGAKGDSGNAGLPGLPGPDGRPGESGIVGNPGQDGRRGSPGVkgaagepgaaglQGIPGA 1982
Cdd:NF038329  107 DEGLQQLKGD-GEKG----EPGPAGPAGPAGEQGPRGDRGETGPAGPAGPPGPQGERGEKGP------------AGPQGE 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1983 SGPQGTRGVRGQPGPRGIPGLPGPQGGPGSVGGPGAAGRRGGNGQKGQPGDPGDKGVPGPL-----GPRGMPGEDGRDGY 2057
Cdd:NF038329  170 AGPQGPAGKDGEAGAKGPAGEKGPQGPRGETGPAGEQGPAGPAGPDGEAGPAGEDGPAGPAgdgqqGPDGDPGPTGEDGP 249

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2058 ----GPAGRKGVKGDPGFPGYPGLLGEDGLQGPKGLPGRKGNRGRGGNSGRSGESGISGDPGYAGHRGPRGLPG 2127
Cdd:NF038329  250 qgpdGPAGKDGPRGDRGEAGPDGPDGKDGERGPVGPAGKDGQNGKDGLPGKDGKDGQNGKDGLPGKDGKDGQPG 323

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 105.17 E-value: 1.82e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGmENFEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRT--EFLLNTFQNKNDILQYVSKLPYMGGG 110
Cdd:cd01476     1 LDLLFVLDSSGSVR-GKFEKYKKYIERIVEGLEIGPTATRVALITYSGRGRQrvRFNLPKHNDGEELLEKVDNLRFIGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  111 THTGRGLDFMLrNHFVEASGSRAGqkVPQIAVVITDGKSQDTVESHAEELRKR-GIVLYAIGIKD---ADEDQLKEIANK 186
Cdd:cd01476    80 TATGAAIEVAL-QQLDPSEGRREG--IPKVVVVLTDGRSHDDPEKQARILRAVpNIETFAVGTGDpgtVDTEELHSITGN 156


                  ...
gi 657584104  187 PHS 189
Cdd:cd01476   157 EDH 159

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 104.02 E-value: 4.75e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGiSNFQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQ--EFLLKDHMDKQSLLAAVDTFQYRTGG 313
Cdd:cd01476     1 LDLLFVLDSSGSVR-GKFEKYKKYIERIVEGLEIGPTATRVALITYSGRGRQrvRFNLPKHNDGEELLEKVDNLRFIGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  314 TETGEAIDFLMnQYFTEDAGsrAKQRVPQIAVVITDGDSTDDVAAPALRLR-QHGVIMFAIGVG---KANPTELEAIANR 389
Cdd:cd01476    80 TATGAAIEVAL-QQLDPSEG--RREGIPKVVVVLTDGRSHDDPEKQARILRaVPNIETFAVGTGdpgTVDTEELHSITGN 156


                  ....*.
gi 657584104  390 PPKRFM 395
Cdd:cd01476   157 EDHIFT 162

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 102.82 E-value: 1.77e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFNMRQLGGGTNI 1477
Cdd:cd01469     2 DIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1478 GLALDSIR-EYFEASRGCRRSAgiSQNLVLITDGESQDD-----VEDAAERlraLGIEVFAIGIGNVHDL-----ELLQI 1546
Cdd:cd01469    82 ATAIQYVVtELFSESNGARKDA--TKVLVVITDGESHDDpllkdVIPQAER---EGIIRYAIGVGGHFQRensreELKTI 156

                         170       180
                  ....*....|....*....|.
gi 657584104 1547 TGTP--ERLFTVENFGSLEKI 1565
Cdd:cd01469   157 ASKPpeEHFFNVTDFAALKDI 177

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 101.60 E-value: 2.75e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVDS--GISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTN 508
Cdd:cd01450     1 LDIVFLLDGseSVGPENFEKVKDFIEKLVEKLDIGPDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNLKYLGGGGT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  509 eprNLGSALQYASANFFTseaGSRADQGYRQYLVVLS-GKDSDDE-VFRQSRLIKSEGVTVVGMSLG-ASMNEIRVISTA 585
Cdd:cd01450    81 ---NTGKALQYALEQLFS---ESNARENVPKVIIVLTdGRSDDGGdPKEAAAKLKDEGIKVFVVGVGpADEEELREIASC 154


                  .
gi 657584104  586 P 586
Cdd:cd01450   155 P 155

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 100.17 E-value: 8.14e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTdFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPN--LEFDLTDYSDAKSVEKAVEGIRQIGGG 909
Cdd:cd01476     1 LDLLFVLDSSGSVRGK-FEKYKKYIERIVEGLEIGPTATRVALITYSGRGRqrVRFNLPKHNDGEELLEKVDNLRFIGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  910 TETGRALAFMSPHFDRAMTTRgHKVPEYLVVITDGKSSDKVKVPAEQLRAQ-GVIVYSIGVK---SADMEELREISGDPK 985
Cdd:cd01476    80 TATGAAIEVALQQLDPSEGRR-EGIPKVVVVLTDGRSHDDPEKQARILRAVpNIETFAVGTGdpgTVDTEELHSITGNED 158


                  ....
gi 657584104  986 RTFF 989
Cdd:cd01476   159 HIFT 162

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: 96.18 E-value: 9.80e-24

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2715 CFLSQDQGS-CQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22635     1 CLLDKDAGTvCGDYVQRWYYDPATGACNRFWYGGCGGNANRFATEAECLRTC 52

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 100.54 E-value: 1.44e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVIS------GLDIGADKVRIGLAQYSDEPYQEF-LLKDHMDKQSLLAAVDTFQ 308
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAErflkdyYRKDPAGSWRVGVVQYSDQQEVEAgFLRDIRNYTSLKEAVDNLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  309 YRTGGTETGEAIDFLMNQYFTedaGSRAKQRvpQIAVVITDGDS---TDDVAAPALRLRQH-GVIMFAIGVGKANPTELE 384
Cdd:cd01480    83 YIGGGTFTDCALKYATEQLLE---GSHQKEN--KFLLVITDGHSdgsPDGGIEKAVNEADHlGIKIFFVAVGSQNEEPLS 157

                         170       180
                  ....*....|....*....|....*....
gi 657584104  385 AIANRPPK----------RFMFTIDNYEA 403
Cdd:cd01480   158 RIACDGKSalyrenfaelLWSFFIDDETA 186

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: 94.92 E-value: 2.58e-23

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd00109     1 CLLPPDPGPCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51

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: 94.25 E-value: 3.98e-23

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 657584104  2714 ACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:pfam00014    1 ICSLPPDSGPCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTC 52

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

Pssm-ID: 197529 Cd Length: 53 Bit Score: 93.48 E-value: 8.21e-23

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 657584104   2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:smart00131    1 DVCLLPPDTGPCGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53

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: 92.73 E-value: 1.40e-22

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22628     1 CLEPLDPGPCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 103.06 E-value: 2.13e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1796 EGIRGSRGLPGSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPqgvqgcsgrrgvkgfRGLRGNRGEDGEDGLDGVDGEQG 1875
Cdd:NF038329  232 DGQQGPDGDPGPTGEDGPQGPDGPAGKDGPRGDRGEAGPDGP---------------DGKDGERGPVGPAGKDGQNGKDG 296

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104 1876 LTGADGGRGERgnpGNPGIPGIRGEAGLKGQRGLrgdPGEPGADnnspgakgdsgnaGLPGLPGP 1940
Cdd:NF038329  297 LPGKDGKDGQN---GKDGLPGKDGKDGQPGKDGL---PGKDGKD-------------GQPGKPAP 342

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 96.69 E-value: 3.05e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSF------DVGPDHVRIGLVQYSTTPRTEF-LLNTFQNKNDILQYVSKLP 105
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAERFlkdyyrKDPAGSWRVGVVQYSDQQEVEAgFLRDIRNYTSLKEAVDNLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  106 YMGGGTHTGRGLDFMLRNhFVEASgsraGQKVPQIAVVITDGKSQ----DTVESHAEELRKRGIVLYAIGIKDADEDQLK 181
Cdd:cd01480    83 YIGGGTFTDCALKYATEQ-LLEGS----HQKENKFLLVITDGHSDgspdGGIEKAVNEADHLGIKIFFVAVGSQNEEPLS 157

                         170
                  ....*....|.
gi 657584104  182 EIANKPHSQHV 192
Cdd:cd01480   158 RIACDGKSALY 168

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 95.92 E-value: 5.48e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFR------ISPQHVRLGVAKYADSPNLEF-DLTDYSDAKSVEKAVEGIR 904
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAERFLkdyyrkDPAGSWRVGVVQYSDQQEVEAgFLRDIRNYTSLKEAVDNLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  905 QIGGGTETGRALAFMSphfDRAMTTRGHKVPEYLVVITDGKSS----DKVKVPAEQLRAQGVIVYSIGVKSADMEELREI 980
Cdd:cd01480    83 YIGGGTFTDCALKYAT---EQLLEGSHQKENKFLLVITDGHSDgspdGGIEKAVNEADHLGIKIFFVAVGSQNEEPLSRI 159

                         170
                  ....*....|....*...
gi 657584104  981 SGDPKRTFFVNNFDALKP 998
Cdd:cd01480   160 ACDGKSALYRENFAELLW 177

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: 88.95 E-value: 3.33e-21

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22637     1 CDQPKDTGPCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 93.22 E-value: 5.02e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   34 DIVFMVDGSWSIGMEN-FEQIRQFLHTLVNSFDVGPDHVRIGLVQYSTTPRTEFLLNTFQNKN-----DILQYVSKLPYM 107
Cdd:cd01471     2 DLYLLVDGSGSIGYSNwVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPNSTNkdlalNAIRALLSLYYP 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104  108 GGGTHTGRGLDfMLRNHFVEASGSRagQKVPQIAVVITDGKS---QDTVEShAEELRKRGIVLYAIGI 172
Cdd:cd01471    82 NGSTNTTSALL-VVEKHLFDTRGNR--ENAPQLVIIMTDGIPdskFRTLKE-ARKLRERGVIIAVLGV 145

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: 88.02 E-value: 5.66e-21

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:cd22639     1 CSLPKDRGP-CRNYTVKWYFDMAYGGCSRFWYGGCGGNGNRFDTEEECKAVCV 52

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

Pssm-ID: 438674 [Multi-domain] Cd Length: 51 Bit Score: 86.13 E-value: 2.53e-20

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22631     1 CLLGQDAG-SCQNYTMMWFFDSKQGRCSRFWYGGCGGNANRFETQEECENLC 51

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

Pssm-ID: 438633 Cd Length: 51 Bit Score: 86.06 E-value: 2.64e-20

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd00109     1 CLLPPDPG-PCRAYFPRWYYNSETGQCEEFIYGGCGGNANNFETKEECEATC 51

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 90.59 E-value: 3.01e-20

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    432 DIFFLVD-SG-ISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTNe 509
Cdd:smart00327    1 DVVFLLDgSGsMGGNRFELAKEFVLKLVEQLDIGPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASLSYKLGGGT- 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    510 prNLGSALQYASANFFTSEAGSRAdqGYRQYLVVLS-GKDSDD--EVFRQSRLIKSEGVTV--VGMSLGASMNEIRVIST 584
Cdd:smart00327   80 --NLGAALQYALENLFSKSAGSRR--GAPKVVILITdGESNDGpkDLLKAAKELKRSGVKVfvVGVGNDVDEEELKKLAS 155


                    ..
gi 657584104    585 AP 586
Cdd:smart00327  156 AP 157

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 90.91 E-value: 3.24e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIIS------GLEISPTRVRVGIVMYNDRPadQAQQVYLNTFNNKDELLKFIKI 695
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAErflkdyYRKDPAGSWRVGVVQYSDQQ--EVEAGFLRDIRNYTSLKEAVDN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  696 LPYHGGGTNTGAALKFARESVFIkerGSRkdKGVQQVAVVITDGESqdDVSQPAADLR------RAGVTIYSVGVKNANK 769
Cdd:cd01480    81 LEYIGGGTFTDCALKYATEQLLE---GSH--QKENKFLLVITDGHS--DGSPDGGIEKavneadHLGIKIFFVAVGSQNE 153

                         170
                  ....*....|....*
gi 657584104  770 VQLVEMASHPPNKHV 784
Cdd:cd01480   154 EPLSRIACDGKSALY 168

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 90.52 E-value: 3.68e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1017 PGDLLFLIDSSGSIYPQDYNKMKDFMKSVISKsFIGQN-------EVHVGVMQFSTIQKLEFPLNRFY-SKGEMSKAIDD 1088
Cdd:cd01480     2 PVDITFVLDSSESVGLQNFDITKNFVKRVAER-FLKDYyrkdpagSWRVGVVQYSDQQEVEAGFLRDIrNYTSLKEAVDN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1089 MQQIGGGTHTGEAITDVS-QYFDSSRGGRpglRQRLVVITDGEAQ--------DVVRGPAAAlrakGVVVYAIGVVDANT 1159
Cdd:cd01480    81 LEYIGGGTFTDCALKYATeQLLEGSHQKE---NKFLLVITDGHSDgspdggieKAVNEADHL----GIKIFFVAVGSQNE 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 657584104 1160 TQLLEISGSP-----DRMYAERDFDALKDLES 1186
Cdd:cd01480   154 EPLSRIACDGksalyRENFAELLWSFFIDDET 185

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 90.52 E-value: 3.97e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVAN-FQMVRTFLHSIISGLEISPTRVRVGIVMYNdrpADQAQQVYLNTFN--NKDELLKFI---KIL 696
Cdd:cd01471     2 DLYLLVDGSGSIGYSNwVTHVVPFLHTFVQNLNISPDEINLYLVTFS---TNAKELIRLSSPNstNKDLALNAIralLSL 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  697 PYHGGGTNTGAALKFARESVFiKERGSRKDkgVQQVAVVITDGESQDDVS--QPAADLRRAGVTIYSVGV 764
Cdd:cd01471    79 YYPNGSTNTTSALLVVEKHLF-DTRGNREN--APQLVIIMTDGIPDSKFRtlKEARKLRERGVIIAVLGV 145

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: 85.39 E-value: 6.32e-20

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 657584104  2641 RCQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:pfam00014    1 ICSLPPDSG-PCKASIPRWYYNPTTGTCEPFTYGGCGGNANNFESLEECESTCR 53

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 87.73 E-value: 2.04e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVDSG--ISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTN 508
Cdd:cd01482     1 ADIVFLVDGSwsIGRSNFNLVRSFLSSVVEAFEIGPDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPYKGGNTR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  509 EprnlGSALQYASANFFTSEAGSRAdqGYRQYLVVLSGKDSDDEVFRQSRLIKSEGVTV--VGMSlGASMNEIRVISTAP 586
Cdd:cd01482    81 T----GKALTHVREKNFTPDAGARP--GVPKVVILITDGKSQDDVELPARVLRNLGVNVfaVGVK-DADESELKMIASKP 153

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: 83.81 E-value: 2.08e-19

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:cd22630     3 CSLDQDEG-ECQNYVLKWYYDQEQKECSQFWYGGCGGNKNRFETQEECEALCV 54

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: 82.68 E-value: 5.37e-19

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22627     1 DPCLLPMDEGSCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53

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

Pssm-ID: 197529 Cd Length: 53 Bit Score: 82.31 E-value: 6.33e-19

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 657584104   2641 RCQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:smart00131    2 VCLLPPDTGP-CGGSIPRYYYDPETGTCEPFTYGGCGGNANNFESLEECERTC 53

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 85.79 E-value: 1.16e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  2159 ELVFGLDMSDDVTPTAFERQRSALLALLEEINIaesnCPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIALeRT 2238
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDI----GPDGTRVGLVQYSSDVRTEFPLNDYSSKEELLSAVDNLRY-LG 75

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 657584104  2239 SNKRHLGAAMHFVAQNVFKRVRSGMV-MRKVAVFFSNGPSQEvNDIPGAVMEYRGLNIVPAVI 2300
Cdd:pfam00092   76 GGTTNTGKALKYALENLFSSAAGARPgAPKVVVLLTDGRSQD-GDPEEVARELKSAGVTVFAV 137

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: 81.65 E-value: 1.26e-18

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22629     3 CKLPKDEG-TCRDFVLKWYYDPETKSCARFWYGGCGGNENRFDSQEECEKVC 53

von Willebrand factor type A domain;

Pssm-ID: 459670 [Multi-domain] Cd Length: 174 Bit Score: 84.25 E-value: 3.76e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  2369 DLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPQprragnQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLTQKM 2448
Cdd:pfam00092    1 DIVFLLDGSGSIGGDNFEKVKEFLKKLVESLDIGPD------GTRVGLVQYSS--DVRTEFPLNDYSSKEELLSAVDNLR 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  2449 RQQGGSSALGQTLDYTLkEVLLKAGQPSRKKALLAVV----GTSTAWEDQArlhyVSQKAKCEGVALFVVTVGDHYNRtQ 2524
Cdd:pfam00092   73 YLGGGTTNTGKALKYAL-ENLFSSAAGARPGAPKVVVlltdGRSQDGDPEE----VARELKSAGVTVFAVGVGNADDE-E 146

                          170
                   ....*....|....*..
gi 657584104  2525 VEELASLPLQQHLIHVS 2541
Cdd:pfam00092  147 LRKIASEPGEGHVFTVS 163

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 84.74 E-value: 3.97e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSF------KVSEDLVRVGLAQFSSNFQNEFYLNQFYTE-EAVSKHIFNMR 1469
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAERFlkdyyrKDPAGSWRVGVVQYSDQQEVEAGFLRDIRNyTSLKEAVDNLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1470 QLGGGTNIGLALDSIRE-YFEASRGCRRsagisQNLVLITDGESQ----DDVEDAAERLRALGIEVFAIGIGNVHDLELL 1544
Cdd:cd01480    83 YIGGGTFTDCALKYATEqLLEGSHQKEN-----KFLLVITDGHSDgspdGGIEKAVNEADHLGIKIFFVAVGSQNEEPLS 157

                         170
                  ....*....|....*...
gi 657584104 1545 QITGTPERLFTVENFGSL 1562
Cdd:cd01480   158 RIACDGKSALYRENFAEL 175

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: 80.09 E-value: 4.24e-18

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22637     1 CDQPKDTG-PCDNWVLKWYYDSKKGSCRQFYYGGCGGNDNRFDTEEECEARC 51

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: 77.71 E-value: 2.37e-17

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22628     1 CLEPLDPG-PCREYVVKWYYDKQANSCAQFWYGGCEGNRNRFETEEECRKTC 51

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: 76.40 E-value: 8.97e-17

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 657584104 2718 SQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22634    10 GGDGISCFAYIPSWSYNPDKNECEEFIYGGCGGNDNRFSTKAECEQKC 57

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 79.75 E-value: 1.02e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSiTLAKFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKS--VFTLNQYSSKKEVVKAISNLRSPFGD 1282
Cdd:cd01476     1 LDLLFVLDSSGS-VRGKFEKYKKYIERIVEGLEIGPTATRVALITYSGRGRQrvRFNLPKHNDGEELLEKVDNLRFIGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1283 TYTGKALAYSLQFFDAQHGGRAAlqVPQILMVITDGDATDrnSLVAPSVALRDH-GVSVFSIGV---EGANMTQLEIMAG 1358
Cdd:cd01476    80 TATGAAIEVALQQLDPSEGRREG--IPKVVVVLTDGRSHD--DPEKQARILRAVpNIETFAVGTgdpGTVDTEELHSITG 155


                  ....*..
gi 657584104 1359 YDRSKVF 1365
Cdd:cd01476   156 NEDHIFT 162

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 80.51 E-value: 1.12e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSI-YPQDYNKMKDFMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPLNRFYS--KGEMSKAIDDMQQI--- 1092
Cdd:cd01471     2 DLYLLVDGSGSIgYSNWVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPNStnKDLALNAIRALLSLyyp 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 657584104 1093 GGGTHTGEAITDVSQYFDSSRGGRPGLRQRLVVITDGEAQDVVRG--PAAALRAKGVVVYAIGV 1154
Cdd:cd01471    82 NGSTNTTSALLVVEKHLFDTRGNRENAPQLVIIMTDGIPDSKFRTlkEARKLRERGVIIAVLGV 145

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 78.87 E-value: 1.99e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLtQK 2447
Cdd:cd01450     1 LDIVFLLDGSESVGPENFEKVKDFIEKLVEKLDIGP------DKTRVGLVQYSD--DVRVEFSLNDYKSKDDLLKAV-KN 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2448 MRQQGGS-SALGQTLDYTLKEVLLKAGQPSR-KKALLAVVGTSTAWEDQARLhyVSQKAKCEGVALFVVTVGDHyNRTQV 2525
Cdd:cd01450    72 LKYLGGGgTNTGKALQYALEQLFSESNARENvPKVIIVLTDGRSDDGGDPKE--AAAKLKDEGIKVFVVGVGPA-DEEEL 148

                         170
                  ....*....|...
gi 657584104 2526 EELASLPLQQHLI 2538
Cdd:cd01450   149 REIASCPSERHVF 161

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 78.65 E-value: 3.69e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   2369 DLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLtQKM 2448
Cdd:smart00327    1 DVVFLLDGSGSMGGNRFELAKEFVLKLVEQLDIGP------DGDRVGLVTFSD--DARVLFPLNDSRSKDALLEAL-ASL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   2449 RQQ-GGSSALGQTLDYTLKEVLLKA--GQPSRKKALLAVV-GTSTAWEDQARLhyVSQKAKCEGVALFVVTVGDHYNRTQ 2524
Cdd:smart00327   72 SYKlGGGTNLGAALQYALENLFSKSagSRRGAPKVVILITdGESNDGPKDLLK--AAKELKRSGVKVFVVGVGNDVDEEE 149


                    ....*...
gi 657584104   2525 VEELASLP 2532
Cdd:smart00327  150 LKKLASAP 157

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 78.97 E-value: 3.86e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  237 DIVFLIDGSSSIGISN-FQEIRQFLRSVISGLDIGADKVRIGLAQYSDEPYQEFLLKDH--MDKQSLL---AAVDTFQYR 310
Cdd:cd01471     2 DLYLLVDGSGSIGYSNwVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPnsTNKDLALnaiRALLSLYYP 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104  311 TGGTETGEAIDFLMNQYFtEDAGSRakQRVPQIAVVITDG--DSTDDVAAPALRLRQHGVIMFAIGVG 376
Cdd:cd01471    82 NGSTNTTSALLVVEKHLF-DTRGNR--ENAPQLVIIMTDGipDSKFRTLKEARKLRERGVIIAVLGVG 146

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 80.75 E-value: 4.32e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTD-YSIMKKFTTELVNSFkVSEDlvRVGLAQFSSnfqnEFYLNQFYTE--EAVSKHIFNMrQLGG 1473
Cdd:COG1240    93 RDVVLVVDASGSMAAENrLEAAKGALLDFLDDY-RPRD--RVGLVAFGG----EAEVLLPLTRdrEALKRALDEL-PPGG 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1474 GTNIGLALDSIREYFEASRGCRRSAgisqnLVLITDGE---SQDDVEDAAERLRALGIEVFAIGIG-NVHDLELLQ---- 1545
Cdd:COG1240   165 GTPLGDALALALELLKRADPARRKV-----IVLLTDGRdnaGRIDPLEAAELAAAAGIRIYTIGVGtEAVDEGLLReiae 239

                         170       180
                  ....*....|....*....|
gi 657584104 1546 ITGTpeRLFTVENFGSLEKI 1565
Cdd:COG1240   240 ATGG--RYFRADDLSELAAI 257

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 78.27 E-value: 4.64e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   2160 LVFGLDMSDDVTPTAFERQRSALLALLEEINIaesnCPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIaLERTS 2239
Cdd:smart00327    2 VVFLLDGSGSMGGNRFELAKEFVLKLVEQLDI----GPDGDRVGLVTFSDDARVLFPLNDSRSKDALLEALASL-SYKLG 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   2240 NKRHLGAAMHFVAQNVFKRVRSGMVM-RKVAVFFSNGPSQE-VNDIPGAVMEYRGLNIVPAVISLTNTPAIRQALAVDDT 2317
Cdd:smart00327   77 GGTNLGAALQYALENLFSKSAGSRRGaPKVVILITDGESNDgPKDLLKAAKELKRSGVKVFVVGVGNDVDEEELKKLASA 156

                           170
                    ....*....|...
gi 657584104   2318 GNSIFTVLRRQQD 2330
Cdd:smart00327  157 PGGVYVFLPELLD 169

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 78.32 E-value: 6.64e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIG---VANFQMVRTFLHSIISgleispTRVRVGIVMYndrpADQAQQVYLNTFNNKDE---LLKFIKI 695
Cdd:cd01474     5 FDLYFVLDKSGSVAanwIEIYDFVEQLVDRFNS------PGLRFSFITF----STRATKILPLTDDSSAIikgLEVLKKV 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  696 LPyhGGGTNTGAALKFARESVFIKERGSRKdkgVQQVAVVITDGESQDDV----SQPAADLRRAGVTIYSVGVKNANKVQ 771
Cdd:cd01474    75 TP--SGQTYIHEGLENANEQIFNRNGGGRE---TVSVIIALTDGQLLLNGhkypEHEAKLSRKLGAIVYCVGVTDFLKSQ 149

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 657584104  772 LVEMASHPpnKHVFIVD-SFAKLKSMEQSLQKILCYNI 808
Cdd:cd01474   150 LINIADSK--EYVFPVTsGFQALSGIIESVVKKACIEI 185

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 79.98 E-value: 8.65e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVAN-FQMVRTFLHSIISGLeisPTRVRVGIVMYNDRPadqaqQVYLNTFNNKDELLKFIKILPYhG 700
Cdd:COG1240    93 RDVVLVVDASGSMAAENrLEAAKGALLDFLDDY---RPRDRVGLVAFGGEA-----EVLLPLTRDREALKRALDELPP-G 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  701 GGTNTGAALKFAREsvfikeRGSRKDKGVQQVAVVITDGE---SQDDVSQPAADLRRAGVTIYSVGV--KNANKVQLVEM 775
Cdd:COG1240   164 GGTPLGDALALALE------LLKRADPARRKVIVLLTDGRdnaGRIDPLEAAELAAAAGIRIYTIGVgtEAVDEGLLREI 237


                  .
gi 657584104  776 A 776
Cdd:COG1240   238 A 238

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 79.60 E-value: 1.08e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMEN-FEQIRQFLHTLVNSFdvgPDHVRIGLVQYSTTPRTefLLNTFQNKNDILQYVSKLPyMGGGT 111
Cdd:COG1240    93 RDVVLVVDASGSMAAENrLEAAKGALLDFLDDY---RPRDRVGLVAFGGEAEV--LLPLTRDREALKRALDELP-PGGGT 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  112 HTGRGLDfMLRNHFveASGSRAGQKVpqiAVVITDGK---SQDTVESHAEELRKRGIVLYAIGIKDA--DEDQLKEIANK 186
Cdd:COG1240   167 PLGDALA-LALELL--KRADPARRKV---IVLLTDGRdnaGRIDPLEAAELAAAAGIRIYTIGVGTEavDEGLLREIAEA 240

                         170       180
                  ....*....|....*....|..
gi 657584104  187 PHSQHvYSVSDFAALQGISQSI 208
Cdd:COG1240   241 TGGRY-FRADDLSELAAIYREI 261

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 77.43 E-value: 1.14e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1206 DIIFLVDGSTSITLA-KFRNMQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSS--KKEVVKAISNLRS---P 1279
Cdd:cd01471     2 DLYLLVDGSGSIGYSnWVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPNStnKDLALNAIRALLSlyyP 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1280 FGDTYTGKALAYSLQFFDAQHGGRAalQVPQILMVITDGDATDRNSLVAPSVALRDHGVSVFSIGV-EGANMTQLEIMAG 1358
Cdd:cd01471    82 NGSTNTTSALLVVEKHLFDTRGNRE--NAPQLVIIMTDGIPDSKFRTLKEARKLRERGVIIAVLGVgQGVNHEENRSLVG 159


                  ....
gi 657584104 1359 YDRS 1362
Cdd:cd01471   160 CDPD 163

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: 72.81 E-value: 1.32e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22638     1 CTLKPETGPCRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 76.63 E-value: 2.08e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPQprragnQARVAVVQQGgaRSAKVEFNLQTYQNQELMRThLTQK 2447
Cdd:cd01469     1 MDIVFVLDGSGSIYPDDFQKVKNFLSTVMKKLDIGPT------KTQFGLVQYS--ESFRTEFTLNEYRTKEEPLS-LVKH 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2448 MRQQGGSSALGQTLDYTLKEVLLKA--GQPSRKKALlaVVGTSTAWEDQARLHYVSQKAKCEGVALFVVTVGDHYNR-TQ 2524
Cdd:cd01469    72 ISQLLGLTNTATAIQYVVTELFSESngARKDATKVL--VVITDGESHDDPLLKDVIPQAEREGIIRYAIGVGGHFQReNS 149

                         170       180
                  ....*....|....*....|
gi 657584104 2525 VEEL---ASLPLQQHLIHVS 2541
Cdd:cd01469   150 REELktiASKPPEEHFFNVT 169

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: 72.34 E-value: 2.10e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22614     3 DFCFLEEDPGICRGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTC 55

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 76.40 E-value: 2.82e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSI---YPQDYNKMKDFMKSVISKsfigqnEVHVGVMQFSTIQKLEFPLNRFysKGEMSKAIDDMQQI--G 1093
Cdd:cd01474     6 DLYFVLDKSGSVaanWIEIYDFVEQLVDRFNSP------GLRFSFITFSTRATKILPLTDD--SSAIIKGLEVLKKVtpS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1094 GGTHTGEAITDVS-QYFDSSRGGRpglRQRLVVI--TDGE-AQDVVRGP---AAALRAKGVVVYAIGVVDANTTQLLEIS 1166
Cdd:cd01474    78 GQTYIHEGLENANeQIFNRNGGGR---ETVSVIIalTDGQlLLNGHKYPeheAKLSRKLGAIVYCVGVTDFLKSQLINIA 154

                         170
                  ....*....|....*..
gi 657584104 1167 GSPDRMYAERD-FDALK 1182
Cdd:cd01474   155 DSKEYVFPVTSgFQALS 171

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: 71.65 E-value: 4.13e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22638     1 CTLKPETGP-CRAYIEKWYYDPSTQSCKTFIYGGCGGNGNRFDSEEDCQETC 51

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 75.24 E-value: 7.36e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSItLAKFRNMQRFMESMVNQTTvgKDLTRFGVILYSNDPKSVFTLNQYSskKEVVKAISNLRS--PFGD 1282
Cdd:cd01474     5 FDLYFVLDKSGSV-AANWIEIYDFVEQLVDRFN--SPGLRFSFITFSTRATKILPLTDDS--SAIIKGLEVLKKvtPSGQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1283 TYTGKALAY-SLQFFDAQHGGRaalQVPQILMVITDGDATDRNSLVAPSVA--LRDHGVSVFSIGVEGANMTQLEIMAGy 1359
Cdd:cd01474    80 TYIHEGLENaNEQIFNRNGGGR---ETVSVIIALTDGQLLLNGHKYPEHEAklSRKLGAIVYCVGVTDFLKSQLINIAD- 155

                         170       180
                  ....*....|....*....|....*..
gi 657584104 1360 DRSKVFYVDN-FEALETLYKNITQVLC 1385
Cdd:cd01474   156 SKEYVFPVTSgFQALSGIIESVVKKAC 182

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains

Pssm-ID: 238727 [Multi-domain] Cd Length: 161 Bit Score: 74.25 E-value: 8.38e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2160 LVFGLDMSDDVTPTAFERQRSALLALLEEINIAesncPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIaLERTS 2239
Cdd:cd01450     3 IVFLLDGSESVGPENFEKVKDFIEKLVEKLDIG----PDKTRVGLVQYSDDVRVEFSLNDYKSKDDLLKAVKNL-KYLGG 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104 2240 NKRHLGAAMHFVAQNVFKRVRSGMVMRKVAVFFSNGPSQEVNDIPGAVMEYRGLNIVPAVISLTN 2304
Cdd:cd01450    78 GGTNTGKALQYALEQLFSESNARENVPKVIIVLTDGRSDDGGDPKEAAAKLKDEGIKVFVVGVGP 142

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 70.60 E-value: 9.01e-15

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 657584104  1869 GVDGEQGLTGADGGRGERGNPGNPGIPGIRGEAGLKGQRGLRGDPGEPGAdnnsPGAKG 1927
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGA----PGAPG 55

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: 70.49 E-value: 9.01e-15

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22597     2 AACRLPIVPGPCKGFVDLWAFDAVQGKCVPFSYGGCQGNGNKFYSEKECEEYC 54

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 77.03 E-value: 9.42e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEdlvRVGLAQFSSNFQNEFYLNQFYTEEAVSKHIFnMRQLGGGTNI 1477
Cdd:COG2425   120 PVVLCVDTSGSMAGSKEAAAKAAALALLRALRPNR---RFGVILFDTEVVEDLPLTADDGLEDAIEFLS-GLFAGGGTDI 195

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 657584104 1478 GLALDSIREYFEASRGCRRSagisqnLVLITDGESQDDVEDAAERLRA--LGIEVFAIGIGNVHDLELLQI 1546
Cdd:COG2425   196 APALRAALELLEEPDYRNAD------IVLITDGEAGVSPEELLREVRAkeSGVRLFTVAIGDAGNPGLLEA 260

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: 70.42 E-value: 1.14e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:cd22594     5 CELPADPG-PCNAYKPAFYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTCA 56

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: 70.20 E-value: 1.72e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22599     6 CRLPADEGICRALIPRFYFNTETGQCTEFIYGGCGGNENNFETIEECEKAC 56

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 74.08 E-value: 1.88e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIgMENFEQIRQFLHTLVNSFdVGPDhVRIGLVQYSTTPRTEFLLNTFQNK-NDILQYVSK-LPymGGG 110
Cdd:cd01474     5 FDLYFVLDKSGSV-AANWIEIYDFVEQLVDRF-NSPG-LRFSFITFSTRATKILPLTDDSSAiIKGLEVLKKvTP--SGQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  111 THTGRGLDFMLRNHFVEASGsraGQKVPQIAVVITDGKSQDTVESHAEE----LRKRGIVLYAIGIKDADEDQLKEIANK 186
Cdd:cd01474    80 TYIHEGLENANEQIFNRNGG---GRETVSVIIALTDGQLLLNGHKYPEHeaklSRKLGAIVYCVGVTDFLKSQLINIADS 156

                         170       180       190
                  ....*....|....*....|....*....|.
gi 657584104  187 PhsQHVYSVSD-FAALQGISQSIVQTLCTTV 216
Cdd:cd01474   157 K--EYVFPVTSgFQALSGIIESVVKKACIEI 185

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: 68.99 E-value: 3.06e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2714 ACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCL 2766
Cdd:cd22600     1 GCKPAAESGLCAAYLERWFFNVTTGACETFVYGGCGGNANNYKSQEECELACL 53

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 75.36 E-value: 3.11e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1014 KDIPGDLLFLIDSSGSIypQDYNKMkDFMKSVIsKSFIG--QNEVHVGVMQFSTIQKLEFPLNRfySKGEMSKAIDDMQq 1091
Cdd:COG1240    89 PQRGRDVVLVVDASGSM--AAENRL-EAAKGAL-LDFLDdyRPRDRVGLVAFGGEAEVLLPLTR--DREALKRALDELP- 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1092 IGGGTHTGEAITDVSQYFDSSRggrPGLRQRLVVITDGEAQDVVRGP---AAALRAKGVVVYAIGVVDA--NTTQLLEIS 1166
Cdd:COG1240   162 PGGGTPLGDALALALELLKRAD---PARRKVIVLLTDGRDNAGRIDPleaAELAAAAGIRIYTIGVGTEavDEGLLREIA 238

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: 68.81 E-value: 3.44e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2641 RCQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22627     2 PCLLPMDEG-SCSDYTLLWYYHQKAGECRPFVYGGCGGNANRFSSKEDCELRC 53

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 69.06 E-value: 3.60e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  1860 GEDGEDGLDGVDGEQGLTGADGGRGERGNPGNPGIPGIRGEAGLKGQRGLRGDPGEP 1916
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGAPGPP 57

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 68.67 E-value: 4.83e-14

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  1830 GSPGPSGPQGVQGCSGRRGVKGFRGLRGNRGEDGEDGLDGVDGEQGLTGADGGRGER 1886
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGAPGPP 57

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: 68.20 E-value: 5.98e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCLTKS 2769
Cdd:cd22611     1 DVCSLPKESGPCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNICKKKR 57

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: 67.84 E-value: 7.90e-14

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22603     1 EDCLLPSETGPCKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53

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: 67.65 E-value: 1.09e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22616     3 EICLLPPDEGPCRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTC 55

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: 67.38 E-value: 1.34e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2714 ACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22606     1 ICSLPAVQGPCKAWEPRWAYNSLLKQCQSFVYGGCEGNENNFESKEACEDAC 52

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 67.13 E-value: 1.77e-13

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 657584104  1797 GIRGSRGLPGSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPQGVQGCSGRRGVKG 1851
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGAPG 55

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 71.00 E-value: 1.93e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  832 ADIFFLIDHSGSIyPTDFQDMKKFIIEFIHTFrISPQhVRLGVAKYADSPNLEFDLTDYSdaKSVEKAVEGIRQI--GGG 909
Cdd:cd01474     5 FDLYFVLDKSGSV-AANWIEIYDFVEQLVDRF-NSPG-LRFSFITFSTRATKILPLTDDS--SAIIKGLEVLKKVtpSGQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  910 TETGRALAFMSPHFdRAMTTRGHKVPEYLVVITDGKSSDKVKVPAEQ----LRAQGVIVYSIGVKSADMEELREISGDPK 985
Cdd:cd01474    80 TYIHEGLENANEQI-FNRNGGGRETVSVIIALTDGQLLLNGHKYPEHeaklSRKLGAIVYCVGVTDFLKSQLINIADSKE 158

                         170       180
                  ....*....|....*....|....
gi 657584104  986 RTFFVNN-FDALKPIKDDIITDIC 1008
Cdd:cd01474   159 YVFPVTSgFQALSGIIESVVKKAC 182

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 72.66 E-value: 2.34e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1130 EAQDVVRGPAAALRAKGVVVYAIGVVDANTTQLLEISGSPDRMYAERDFDALKDLESQVALELCDPERDCKKTEKADIIF 1209
Cdd:COG1240    18 LLLALLLPLLPLLLLPLPLDLLLALPLAGLALLLGLAGLGLLALLLAALLLLLAVLLLLLALALAPLALARPQRGRDVVL 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1210 LVDGSTS-ITLAKFRNMQRFMESMVNQTTVGkdlTRFGVILYSNDPKSV--FTlnqySSKKEVVKAISNLRsPFGDTYTG 1286
Cdd:COG1240    98 VVDASGSmAAENRLEAAKGALLDFLDDYRPR---DRVGLVAFGGEAEVLlpLT----RDREALKRALDELP-PGGGTPLG 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1287 KALAYSLQFFDAQHGGRAAlqvpqILMVITDGDATD-RNSLVAPSVALRDHGVSVFSIGV--EGANMTQLEIMAGYDRSK 1363
Cdd:COG1240   170 DALALALELLKRADPARRK-----VIVLLTDGRDNAgRIDPLEAAELAAAAGIRIYTIGVgtEAVDEGLLREIAEATGGR 244

                         250
                  ....*....|....*..
gi 657584104 1364 VFYVDNFEALETLYKNI 1380
Cdd:COG1240   245 YFRADDLSELAAIYREI 261

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 72.79 E-value: 2.41e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFLhsiISGLEISPTRVRVGIVMYNDRPadqAQQVYLNTFNNKDELLKFIKILPyHGGG 702
Cdd:COG2425   120 PVVLCVDTSGSMAGSKEAAAKAAA---LALLRALRPNRRFGVILFDTEV---VEDLPLTADDGLEDAIEFLSGLF-AGGG 192

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  703 TNTGAALKFARESvfIKERGSRKDkgvqqVAVVITDGESQDDVSQ--PAADLRRAGVTIYSVGVKNANKVQLVEMAS 777
Cdd:COG2425   193 TDIAPALRAALEL--LEEPDYRNA-----DIVLITDGEAGVSPEEllREVRAKESGVRLFTVAIGDAGNPGLLEALA 262

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: 66.32 E-value: 3.06e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22604     4 KQCSPTADSGPCFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56

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: 66.17 E-value: 3.13e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22608     4 CYLPADPGPCKAYIPRFYYNSASNKCQQFIYGGCKGNANNFETKDECRYTC 54

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 65.98 E-value: 3.47e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 657584104  1803 GLPGSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPQGVqgcsgrRGVKGFRGLRGNRGEDGE 1864
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGP------PGPPGPPGPPGAPGAPGP 56

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: 66.17 E-value: 3.76e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTeqNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22598     1 DTCRLPSDRGRCKASFERWYFNG--RTCAKFIYGGCGGNDNKFPTQEACMKRC 51

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 65.98 E-value: 3.90e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1866 GLDGVDGEQGLTGADGGRGERGNPGNPGIPGIRGEAGLKGQRGLRGDPGEPGAdnnsPGA 1925
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGA----PGP 56

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: 65.91 E-value: 4.53e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22600     2 CKPAAESGL-CAAYLERWFFNVTTGACETFVYGGCGGNANNYKSQEECELAC 52

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

Pssm-ID: 438637 Cd Length: 56 Bit Score: 65.80 E-value: 4.63e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22594     5 CELPADPGPCNAYKPAFYYNPASHKCLEFIYGGCGGNANNFKTIDECHRTC 55

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 69.72 E-value: 5.43e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  833 DIFFLIDHSGSI-YPTDFQDMKKFIIEFIHTFRISPQHVRLGVAKYADSPNLEFDLTDY--SDAKSVEKAVEGIRQI--- 906
Cdd:cd01471     2 DLYLLVDGSGSIgYSNWVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPnsTNKDLALNAIRALLSLyyp 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  907 GGGTETGRALAFMSPH-FDRAMtTRGHkVPEYLVVITDGKSSDK---VKVpAEQLRAQGVIVYSIGVKSA-DMEELREIS 981
Cdd:cd01471    82 NGSTNTTSALLVVEKHlFDTRG-NREN-APQLVIIMTDGIPDSKfrtLKE-ARKLRERGVIIAVLGVGQGvNHEENRSLV 158


                  ....*.
gi 657584104  982 GDPKRT 987
Cdd:cd01471   159 GCDPDD 164

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: 65.45 E-value: 5.83e-13

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCL 2766
Cdd:cd22613     4 CAFKADDGPCKAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTCI 55

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 71.51 E-value: 6.71e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  828 QTDEADIFFLIDHSGSIYPTD-FQDMKKFIIEFIHTFRispQHVRLGVAKYADSPNLEFDLTdySDAKSVEKAVEGIrQI 906
Cdd:COG1240    89 PQRGRDVVLVVDASGSMAAENrLEAAKGALLDFLDDYR---PRDRVGLVAFGGEAEVLLPLT--RDREALKRALDEL-PP 162

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  907 GGGTETGRALAFMSPHFDRAMTTRgHKVpeyLVVITDGKSSDKVKVP---AEQLRAQGVIVYSIGV--KSADMEELREIS 981
Cdd:COG1240   163 GGGTPLGDALALALELLKRADPAR-RKV---IVLLTDGRDNAGRIDPleaAELAAAAGIRIYTIGVgtEAVDEGLLREIA 238

                         170       180
                  ....*....|....*....|..
gi 657584104  982 gdpKRT----FFVNNFDALKPI 999
Cdd:COG1240   239 ---EATggryFRADDLSELAAI 257

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: 64.85 E-value: 1.07e-12

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 657584104 2722 GSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22624     9 GPCRASFTRWYYDPLSRKCHRFTYGGCDGNENNFETEDECMETC 52

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: 64.83 E-value: 1.16e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22601     2 DVCDLPADRGPCTAYIPRWFYNKTTKKCEKFVYGGCQGNKNRFETKDDCLANC 54

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 68.57 E-value: 1.41e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQT------TVGKDLTRFGVILYSNDPKSVFTLNQ-YSSKKEVVKAISNLR 1277
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAERFlkdyyrKDPAGSWRVGVVQYSDQQEVEAGFLRdIRNYTSLKEAVDNLE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1278 SPFGDTYTGKALAYSLQFFdaQHGGRAAlqVPQILMVITDGDA-TDRNSLVAPSVALRDH-GVSVFSIGVEGANMTQLEI 1355
Cdd:cd01480    83 YIGGGTFTDCALKYATEQL--LEGSHQK--ENKFLLVITDGHSdGSPDGGIEKAVNEADHlGIKIFFVAVGSQNEEPLSR 158

                         170
                  ....*....|....*...
gi 657584104 1356 MAgYDRSKVFYVDNFEAL 1373
Cdd:cd01480   159 IA-CDGKSALYRENFAEL 175

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 66.16 E-value: 1.43e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1020 LLFLIDSSGSIYPQDYNK-----MKDFMKSVISKsfigQNEVHVGVMQFSTIQKLEFPLNRfySKGEMSKAIDDMQQIGG 1094
Cdd:pfam13519    1 LVFVLDTSGSMRNGDYGPtrleaAKDAVLALLKS----LPGDRVGLVTFGDGPEVLIPLTK--DRAKILRALRRLEPKGG 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 657584104  1095 GTHTGEAITDVSQYFDSSRGGRPglrQRLVVI 1126
Cdd:pfam13519   75 GTNLAAALQLARAALKHRRKNQP---RRIVLI 103

CTRP for CS protein-TRAP-related protein: Adhesion of Plasmodium to host cells is an important phenomenon in parasite invasion and in malaria associated pathology.CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transmembrane domain, and a short cytoplasmic segment. The extracellular region of CTRP contains two separated adhesive domains. The first domain contains six 210-amino acid-long homologous VWA domain repeats. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecules. Finally, CTRP also contains consensus motifs found in the superfamily of haematopoietin receptors. The VWA domains in these proteins likely mediate protein-protein interactions.

Pssm-ID: 238750 [Multi-domain] Cd Length: 192 Bit Score: 68.88 E-value: 1.49e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1206 DIIFLVDGSTSITLAKFRN-MQRFMESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSS--KKEVVKAISNLRSPF-- 1280
Cdd:cd01473     2 DLTLILDESASIGYSNWRKdVIPFTEKIINNLNISKDKVHVGILLFAEKNRDVVPFSDEERydKNELLKKINDLKNSYrs 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1281 -GDTYTGKALAYSLQFFdAQHGGRaALQVPQILMVITDGDATDRNSLVAPSVAL--RDHGVSVFSIGVEGANMTQLEIMA 1357
Cdd:cd01473    82 gGETYIVEALKYGLKNY-TKHGNR-RKDAPKVTMLFTDGNDTSASKKELQDISLlyKEENVKLLVVGVGAASENKLKLLA 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 657584104 1358 GYDRSKV----FYVDNFEALETLYKNITQVLCN 1386
Cdd:cd01473   160 GCDINNDncpnVIKTEWNNLNGISKFLTDKICD 192

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: 64.09 E-value: 1.98e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22633     5 CLLPKDVGGCRARFPRYYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 63.28 E-value: 3.18e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 657584104  1930 GNAGLPGLPGPDGRPGESGIVGNPGQDGRRGSPGvkgaagepgaagLQGIPGASGPQGTRGVRGQPGPR 1998
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPG------------PPGPPGPPGPPGPPGAPGAPGPP 57

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 63.28 E-value: 3.76e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 657584104  1914 GEPGAdnnsPGAKGDSGNAGLPGLPGPDGRPGESGIVGNPGQDGRRGSPGvkgaagepgaagLQGIPGASGP 1985
Cdd:pfam01391    1 GPPGP----PGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPPGPPG------------PPGAPGAPGP 56

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: 63.17 E-value: 3.83e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2640 ARCQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22597     2 AACRLPIVPG-PCKGFVDLWAFDAVQGKCVPFSYGGCQGNGNKFYSEKECEEYC 54

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: 62.53 E-value: 6.21e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104 2642 CQL----DSDSGIQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22634     2 CGQphslGGGDGISCFAYIPSWSYNPDKNECEEFIYGGCGGNDNRFSTKAECEQKC 57

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: 62.38 E-value: 6.94e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22605     2 CLKEPDREDCGEEQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52

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: 62.49 E-value: 8.06e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCVA 2695
Cdd:cd22599     6 CRLPADEGI-CRALIPRFYFNTETGQCTEFIYGGCGGNENNFETIEECEKACGA 58

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: 62.46 E-value: 8.11e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:cd22595     4 CKLPVRPG-PCKAFISAFYYNWKAKKCHPFTYSGCGGNANRFKTIEECRRTCV 55

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: 62.06 E-value: 9.10e-12

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22603     3 CLLPSETGP-CKGSFPRYYYDKETGKCKEFIYGGCQGNANNFETKEECERAC 53

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

Pssm-ID: 438636 Cd Length: 51 Bit Score: 61.85 E-value: 1.06e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22593     1 CSLPLDEGSGNSSLTRWYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51

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: 61.93 E-value: 1.16e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHigACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22598     3 CRLPSDRG-RCKASFERWYFNGR--TCAKFIYGGCGGNDNKFPTQEACMKRC 51

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 61.74 E-value: 1.30e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104  1854 GLRGNRGEDGEDGLDGVDGEQGLTGADGGRGERGNPGNPGIPgirgeaglkGQRGLRGDPGEPGA 1918
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPPGEPGPPGPPGPP---------GPPGPPGAPGAPGP 56

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 65.33 E-value: 1.30e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLtQK 2447
Cdd:cd01472     1 ADIVFLVDGSESIGLSNFNLVKDFVKRVVERLDIGP------DGVRVGVVQYSD--DPRTEFYLNTYRSKDDVLEAV-KN 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2448 MRQQGGSSALGQTLDYTLKEVLLKAGQPS---RKKALLAVVGTSTaweDQARLHyvSQKAKCEGVALFVVTVGDHyNRTQ 2524
Cdd:cd01472    72 LRYIGGGTNTGKALKYVRENLFTEASGSRegvPKVLVVITDGKSQ---DDVEEP--AVELKQAGIEVFAVGVKNA-DEEE 145

                         170
                  ....*....|..
gi 657584104 2525 VEELASLPLQQH 2536
Cdd:cd01472   146 LKQIASDPKELY 157

Integrins are a class of adhesion receptors that link the extracellular matrix to the cytoskeleton and cooperate with growth factor receptors to promote celll survival, cell cycle progression and cell migration. Integrins consist of an alpha and a beta sub-unit. Each sub-unit has a large extracellular portion, a single transmembrane segment and a short cytoplasmic domain. The N-terminal domains of the alpha and beta subunits associate to form the integrin headpiece, which contains the ligand binding site, whereas the C-terminal segments traverse the plasma membrane and mediate interaction with the cytoskeleton and with signalling proteins.The VWA domains present in the alpha subunits of integrins seem to be a chordate specific radiation of the gene family being found only in vertebrates. They mediate protein-protein interactions.

Pssm-ID: 238746 [Multi-domain] Cd Length: 177 Bit Score: 65.07 E-value: 2.25e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  432 DIFFLVD-SG-ISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTNE 509
Cdd:cd01469     2 DIVFVLDgSGsIYPDDFQKVKNFLSTVMKKLDIGPTKTQFGLVQYSESFRTEFTLNEYRTKEEPLSLVKHISQLLGLTNT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  510 prnlGSALQYASANFFTSEAGSRADqGYRQYLVVLSGKDSDDE----VFRQSrliKSEGVTVVGMSLG------ASMNEI 579
Cdd:cd01469    82 ----ATAIQYVVTELFSESNGARKD-ATKVLVVITDGESHDDPllkdVIPQA---EREGIIRYAIGVGghfqreNSREEL 153


                  ....*..
gi 657584104  580 RVISTAP 586
Cdd:cd01469   154 KTIASKP 160

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: 60.90 E-value: 2.43e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2715 CFLSQDQGSCQnySMM--WFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22607     2 CSEQAETGPCR--AMMprWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52

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

Pssm-ID: 438657 Cd Length: 56 Bit Score: 60.79 E-value: 2.48e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22614     5 CFLEEDPGI-CRGLITRYFYNNQSKQCERFKYGGCLGNQNNFESLEECQNTC 55

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 64.84 E-value: 3.28e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKkFTTELVNSFKVSEdlVRVGLAQFSSNFQNEFYLNQFytEEAVSKHIFNMRQL--GGG 1474
Cdd:cd01474     5 FDLYFVLDKSGSVAANWIEIYD-FVEQLVDRFNSPG--LRFSFITFSTRATKILPLTDD--SSAIIKGLEVLKKVtpSGQ 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1475 TNIGLALDSIRE-YFEASRGCRRSAGIsqnLVLITDGESQDDV----EDAAERLRALGIEVFAIGIGNVHDLELLQITGT 1549
Cdd:cd01474    80 TYIHEGLENANEqIFNRNGGGRETVSV---IIALTDGQLLLNGhkypEHEAKLSRKLGAIVYCVGVTDFLKSQLINIADS 156

                         170       180
                  ....*....|....*....|....*.
gi 657584104 1550 PERLFTV-ENFGSLEKIKQKVINTIC 1574
Cdd:cd01474   157 KEYVFPVtSGFQALSGIIESVVKKAC 182

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 61.92 E-value: 3.49e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   836 FLIDHSGSIYPTD-----FQDMKKFIIEFIHTFRispqHVRLGVAKYADSPNLEFDLTDysDAKSVEKAVEGIRQIGGGT 910
Cdd:pfam13519    3 FVLDTSGSMRNGDygptrLEAAKDAVLALLKSLP----GDRVGLVTFGDGPEVLIPLTK--DRAKILRALRRLEPKGGGT 76

                           90       100       110
                   ....*....|....*....|....*....|.
gi 657584104   911 ETGRALAFMSphfdRAMTTRGHKVPEYLVVI 941
Cdd:pfam13519   77 NLAAALQLAR----AALKHRRKNQPRRIVLI 103

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 65.10 E-value: 5.58e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVDSGIS--QAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQRRLQTN 508
Cdd:cd01475     3 TDLVFLIDSSRSvrPENFELVKQFLNQIIDSLDVGPDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEYLETGTM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  509 EprnlGSALQYASANFFTSEAGSR--ADQGYRQYLVVLSGKDSDD--EVFRQSRlikSEGVTVVGMSLG-ASMNEIRVIS 583
Cdd:cd01475    83 T----GLAIQYAMNNAFSEAEGARpgSERVPRVGIVVTDGRPQDDvsEVAAKAR---ALGIEMFAVGVGrADEEELREIA 155


                  ....*
gi 657584104  584 TAPYA 588
Cdd:cd01475   156 SEPLA 160

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: 59.82 E-value: 6.01e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22601     4 CDLPADRG-PCTAYIPRWFYNKTTKKCEKFVYGGCQGNKNRFETKDDCLANC 54

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: 6.38e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22632     4 CQLPPARGPCRSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTC 54

CTRP for CS protein-TRAP-related protein: Adhesion of Plasmodium to host cells is an important phenomenon in parasite invasion and in malaria associated pathology.CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transmembrane domain, and a short cytoplasmic segment. The extracellular region of CTRP contains two separated adhesive domains. The first domain contains six 210-amino acid-long homologous VWA domain repeats. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecules. Finally, CTRP also contains consensus motifs found in the superfamily of haematopoietin receptors. The VWA domains in these proteins likely mediate protein-protein interactions.

Pssm-ID: 238750 [Multi-domain] Cd Length: 192 Bit Score: 63.88 E-value: 6.90e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQM-VRTFLHSIISGLEISPTRVRVGIVMYNDRPADqaqqvyLNTFN-----NKDELLKFIKIL 696
Cdd:cd01473     2 DLTLILDESASIGYSNWRKdVIPFTEKIINNLNISKDKVHVGILLFAEKNRD------VVPFSdeeryDKNELLKKINDL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  697 PYH---GGGTNTGAALKFARESvFIKERGSRKDkgVQQVAVVITDG----ESQDDVSQPAADLRRAGVTIYSVGVKNANK 769
Cdd:cd01473    76 KNSyrsGGETYIVEALKYGLKN-YTKHGNRRKD--APKVTMLFTDGndtsASKKELQDISLLYKEENVKLLVVGVGAASE 152


                  ...
gi 657584104  770 VQL 772
Cdd:cd01473   153 NKL 155

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 63.56 E-value: 7.19e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIA-STDYSIMKKFTTELVNSFKVSEDLVRVGLAQFSSNFQNEFYLNQFY-----TEEAVSKHIFNMRQL 1471
Cdd:cd01471     2 DLYLLVDGSGSIGySNWVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPNstnkdLALNAIRALLSLYYP 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104 1472 GGGTNIGLALDSIREYFEASRGCRRSAgiSQNLVLITDGESQDDVE--DAAERLRALGIEVFAIGIG 1536
Cdd:cd01471    82 NGSTNTTSALLVVEKHLFDTRGNRENA--PQLVIIMTDGIPDSKFRtlKEARKLRERGVIIAVLGVG 146

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 59.43 E-value: 7.26e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1978 GIPGASGPQGTRGVRGQPGPRgipglpgpqggpgsvggpgaagrrggngqkGQPGDPGDKGVPGPLGPRGMPgedgrdgy 2057
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPP------------------------------GPPGPPGPPGEPGPPGPPGPP-------- 42

                           90
                   ....*....|...
gi 657584104  2058 GPAGRKGVKGDPG 2070
Cdd:pfam01391   43 GPPGPPGAPGAPG 55

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: 59.40 E-value: 8.75e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22626     1 CSLELDYGVGKAYIPRWYFNTSNARCEMFIFGGIGGNKNNFETLEECKKTC 51

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: 59.09 E-value: 8.90e-11

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 657584104 2722 GSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22618     9 GPCKAYFPRFYFDSETGKCTPFIYGGCGGNGNNFETLHACRAIC 52

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: 59.09 E-value: 9.69e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22602     1 CSLPSKVG-PCRVSARRWFHNPETEKCEVFIYGGCHGNANRFATETECQEVC 51

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: 59.00 E-value: 1.01e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22604     6 CSPTADSGP-CFAYFPMWWYNVKTGQCEEFIYGGCQGNDNRYETEEECEKTC 56

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 60.77 E-value: 1.14e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   238 IVFLIDGSSSI-----GISNFQEIRQFLRSVISGLDIgadkVRIGLAQYSDEPYQEFLLKDhmDKQSLLAAVDTFQYRTG 312
Cdd:pfam13519    1 LVFVLDTSGSMrngdyGPTRLEAAKDAVLALLKSLPG----DRVGLVTFGDGPEVLIPLTK--DRAKILRALRRLEPKGG 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 657584104   313 GTETGEAIDFLMNQYFTEDAGsrakqrVPQIAVVI 347
Cdd:pfam13519   75 GTNLAAALQLARAALKHRRKN------QPRRIVLI 103

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: 58.71 E-value: 1.15e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22602     1 CSLPSKVGPCRVSARRWFHNPETEKCEVFIYGGCHGNANRFATETECQEVC 51

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: 58.91 E-value: 1.26e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22622     1 EYCAAPRVTGPCRAAFPRWYYDPESQSCKEFIYGGCRGNKNNYLSEEECMDRC 53

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 62.20 E-value: 1.31e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2160 LVFGLDMSDDVTPTAFERQRSALLALLEEIniaeSNCPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIALERTS 2239
Cdd:cd00198     3 IVFLLDVSGSMGGEKLDKAKEALKALVSSL----SASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKKGLGG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2240 NkRHLGAAMHFVAQNVFKRVRSGmvMRKVAVFFSNG-PSQEVNDIPGAVMEYRGLNIVPAVISLTNTPAIRQ--ALAVDD 2316
Cdd:cd00198    79 G-TNIGAALRLALELLKSAKRPN--ARRVIILLTDGePNDGPELLAEAARELRKLGITVYTIGIGDDANEDElkEIADKT 155


                  ....*.
gi 657584104 2317 TGNSIF 2322
Cdd:cd00198   156 TGGAVF 161

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: 58.60 E-value: 1.42e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22632     4 CQLPPARG-PCRSNILRYFYNSTSRECEPFIYGGCNGNANNFETVEMCLRTC 54

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: 58.40 E-value: 1.76e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22616     5 CLLPPDEGP-CRALIPRYYYDRYTQTCREFSYGGCEGNANNFESLEDCEKTC 55

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: 58.22 E-value: 2.02e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2714 ACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCL 2766
Cdd:cd22595     3 FCKLPVRPGPCKAFISAFYYNWKAKKCHPFTYSGCGGNANRFKTIEECRRTCV 55

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 61.43 E-value: 2.54e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPQprragnQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLTQK 2447
Cdd:cd00198     1 ADIVFLLDVSGSMGGEKLDKAKEALKALVSSLSASPP------GDRVGLVTFGS--NARVVLPLTTDTDKADLLEAIDAL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2448 MRQQGGSSALGQTLDYTLkEVLLKAGQPSRKKALLAVV-GTSTawEDQARLHYVSQKAKCEGVALFVVTVGDHYNRTQVE 2526
Cdd:cd00198    73 KKGLGGGTNIGAALRLAL-ELLKSAKRPNARRVIILLTdGEPN--DGPELLAEAARELRKLGITVYTIGIGDDANEDELK 149

                         170
                  ....*....|..
gi 657584104 2527 ELASLPLQQHLI 2538
Cdd:cd00198   150 EIADKTTGGAVF 161

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 61.15 E-value: 3.36e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2369 DLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLtQKM 2448
Cdd:cd01482     2 DIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIGP------DGVQVGLVQYSD--DPRTEFDLNAYTSKEDVLAAI-KNL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2449 RQQGGSSALGQTLDYTLKEVLLKAgQPSRKKA-LLAVVGTSTAWEDQARLhyVSQKAKCEGVALFVVTVGDHyNRTQVEE 2527
Cdd:cd01482    73 PYKGGNTRTGKALTHVREKNFTPD-AGARPGVpKVVILITDGKSQDDVEL--PARVLRNLGVNVFAVGVKDA-DESELKM 148

                         170
                  ....*....|...
gi 657584104 2528 LASLPLQQHLIHV 2540
Cdd:cd01482   149 IASKPSETHVFNV 161

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 59.23 E-value: 3.44e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104    35 IVFMVDGSWSI-----GMENFEQIRQFLHTLVNSFDvgpdHVRIGLVQYSTTPRTEFLLNTfqNKNDILQYVSKLPYMGG 109
Cdd:pfam13519    1 LVFVLDTSGSMrngdyGPTRLEAAKDAVLALLKSLP----GDRVGLVTFGDGPEVLIPLTK--DRAKILRALRRLEPKGG 74

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 657584104   110 GTHTGRGLDfMLRNHFveasgSRAGQKVPQIAVVI 144
Cdd:pfam13519   75 GTNLAAALQ-LARAAL-----KHRRKNQPRRIVLI 103

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

Pssm-ID: 438656 Cd Length: 55 Bit Score: 57.36 E-value: 3.87e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCV 2694
Cdd:cd22613     4 CAFKADDG-PCKAIMKRFFFNIFTRQCEEFIYGGCEGNENRFETLEECKKTCI 55

Uncharacterized conserved protein YegL, contains vWA domain of TerY type [Function unknown];

Pssm-ID: 443387 [Multi-domain] Cd Length: 196 Bit Score: 61.86 E-value: 4.20e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1400 VFLIDQSGSIASTDYSIMKKFTTELVNSFKVSEDL---VRVGLAQFSSNFQ--------NEFYLNQFYTeeavskhifnm 1468
Cdd:COG4245     9 YLLLDTSGSMSGEPIEALNEGLQALIDELRQDPYAletVEVSVITFDGEAKvllpltdlEDFQPPDLSA----------- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1469 rqlGGGTNIGLALDSIREYFEASRGCRRSAGISQN---LVLITDGESQD-DVEDAAERLRAL----GIEVFAIGIGNVHD 1540
Cdd:COG4245    78 ---SGGTPLGAALELLLDLIERRVQKYTAEGKGDWrpvVFLITDGEPTDsDWEAALQRLKDGeaakKANIFAIGVGPDAD 154

                         170       180       190
                  ....*....|....*....|....*....|...
gi 657584104 1541 LELLQITGTPERLFTVENFGSLEKIKQKVINTI 1573
Cdd:COG4245   155 TEVLKQLTDPVRALDALDGLDFREFFKWLSASV 187

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: 56.88 E-value: 6.05e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22596     3 CKLPPDAGP-CFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTC 53

vWFA (von Willebrand factor type A) domain of Mg and Co chelatases [Coenzyme transport and metabolism];

Pssm-ID: 440853 [Multi-domain] Cd Length: 262 Bit Score: 62.65 E-value: 6.43e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISN-FQEIRQFLRSVISGLDigaDKVRIGLAQYSDEPYQEFLLKDhmDKQSLLAAVDTFQYRtGGT 314
Cdd:COG1240    93 RDVVLVVDASGSMAAENrLEAAKGALLDFLDDYR---PRDRVGLVAFGGEAEVLLPLTR--DREALKRALDELPPG-GGT 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  315 ETGEAIdflmnqyftEDAGSRAKQRVPQ---IAVVITDGDSTDDVAAP---ALRLRQHGVIMFAIGVGKA--NPTELEAI 386
Cdd:COG1240   167 PLGDAL---------ALALELLKRADPArrkVIVLLTDGRDNAGRIDPleaAELAAAAGIRIYTIGVGTEavDEGLLREI 237

                         170       180
                  ....*....|....*....|....*
gi 657584104  387 ANRPPKRFmFTIDNYEALQRLTEGL 411
Cdd:COG1240   238 AEATGGRY-FRADDLSELAAIYREI 261

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: 57.01 E-value: 6.46e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22617     2 KVCREVPDEGPCRALITRYFYNMTSMRCEEFTYGGCYGNGNNFRDKSSCISAC 54

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 62.39 E-value: 6.72e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1206 DIIFLVDGSTS-----ITLAKFrNMQRFMESMVnqttvGKDltRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRsPF 1280
Cdd:COG2425   120 PVVLCVDTSGSmagskEAAAKA-AALALLRALR-----PNR--RFGVILFDTEVVEDLPLTADDGLEDAIEFLSGLF-AG 190

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 657584104 1281 GDTYTGKALAYSLQFFDAQHGGRAalqvpqILMVITDGDATDRNSLVAPSVALRDHGVSVFSIGVEGANMTQL 1353
Cdd:COG2425   191 GGTDIAPALRAALELLEEPDYRNA------DIVLITDGEAGVSPEELLREVRAKESGVRLFTVAIGDAGNPGL 257

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: 56.77 E-value: 7.69e-10

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIQCADFVQvWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22633     5 CLLPKDVGGCRARFPR-YYYNSSTRRCEKFRYGGCGGNANNFHTLEECEKVC 55

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 58.07 E-value: 9.65e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1399 LVFLIDQSGSIASTDY-----SIMKKFTTELVNSFKvsEDlvRVGLAQFSSNFQNEFYLNQFYteEAVSKHIFNMRQLGG 1473
Cdd:pfam13519    1 LVFVLDTSGSMRNGDYgptrlEAAKDAVLALLKSLP--GD--RVGLVTFGDGPEVLIPLTKDR--AKILRALRRLEPKGG 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 657584104  1474 GTNIGLALDSIREYFEasrgcRRSAGISQNLVLI 1507
Cdd:pfam13519   75 GTNLAAALQLARAALK-----HRRKNQPRRIVLI 103

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 57.69 E-value: 1.07e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   624 IVFIVDESGSI-----GVANFQMVRTFLHSIISGLEisptRVRVGIVMYNDRPadqaqQVYLNTFNNKDELLKFIKILPY 698
Cdd:pfam13519    1 LVFVLDTSGSMrngdyGPTRLEAAKDAVLALLKSLP----GDRVGLVTFGDGP-----EVLIPLTKDRAKILRALRRLEP 71

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 657584104   699 HGGGTNTGAALKFARESVFikergsRKDKGVQQVAVVI 736
Cdd:pfam13519   72 KGGGTNLAAALQLARAALK------HRRKNQPRRIVLI 103

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: 55.56 E-value: 1.73e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2641 RCQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22621     2 FCHLPKVVG-RCRASFPRWWYNATSQSCQEFIFGGCKGNLNNFLSEQECLQKC 53

Uncharacterized conserved protein YegL, contains vWA domain of TerY type [Function unknown];

Pssm-ID: 443387 [Multi-domain] Cd Length: 196 Bit Score: 59.94 E-value: 1.74e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1022 FLIDSSGSIYPQDYNKMKDFMKSVIS---KSFIGQNEVHVGVMQFSTIQKLEFPL---NRFYskgemskaIDDMQqIGGG 1095
Cdd:COG4245    10 LLLDTSGSMSGEPIEALNEGLQALIDelrQDPYALETVEVSVITFDGEAKVLLPLtdlEDFQ--------PPDLS-ASGG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1096 THTGEAIT--------DVSQYfdsSRGGRPGLRQRLVVITDGEAQDV-VRGPAAALR----AKGVVVYAIGV-VDANTTQ 1161
Cdd:COG4245    81 TPLGAALEllldlierRVQKY---TAEGKGDWRPVVFLITDGEPTDSdWEAALQRLKdgeaAKKANIFAIGVgPDADTEV 157

                         170       180
                  ....*....|....*....|....
gi 657584104 1162 LLEISGspdrmyAERDFDALKDLE 1185
Cdd:COG4245   158 LKQLTD------PVRALDALDGLD 175

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: 55.65 E-value: 1.75e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCLTKS 2769
Cdd:cd22620     3 CQLPSDTGRGKASFTRYYYNEESGKCETFIYGGVGGNSNNFLTKEDCCKECAQGS 57

von Willebrand factor (vWF) type A domain; equivalent to the I-domain of integrins. This domain has a variety of functions including: intermolecular adhesion, cell migration, signalling, transcription, and DNA repair. In integrins these domains form heterodimers while in vWF it forms homodimers and multimers. There are different interaction surfaces of this domain as seen by its complexes with collagen with either integrin or human vWFA. In integrins collagen binding occurs via the metal ion-dependent adhesion site (MIDAS) and involves three surface loops located on the upper surface of the molecule. In human vWFA, collagen binding is thought to occur on the bottom of the molecule and does not involve the vestigial MIDAS motif.

Pssm-ID: 238749 [Multi-domain] Cd Length: 164 Bit Score: 58.78 E-value: 2.10e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2160 LVFGLDMSDDVTPTAFERQRSALLALLEEINIAesncPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIALeRTS 2239
Cdd:cd01472     3 IVFLVDGSESIGLSNFNLVKDFVKRVVERLDIG----PDGVRVGVVQYSDDPRTEFYLNTYRSKDDVLEAVKNLRY-IGG 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104 2240 NKRhLGAAMHFVAQNVFK---RVRSGmvMRKVAVFFSNGPSQEvnDIPGAVMEYRGLNIVPAVISLTN 2304
Cdd:cd01472    78 GTN-TGKALKYVRENLFTeasGSREG--VPKVLVVITDGKSQD--DVEEPAVELKQAGIEVFAVGVKN 140

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: 55.00 E-value: 2.44e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22608     4 CYLPADPGP-CKAYIPRFYYNSASNKCQQFIYGGCKGNANNFETKDECRYTC 54

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: 55.22 E-value: 2.74e-09

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2659 WFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22624    18 WYYDPLSRKCHRFTYGGCDGNENNFETEDECMETC 52

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 55.19 E-value: 2.84e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1993 GQPGPRGIpglpgpqggpgsvggpgaagrrggngqKGQPGDPGDKGVPGPLGPRGMPGEDGRDgyGPAGRKGVKGDPGFP 2072
Cdd:pfam01391    1 GPPGPPGP---------------------------PGPPGPPGPPGPPGPPGPPGPPGEPGPP--GPPGPPGPPGPPGAP 51


                   ....
gi 657584104  2073 GYPG 2076
Cdd:pfam01391   52 GAPG 55

Secreted protein containing bacterial Ig-like domain and vWFA domain [General function prediction only];

Pssm-ID: 441879 [Multi-domain] Cd Length: 289 Bit Score: 60.89 E-value: 3.09e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTTELVNSFKvSEDlvRVGLAQFSSNFQnEFYLNQFYTE-EAVSKHIfNMRQLGGGT 1475
Cdd:COG2304    92 LNLVFVIDVSGSMSGDKLELAKEAAKLLVDQLR-PGD--RVSIVTFAGDAR-VLLPPTPATDrAKILAAI-DRLQAGGGT 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1476 NIG----LALDSIREYFEASRGCRrsagisqnLVLITDGE------SQDDVEDAAERLRALGIEVFAIGIGNVHDLELLQ 1545
Cdd:COG2304   167 ALGagleLAYELARKHFIPGRVNR--------VILLTDGDanvgitDPEELLKLAEEAREEGITLTTLGVGSDYNEDLLE 238

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: 54.67 E-value: 3.22e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22605     2 CLKEPDRE-DCGEEQVRWYFDAKRGNCFTFTYGGCDGNRNHFETYEECRLAC 52

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 60.08 E-value: 4.56e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1017 PGDLLFLIDSSGSiypqdynkMKDFmKSVISKSFI------GQNEVHVGVMQFSTIQKLEFPLNrfySKGEMSKAIDDMQ 1090
Cdd:COG2425   118 EGPVVLCVDTSGS--------MAGS-KEAAAKAAAlallraLRPNRRFGVILFDTEVVEDLPLT---ADDGLEDAIEFLS 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1091 QI--GGGTHTGEAITDVSQYFDSSRGGRpglrQRLVVITDGEAQ----DVVRgpAAALRAKGVVVYAIGVVDANTTQLLE 1164
Cdd:COG2425   186 GLfaGGGTDIAPALRAALELLEEPDYRN----ADIVLITDGEAGvspeELLR--EVRAKESGVRLFTVAIGDAGNPGLLE 259


                  .
gi 657584104 1165 I 1165
Cdd:COG2425   260 A 260

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: 54.39 E-value: 5.07e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIQCADFVQvWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22626     1 CSLELDYGVGKAYIPR-WYFNTSNARCEMFIFGGIGGNKNNFETLEECKKTC 51

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: 54.22 E-value: 5.64e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22615     4 CLSPKDEGLCSASVTRYYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54

Uncharacterized conserved protein YegL, contains vWA domain of TerY type [Function unknown];

Pssm-ID: 443387 [Multi-domain] Cd Length: 196 Bit Score: 58.40 E-value: 5.84e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  237 DIVFLIDGSSSIGISNFQEIRQFLRSVISGL---DIGADKVRIGLAQYSDEPYQefllkdHMDkqslLAAVDTFQ----Y 309
Cdd:COG4245     7 PVYLLLDTSGSMSGEPIEALNEGLQALIDELrqdPYALETVEVSVITFDGEAKV------LLP----LTDLEDFQppdlS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  310 RTGGTETGEAIDFLMNQYFTEDAGSRAKQRV--PQIAVVITDGDSTDDVAAPALR-----LRQHGVIMFAIGVG-KANPT 381
Cdd:COG4245    77 ASGGTPLGAALELLLDLIERRVQKYTAEGKGdwRPVVFLITDGEPTDSDWEAALQrlkdgEAAKKANIFAIGVGpDADTE 156


                  ....*..
gi 657584104  382 ELEAIAN 388
Cdd:COG4245   157 VLKQLTD 163

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: 54.08 E-value: 5.86e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 657584104 2652 CADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22618    11 CKAYFPRFYFDSETGKCTPFIYGGCGGNGNNFETLHACRAIC 52

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: 54.18 E-value: 5.91e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22596     1 DSCKLPPDAGPCFGMIQRYFYNSSSMACQTFNYGGCLGNQNNFVTEKECLQTC 53

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: 54.33 E-value: 6.04e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22611     3 CSLPKESG-PCMAYFPRWWYDKETNTCSKFIYGGCQGNNNNFQSEAICQNIC 53

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.

Pssm-ID: 238119 [Multi-domain] Cd Length: 161 Bit Score: 57.58 E-value: 6.13e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVD-SG-ISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGGIKRFRQrrlQTN 508
Cdd:cd00198     1 ADIVFLLDvSGsMGGEKLDKAKEALKALVSSLSASPPGDRVGLVTFGSNARVVLPLTTDTDKADLLEAIDALKK---GLG 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 657584104  509 EPRNLGSALQYASANFFtseagSRADQGYRQYLVVLS-GKDSDD--EVFRQSRLIKSEGVTVVGMSLGASMNE 578
Cdd:cd00198    78 GGTNIGAALRLALELLK-----SAKRPNARRVIILLTdGEPNDGpeLLAEAARELRKLGITVYTIGIGDDANE 145

Collagen: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238759 [Multi-domain] Cd Length: 164 Bit Score: 57.30 E-value: 6.18e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2158 TELVFGLDMSDDVTPTAFERQRSALLALLEEINIAesncPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIALeR 2237
Cdd:cd01482     1 ADIVFLVDGSWSIGRSNFNLVRSFLSSVVEAFEIG----PDGVQVGLVQYSDDPRTEFDLNAYTSKEDVLAAIKNLPY-K 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2238 TSNKRhLGAAMHFVAQNVFK---RVRSGMvmRKVAVFFSNGPSQEVNDIPGAVMEYRGLNI 2295
Cdd:cd01482    76 GGNTR-TGKALTHVREKNFTpdaGARPGV--PKVVILITDGKSQDDVELPARVLRNLGVNV 133

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 54.04 E-value: 6.28e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  2061 GRKGVKGDPGFPGYPGLLGEDGLQGPKGLPgrkgnrgrggnsgrsgesGISGDPGYAGHRGPRGLPG 2127
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPGPPGPP------------------GEPGPPGPPGPPGPPGPPG 49

hypothetical protein; Provisional

Pssm-ID: 223003 [Multi-domain] Cd Length: 413 Bit Score: 60.37 E-value: 8.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1780 VSDRECCNVMCKCSGHEGIR-GSRGLPGSKGVSGQKGYPGFPGEEGIAGDRGSPGPSGPQGVQGCSGRRGVKGFRGLRGN 1858
Cdd:PHA03169   13 HTLRSSCRGHCKRHGGTREQaGRRRGTAARAAKPAPPAPTTSGPQVRAVAEQGHRQTESDTETAEESRHGEKEERGQGGP 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1859 RGE--DGEDGLDGVDGEQGLTGADGGRGERGNPGNPGIPGIRGEAGLKGQRGLRGDPGEPGADNNSPGAKGDSGNAGL-- 1934
Cdd:PHA03169   93 SGSgsESVGSPTPSPSGSAEELASGLSPENTSGSSPESPASHSPPPSPPSHPGPHEPAPPESHNPSPNQQPSSFLQPShe 172

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104 1935 ----PGlPGPDGRPGESGIVGNPGQDGRRGSPGVKGAAGepgaaglQGIPGASGPQGTRGVRGQPG 1996
Cdd:PHA03169  173 dspeEP-EPPTSEPEPDSPGPPQSETPTSSPPPQSPPDE-------PGEPQSPTPQQAPSPNTQQA 230

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: 53.41 E-value: 8.95e-09

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 657584104 2722 GSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22592     9 GPCKARIIRYFYNAKSGLCETFVYGGCRAKRNNFLSAEDCMRTC 52

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: 53.45 E-value: 9.57e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22615     4 CLSPKDEGL-CSASVTRYYYNSATKTCEPFNYTGCGGNNNNFTSKKDCLRVC 54

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: 53.73 E-value: 1.03e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104 2642 CQLDSDSGIQCADFVQvWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTCVAHS 2697
Cdd:cd22620     3 CQLPSDTGRGKASFTR-YYYNEESGKCETFIYGGVGGNSNNFLTKEDCCKECAQGS 57

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 53.27 E-value: 1.23e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1957 GRRGSPGvkgaagepgaagLQGIPGASGPQGTRGVRGQPGPRGIPglpgpqggpgsvggpgaagrrggngqkGQPGDPGD 2036
Cdd:pfam01391    1 GPPGPPG------------PPGPPGPPGPPGPPGPPGPPGPPGEP---------------------------GPPGPPGP 41

                           90
                   ....*....|....*
gi 657584104  2037 KGVPGPLGPRGMPGE 2051
Cdd:pfam01391   42 PGPPGPPGAPGAPGP 56

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: 53.03 E-value: 1.40e-08

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2659 WFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22592    18 YFYNAKSGLCETFVYGGCRAKRNNFLSAEDCMRTC 52

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: 52.74 E-value: 1.65e-08

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2659 WFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22622    19 WYYDPESQSCKEFIYGGCRGNKNNYLSEEECMDRC 53

CTRP for CS protein-TRAP-related protein: Adhesion of Plasmodium to host cells is an important phenomenon in parasite invasion and in malaria associated pathology.CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transmembrane domain, and a short cytoplasmic segment. The extracellular region of CTRP contains two separated adhesive domains. The first domain contains six 210-amino acid-long homologous VWA domain repeats. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecules. Finally, CTRP also contains consensus motifs found in the superfamily of haematopoietin receptors. The VWA domains in these proteins likely mediate protein-protein interactions.

Pssm-ID: 238750 [Multi-domain] Cd Length: 192 Bit Score: 56.94 E-value: 1.79e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  237 DIVFLIDGSSSIGISNFQ-EIRQFLRSVISGLDIGADKVRIGLAQYSDE--PYQEFLLKDHMDKQSLLAAVDTFQ--YRT 311
Cdd:cd01473     2 DLTLILDESASIGYSNWRkDVIPFTEKIINNLNISKDKVHVGILLFAEKnrDVVPFSDEERYDKNELLKKINDLKnsYRS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  312 GG-TETGEAIDFLMNQYFtedAGSRAKQRVPQIAVVITDG--DSTDDVAAP--ALRLRQHGVIMFAIGVGKANPTELEAI 386
Cdd:cd01473    82 GGeTYIVEALKYGLKNYT---KHGNRRKDAPKVTMLFTDGndTSASKKELQdiSLLYKEENVKLLVVGVGAASENKLKLL 158


                  .
gi 657584104  387 A 387
Cdd:cd01473   159 A 159

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: 52.43 E-value: 2.04e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGiQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22607     2 CSEQAETG-PCRAMMPRWYFDVTEGKCAPFIYGGCGGNRNNFESEEYCMAVC 52

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: 52.45 E-value: 2.13e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2715 CFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22609     2 CLEPKVVGVCKASMTRYFYNAQTGHCEQFVYGGCGGNRNNFLTLEDCMKTC 52

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: 52.06 E-value: 2.97e-08

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 657584104 2652 CADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22609    11 CKASMTRYFYNAQTGHCEQFVYGGCGGNRNNFLTLEDCMKTC 52

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 57.38 E-value: 3.10e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  231 AKANMADIVFLIDGSSSIGISNFQEIRQFLrsvISGLDIGADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQyR 310
Cdd:COG2425   114 VPLLEGPVVLCVDTSGSMAGSKEAAAKAAA---LALLRALRPNRRFGVILFDTEVVEDLPLTADDGLEDAIEFLSGLF-A 189

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  311 TGGTETGEAIDfLMNQYFTEDAGSRAkqrvpqIAVVITDGDSTDDVAA--PALRLRQHGVIMFAIGVGKANPTELEAIAN 388
Cdd:COG2425   190 GGGTDIAPALR-AALELLEEPDYRNA------DIVLITDGEAGVSPEEllREVRAKESGVRLFTVAIGDAGNPGLLEALA 262


                  .
gi 657584104  389 R 389
Cdd:COG2425   263 D 263

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 51.73 E-value: 3.77e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1939 GPDGRPGESGIVGNPGQDGRRGSPGvkgaagepgaaglqgIPGASGPQGTRGVRGQPGPRgipglpgpqggpgsvggpga 2018
Cdd:pfam01391    1 GPPGPPGPPGPPGPPGPPGPPGPPG---------------PPGPPGEPGPPGPPGPPGPP-------------------- 45

                           90       100
                   ....*....|....*....|..
gi 657584104  2019 agrrggngqkGQPGDPGDKGVP 2040
Cdd:pfam01391   46 ----------GPPGAPGAPGPP 57

ATR (Anthrax Toxin Receptor): Anthrax toxin is a key virulence factor for Bacillus anthracis, the causative agent of anthrax. ATR is the cellular receptor for the anthrax protective antigen and facilitates entry of the toxin into cells. The VWA domain in ATR contains the toxin binding site and mediates interaction with protective antigen. The binding is mediated by divalent cations that binds to the MIDAS motif. These proteins are a family of vertebrate ECM receptors expressed by endothelial cells.

Pssm-ID: 238751 [Multi-domain] Cd Length: 185 Bit Score: 55.59 E-value: 4.17e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  230 CAKAnmADIVFLIDGSSSIGiSNFQEIRQFLRSVISGLDigADKVRIGLAQYSDEPYQEFLLKDHMDKQSLLAAVDTFQY 309
Cdd:cd01474     1 CAGH--FDLYFVLDKSGSVA-ANWIEIYDFVEQLVDRFN--SPGLRFSFITFSTRATKILPLTDDSSAIIKGLEVLKKVT 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  310 RTGGTETGEAIDFLMNQYFTEDAGSRakqRVPQIAVVITDGDSTDDV----AAPALRLRQHGVIMFAIGVGKANPTELEA 385
Cdd:cd01474    76 PSGQTYIHEGLENANEQIFNRNGGGR---ETVSVIIALTDGQLLLNGhkypEHEAKLSRKLGAIVYCVGVTDFLKSQLIN 152

                         170       180       190
                  ....*....|....*....|....*....|...
gi 657584104  386 IANRPPKRFMFTiDNYEALQRLTEGLLQTVCIS 418
Cdd:cd01474   153 IADSKEYVFPVT-SGFQALSGIIESVVKKACIE 184

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: 51.71 E-value: 4.43e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2713 DACFLSQDQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22621     1 DFCHLPKVVGRCRASFPRWWYNATSQSCQEFIFGGCKGNLNNFLSEQECLQKC 53

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 56.24 E-value: 4.50e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQGGarSAKVEFNLQTYQNQELMRTHLtQK 2447
Cdd:cd01475     3 TDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVGP------DATRVGLVQYSS--TVKQEFPLGRFKSKADLKRAV-RR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2448 MRQQGGSSALGQTLDYTLkEVLLKAGQPSRKKAL----LAVVGTSTawEDQARLHYVSQKAKCEGVALFVVTVGdhynRT 2523
Cdd:cd01475    74 MEYLETGTMTGLAIQYAM-NNAFSEAEGARPGSErvprVGIVVTDG--RPQDDVSEVAAKARALGIEMFAVGVG----RA 146

                         170       180
                  ....*....|....*....|....*...
gi 657584104 2524 QVEEL---ASLPLQQHLIHVSRLKAGEQ 2548
Cdd:cd01475   147 DEEELreiASEPLADHVFYVEDFSTIEE 174

von Willebrand factor type A domain;

Pssm-ID: 463909 [Multi-domain] Cd Length: 103 Bit Score: 53.06 E-value: 4.51e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  1207 IIFLVDGSTSIT-----LAKFRNMQRFMESMVNQTtvgkDLTRFGVILYSNDPKSVFTLNqySSKKEVVKAISNLRSPFG 1281
Cdd:pfam13519    1 LVFVLDTSGSMRngdygPTRLEAAKDAVLALLKSL----PGDRVGLVTFGDGPEVLIPLT--KDRAKILRALRRLEPKGG 74

                           90       100       110
                   ....*....|....*....|....*....|....
gi 657584104  1282 DTYTGKALAYSLQFFDaqhggRAALQVPQILMVI 1315
Cdd:pfam13519   75 GTNLAAALQLARAALK-----HRRKNQPRRIVLI 103

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: 51.45 E-value: 4.96e-08

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIQCADfVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22593     1 CSLPLDEGSGNSS-LTRWYYDPKKGQCKPFTYKGKGGNENNFLTKEDCEETC 51

Uncharacterized conserved protein YegL, contains vWA domain of TerY type [Function unknown];

Pssm-ID: 443387 [Multi-domain] Cd Length: 196 Bit Score: 54.93 E-value: 7.40e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  833 DIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISPQH---VRLGVAKYADSPNLEFDLTDYSDAKsvekavegIRQI--G 907
Cdd:COG4245     7 PVYLLLDTSGSMSGEPIEALNEGLQALIDELRQDPYAletVEVSVITFDGEAKVLLPLTDLEDFQ--------PPDLsaS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  908 GGTETGRALAFMSPHFD-RAMTTRGHKVPEY---LVVITDGKSSDKVKVPA-----EQLRAQGVIVYSIGV-KSADMEEL 977
Cdd:COG4245    79 GGTPLGAALELLLDLIErRVQKYTAEGKGDWrpvVFLITDGEPTDSDWEAAlqrlkDGEAAKKANIFAIGVgPDADTEVL 158

                         170       180
                  ....*....|....*....|
gi 657584104  978 REISgDPKRTFFVNNFDALK 997
Cdd:COG4245   159 KQLT-DPVRALDALDGLDFR 177

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 54.33 E-value: 7.61e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2369 DLVMVADSSREIQaDQYAGVQQLLGSVVEQLAVSPQPRRagnqarVAVVQQGGARSAKVEFNLQTYQNQELMRTHLtQKM 2448
Cdd:cd01476     2 DLLFVLDSSGSVR-GKFEKYKKYIERIVEGLEIGPTATR------VALITYSGRGRQRVRFNLPKHNDGEELLEKV-DNL 73

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104 2449 RQQGGSSALGQTLDYTLKevLLKAGQPSRKKALLAVVGTSTAW-----EDQARLhYVSQKakceGVALFVVTVGD 2518
Cdd:cd01476    74 RFIGGTTATGAAIEVALQ--QLDPSEGRREGIPKVVVVLTDGRshddpEKQARI-LRAVP----NIETFAVGTGD 141

Uncharacterized conserved protein YegL, contains vWA domain of TerY type [Function unknown];

Pssm-ID: 443387 [Multi-domain] Cd Length: 196 Bit Score: 54.55 E-value: 1.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPT---RVRVGIVmyndrpadqaqqvylnTFNNKDELL-------KF 692
Cdd:COG4245     7 PVYLLLDTSGSMSGEPIEALNEGLQALIDELRQDPYaleTVEVSVI----------------TFDGEAKVLlpltdleDF 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  693 -IKILPYhGGGTNTGAALKFARESVFI-KERGSRKDKGV-QQVAVVITDGESQD-DVSQPAADLRRA----GVTIYSVGV 764
Cdd:COG4245    71 qPPDLSA-SGGTPLGAALELLLDLIERrVQKYTAEGKGDwRPVVFLITDGEPTDsDWEAALQRLKDGeaakKANIFAIGV 149


                  ....*
gi 657584104  765 -KNAN 768
Cdd:COG4245   150 gPDAD 154

Complement factors B and C2 are two critical proteases for complement activation. They both contain three CCP or Sushi domains, a trypsin-type serine protease domain and a single VWA domain with a conserved metal ion dependent adhesion site referred commonly as the MIDAS motif. Orthologues of these molecules are found from echinoderms to chordates. During complement activation, the CCP domains are cleaved off, resulting in the formation of an active protease that cleaves and activates complement C3. Complement C2 is in the classical pathway and complement B is in the alternative pathway. The interaction of C2 with C4 and of factor B with C3b are both dependent on Mg2+ binding sites within the VWA domains and the VWA domain of factor B has been shown to mediate the binding of C3. This is consistent with the common inferred function of VWA domains as magnesium-dependent protein interaction domains.

Pssm-ID: 238747 [Multi-domain] Cd Length: 198 Bit Score: 54.60 E-value: 1.07e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  625 VFIV-DESGSIGVANFQMVRTFLHSII---SGLEISPtrvRVGIVMYNDRPADQAQQVYLNTfNNKDELLKFIKILPY-- 698
Cdd:cd01470     3 IYIAlDASDSIGEEDFDEAKNAIKTLIekiSSYEVSP---RYEIISYASDPKEIVSIRDFNS-NDADDVIKRLEDFNYdd 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  699 HGG--GTNTGAALKFARES-VFIKERGSRKDKGVQQVAVVITDGES-------------QDDV--SQPAADLRRAGVTIY 760
Cdd:cd01470    79 HGDktGTNTAAALKKVYERmALEKVRNKEAFNETRHVIILFTDGKSnmggsplptvdkiKNLVykNNKSDNPREDYLDVY 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 657584104  761 SVGV-KNANKVQLVEMASHPPN-KHVFivdsfaKLKSMEQ 798
Cdd:cd01470   159 VFGVgDDVNKEELNDLASKKDNeRHFF------KLKDYED 192

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: 50.62 E-value: 1.12e-07

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2731 WFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22623    22 WHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSAC 56

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 53.48 E-value: 1.41e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2369 DLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPqprragNQARVAVVQQggARSAKVEFNLQTYQNQELMRTHLtQKM 2448
Cdd:cd01481     2 DIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVGP------DKIRVAVVQF--SDTPRPEFYLNTHSTKADVLGAV-RRL 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2449 RQQGGSSA-LGQTLDYTLKEVLLKAGQPSRKKALLAVVGTSTAWEDQARLHYVSQKAKCEGVALFVVTVGDhYNRTQVEE 2527
Cdd:cd01481    73 RLRGGSQLnTGSALDYVVKNLFTKSAGSRIEEGVPQFLVLITGGKSQDDVERPAVALKRAGIVPFAIGARN-ADLAELQQ 151


                  ....*
gi 657584104 2528 LASLP 2532
Cdd:cd01481   152 IAFDP 156

VWA subgroup: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Not much is known about the function of the VWA domain in these proteins. The members do have a conserved MIDAS motif. The biochemical function however is not known.

Pssm-ID: 238742 [Multi-domain] Cd Length: 170 Bit Score: 51.89 E-value: 5.44e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1205 ADIIFLVDGSTSITLAKFRNMQRFMESMVNQTtvgKDLTRFGVILYSNDPKSVFTLNQYSSKKEVVKAISNLRsPFGDT- 1283
Cdd:cd01465     1 LNLVFVIDRSGSMDGPKLPLVKSALKLLVDQL---RPDDRLAIVTYDGAAETVLPATPVRDKAAILAAIDRLT-AGGSTa 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1284 -YTGKALAYSLqffdAQHGGRAAlQVPQILMvITDGDA----TDRNSLVAPSVALRDHGVSVFSIGVEGANMTQL-EIMA 1357
Cdd:cd01465    77 gGAGIQLGYQE----AQKHFVPG-GVNRILL-ATDGDFnvgeTDPDELARLVAQKRESGITLSTLGFGDNYNEDLmEAIA 150

                         170       180
                  ....*....|....*....|
gi 657584104 1358 GYDRSKVFYVDNF-EALETL 1376
Cdd:cd01465   151 DAGNGNTAYIDNLaEARKVF 170

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 53.53 E-value: 6.89e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   34 DIVFMVDGSWSIGMENFEQIRQFLHTLVNSFdvgPDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPYmGGGTHT 113
Cdd:COG2425   120 PVVLCVDTSGSMAGSKEAAAKAAALALLRAL---RPNRRFGVILFDTEVVEDLPLTADDGLEDAIEFLSGLFA-GGGTDI 195

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104  114 GRGLDFMLRnhFVEASGSRAGQkvpqiAVVITDGKSQDTVESHAEELRKR--GIVLYAIGIKDADEDQLKEIANK 186
Cdd:COG2425   196 APALRAALE--LLEEPDYRNAD-----IVLITDGEAGVSPEELLREVRAKesGVRLFTVAIGDAGNPGLLEALAD 263

Secreted protein containing bacterial Ig-like domain and vWFA domain [General function prediction only];

Pssm-ID: 441879 [Multi-domain] Cd Length: 289 Bit Score: 53.57 E-value: 8.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  836 FLIDHSGSIYPTDFQDMKKFIIEFIHtfRISPQHvRLGVAKYADSPNLEFDLTDYSDAKSVEKAVEGIRQiGGGTETGRA 915
Cdd:COG2304    96 FVIDVSGSMSGDKLELAKEAAKLLVD--QLRPGD-RVSIVTFAGDARVLLPPTPATDRAKILAAIDRLQA-GGGTALGAG 171

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104  916 L----AFMSPHFDRAMTTRghkvpeyLVVITDGKSSDKVKVP------AEQLRAQGVIVYSIGV----KSADMEEL 977
Cdd:COG2304   172 LelayELARKHFIPGRVNR-------VILLTDGDANVGITDPeellklAEEAREEGITLTTLGVgsdyNEDLLERL 240

VWA_Matrilin: In cartilaginous plate, extracellular matrix molecules mediate cell-matrix and matrix-matrix interactions thereby providing tissue integrity. Some members of the matrilin family are expressed specifically in developing cartilage rudiments. The matrilin family consists of at least four members. All the members of the matrilin family contain VWA domains, EGF-like domains and a heptad repeat coiled-coiled domain at the carboxy terminus which is responsible for the oligomerization of the matrilins. The VWA domains have been shown to be essential for matrilin network formation by interacting with matrix ligands.

Pssm-ID: 238752 [Multi-domain] Cd Length: 224 Bit Score: 52.39 E-value: 9.63e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2157 PTELVFGLDMSDDVTPTAFERQRSALLALLEEINIAesncPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIA-L 2235
Cdd:cd01475     2 PTDLVFLIDSSRSVRPENFELVKQFLNQIIDSLDVG----PDATRVGLVQYSSTVKQEFPLGRFKSKADLKRAVRRMEyL 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2236 ERTSnkrHLGAAMHFVAQNVFK-----RVRSGMVMRkVAVFFSNGPSQE-VNDI 2283
Cdd:cd01475    78 ETGT---MTGLAIQYAMNNAFSeaegaRPGSERVPR-VGIVVTDGRPQDdVSEV 127

Secreted protein containing bacterial Ig-like domain and vWFA domain [General function prediction only];

Pssm-ID: 441879 [Multi-domain] Cd Length: 289 Bit Score: 52.80 E-value: 1.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1017 PGDLLFLIDSSGSiypQDYNKM---KDFMKSVISKsfIGQNEvHVGVMQFSTIQKLEFPLNRFYSKGEMSKAIDDMQQiG 1093
Cdd:COG2304    91 PLNLVFVIDVSGS---MSGDKLelaKEAAKLLVDQ--LRPGD-RVSIVTFAGDARVLLPPTPATDRAKILAAIDRLQA-G 163

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104 1094 GGTHTGEAITDVSQYFdsSRGGRPGLRQRLVVITDGEA------QDVVRGPAAALRAKGVVVYAIGV-VDANtTQLLE 1164
Cdd:COG2304   164 GGTALGAGLELAYELA--RKHFIPGRVNRVILLTDGDAnvgitdPEELLKLAEEAREEGITLTTLGVgSDYN-EDLLE 238

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 47.49 E-value: 1.49e-06

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 657584104  1794 GHEGIRGSRGLPGSKGVSGQKGYPGFPGEEGIAGDRGSP 1832
Cdd:pfam01391   19 GPPGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGAPGPP 57

Uncharacterized conserved protein, contains a von Willebrand factor type A (vWA) domain [Function unknown];

Pssm-ID: 441973 [Multi-domain] Cd Length: 263 Bit Score: 52.37 E-value: 1.68e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  827 VQTDEADIFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRispQHVRLGVAKYADSPNLEFDLTDYsdaKSVEKAVEGIRQI 906
Cdd:COG2425   114 VPLLEGPVVLCVDTSGSMAGSKEAAAKAAALALLRALR---PNRRFGVILFDTEVVEDLPLTAD---DGLEDAIEFLSGL 187

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 657584104  907 --GGGTETGRALAFMSPHFDRAMTTRGHkvpeyLVVITDGKSSDKVKVPAEQLRAQ--GVIVYSIGVKSADMEEL 977
Cdd:COG2425   188 faGGGTDIAPALRAALELLEEPDYRNAD-----IVLITDGEAGVSPEELLREVRAKesGVRLFTVAIGDAGNPGL 257

VWA subgroup: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Not much is known about the function of the VWA domain in these proteins. The members do have a conserved MIDAS motif. The biochemical function however is not known.

Pssm-ID: 238742 [Multi-domain] Cd Length: 170 Bit Score: 49.96 E-value: 2.41e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPtrvRVGIVMYNDRpadqAQQVYLNT-FNNKDELLKFIKILPyHG 700
Cdd:cd01465     1 LNLVFVIDRSGSMDGPKLPLVKSALKLLVDQLRPDD---RLAIVTYDGA----AETVLPATpVRDKAAILAAIDRLT-AG 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  701 GGTNTGAALKFARESV---FIKERGSRkdkgvqqvAVVITDGE------SQDDVSQPAADLRRAGVTIYSVGVKNANKVQ 771
Cdd:cd01465    73 GSTAGGAGIQLGYQEAqkhFVPGGVNR--------ILLATDGDfnvgetDPDELARLVAQKRESGITLSTLGFGDNYNED 144

                         170
                  ....*....|....*...
gi 657584104  772 LVEMASHPPNKHVFIVDS 789
Cdd:cd01465   145 LMEAIADAGNGNTAYIDN 162

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: 46.78 E-value: 2.73e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 657584104 2720 DQGSCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLCL 2766
Cdd:cd22619    12 DTKRCKRVVRAFYYNPSAKTCLQFVYGGCNGNGNHFKSKALCRCHCH 58

VWA ORF176 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses. In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup are Eubacterial in origin and have a conserved MIDAS motif. Not much is known about the biochemistry of these.

Pssm-ID: 238734 Cd Length: 199 Bit Score: 50.18 E-value: 3.16e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1396 KADLVFLIDQSGSIASTD-------YSIMKKFTTELVNS-FKVSEDLVRVGLaqFSSNFQNEFYLNQfyteeAVSKHIFN 1467
Cdd:cd01457     2 NRDYTLLIDKSGSMAEADeakersrWEEAQESTRALARKcEEYDSDGITVYL--FSGDFRRYDNVNS-----SKVDQLFA 74

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 657584104 1468 MRQLGGGTNI-GLALDSIREYFEasrgcRRSAG----ISQNLVLITDGESQDdvEDAAERL 1523
Cdd:cd01457    75 ENSPDGGTNLaAVLQDALNNYFQ-----RKENGatcpEGETFLVITDGAPDD--KDAVERV 128

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 49.65 E-value: 3.60e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   35 IVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVGP---DHVRIGLVQYSTTPRTEFLLNTFQNkndilQYVSKLPyMGGGT 111
Cdd:cd01464     6 IYLLLDTSGSMAGEPIEALNQGLQMLQSELRQDPyalESVEISVITFDSAARVIVPLTPLES-----FQPPRLT-ASGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  112 HTGRGLDFMLRNHFVEASGSRAGQK---VPQIaVVITDGKSQDTVESHAE---ELRKRGIVLYAIGI-KDADEDQLKEIA 184
Cdd:cd01464    80 SMGAALELALDCIDRRVQRYRADQKgdwRPWV-FLLTDGEPTDDLTAAIErikEARDSKGRIVACAVgPKADLDTLKQIT 158

                         170
                  ....*....|....*
gi 657584104  185 -NKPHSQHVYSVSDF 198
Cdd:cd01464   159 eGVPLLDDALSGLNF 173

VWA BatA type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses. In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup are bacterial in origin. They are typified by the presence of a MIDAS motif.

Pssm-ID: 238744 [Multi-domain] Cd Length: 180 Bit Score: 49.64 E-value: 3.70e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQF--LRSVISGLDIGADKVRIGLAQYSDEPY-QEFLLKDHMDKQSLLAAVDTFQyrTG 312
Cdd:cd01467     3 RDIMIALDVSGSMLAQDFVKPSRLeaAKEVLSDFIDRRENDRIGLVVFAGAAFtQAPLTLDRESLKELLEDIKIGL--AG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  313 -GTETGEAIDFLMNQyFTEdagSRAKQRVpqiAVVITDGDSTDDVAAP--ALRL-RQHGVIMFAIGVGKANPTE------ 382
Cdd:cd01467    81 qGTAIGDAIGLAIKR-LKN---SEAKERV---IVLLTDGENNAGEIDPatAAELaKNKGVRIYTIGVGKSGSGPkpdgst 153

                         170       180
                  ....*....|....*....|....*.
gi 657584104  383 ------LEAIANRPPKRFMFTIDNYE 402
Cdd:cd01467   154 ildedsLVEIADKTGGRIFRALDGFE 179

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 49.65 E-value: 4.15e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1022 FLIDSSGSIYPQDYNKMKD---FMKSVISKSFIGQNEVHVGVMQFSTIQKLEFPL---NRFYSKgemskaiddMQQIGGG 1095
Cdd:cd01464     8 LLLDTSGSMAGEPIEALNQglqMLQSELRQDPYALESVEISVITFDSAARVIVPLtplESFQPP---------RLTASGG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1096 THTGEAIT--------DVSqyfDSSRGGRPGLRQRLVVITDGEAQDVVRGPAAALRA----KGVVVyAIGV-VDANTTQL 1162
Cdd:cd01464    79 TSMGAALElaldcidrRVQ---RYRADQKGDWRPWVFLLTDGEPTDDLTAAIERIKEardsKGRIV-ACAVgPKADLDTL 154


                  ....
gi 657584104 1163 LEIS 1166
Cdd:cd01464   155 KQIT 158

dermokine; Dermokine, also known as epidermis-specific secreted protein SK30/SK89, is a skin-specific glycoprotein that may play a regulatory role in the crosstalk between barrier dysfunction and inflammation, and therefore play a role in inflammatory diseases such as psoriasis. Dermokine is one of the most highly expressed proteins in differentiating keratinocytes, found mainly in the spinous and granular layers of the epidermis, but also in the epithelia of the small intestine, macrophages of the lung, and endothelial cells of the lung. Mouse dermokine has been reported to be encoded by 22 exons, and its expression leads to alpha, beta, and gamma transcripts.

Pssm-ID: 411053 [Multi-domain] Cd Length: 495 Bit Score: 51.92 E-value: 4.47e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1686 LKSFGQKFKAESRAGVKVLLIFSDGLDDDVmklEQESELLRQSGISALLTvalEGVRDIAQLQMVEFGRGFGYRLPLSI- 1764
Cdd:cd21118    20 LHSGGEGTGAGESAGHGLGDAISHGIGEAV---GQGAKEAASSGIQNALG---QGHGEEGGSTLGSRGDVFEHRLGEAAr 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1765 GMPSVGSTILKQIDTVSDReccnvmckcsGHEGIRGSRGLPGSKGVSGQKGYPGFPGEeGIAGDRGSPGPSG-PQGVQGC 1843
Cdd:cd21118    94 SLGNAGNEIGRQAEDIIRH----------GVDAVHNSWQGSGGHGAYGSQGGPGVQGH-GIPGGTGGPWASGgNYGTNSL 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1844 SGRRGVKGFRG-------LRGNRGEDGEDGLDGVDGEQGLT-----GADGGRGERGNPGNPGIPGIRGEAGLKGQRGLRG 1911
Cdd:cd21118   163 GGSVGQGGNGGplnygtnSQGAVAQPGYGTVRGNNQNSGCTnpppsGSHESFSNSGGSSSSGSSGSQGSHGSNGQGSSGS 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1912 DPGEPGADNNSpGAKGDSGNAGlpglpgpDGRPGESGIVGNPGQDGRRGSPGVkgaagepgaaglQGIPGASGPQGTRGV 1991
Cdd:cd21118   243 SGGQGNGGNNG-SSSSNSGNSG-------GSNGGSSGNSGSGSGGSSSGGSNG------------WGGSSSSGGSGGSGG 302


                  ....*.
gi 657584104 1992 RGQPGP 1997
Cdd:cd21118   303 GNKPEC 308

VWA_integrin (invertebrates): Integrins are a family of cell surface receptors that have diverse functions in cell-cell and cell-extracellular matrix interactions. Because of their involvement in many biologically important adhesion processes, integrins are conserved across a wide range of multicellular animals. Integrins from invertebrates have been identified from six phyla. There are no data to date to suggest any immunological functions for the invertebrate integrins. The members of this sub-group have the conserved MIDAS motif that is charateristic of this domain suggesting the involvement of the integrins in the recognition and binding of multi-ligands.

Pssm-ID: 238753 [Multi-domain] Cd Length: 163 Bit Score: 49.32 E-value: 4.54e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  431 ADIFFLVD-SGISQAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIK--VEFLLNAFQSKDEMQGGIKRFRQRRLQT 507
Cdd:cd01476     1 LDLLFVLDsSGSVRGKFEKYKKYIERIVEGLEIGPTATRVALITYSGRGRqrVRFNLPKHNDGEELLEKVDNLRFIGGTT 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  508 neprNLGSALQYAsANFFTSEAGSRadQGYRQYLVVLSGKDSDDEVFRQSRLIKSegvtVVGMSLGA 574
Cdd:cd01476    81 ----ATGAAIEVA-LQQLDPSEGRR--EGIPKVVVVLTDGRSHDDPEKQARILRA----VPNIETFA 136

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: 45.43 E-value: 6.28e-06

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2659 WFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22606    18 WAYNSLLKQCQSFVYGGCEGNENNFESKEACEDAC 52

VWA BatA type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses. In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup are bacterial in origin. They are typified by the presence of a MIDAS motif.

Pssm-ID: 238744 [Multi-domain] Cd Length: 180 Bit Score: 48.48 E-value: 9.49e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1397 ADLVFLIDQSGSIASTDYSIMKKFTT--ELVNSF--KVSEDlvRVGLAQFSsnfQNEFYLNQFYTEEAVSKHIFNMRQ-- 1470
Cdd:cd01467     3 RDIMIALDVSGSMLAQDFVKPSRLEAakEVLSDFidRREND--RIGLVVFA---GAAFTQAPLTLDRESLKELLEDIKig 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1471 -LGGGTNIGLALDSIREYFEASRGCRRSagisqnLVLITDGESQDDV---EDAAERLRALGIEVFAIGIGNvhdlELLQI 1546
Cdd:cd01467    78 lAGQGTAIGDAIGLAIKRLKNSEAKERV------IVLLTDGENNAGEidpATAAELAKNKGVRIYTIGVGK----SGSGP 147

                         170       180
                  ....*....|....*....|..
gi 657584104 1547 TGTPErlfTVENFGSLEKIKQK 1568
Cdd:cd01467   148 KPDGS---TILDEDSLVEIADK 166

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 47.72 E-value: 1.56e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  238 IVFLIDGSSSIGISNFQEIRQFLRSVISGL---DIGADKVRIGLAQYSDEPYQEfllkdhmdkqSLLAAVDTFQYRT--- 311
Cdd:cd01464     6 IYLLLDTSGSMAGEPIEALNQGLQMLQSELrqdPYALESVEISVITFDSAARVI----------VPLTPLESFQPPRlta 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  312 -GGTETGEAIDFLMNQYFTEDAGSRAKQR---VPQIaVVITDGDSTDDVAAPALRLRQHG-----VIMFAIGVgKANPTE 382
Cdd:cd01464    76 sGGTSMGAALELALDCIDRRVQRYRADQKgdwRPWV-FLLTDGEPTDDLTAAIERIKEARdskgrIVACAVGP-KADLDT 153

                         170
                  ....*....|
gi 657584104  383 LEAIANRPPK 392
Cdd:cd01464   154 LKQITEGVPL 163

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: 44.56 E-value: 1.60e-05

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 657584104 2719 QDQGSCQNYSM-MWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22625     6 QEITTCESQPTkRYGYNKKTQQCEEFLGTECGGGGNSFEEAKECWSSC 53

VWA BatA type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses. In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup are bacterial in origin. They are typified by the presence of a MIDAS motif.

Pssm-ID: 238744 [Multi-domain] Cd Length: 180 Bit Score: 47.71 E-value: 1.62e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  622 ADIVFIVDESGSIG------VANFQMVRTFLHSIISGLEISptrvRVGIVMYNDRPADQA----QQVYLNtfnnkdELLK 691
Cdd:cd01467     3 RDIMIALDVSGSMLaqdfvkPSRLEAAKEVLSDFIDRREND----RIGLVVFAGAAFTQApltlDRESLK------ELLE 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104  692 FIKILpYHGGGTNTGAALKFARESVfikergsRKDKGVQQVAVVITDGESQDDVSQP--AADLRRA-GVTIYSVGV 764
Cdd:cd01467    73 DIKIG-LAGQGTAIGDAIGLAIKRL-------KNSEAKERVIVLLTDGENNAGEIDPatAAELAKNkGVRIYTIGV 140

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: 44.30 E-value: 1.92e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2641 RCQLDSDSGIQCADFVQvWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22617     3 VCREVPDEGPCRALITR-YFYNMTSMRCEEFTYGGCYGNGNNFRDKSSCISAC 54

CTRP for CS protein-TRAP-related protein: Adhesion of Plasmodium to host cells is an important phenomenon in parasite invasion and in malaria associated pathology.CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transmembrane domain, and a short cytoplasmic segment. The extracellular region of CTRP contains two separated adhesive domains. The first domain contains six 210-amino acid-long homologous VWA domain repeats. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecules. Finally, CTRP also contains consensus motifs found in the superfamily of haematopoietin receptors. The VWA domains in these proteins likely mediate protein-protein interactions.

Pssm-ID: 238750 [Multi-domain] Cd Length: 192 Bit Score: 47.70 E-value: 2.15e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIastDYSIMKK----FTTELVNSFKVSEDLVRVGLAQFSSnFQNEFylNQFYTEEAVSK---------- 1463
Cdd:cd01473     2 DLTLILDESASI---GYSNWRKdvipFTEKIINNLNISKDKVHVGILLFAE-KNRDV--VPFSDEERYDKnellkkindl 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1464 --HIFNmrqlGGGTNIGLALD-SIREYFEasRGCRRSAGISQNlVLITDG----ESQDDVEDAAERLRALGIEVFAIGIG 1536
Cdd:cd01473    76 knSYRS----GGETYIVEALKyGLKNYTK--HGNRRKDAPKVT-MLFTDGndtsASKKELQDISLLYKEENVKLLVVGVG 148

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 657584104 1537 --NVHDLELL---QITGTPERLFTVENFGSLEKIKQKVINTIC 1574
Cdd:cd01473   149 aaSENKLKLLagcDINNDNCPNVIKTEWNNLNGISKFLTDKIC 191

VWA F09G8.8 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup lack the MIDAS motif. This subgroup is found only in C. elegans and the members identified thus far are always found fused to a C-Lectin type domain. Biochemical function thus far has not be attributed to any of the members of this subgroup.

Pssm-ID: 238754 [Multi-domain] Cd Length: 193 Bit Score: 47.80 E-value: 2.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEISPTR------VRVGIVMYNDRPADQAQ----QVYLNTFNNKDELLKF 692
Cdd:cd01477    21 DIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIGTDyddprsTRVGLVTYNSNATVVADlndlQSFDDLYSQIQGSLTD 100

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 657584104  693 IKILPyhggGTNTGAALKFARESVFIKERGSRkdKGVQQVAVVIT---DGESQDDVSQPAADLRRAGVTIYSV 762
Cdd:cd01477   101 VSSTN----ASYLDTGLQAAEQMLAAGKRTSR--ENYKKVVIVFAsdyNDEGSNDPRPIAARLKSTGIAIITV 167

VWA YIEM type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have a conserved MIDAS motif, however, their biochemical function is not well characterised.

Pssm-ID: 238739 [Multi-domain] Cd Length: 152 Bit Score: 46.57 E-value: 3.13e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFlhsIISGLEISPTR-VRVGIVMYNDR----PADQAQQVylntfnnkDELLKFIKILP 697
Cdd:cd01462     2 PVILLVDQSGSMYGAPEEVAKAV---ALALLRIALAEnRDTYLILFDSEfqtkIVDKTDDL--------EEPVEFLSGVQ 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  698 YhGGGTNTGAALKFARESvfIKERGSRKdkgvqQVAVVITDG---ESQDDVSQPAADLRRAGVTIYSVGVKNANKVQLVE 774
Cdd:cd01462    71 L-GGGTDINKALRYALEL--IERRDPRK-----ADIVLITDGyegGVSDELLREVELKRSRVARFVALALGDHGNPGYDR 142


                  ....
gi 657584104  775 MASH 778
Cdd:cd01462   143 ISAE 146

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: 43.69 E-value: 3.53e-05

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 657584104 2659 WFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22623    22 WHYNAASGKCEEFVFGGCKGNKNNYLSEEECLSAC 56

VWA subgroup: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Not much is known about the function of the VWA domain in these proteins. The members do have a conserved MIDAS motif. The biochemical function however is not known.

Pssm-ID: 238742 [Multi-domain] Cd Length: 170 Bit Score: 46.50 E-value: 3.76e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  236 ADIVFLIDGSSSIGISNFQEIRQFLRSVISGLDigaDKVRIGLAQYSDE-----PYQEFllkdhMDKQSLLAAVDTFQyR 310
Cdd:cd01465     1 LNLVFVIDRSGSMDGPKLPLVKSALKLLVDQLR---PDDRLAIVTYDGAaetvlPATPV-----RDKAAILAAIDRLT-A 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  311 TGGTETGEAIDfLMNQYFTEDAGSRAKQRVpqiaVVITDGDST------DDVAAPALRLRQHGVIMFAIGVGKA-NPTEL 383
Cdd:cd01465    72 GGSTAGGAGIQ-LGYQEAQKHFVPGGVNRI----LLATDGDFNvgetdpDELARLVAQKRESGITLSTLGFGDNyNEDLM 146


                  ....
gi 657584104  384 EAIA 387
Cdd:cd01465   147 EAIA 150

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 46.18 E-value: 5.60e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  834 IFFLIDHSGSIYPTDFQDMKKFIIEFIHTFRISP---QHVRLGVAKYADSPNLEFDLTDysdaksVEKAVEGIRQIGGGT 910
Cdd:cd01464     6 IYLLLDTSGSMAGEPIEALNQGLQMLQSELRQDPyalESVEISVITFDSAARVIVPLTP------LESFQPPRLTASGGT 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  911 ETGRALAFMSPHFDRAMT-TRGHKVPEY---LVVITDGKSSDKVKVPAEQLRAQG-----VIVYSIGVKsADMEELREIS 981
Cdd:cd01464    80 SMGAALELALDCIDRRVQrYRADQKGDWrpwVFLLTDGEPTDDLTAAIERIKEARdskgrIVACAVGPK-ADLDTLKQIT 158

sporozoite surface protein 2 (SSP2); Provisional

Pssm-ID: 240420 [Multi-domain] Cd Length: 576 Bit Score: 48.42 E-value: 6.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1203 EKADIIFLVDGSTSITLAKFRNMQRFM-ESMVNQTTVGKDLTRFGVILYSNDPKSVFTLNQYSS--KKEVVKAISNLRS- 1278
Cdd:PTZ00441   41 EEVDLYLLVDGSGSIGYHNWITHVIPMlMGLIQQLNLSDDAINLYMSLFSNNTTELIRLGSGASkdKEQALIIVKSLRKt 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1279 --PFGDTYTGKALAYSLQFFDAQHGGRAALQvpqILMVITDGDATDRNSLVAPSVALRDHGVSVFSIGV-EGANMTQLEI 1355
Cdd:PTZ00441  121 ylPYGKTNMTDALLEVRKHLNDRVNRENAIQ---LVILMTDGIPNSKYRALEESRKLKDRNVKLAVIGIgQGINHQFNRL 197

                         170
                  ....*....|....*.
gi 657584104 1356 MAG---YDRSKVFYVD 1368
Cdd:PTZ00441  198 LAGcrpREGKCKFYSD 213

VWA YIEM type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have a conserved MIDAS motif, however, their biochemical function is not well characterised.

Pssm-ID: 238739 [Multi-domain] Cd Length: 152 Bit Score: 44.65 E-value: 1.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIASTDYSIMKKFTTELVnsFKVSEDLVRVGLAQFSSNFQNEFYLNQFYTEEAVSkhiFNMR-QLGGGTN 1476
Cdd:cd01462     2 PVILLVDQSGSMYGAPEEVAKAVALALL--RIALAENRDTYLILFDSEFQTKIVDKTDDLEEPVE---FLSGvQLGGGTD 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 657584104 1477 IGLALDSIREYFEaSRGCRRSagisqNLVLITDG---ESQDDV--EDAAERLRALGIEVFAIGI 1535
Cdd:cd01462    77 INKALRYALELIE-RRDPRKA-----DIVLITDGyegGVSDELlrEVELKRSRVARFVALALGD 134

VWA C3HC4-type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Membes of this subgroup belong to Zinc-finger family as they are found fused to RING finger domains. The MIDAS motif is not conserved in all the members of this family. The function of vWA domains however is not known.

Pssm-ID: 238743 [Multi-domain] Cd Length: 155 Bit Score: 44.69 E-value: 1.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  623 DIVFIVDESGSIGVANFQMVRTFLHSIISGLEispTRVRVGIVMYNDRPAdQAQQVYLNTFNNKDELLKFIKILpYHGGG 702
Cdd:cd01466     2 DLVAVLDVSGSMAGDKLQLVKHALRFVISSLG---DADRLSIVTFSTSAK-RLSPLRRMTAKGKRSAKRVVDGL-QAGGG 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 657584104  703 TNTGAALKFAresvfIKERGSRKDKGVQQVAVVITDGESQDDVSQPAADLrrAGVTIYSVGVKNANKVQLVEMASHPPN 781
Cdd:cd01466    77 TNVVGGLKKA-----LKVLGDRRQKNPVASIMLLSDGQDNHGAVVLRADN--APIPIHTFGLGASHDPALLAFIAEITG 148

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 45.07 E-value: 1.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2157 PTELVFGLDMSDDVTPTAFERQRSALLALLEEINIAESNCPS--GARVAVVGYS-AYTKYLIRFQDYRRKTQLEDAVKNi 2233
Cdd:cd01480     2 PVDITFVLDSSESVGLQNFDITKNFVKRVAERFLKDYYRKDPagSWRVGVVQYSdQQEVEAGFLRDIRNYTSLKEAVDN- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 657584104 2234 aLERTSNKRHLGAAMHFVAQNVFKRVRSGmvMRKVAVFFSNGPSQ 2278
Cdd:cd01480    81 -LEYIGGGTFTDCALKYATEQLLEGSHQK--ENKFLLVITDGHSD 122

VWA BatA type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses. In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup are bacterial in origin. They are typified by the presence of a MIDAS motif.

Pssm-ID: 238744 [Multi-domain] Cd Length: 180 Bit Score: 45.01 E-value: 1.56e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIYPQDYNKMK--DFMKSVISKsFIGQNEV-HVGVMQFSTIQKLEFPLNRFY-SKGEMSKAIDDMQqIGG 1094
Cdd:cd01467     4 DIMIALDVSGSMLAQDFVKPSrlEAAKEVLSD-FIDRRENdRIGLVVFAGAAFTQAPLTLDReSLKELLEDIKIGL-AGQ 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 657584104 1095 GTHTGEAITDVSQYFDSSRGgrpglRQR-LVVITDGE--AQDVVRGPAAAL-RAKGVVVYAIGV 1154
Cdd:cd01467    82 GTAIGDAIGLAIKRLKNSEA-----KERvIVLLTDGEnnAGEIDPATAAELaKNKGVRIYTIGV 140

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 45.02 E-value: 1.61e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1466 FNMRQL--GGGTNIGLAL--------DSIREYFEASRGCRRSAgisqnLVLITDGESQDDVEDAAERLRALGIE---VFA 1532
Cdd:cd01464    68 FQPPRLtaSGGTSMGAALelaldcidRRVQRYRADQKGDWRPW-----VFLLTDGEPTDDLTAAIERIKEARDSkgrIVA 142

                          90
                  ....*....|....*.
gi 657584104 1533 IGIGNVHDLELL-QIT 1547
Cdd:cd01464   143 CAVGPKADLDTLkQIT 158

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: 41.48 E-value: 1.73e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 657584104 2642 CQLDSDSGIQCADFVQVWF-FDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22625     1 CTLPIQEITTCESQPTKRYgYNKKTQQCEEFLGTECGGGGNSFEEAKECWSSC 53

CTRP for CS protein-TRAP-related protein: Adhesion of Plasmodium to host cells is an important phenomenon in parasite invasion and in malaria associated pathology.CTRP encodes a protein containing a putative signal sequence followed by a long extracellular region of 1990 amino acids, a transmembrane domain, and a short cytoplasmic segment. The extracellular region of CTRP contains two separated adhesive domains. The first domain contains six 210-amino acid-long homologous VWA domain repeats. The second domain contains seven repeats of 87-60 amino acids in length, which share similarities with the thrombospondin type 1 domain found in a variety of adhesive molecules. Finally, CTRP also contains consensus motifs found in the superfamily of haematopoietin receptors. The VWA domains in these proteins likely mediate protein-protein interactions.

Pssm-ID: 238750 [Multi-domain] Cd Length: 192 Bit Score: 45.00 E-value: 1.84e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1019 DLLFLIDSSGSIypQDYNKMKDFM---KSVISKSFIGQNEVHVGVMQFSTIQKLefpLNRF-----YSKGEMSKAIDDMQ 1090
Cdd:cd01473     2 DLTLILDESASI--GYSNWRKDVIpftEKIINNLNISKDKVHVGILLFAEKNRD---VVPFsdeerYDKNELLKKINDLK 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1091 Q---IGGGTHTGEAIT-DVSQYF--DSSRGGRPGLRqrlVVITDG--------EAQDVVRgpaaALRAKGVVVYAIGVVD 1156
Cdd:cd01473    77 NsyrSGGETYIVEALKyGLKNYTkhGNRRKDAPKVT---MLFTDGndtsaskkELQDISL----LYKEENVKLLVVGVGA 149

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 657584104 1157 ANTTQLLEISG-------SPDRMYAErdFDALKDLESQVALELCD 1194
Cdd:cd01473   150 ASENKLKLLAGcdinndnCPNVIKTE--WNNLNGISKFLTDKICD 192

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: 41.39 E-value: 2.36e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 657584104 2642 CQLDSDSGIqCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22619     7 CDKPPDTKR-CKRVVRAFYYNPSAKTCLQFVYGGCNGNGNHFKSKALCRCHC 57

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

Pssm-ID: 438653 Cd Length: 59 Bit Score: 41.16 E-value: 2.78e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2640 ARCQLDSDSGIQCADFVQVWFFDKHIGACSPFWYGGCGGNANRFNTEHECFRTC 2693
Cdd:cd22610     4 AFCYEDPPFFQKCGAFVDSYYFNRSRITCVHFFYGQCDVNQNHFTTMSECNRVC 57

Collagen triple helix repeat (20 copies); Members of this family belong to the collagen superfamily. Collagens are generally extracellular structural proteins involved in formation of connective tissue structure. The alignment contains 20 copies of the G-X-Y repeat that forms a triple helix. The first position of the repeat is glycine, the second and third positions can be any residue but are frequently proline and hydroxy-proline. Collagens are post translationally modified by proline hydroxylase to form the hydroxy-proline residues. Defective hydroxylation is the cause of scurvy. Some members of the collagen superfamily are not involved in connective tissue structure but share the same triple helical structure. The family includes bacterial collagen-like triple-helix repeat proteins.

Pssm-ID: 460189 [Multi-domain] Cd Length: 57 Bit Score: 40.55 E-value: 3.93e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 657584104  1793 SGHEGIRGSRGLPGSKGVSGQKGYPGFPGEEGIAGDR 1829
Cdd:pfam01391   21 PGPPGPPGPPGEPGPPGPPGPPGPPGPPGAPGAPGPP 57

VWA_collagen alpha(VI) type: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238757 [Multi-domain] Cd Length: 186 Bit Score: 43.53 E-value: 5.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2368 VDLVMVADSSREIQADQYAGVQQLLGSVVEQLAVSPQPRRAGNQARVAVVQQGGARSAKVEFnLQTYQNQELMRTHLtQK 2447
Cdd:cd01480     3 VDITFVLDSSESVGLQNFDITKNFVKRVAERFLKDYYRKDPAGSWRVGVVQYSDQQEVEAGF-LRDIRNYTSLKEAV-DN 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 657584104 2448 MRQQGGSSALGQTLDYTLKEVLLKAGQPSRKKALLAVVGTSTAWEDQARLHYVsQKAKCEGVALFVVTVGDHYN 2521
Cdd:cd01480    81 LEYIGGGTFTDCALKYATEQLLEGSHQKENKFLLVITDGHSDGSPDGGIEKAV-NEADHLGIKIFFVAVGSQNE 153

Micronemal proteins: The Toxoplasma lytic cycle begins when the parasite actively invades a target cell. In association with invasion, T. gondii sequentially discharges three sets of secretory organelles beginning with the micronemes, which contain adhesive proteins involved in parasite attachment to a host cell. Deployed as protein complexes, several micronemal proteins possess vertebrate-derived adhesive sequences that function in binding receptors. The VWA domain likely mediates the protein-protein interactions of these with their interacting partners.

Pssm-ID: 238748 [Multi-domain] Cd Length: 186 Bit Score: 42.76 E-value: 1.05e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  432 DIFFLVDSGIS---QAEFQQVRSVLVRLTNQVNFGASAHRLGLAQYGQDIKVEFLLNAFQSKDEMQGgikRFRQRRLQTN 508
Cdd:cd01471     2 DLYLLVDGSGSigySNWVTHVVPFLHTFVQNLNISPDEINLYLVTFSTNAKELIRLSSPNSTNKDLA---LNAIRALLSL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  509 -EPR---NLGSALQYASANFFTSeAGSRADQgyRQYLVVLSG--KDSDDEVFRQSRLIKSEGV--TVVGMSLGASMNEIR 580
Cdd:cd01471    79 yYPNgstNTTSALLVVEKHLFDT-RGNRENA--PQLVIIMTDgiPDSKFRTLKEARKLRERGViiAVLGVGQGVNHEENR 155

                         170       180       190
                  ....*....|....*....|....*....|
gi 657584104  581 VI-----STAP---YAYQSISNAVPVLKGI 602
Cdd:cd01471   156 SLvgcdpDDSPcplYLQSSWSEVQNVIKPF 185

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

Pssm-ID: 468478 [Multi-domain] Cd Length: 440 Bit Score: 44.13 E-value: 1.05e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 657584104 2064 GVKGDPGFPGYPGllgEDGLQGPKGLPGRKGNRGRGGNSGRSGESGISGDPGYAGHRGPRGLPGSK 2129
Cdd:NF038329  117 GEKGEPGPAGPAG---PAGEQGPRGDRGETGPAGPAGPPGPQGERGEKGPAGPQGEAGPQGPAGKD 179

VWA_collagen alpha 3(VI) like: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified thus far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. Some collagens have about 15-18 vWA domains in them. The VWA domains present in these collagens mediate protein-protein interactions.

Pssm-ID: 238758 Cd Length: 165 Bit Score: 42.31 E-value: 1.05e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 2159 ELVFGLDMSDDVTPTAFERQRSALLALLEEINIAesncPSGARVAVVGYSAYTKYLIRFQDYRRKTQLEDAVKNIALeRT 2238
Cdd:cd01481     2 DIVFLIDGSDNVGSGNFPAIRDFIERIVQSLDVG----PDKIRVAVVQFSDTPRPEFYLNTHSTKADVLGAVRRLRL-RG 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 657584104 2239 SNKRHLGAAMHFVAQNVFK-----RVRSGMVmrKVAVFFSNGPSQEVNDIPGAVMEYRGlnIVPAVISLTN 2304
Cdd:cd01481    77 GSQLNTGSALDYVVKNLFTksagsRIEEGVP--QFLVLITGGKSQDDVERPAVALKRAG--IVPFAIGARN 143

VWA F09G8.8 type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. The members of this subgroup lack the MIDAS motif. This subgroup is found only in C. elegans and the members identified thus far are always found fused to a C-Lectin type domain. Biochemical function thus far has not be attributed to any of the members of this subgroup.

Pssm-ID: 238754 [Multi-domain] Cd Length: 193 Bit Score: 42.79 E-value: 1.06e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   34 DIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDVG------PDHVRIGLVQYSTTPRTEFLLNTFQNKNDI 97
Cdd:cd01477    21 DIVFVVDNSKGMTQGGLWQVRATISSLFGSSSQIgtdyddPRSTRVGLVTYNSNATVVADLNDLQSFDDL 90

VWA subfamily: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Members of this subgroup have no assigned function. This subfamily is typified by the presence of a conserved MIDAS motif.

Pssm-ID: 238741 [Multi-domain] Cd Length: 176 Bit Score: 41.94 E-value: 1.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  624 IVFIVDESGSIGVANFQMVRTFLHSIISGL---EISPTRVRVGIVMYndrpADQAQQVYLNTfnnkdELLKFI-KILPYh 699
Cdd:cd01464     6 IYLLLDTSGSMAGEPIEALNQGLQMLQSELrqdPYALESVEISVITF----DSAARVIVPLT-----PLESFQpPRLTA- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  700 GGGTNTGAALKFARESVFI-KERGSRKDKG-VQQVAVVITDGESQDDVSQPAADLRRAG-----VTIYSVGVKnANKVQL 772
Cdd:cd01464    76 SGGTSMGAALELALDCIDRrVQRYRADQKGdWRPWVFLLTDGEPTDDLTAAIERIKEARdskgrIVACAVGPK-ADLDTL 154


                  ....*...
gi 657584104  773 VEMASHPP 780
Cdd:cd01464   155 KQITEGVP 162

VWA C3HC4-type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Membes of this subgroup belong to Zinc-finger family as they are found fused to RING finger domains. The MIDAS motif is not conserved in all the members of this family. The function of vWA domains however is not known.

Pssm-ID: 238743 [Multi-domain] Cd Length: 155 Bit Score: 41.61 E-value: 1.68e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIASTDYSIMKKFTTELVNSFKvseDLVRVGLAQFSSNFQNEFYLnQFYTEEA--VSKHIFNMRQLGGGT 1475
Cdd:cd01466     2 DLVAVLDVSGSMAGDKLQLVKHALRFVISSLG---DADRLSIVTFSTSAKRLSPL-RRMTAKGkrSAKRVVDGLQAGGGT 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104 1476 NIGLALDsireyfEASR--GCRRSAGISQNLVLITDGESQDDVEDAaeRLRALGIEVFAIGIGNVHDLELLQITGTP 1550
Cdd:cd01466    78 NVVGGLK------KALKvlGDRRQKNPVASIMLLSDGQDNHGAVVL--RADNAPIPIHTFGLGASHDPALLAFIAEI 146

vWA_interalpha trypsin inhibitor (ITI): ITI is a glycoprotein composed of three polypeptides- two heavy chains and one light chain (bikunin). Bikunin confers the protease-inhibitor function while the heavy chains are involved in rendering stability to the extracellular matrix by binding to hyaluronic acid. The heavy chains carry the VWA domain with a conserved MIDAS motif. Although the exact role of the VWA domains remains unknown, it has been speculated to be involved in mediating protein-protein interactions with the components of the extracellular matrix.

Pssm-ID: 238738 [Multi-domain] Cd Length: 171 Bit Score: 41.43 E-value: 2.26e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1398 DLVFLIDQSGSIASTdySI------MKKFTTEL--VNSFKVSEdlvrvglaqFSSNFQNEFYLNQFYTEEAVSKHIFNMR 1469
Cdd:cd01461     4 EVVFVIDTSGSMSGT--KIeqtkeaLLTALKDLppGDYFNIIG---------FSDTVEEFSPSSVSATAENVAAAIEYVN 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1470 QL--GGGTNIGLALDsireyfEASRGCRRSAGISQNLVLITDGESQDDVEDAAERLRALG--IEVFAIGIGNVHDLELLQ 1545
Cdd:cd01461    73 RLqaLGGTNMNDALE------AALELLNSSPGSVPQIILLTDGEVTNESQILKNVREALSgrIRLFTFGIGSDVNTYLLE 146

von Willebrand factor (vWF) type A domain; VWA domains in extracellular eukaryotic proteins mediate adhesion via metal ion-dependent adhesion sites (MIDAS). Intracellular VWA domains and homologues in prokaryotes have recently been identified. The proposed VWA domains in integrin beta subunits have recently been substantiated using sequence-based methods.

Pssm-ID: 214621 [Multi-domain] Cd Length: 175 Bit Score: 41.29 E-value: 2.60e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   1654 LYDFNFEGYSEDVVQKVMTLS--LAEPTYFNTAMLKSFGQKFKAE--SRAGV-KVLLIFSDGLDDDVMK-LEQESELLRQ 1727
Cdd:smart00327   52 LFPLNDSRSKDALLEALASLSykLGGGTNLGAALQYALENLFSKSagSRRGApKVVILITDGESNDGPKdLLKAAKELKR 131

                            90       100       110
                    ....*....|....*....|....*....|.
gi 657584104   1728 SGISaLLTVALEGVRDIAQLQMVEFGRGFGY 1758
Cdd:smart00327  132 SGVK-VFVVGVGNDVDEEELKKLASAPGGVY 161

Complement factors B and C2 are two critical proteases for complement activation. They both contain three CCP or Sushi domains, a trypsin-type serine protease domain and a single VWA domain with a conserved metal ion dependent adhesion site referred commonly as the MIDAS motif. Orthologues of these molecules are found from echinoderms to chordates. During complement activation, the CCP domains are cleaved off, resulting in the formation of an active protease that cleaves and activates complement C3. Complement C2 is in the classical pathway and complement B is in the alternative pathway. The interaction of C2 with C4 and of factor B with C3b are both dependent on Mg2+ binding sites within the VWA domains and the VWA domain of factor B has been shown to mediate the binding of C3. This is consistent with the common inferred function of VWA domains as magnesium-dependent protein interaction domains.

Pssm-ID: 238747 [Multi-domain] Cd Length: 198 Bit Score: 41.50 E-value: 3.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  833 DIFFLIDHSGSIYPTDFQDMKKFI---IEFIHTFRISPqhvRLGVAKYADSPNLEFDLTDY--SDAKSVEKAVE----GI 903
Cdd:cd01470     2 NIYIALDASDSIGEEDFDEAKNAIktlIEKISSYEVSP---RYEIISYASDPKEIVSIRDFnsNDADDVIKRLEdfnyDD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  904 RQIGGGTETGRALAFMSPHF--------DRAMTTRgHKVpeylVVITDGKSS---------DKVK------VPAEQLRAQ 960
Cdd:cd01470    79 HGDKTGTNTAAALKKVYERMalekvrnkEAFNETR-HVI----ILFTDGKSNmggsplptvDKIKnlvyknNKSDNPRED 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 657584104  961 GVIVYSIGV-KSADMEELREIS---GDPKRTFFVNNFDALK 997
Cdd:cd01470   154 YLDVYVFGVgDDVNKEELNDLAskkDNERHFFKLKDYEDLQ 194

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

Pssm-ID: 438653 Cd Length: 59 Bit Score: 38.08 E-value: 3.59e-03

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 657584104 2708 SFISKDACFLSQdqgsCQNYSMMWFFDTEQNECARFWYGGCGGNENRFKTQEECENLC 2765
Cdd:cd22610     4 AFCYEDPPFFQK----CGAFVDSYYFNRSRITCVHFFYGQCDVNQNHFTTMSECNRVC 57

VWA C3HC4-type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Membes of this subgroup belong to Zinc-finger family as they are found fused to RING finger domains. The MIDAS motif is not conserved in all the members of this family. The function of vWA domains however is not known.

Pssm-ID: 238743 [Multi-domain] Cd Length: 155 Bit Score: 40.45 E-value: 3.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  237 DIVFLIDGSSSIGISNFQEIRQFLRSVISGLdigADKVRIGLAQYSDEPYQEFLLKdHMD---KQSLLAAVDTFQyRTGG 313
Cdd:cd01466     2 DLVAVLDVSGSMAGDKLQLVKHALRFVISSL---GDADRLSIVTFSTSAKRLSPLR-RMTakgKRSAKRVVDGLQ-AGGG 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 657584104  314 TETGEAIDFLMNQYftedAGSRAKQRVPQIaVVITDGDSTDDVAapALRLRQHGVIMFAIGVGKAN-PTELEAIANR 389
Cdd:cd01466    77 TNVVGGLKKALKVL----GDRRQKNPVASI-MLLSDGQDNHGAV--VLRADNAPIPIHTFGLGASHdPALLAFIAEI 146

VWA subgroup: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Not much is known about the function of the VWA domain in these proteins. The members do have a conserved MIDAS motif. The biochemical function however is not known.

Pssm-ID: 238742 [Multi-domain] Cd Length: 170 Bit Score: 40.33 E-value: 5.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104   33 ADIVFMVDGSWSIGMENFEQIRQFLHTLVNSFDvgpDHVRIGLVQYSTTPRTEFLLNTFQNKNDILQYVSKLPyMGGGTH 112
Cdd:cd01465     1 LNLVFVIDRSGSMDGPKLPLVKSALKLLVDQLR---PDDRLAIVTYDGAAETVLPATPVRDKAAILAAIDRLT-AGGSTA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104  113 TGRGLDF---MLRNHFVEASGSRAgqkvpqiaVVITDGK------SQDTVESHAEELRKRGIVLYAIGIKDA-DEDQLKE 182
Cdd:cd01465    77 GGAGIQLgyqEAQKHFVPGGVNRI--------LLATDGDfnvgetDPDELARLVAQKRESGITLSTLGFGDNyNEDLMEA 148

                         170
                  ....*....|.
gi 657584104  183 IANKPHSQHVY 193
Cdd:cd01465   149 IADAGNGNTAY 159

Tick anticoagulant peptide, and similar proteins; Tick anticoagulant peptide (TAP) is a competitive inhibitor of factor Xa, a serine protease that converts prothrombin into thrombin, which acts to convert fibrinogen into fibrin, the insoluble matrix of blood clots. TAP is one of the antihemostatic components evolved in the blood-feeding tick. This subfamily also includes the N-terminal Kunitz inhibitor domain of ornithodorin which binds to the active site of thrombin, while the C-terminal domain binds at the fibrinogen recognition exosite. The TAP structure 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: 438634 Cd Length: 60 Bit Score: 37.55 E-value: 5.32e-03

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                  ....*....|....*....|....*....|....*....|....*.
gi 657584104 2651 QC--ADFVQVWFFDKHiGACSPFWYGGCGGN-ANRFNTEHECFRTC 2693
Cdd:cd21630    15 ECdsEAWERRYFRNGK-GGCESFWYCDEEDTgANYFSSMEDCFNAC 59

VWA C3HC4-type: Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains. Membes of this subgroup belong to Zinc-finger family as they are found fused to RING finger domains. The MIDAS motif is not conserved in all the members of this family. The function of vWA domains however is not known.

Pssm-ID: 238743 [Multi-domain] Cd Length: 155 Bit Score: 39.68 E-value: 6.70e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 657584104 1018 GDLLFLIDSSGSIYPQDYNKMKDFMKSVISKsfIGQNEvHVGVMQFSTIQKLEFPLNRFYSKG--EMSKAIDDMQQiGGG 1095
Cdd:cd01466     1 VDLVAVLDVSGSMAGDKLQLVKHALRFVISS--LGDAD-RLSIVTFSTSAKRLSPLRRMTAKGkrSAKRVVDGLQA-GGG 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 657584104 1096 THTGEAITDVSQYFDSSRGGRPGlrQRLVVITDGEAQDVvrgpAAALRAKGVVVY 1150
Cdd:cd01466    77 TNVVGGLKKALKVLGDRRQKNPV--ASIMLLSDGQDNHG----AVVLRADNAPIP 125