Agrin NtA domain; Agrin is a multidomain heparan sulphate proteoglycan, that is a key organizer for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain. This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The structure of this domain is an OB-fold.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773   30 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKELVARESLLDGGNKVVISGFGDPLICDNQVSTG 109
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622835773  110 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 145
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1327 FRALELQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGRWHRLELSRHWRRGTLSVDGETPVLGE 1406
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTERDFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPTGE 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622835773 1407 SPSGTDG-LNLDTDLFVGGVPEDqaAVALERTSVGAGLRGCIRLLDVNNQLLE 1458
Cdd:pfam00054   81 SPLGATTdLDVDGPLYVGGLPSL--GVKKRRLAISPSFDGCIRDVIVNGKPLD 131

Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating or binding carbohydrate sidechains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773  1057 ATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFWNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFD 1136
Cdd:smart00200    1 PTQSFGVSLSVLSVEGENLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGKTDLKPDFVGTEVIEFRNGSVVVDLGLLFNE 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 1622835773  1137 PTTAfrAPDVARALLRQIQVSrRRSLGVRRplQEHVRFMDFDWFP 1181
Cdd:smart00200   81 GVTN--GQDVEEDLLQVIKQA-AYSLKITN--VNVVDVLDPDSAD 120

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1622835773   481 VCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASTGPC 526
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 1622835773   631 VCDFSCQSVLGgPVCGSDGVTYSTECELKKARCESRQELSVAAQGAC 677
Cdd:smart00280    1 DCPEACPREYD-PVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 1622835773   849 VCPVlTCPEaNVTKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPC 896
Cdd:smart00280    1 DCPE-ACPR-EYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622835773  348 CDGAYRPVCAQDGHTYDSDCWRQQAECQQQRAIPSKHQGPC 388
Cdd:cd00104      1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622835773  276 CPARRAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQC 316
Cdd:pfam00050    9 CPRIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 49

EGF-like domain; There is no clear separation between noise and signal. pfam00053 is very similar, but has 8 instead of 6 conserved cysteines. Includes some cytokine receptors. The EGF domain misses the N-terminus regions of the Ca2+ binding EGF domains (this is the main reason of discrepancy between swiss-prot domain start/end and Pfam). The family is hard to model due to many similar but different sub-types of EGF domains. Pfam certainly misses a number of EGF domains.

                           10        20        30
                   ....*....|....*....|....*....|...
gi 1622835773 1260 CDSQPCFHGGTCQHqvSGGGFTCSCPAGRGGAT 1292
Cdd:pfam00008    1 CAPNPCSNGGTCVD--TPGGYTCICPEGYTGKR 31

Agrin NtA domain; Agrin is a multidomain heparan sulphate proteoglycan, that is a key organizer for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain. This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The structure of this domain is an OB-fold.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773   30 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKELVARESLLDGGNKVVISGFGDPLICDNQVSTG 109
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622835773  110 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 145
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1327 FRALELQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGRWHRLELSRHWRRGTLSVDGETPVLGE 1406
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTERDFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPTGE 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622835773 1407 SPSGTDG-LNLDTDLFVGGVPEDqaAVALERTSVGAGLRGCIRLLDVNNQLLE 1458
Cdd:pfam00054   81 SPLGATTdLDVDGPLYVGGLPSL--GVKKRRLAISPSFDGCIRDVIVNGKPLD 131

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1595 FLARGPSGLLLYNGQKTDGkgDFVSLALQDRRLEFRYDLGKGAAVIRSKEPVTLGAWTRVSLERNGRKGAMRVGDGPRVL 1674
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTER--DFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPT 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622835773 1675 GESPKSRKvphTVLNLKEPLYVGGAPDFSELARAAAVSSGFNGAIQLVSLGGRQLL 1730
Cdd:pfam00054   79 GESPLGAT---TDLDVDGPLYVGGLPSLGVKKRRLAISPSFDGCIRDVIVNGKPLD 131

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1839 QSNHFELSLRTEATQGLVLWSGKATeRADYVALAIVDGHLQLSYNLGSQPVVLRSTVPVNTNRWLRVVAHREQREGSLQV 1918
Cdd:cd00110     20 TRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWHSVSVERNGRSVTLSV 98

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622835773 1919 GNEAPVTGSSPLGATQLDTDGALWLGGLPELPVGPALPkaYGTGFVGCLRDVVV 1972
Cdd:cd00110     99 DGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSPGLP--VSPGFVGCIRDLKV 150

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1564 VADFNGFSHLELRGLHTFARDlgekMALEVVFLARGPSGLLLYNGQKTdgKGDFVSLALQDRRLEFRYDLGKGAAVIRSK 1643
Cdd:cd00110      1 GVSFSGSSYVRLPTLPAPRTR----LSISFSFRTTSPNGLLLYAGSQN--GGDFLALELEDGRLVLRYDLGSGSLVLSSK 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1644 EPVTLGAWTRVSLERNGRKGAMRVgDGPRVLgESPKSRKVPHtvLNLKEPLYVGGAPDFSELaRAAAVSSGFNGAIQLVS 1723
Cdd:cd00110     75 TPLNDGQWHSVSVERNGRSVTLSV-DGERVV-ESGSPGGSAL--LNLDGPLYLGGLPEDLKS-PGLPVSPGFVGCIRDLK 149

                   .
gi 1622835773 1724 L 1724
Cdd:cd00110    150 V 150

Domain found in sea urchin sperm protein, enterokinase, agrin; Proposed function of regulating or binding carbohydrate sidechains.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773  1057 ATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFWNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFD 1136
Cdd:smart00200    1 PTQSFGVSLSVLSVEGENLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGKTDLKPDFVGTEVIEFRNGSVVVDLGLLFNE 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 1622835773  1137 PTTAfrAPDVARALLRQIQVSrRRSLGVRRplQEHVRFMDFDWFP 1181
Cdd:smart00200   81 GVTN--GQDVEEDLLQVIKQA-AYSLKITN--VNVVDVLDPDSAD 120

Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in tandem arrays; the domain contains 4 disulfide bonds (loops a-d) the first three resemble epidermal growth factor (EGF); the number of copies of this domain in the different forms of laminins is highly variable ranging from 3 up to 22 copies

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1622835773  719 ACQCNPHGSYGGTCDPVTGQCSCRPGVGGLRCDRCEPGFWNF 760
Cdd:cd00055      1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGYYGL 42

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1622835773   481 VCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASTGPC 526
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

SEA domain; Domain found in Sea urchin sperm protein, Enterokinase, Agrin (SEA). Proposed function of regulating or binding carbohydrate side chains. Recently a proteolytic activity has been shown for a SEA domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1075 LFYTPEMADPKSELFGETARSIESTLDDLFWNSDVKKDFRSVRLRDLGPGK-SVRAIVDVHFDPTTAFRAPDVAR---AL 1150
Cdd:pfam01390   12 LQYTPDLGNPSSQEFKSLSRRIESLLNELFRNSSLRKQYIKSHVLRLRPDGgSVVVDVVLVFRFPSTEPALDREKlieEI 91

                   ...
gi 1622835773 1151 LRQ 1153
Cdd:pfam01390   92 LRQ 94

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1622835773   546 VCPRCEHPPPGPVCGSDGVTYGSACELREAACRQQTQIEEARAGPC 591
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1622835773  547 CPRCEHPppgpVCGSDGVTYGSACELREAACRQQTQIEEARAGPC 591
Cdd:cd00104      1 CPKEYDP----VCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622835773  421 CSSLYDPVCGGDGVTYGSTCELEATACTLGREIRVARKGPC 461
Cdd:cd00104      1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1622835773  855 CPEaNVTKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPC 896
Cdd:cd00104      1 CPK-EYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1622835773  643 PVCGSDGVTYSTECELKKARCESRQELSVAAQGAC 677
Cdd:cd00104      7 PVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 1622835773   343 CDRVtCDGAYRPVCAQDGHTYDSDCWRQQAECQQQRAIPSKHQGPC 388
Cdd:smart00280    2 CPEA-CPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622835773  632 CDFSCQSVLGGPVCGSDGVTYSTECELKKARCESRQELSVAAQ---GAC 677
Cdd:pfam07648    2 CNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKEEKVkydGSC 50

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides. Alignment also includes a single domain from transporters in the OATP/PGT family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622835773  276 CPARRAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQC 316
Cdd:pfam00050    9 CPRIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 49

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 1622835773   273 PESCPARRAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQC 316
Cdd:smart00280    3 PEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1622835773  276 CPARRAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQC 316
Cdd:cd00104      1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1622835773  416 ECRQACS-SLYDPVCGGDGVTYGSTCELEATACTLGREIR---VARKGPC 461
Cdd:pfam07648    1 NCNCQCPkTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 1622835773  1752 ASGHPCLNGASCVPREAAYVCLCPGGFS-GPHCE 1784
Cdd:smart00179    6 ASGNPCQNGGTCVNTVGSYRCECPPGYTdGRNCE 39

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622835773  340 RCSCDRVTcdgaYRPVCAQDGHTYDSDCWRQQAECQQQR---AIPSKHQGPC 388
Cdd:pfam07648    3 NCQCPKTE----YEPVCGSDGVTYPSPCALCAAGCKLGKevkEEKVKYDGSC 50

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1622835773  199 CPATCRGAPEGTVCGSDGADYPGECQLLRRACARQENVFK---KFDGPC 244
Cdd:pfam07648    2 CNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKEekvKYDGSC 50

Agrin NtA domain; Agrin is a multidomain heparan sulphate proteoglycan, that is a key organizer for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain. This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The structure of this domain is an OB-fold.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773   30 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKELVARESLLDGGNKVVISGFGDPLICDNQVSTG 109
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1622835773  110 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 145
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1327 FRALELQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGRWHRLELSRHWRRGTLSVDGETPVLGE 1406
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTERDFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPTGE 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622835773 1407 SPSGTDG-LNLDTDLFVGGVPEDqaAVALERTSVGAGLRGCIRLLDVNNQLLE 1458
Cdd:pfam00054   81 SPLGATTdLDVDGPLYVGGLPSL--GVKKRRLAISPSFDGCIRDVIVNGKPLD 131

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1595 FLARGPSGLLLYNGQKTDGkgDFVSLALQDRRLEFRYDLGKGAAVIRSKEPVTLGAWTRVSLERNGRKGAMRVGDGPRVL 1674
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTER--DFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPT 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622835773 1675 GESPKSRKvphTVLNLKEPLYVGGAPDFSELARAAAVSSGFNGAIQLVSLGGRQLL 1730
Cdd:pfam00054   79 GESPLGAT---TDLDVDGPLYVGGLPSLGVKKRRLAISPSFDGCIRDVIVNGKPLD 131

Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of purposes including signal transduction via cell-surface steroid receptors, adhesion, migration and differentiation through mediation of cell adhesion molecules.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622835773 1839 QSNHFELSLRTEATQGLVLWSGKATeRADYVALAIVDGHLQLSYNLGSQPVVLRSTVPVNTNRWLRVVAHREQREGSLQV 1918
Cdd:cd00110     20 TRLSISFSFRTTSPNGLLLYAGSQN-GGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWHSVSVERNGRSVTLSV 98

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622835773 1919 GNEAPVTGSSPLGATQLDTDGALWLGGLPELPVGPALPkaYGTGFVGCLRDVVV 1972
Cdd:cd00110     99 DGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSPGLP--VSPGFVGCIRDLKV 150