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 767904252    31 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTG 110
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 767904252   111 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 146
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904252  1668 FLARGPSGLLLYNGQKTDGkgDFVSLALRDRRLEFRYDLGKGAAVIRSREPVTLGAWTRVSLERNGRKGALRVGDGPRVL 1747
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTER--DFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPT 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 767904252  1748 GESPKSRKvphTVLNLKEPLYVGGAPDFSKLARAAAVSSGFDGAIQLVSLGGRQLL 1803
Cdd:pfam00054   79 GESPLGAT---TDLDVDGPLYVGGLPSLGVKKRRLAISPSFDGCIRDVIVNGKPLD 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 767904252   1130 ATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFD 1209
Cdd:smart00200    1 PTQSFGVSLSVLSVEGENLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGKTDLKPDFVGTEVIEFRNGSVVVDLGLLFNE 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 767904252   1210 PTTAfrAPDVARALLRQIQVSrRRSLGVRRplQEHVRFMDFDWFP 1254
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 767904252    489 ECLQACSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPC 534
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 767904252    704 VCDFSCQSVPgSPVCGSDGVTYSTECELKKARCESQRGLYVAAQGAC 750
Cdd:smart00280    1 DCPEACPREY-DPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 767904252    619 VCPRCEHPPPGPVCGSDGVTYGSACELREAACLQQTQIEEARAGPC 664
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

Laminin EGF domain; This family is like pfam00008 but has 8 conserved cysteines instead of six.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 767904252   847 CSCDPQGAVRDDCEQMTGLCSCKPGVAGPKCGQCPDG 883
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRCKPG 37

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 767904252    272 CPATCRGAPEgTVCGSDGADYPGECQLLRRACARQENVFKKFDGPC 317
Cdd:smart00280    2 CPEACPREYD-PVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                          10        20        30
                  ....*....|....*....|....*....|...
gi 767904252 1825 ASGHPCLNGASCVPREAAYVCLCPGGFSGPHCE 1857
Cdd:cd00054     6 ASGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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

                          10        20        30
                  ....*....|....*....|....*....|.
gi 767904252 1555 PNPCHGGAPCQNLEaGRFHCQCPPGRVGPTC 1585
Cdd:cd00054     8 GNPCQNGGTCVNTV-GSYRCSCPPGYTGRNC 37

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 767904252    31 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTG 110
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 767904252   111 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 146
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

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 767904252 1377 FEGRSFLAFPTLRA-YHTLRLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGQWH 1455
Cdd:cd00110     4 FSGSSYVRLPTLPApRTRLSISFSFRTTSPNGLLLYAGSQNGGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWH 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767904252 1456 RLELSRHWRRGTLSVDGETPVLGESPSGTDGLNLDTDLFVGGVPEDQaavALERTFVGAGLRGCIRLLDVN 1526
Cdd:cd00110    84 SVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDL---KSPGLPVSPGFVGCIRDLKVN 151

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904252   1395 RLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTS-AVPVEPGQWHRLELSRHWRRGTLSVDGE 1473
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYLALELRDGRLVLRYDLGSGPARLTSdPTPLNDGQWHRVAVERNGRSVTLSVDGG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 767904252   1474 TPVLGESPSGTDGLNLDTDLFVGGVPEDQaavALERTFVGAGLRGCIRLLDVNNQ 1528
Cdd:smart00282   81 NRVSGESPGGLTILNLDGPLYLGGLPEDL---KLPPLPVTPGFRGCIRNLKVNGK 132

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 767904252 1640 FNGFSHLELRGLHTFARDlgekMALEVVFLARGPSGLLLYNGQKTdgKGDFVSLALRDRRLEFRYDLGKGAAVIRSREPV 1719
Cdd:cd00110     4 FSGSSYVRLPTLPAPRTR----LSISFSFRTTSPNGLLLYAGSQN--GGDFLALELEDGRLVLRYDLGSGSLVLSSKTPL 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767904252 1720 TLGAWTRVSLERNGRKGALRVgDGPRVLgESPKSRKVPHtvLNLKEPLYVGGAPDFSKLaRAAAVSSGFDGAIQLVSL 1797
Cdd:cd00110    78 NDGQWHSVSVERNGRSVTLSV-DGERVV-ESGSPGGSAL--LNLDGPLYLGGLPEDLKS-PGLPVSPGFVGCIRDLKV 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 767904252   1130 ATKVFQGVLELEGVEGQELFYTPEMADPKSELFGETARSIESTLDDLFRNSDVKKDFRSVRLRDLGPGKSVRAIVDVHFD 1209
Cdd:smart00200    1 PTQSFGVSLSVLSVEGENLQYSPSLEDPSSEEYQELVRDVEKLLEQIYGKTDLKPDFVGTEVIEFRNGSVVVDLGLLFNE 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 767904252   1210 PTTAfrAPDVARALLRQIQVSrRRSLGVRRplQEHVRFMDFDWFP 1254
Cdd:smart00200   81 GVTN--GQDVEEDLLQVIKQA-AYSLKITN--VNVVDVLDPDSAD 120

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904252   1896 HFELSLRTEATQGLVLWSGKAtERADYVALAIVDGHLQLSYNLGSQPVVLRST-VPVNTNRWLRVVAHREQREGSLQVGN 1974
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSK-GGGDYLALELRDGRLVLRYDLGSGPARLTSDpTPLNDGQWHRVAVERNGRSVTLSVDG 79

                            90       100
                    ....*....|....*....|....
gi 767904252   1975 EAPVTGSSPLGATQLDTDGALWLG 1998
Cdd:smart00282   80 GNRVSGESPGGLTILNLDGPLYLG 103

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 767904252  792 ACQCNPHGSYGGTCDPATGQCSCRPGVGGLRCDRCEPGFWNF 833
Cdd:cd00055     1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGYYGL 42

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 767904252    489 ECLQACSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPC 534
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 767904252    554 VCPSECVALAQPVCGSDGHTYPSECMLHVHACTHQISLHVASAGPC 599
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 767904252  494 CSSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPC 534
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 767904252  202 CPSVVAPVCGSDASTYSNECELQRAQCSQQRRIRLLSRGPC 242
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 767904252  555 CPSECvalaQPVCGSDGHTYPSECMLHVHACTHQISLHVASAGPC 599
Cdd:cd00104     1 CPKEY----DPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 767904252    922 VCPMlTCPEANAtKVCGSDGVTYGNECQLKTIACRQGLQISIQSLGPC 969
Cdd:smart00280    1 DCPE-ACPREYD-PVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 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
                  ....*....|....*....|....*....|....*.
gi 767904252  715 SPVCGSDGVTYSTECELKKARCESQRGLYVAAQGAC 750
Cdd:cd00104     6 DPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 767904252  846 PCSCDPQGAVRDDCEQMTGLCSCKPGVAGPKCGQCPDG---RALGPAGCE 892
Cdd:cd00055     1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPGyygLPSQGGGCQ 50

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 767904252    416 CDRVtCDGAYRPVCAQDGRTYDSDCWRQQAECRQQRAIPSKHQGPC 461
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
                   ....*....|....*....|....*....|....*...
gi 767904252   705 CDFSCQSVPGSPVCGSDGVTYSTECELKKARCESQRGL 742
Cdd:pfam07648    2 CNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEV 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. Alignment also includes a single domain from transporters in the OATP/PGT family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 767904252   349 CPARQAPVCGDDGVTYENDCVMGRSGAARGLLLQKVRSGQC 389
Cdd:pfam00050    9 CPRIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 49

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 767904252   489 ECLQACS-SLYDPVCGSDGVTYGSACELEATACTLGREIQ---VARKGPC 534
Cdd:pfam07648    1 NCNCQCPkTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 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        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 767904252   618 CVCPRCEHPPPGPVCGSDGVTYGSACELREAACLQQTQIEEARA---GPC 664
Cdd:pfam07648    1 NCNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKEEKVkydGSC 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 767904252   202 CPSVV-APVCGSDASTYSNECELQRAQCSQQRRIR---LLSRGPC 242
Cdd:pfam07648    6 CPKTEyEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50

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 767904252  284 VCGSDGADYPGECQLLRRACARQENVFKKFDGPC 317
Cdd:cd00104     8 VCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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
                   ....*....|....*....|....*....|....*....|....*.
gi 767904252   927 TCPEANATKVCGSDGVTYGNECQLKTIACRQGLQIS---IQSLGPC 969
Cdd:pfam07648    5 QCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50

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

                          10        20        30
                  ....*....|....*....|....*....|.
gi 767904252 1555 PNPCHGGAPCQNLEaGRFHCQCPPGRVGPTC 1585
Cdd:cd00054     8 GNPCQNGGTCVNTV-GSYRCSCPPGYTGRNC 37

Solute carrier organic anion transporter 4C subfamily of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 4C (SLCO4C), also called Organic anion-transporting polypeptide 4C (OATP4C), subfamily has one mammalian member, OATP4C1 (encoded by SLCO4C1). It is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. It is the only OATP expressed at the basolateral side of proximal tubular cells in human kidney and it mediates the excretion of uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Overexpression of human SLCO4C1 in rat kidney promotes the renal excretion of uremic toxins and reduces hypertension, cardiomegaly, and renal inflammation in renal failure. The SLCO4C/OATP4C subfamily belongs to the Solute carrier organic anion transporter [SLCO, also called organic anion transporting polypeptides (OATPs) or Solute carrier family 21] family of the Major Facilitator Superfamily (MFS) of transporters. MFS proteins are thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904252  467 PCLGVQCAFGATCAVKNGQAACECLQAC-SSLYDPVCGSDGVTYGSACELEATACTLGREIQVARKGPCDRCGQCRFGAL 545
Cdd:cd17463   306 PFAGVSETYNGTGKIGNLTAPCNANCSClSSFYYPVCGADGVQYFSPCFAGCTNENLHDKKKVYYNCSCIGNFTEEFSAN 385

                          90       100
                  ....*....|....*....|..
gi 767904252  546 CEAETGRCVCPSECVALAQPVC 567
Cdd:cd17463   386 TTKCEEGKKCETTCKNLPIFLC 407

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 767904252   272 CPATCRGAPEGTVCGSDGADYPGECQLLRRACARQENVFK---KFDGPC 317
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 767904252    31 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDLVARESLLDGGNKVVISGFGDPLICDNQVSTG 110
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 767904252   111 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 146
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

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 767904252 1377 FEGRSFLAFPTLRA-YHTLRLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTSAVPVEPGQWH 1455
Cdd:cd00110     4 FSGSSYVRLPTLPApRTRLSISFSFRTTSPNGLLLYAGSQNGGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWH 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767904252 1456 RLELSRHWRRGTLSVDGETPVLGESPSGTDGLNLDTDLFVGGVPEDQaavALERTFVGAGLRGCIRLLDVN 1526
Cdd:cd00110    84 SVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDL---KSPGLPVSPGFVGCIRDLKVN 151

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904252   1395 RLALEFRALEPQGLLLYNGNARGKDFLALALLDGRVQLRFDTGSGPAVLTS-AVPVEPGQWHRLELSRHWRRGTLSVDGE 1473
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYLALELRDGRLVLRYDLGSGPARLTSdPTPLNDGQWHRVAVERNGRSVTLSVDGG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 767904252   1474 TPVLGESPSGTDGLNLDTDLFVGGVPEDQaavALERTFVGAGLRGCIRLLDVNNQ 1528
Cdd:smart00282   81 NRVSGESPGGLTILNLDGPLYLGGLPEDL---KLPPLPVTPGFRGCIRNLKVNGK 132