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 755509212    33 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDVVAQESLLDGGNKVVIGGFGDPLICDNQVSTG 112
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 755509212   113 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 148
Cdd:pfam03146   81 DTRIFFLNPAPD-------GELRLNSSLVRITLRNL 109

Laminin G domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509212  1657 FLARGPSGLLLYNGQKTDGkgDFVSLALHNRHLEFRYDLGKGAAIIRSKEPIALGTWVRVFLERNGRKGALQVGDGPRVL 1736
Cdd:pfam00054    1 FRTTEPSGLLLYNGTQTER--DFLALELRDGRLEVSYDLGSGAAVVRSGDKLNDGKWHSVELERNGRSGTLSVDGEARPT 78

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 755509212  1737 GESPV-PHTMLNLKEPLYVGGAPDFSKLARGAAVASGFDGAIQLVSLRGHQLL 1788
Cdd:pfam00054   79 GESPLgATTDLDVDGPLYVGGLPSLGVKKRRLAISPSFDGCIRDVIVNGKPLD 131

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 755509212   795 CHCNPHGSYSGTCDPVTGQCSCRPGVGGLRCDRCEPGFWNFRG 837
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRCKPGYYGLPS 43

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 755509212    556 VCPSECVESAQPVCGSDGHTYASECELHVHACTHQISLYVASAGHC 601
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 755509212    706 VCDFSCQSVLKsPVCGSDGVTYSTECHLKKARCEARQELYVAAQGAC 752
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 755509212    621 VCPRCEHPPPGPVCGSDGVTYLSACELREAACQQQVQIEEARAGPC 666
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 755509212   849 CSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDG 885
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRCKPG 37

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 755509212  423 CDGAYRPVCAQDGHTYDNDCWRQQAECRQQQTIPPKHQGPC 463
Cdd:cd00104     1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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 755509212  1322 CDSQPCLHGGTCqdLDSGKGFSCSCTAGRAG 1352
Cdd:pfam00008    1 CAPNPCSNGGTC--VDTPGGYTCICPEGYTG 29

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 755509212    33 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDVVAQESLLDGGNKVVIGGFGDPLICDNQVSTG 112
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 755509212   113 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 148
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 755509212 1366 FKGHSFLAFPTLRA-YHTLRLALEFRALETEGLLLYNGNARGKDFLALALLDGHVQFRFDTGSGPAVLTSLVPVEPGRWH 1444
Cdd:cd00110     4 FSGSSYVRLPTLPApRTRLSISFSFRTTSPNGLLLYAGSQNGGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWH 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755509212 1445 RLELSRHWRQGTLSVDGEAPVVGESPSGTDGLNLDTKLYVGGLPEEQVATvldRTSVGIGLKGCIRMLDIN 1515
Cdd:cd00110    84 SVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSP---GLPVSPGFVGCIRDLKVN 151

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509212   1384 RLALEFRALETEGLLLYNGNARGKDFLALALLDGHVQFRFDTGSGPAVLTS-LVPVEPGRWHRLELSRHWRQGTLSVDGE 1462
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYLALELRDGRLVLRYDLGSGPARLTSdPTPLNDGQWHRVAVERNGRSVTLSVDGG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 755509212   1463 APVVGESPSGTDGLNLDTKLYVGGLPEEQVATvldRTSVGIGLKGCIRMLDINNQ 1517
Cdd:smart00282   81 NRVSGESPGGLTILNLDGPLYLGGLPEDLKLP---PLPVTPGFRGCIRNLKVNGK 132

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509212   1653 LEMVFLARGPSGLLLYNGQKtdGKGDFVSLALHNRHLEFRYDLGKGAAIIRSK-EPIALGTWVRVFLERNGRKGALQVGD 1731
Cdd:smart00282    2 ISFSFRTTSPNGLLLYAGSK--GGGDYLALELRDGRLVLRYDLGSGPARLTSDpTPLNDGQWHRVAVERNGRSVTLSVDG 79

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....
gi 755509212   1732 GPRVLGESPVPHTMLNLKEPLYVGGAPDFSKLARGaAVASGFDGAIQLVSLRGH 1785
Cdd:smart00282   80 GNRVSGESPGGLTILNLDGPLYLGGLPEDLKLPPL-PVTPGFRGCIRNLKVNGK 132

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509212   1900 HFELSLRTEATQGLVLWIGkVGERADYMALAIVDGHLQLSYDLGSQPVVLRST-VKVNTNRWLRVRAHREHREGSLQVGN 1978
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAG-SKGGGDYLALELRDGRLVLRYDLGSGPARLTSDpTPLNDGQWHRVAVERNGRSVTLSVDG 79

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 755509212   1979 EAPVTGSSPLGATQLDTDGALWLGGlqkLPVGQALPK-AYGTGFVGCLRDVVVGHR 2033
Cdd:smart00282   80 GNRVSGESPGGLTILNLDGPLYLGG---LPEDLKLPPlPVTPGFRGCIRNLKVNGK 132

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 755509212   795 CHCNPHGSYSGTCDPVTGQCSCRPGVGGLRCDRCEPGFWNFRG 837
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRCKPGYYGLPS 43

Laminin-type epidermal growth factor-like domai;

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|...
gi 755509212    795 CHCNPHGSYSGTCDPVTGQCSCRPGVGGLRCDRCEPGFWNFRG 837
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPGYYGDGP 43

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 755509212    556 VCPSECVESAQPVCGSDGHTYASECELHVHACTHQISLYVASAGHC 601
Cdd:smart00280    1 DCPEACPREYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 755509212    706 VCDFSCQSVLKsPVCGSDGVTYSTECHLKKARCEARQELYVAAQGAC 752
Cdd:smart00280    1 DCPEACPREYD-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        40
                  ....*....|....*....|....*....|....*....|.
gi 755509212  496 CSGGYDPVCGSDGVTYGSVCELESMACTLGREIRVARRGPC 536
Cdd:cd00104     1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*.
gi 755509212    274 CPTTCFGAPDgTVCGSDGVDYPSECQLLRHACANQEHIFKKFDGPC 319
Cdd:smart00280    2 CPEACPREYD-PVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*...
gi 755509212    924 VCPTlTCPEaNSTKVCGSDGVTYGNECQLKTIACRQRLDISIQSLGPC 971
Cdd:smart00280    1 DCPE-ACPR-EYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 755509212   849 CSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDG 885
Cdd:pfam00053    1 CDCNPHGSLSDTCDPETGQCLCKPGVTGRHCDRCKPG 37

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 755509212  622 CPRCEHPppgpVCGSDGVTYLSACELREAACQQQVQIEEARAGPC 666
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 755509212  930 CPEaNSTKVCGSDGVTYGNECQLKTIACRQRLDISIQSLGPC 971
Cdd:cd00104     1 CPK-EYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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
                  ....*....|....*....|....*....|....*...
gi 755509212  848 PCSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDG 885
Cdd:cd00055     1 PCDCNGHGSLSGQCDPGTGQCECKPNTTGRRCDRCAPG 38

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 755509212  286 VCGSDGVDYPSECQLLRHACANQEHIFKKFDGPC 319
Cdd:cd00104     8 VCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

Laminin-type epidermal growth factor-like domai;

                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 755509212    849 CSCDPRGAVRDDCEQMTGLCSCRPGVAGPKCGQCPDG 885
Cdd:smart00180    1 CDCDPGGSASGTCDPDTGQCECKPNVTGRRCDRCAPG 37

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 755509212 1810 AVDNPCLNGGSCIPREATYECLCPGGFSGLHCE 1842
Cdd:cd00054     6 ASGNPCQNGGTCVNTVGSYRCSCPPGYTGRNCE 38

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

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 755509212    348 PENCPAQHTPICGDDGVTYENDCVMSRIGAARGLLLQKVRSGQC 391
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 755509212  351 CPAQHTPICGDDGVTYENDCVMSRIGAARGLLLQKVRSGQC 391
Cdd:cd00104     1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

Calcium-binding EGF-like domain;

                            10        20        30
                    ....*....|....*....|....*....|....
gi 755509212   1810 AVDNPCLNGGSCIPREATYECLCPGGFS-GLHCE 1842
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. Alignment also includes a single domain from transporters in the OATP/PGT family.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 755509212   926 PTLTCPeANSTKVCGSDGVTYGNECQLKTIACRQRLDISIQSLGPC 971
Cdd:pfam00050    5 PSGACP-RIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 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
                   ....*....|....*....|....*....
gi 755509212  1812 DNPCLNGGSCIPREATYECLCPGGFSGLH 1840
Cdd:pfam00008    3 PNPCSNGGTCVDTPGGYTCICPEGYTGKR 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 755509212    33 CPERALERREEEANVVLTGTVEEILNVDPVQHTYSCKVRVWRYLKGKDVVAQESLLDGGNKVVIGGFGDPLICDNQVSTG 112
Cdd:pfam03146    1 CPDRTLEEREEEANVVLTGTVEEVMNVDPDGKTYSASVRVKRVMKGKSLLTQLILLDGGNKVTVDGLGDPLICDSQVRRG 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 755509212   113 DTRIFFVNPAPPylwpahkNELMLNSSLMRITLRNL 148
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 755509212 1366 FKGHSFLAFPTLRA-YHTLRLALEFRALETEGLLLYNGNARGKDFLALALLDGHVQFRFDTGSGPAVLTSLVPVEPGRWH 1444
Cdd:cd00110     4 FSGSSYVRLPTLPApRTRLSISFSFRTTSPNGLLLYAGSQNGGDFLALELEDGRLVLRYDLGSGSLVLSSKTPLNDGQWH 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755509212 1445 RLELSRHWRQGTLSVDGEAPVVGESPSGTDGLNLDTKLYVGGLPEEQVATvldRTSVGIGLKGCIRMLDIN 1515
Cdd:cd00110    84 SVSVERNGRSVTLSVDGERVVESGSPGGSALLNLDGPLYLGGLPEDLKSP---GLPVSPGFVGCIRDLKVN 151

Laminin G domain;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755509212   1384 RLALEFRALETEGLLLYNGNARGKDFLALALLDGHVQFRFDTGSGPAVLTS-LVPVEPGRWHRLELSRHWRQGTLSVDGE 1462
Cdd:smart00282    1 SISFSFRTTSPNGLLLYAGSKGGGDYLALELRDGRLVLRYDLGSGPARLTSdPTPLNDGQWHRVAVERNGRSVTLSVDGG 80

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 755509212   1463 APVVGESPSGTDGLNLDTKLYVGGLPEEQVATvldRTSVGIGLKGCIRMLDINNQ 1517
Cdd:smart00282   81 NRVSGESPGGLTILNLDGPLYLGGLPEDLKLP---PLPVTPGFRGCIRNLKVNGK 132

Laminin G domain;