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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 672890584   117 VCAPDCSNItwKGPVCGLDGKTYRNECALLKARCKEQPELEVQYQGKC 164
Cdd:smart00280   1 DCPEACPRE--YDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 672890584   192 CNRICPepsSSEQYLCGNDGVTYSSACHLRKATCLLGRSIGLAYEGKC 239
Cdd:smart00280   2 CPEACP---REYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

Follistatin-N-terminal domain-like; Follistatin-N-terminal domain-like, EGF-like. Region distinct from the kazal-like sequence

                           10        20
                   ....*....|....*....|....
gi 672890584   167 TCRDVFCPGSSTCVVDQTNNAYCV 190
Cdd:smart00274   1 SCRNVQCPFGKVCVVDKNGNARCV 24

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 672890584   117 VCAPDCSNItwKGPVCGLDGKTYRNECALLKARCKEQPELEVQYQGKC 164
Cdd:smart00280   1 DCPEACPRE--YDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins such as collagen and vitronectin. The protein it composed of an N-terminal acidic region, a follistatin (FS) domain and an EF-hand calcium binding domain. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a small hydrophobic core of alpha/beta structure (Kazal domain) and has five disulfide bonds and a conserved N-glycosylation site. The FSL_SPARC domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672890584  95 CENVDCGPGKKCRMNKKNKPRCVCAPDC-SNITWKGPVCGLDGKTYRNECALLKARC-----------KEQPELEVQYQG 162
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCVCIDPCpEEVDDRRKVCTNDNETFDSDCELYRTRClckggkkgcrgPKYQHLHLDYYG 81

                 ....
gi 672890584 163 KCKK 166
Cdd:cd01328   82 ECKE 85

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 672890584 207 CGNDGVTYSSACHLRKATCLLGRSIGLAYEGKC 239
Cdd:cd00104    9 CGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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 672890584  118 CAPDCSNITWKgPVCGLDGKTYRNECALLKARCKEQPELE---VQYQGKC 164
Cdd:pfam07648   2 CNCQCPKTEYE-PVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 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 672890584  270 CDELCPDSKSDePVCASDNATYASECAMKEAACSSGVLLE---VKHSGSC 316
Cdd:pfam07648   2 CNCQCPKTEYE-PVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 50

Follistatin/Osteonectin-like EGF domain; Members of this family are predominantly found in osteonectin and follistatin and adopt an EGF-like fold.

                          10        20
                  ....*....|....*....|..
gi 672890584   95 CENVDCGPGKKCRMNKKNKPRC 116
Cdd:pfam09289   1 CENFQCKRGKVCKVDKEGKPHC 22

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 672890584   117 VCAPDCSNItwKGPVCGLDGKTYRNECALLKARCKEQPELEVQYQGKC 164
Cdd:smart00280   1 DCPEACPRE--YDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins such as collagen and vitronectin. The protein it composed of an N-terminal acidic region, a follistatin (FS) domain and an EF-hand calcium binding domain. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a small hydrophobic core of alpha/beta structure (Kazal domain) and has five disulfide bonds and a conserved N-glycosylation site. The FSL_SPARC domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 672890584  95 CENVDCGPGKKCRMNKKNKPRCVCAPDC-SNITWKGPVCGLDGKTYRNECALLKARC-----------KEQPELEVQYQG 162
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCVCIDPCpEEVDDRRKVCTNDNETFDSDCELYRTRClckggkkgcrgPKYQHLHLDYYG 81

                 ....
gi 672890584 163 KCKK 166
Cdd:cd01328   82 ECKE 85

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 672890584 207 CGNDGVTYSSACHLRKATCLLGRSIGLAYEGKC 239
Cdd:cd00104    9 CGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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 672890584 281 EPVCASDNATYASECAMKEAACSSGVLLEVKHSGSC 316
Cdd:cd00104    6 DPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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 672890584  192 CNRICPEPSSSEqyLCGNDGVTYSSACHLRKATCLLGRSIGLA---YEGKC 239
Cdd:pfam07648   2 CNCQCPKTEYEP--VCGSDGVTYPSPCALCAAGCKLGKEVKEEkvkYDGSC 50

Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins such as collagen and vitronectin. The protein it composed of an N-terminal acidic region, a follistatin (FS) domain and an EF-hand calcium binding domain. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a small hydrophobic core of alpha/beta structure (Kazal domain) and has five disulfide bonds and a conserved N-glycosylation site. The FSL_SPARC domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 672890584 168 CRDVFCPGSSTCVVDQTNNAYCVtCNRICPEPSSSEQYLCGNDGVTYSSACHLRKATCLL 227
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCV-CIDPCPEEVDDRRKVCTNDNETFDSDCELYRTRCLC 60

Follistatin-N-terminal domain-like; Follistatin-N-terminal domain-like, EGF-like. Region distinct from the kazal-like sequence

                           10        20
                   ....*....|....*....|....
gi 672890584    94 TCENVDCGPGKKCRMNKKNKPRCV 117
Cdd:smart00274   1 SCRNVQCPFGKVCVVDKNGNARCV 24

Follistatin/Osteonectin-like EGF domain; Members of this family are predominantly found in osteonectin and follistatin and adopt an EGF-like fold.

                          10        20
                  ....*....|....*....|..
gi 672890584   95 CENVDCGPGKKCRMNKKNKPRC 116
Cdd:pfam09289   1 CENFQCKRGKVCKVDKEGKPHC 22

Solute carrier organic anion transporter 4 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 4 (SLCO4) or Organic anion transporting polypeptide 4 (OATP4) family contains two families: OATP4A and OATP4C, each containing one mammalian member, OATP4A1 and OATP4C1, respectively. OATP4A1 (encoded by SLCO4A1), is ubiquitously expressed and mediates the Na(+)-independent transport of the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and other organic anions such as estrone sulfate and taurocholate. OATP4C1 (encoded by SLCO4C1) is capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate, cAMP, and uremic toxins, which accumulate in patients with chronic kidney diseases (CKDs). The SLCO4/OATP4 family 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 672890584 191 TCNRICPEPSSSEQYLCGNDGVTYSSACHlrkATCLLGRSIG--LAYEG-KCIKAKSCEDIQCGGGKKCLWDS 260
Cdd:cd17403  319 TCNADCHCSEDFYDPVCGSDGVTYYSPCH---AGCTTSHGDDgqKVYSNcSCIQSNSSKTSTAATGKACPCET 388