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 767917401  95 CNNDYVPVCGSNGESYQNECYLRQAACKQQSEILVVSEGSC 135
Cdd:cd00104    1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

EGF-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767917401 227 KSEDGHYARTDYAENANKLEESAREHHI--PCPEHYNGFCMHGKCEHSINMQEPSCRCDAGYTGQHCE 292
Cdd:PHA02887  55 RNFESHISKFNYKENANAQNFKRKNSMFfeKCKNDFNDFCINGECMNIIDLDEKFCICNKGYTGIRCD 122

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 767917401  95 CNNDYVPVCGSNGESYQNECYLRQAACKQQSEILVVSEGSC 135
Cdd:cd00104    1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 767917401   172 VCNIDCSQtNFNPLCASDGKSYDNACQIKEASCQKQEKIEVMSLGRC 218
Cdd:smart00280   1 DCPEACPR-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
                 ....*....|....*....|....*....|....*....
gi 767917401 180 TNFNPLCASDGKSYDNACQIKEASCQKQEKIEVMSLGRC 218
Cdd:cd00104    3 KEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 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 767917401  173 CNIDCSQTNFNPLCASDGKSYDNACQIKEASCQKQEKIE---VMSLGRC 218
Cdd:pfam07648   2 CNCQCPKTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKeekVKYDGSC 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        40
                 ....*....|....*....|....*....|....*....|.
gi 767917401  95 CNNDYVPVCGSNGESYQNECYLRQAACKQQSEILVVSEGSC 135
Cdd:cd00104    1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 767917401   172 VCNIDCSQtNFNPLCASDGKSYDNACQIKEASCQKQEKIEVMSLGRC 218
Cdd:smart00280   1 DCPEACPR-EYDPVCGSDGVTYSNECHLCKAACESGKSIEVKHDGPC 46

EGF-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767917401 227 KSEDGHYARTDYAENANKLEESAREHHI--PCPEHYNGFCMHGKCEHSINMQEPSCRCDAGYTGQHCE 292
Cdd:PHA02887  55 RNFESHISKFNYKENANAQNFKRKNSMFfeKCKNDFNDFCINGECMNIIDLDEKFCICNKGYTGIRCD 122

Solute carrier organic anion transporters of the Major Facilitator Superfamily of transporters; Solute carrier organic anion transporters (SLCOs) are also called organic anion transporting polypeptides (OATPs) or SLC21 (Solute carrier family 21) proteins. They are sodium-independent transporters that mediate the transport of a broad range of endo- as well as xenobiotics. Their substrates are mainly amphipathic organic anions with a molecular weight of more than 300Da, although there are a few known neutral or positively charged substrates. These include drugs including statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antibiotics, antihistaminics, antihypertensives, and anticancer drugs. SLCOs/OATPs can be classified into 6 families (SLCO1-6 or OATP1-6) and each family may have subfamilies (e.g. OATP1A, OATP1B, OATP1C). Within the subfamilies, individual members are numbered according to the chronology of their identification and if there is already an ortholog known, they are given the same number. For example, the first SLCO identified, is rat OATP1A1 (encoded by the Slco1a1 gene). The second SLCO identified is the first human SLCO from the same subfamily and is called OATP1A2 (encoded by the SLCO1A2 gene). There are 11 human SLCOs/OATPs. SLCOs belong to the Major Facilitator Superfamily (MFS) of membrane transport proteins, which 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 767917401  85 DTVTCVCQFKCN---NDYVPVCGSNGESYQNECYlrqAACKQQSEILVV---SEGSCATVHEGSGETSQKETSTCDICQ 157
Cdd:cd17336  306 SPITSSCNSDCNcsdSSFSPVCGSDGITYFSPCH---AGCTSSDAGNGTktySNCSCINSGTATSSGCPPDCSVAPNCC 381

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 767917401   91 CQFKCNND-YVPVCGSNGESYQNECYLRQAACKQQSEI---LVVSEGSC 135
Cdd:pfam07648   2 CNCQCPKTeYEPVCGSDGVTYPSPCALCAAGCKLGKEVkeeKVKYDGSC 50

epidermal growth factor-like protein (EGF-like protein); Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767917401 238 YAENANKLEESARE-----HHIP----CPEHYNGFCMHGKCEHSINMQEPSCRCDAGYTGQHCE 292
Cdd:PHA03099  18 FADSGNAIETTSPEitnatTDIPairlCGPEGDGYCLHGDCIHARDIDGMYCRCSHGYTGIRCQ 81