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.

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                 ....*....|....*....|....*....|....*....|...
gi 19343608   37 NGCTKIYDPVCGTDGNTYPNECVLCFENRKRQTSILIQKSGPC 79
Cdd:pfam00050  7 GACPRIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 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. Alignment also includes a single domain from transporters in the OATP/PGT family.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 19343608   37 NGCTKIYDPVCGTDGNTYPNECVLCFENRKRQTSILIQKSGPC 79
Cdd:pfam00050  7 GACPRIYDPVCGTDGKTYSNECLFCAENGKRGTNLHKVHDGEC 49

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.

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               ....*....|....*....|....*....|....*....|.
gi 19343608 39 CTKIYDPVCGTDGNTYPNECVLCFENRKRQTSILIQKSGPC 79
Cdd:cd00104  1 CPKEYDPVCGSDGKTYSNECHLGCAACRSGRSITVAHNGPC 41

Solute carrier organic anion transporter 3 family of the Major Facilitator Superfamily of transporters; The Solute carrier organic anion transporter 3 (SLCO3) or Organic anion transporting polypeptide 3 (OATP3) family contains only one subfamily, OATP3A, which contains only one mammalian member OATP3A1 (encoded by SLCO3A1). It mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate, prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123, and vasopressin. SLCO3A1 has been identified as a Crohn's disease (CD)-associated gene, which mediates inflammatory processes in intestinal epithelial cells through NF-kappaB transcription activation, resulting in a higher incidence of bowel perforation in CD patients. The SLCO3/OATP3 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.

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                ....*....|....*....|....*....|....
gi 19343608  25 SLGREAKCYNELNGCTKIYDPVCGTDGNTYPNEC 58
Cdd:cd17402 345 SLDPYAPCNSNCECQTDSFSPVCGADGITYLSAC 378