Conserved Protein Domain Family

cd19941: TIL 
trypsin inhibitor-like cysteine rich domain
TIL (trypsin inhibitor-like) cysteine rich domains are found in smapins (small serine proteinase inhibitor), or Ascaris trypsin inhibitor (ATI)-like proteins, whose members include anticoagulant proteins, elastase inhibitors, trypsin inhibitors, thrombin inhibitors, and chymotrypsin inhibitors. The TIL domain is also found in some large modular glycoproteins, including the von Willebrand factor (VWF), mucin-6, mucin-19, and SCO-spondin, among others. The TIL domain is characterized by the presence of five disulfide bonds (two of which are located on either side of the reactive site) in a single small protein domain of 61-62 residues. The cysteine residues that form the disulfide bonds are linked in the pattern: cysteines 1-7, 2-6, 3-5, 4-10 and 8-9. TILs can occur as a single domain or in multiple tandem arrangements. The disulfide bonds account for the unusual resistance to proteolysis and heat denaturation of these proteins. Smapins possess an unusual fold and, with the exception of the reactive site, shows no similarity to other serine protease inhibitors. The serine protease inhibitors comprise a large family of molecules involved in inflammatory responses, blood clotting, and complement activation.
PSSM-Id: 410995
Aligned: 779 rows
Threshold Bit Score: 32.6739
Created: 18-Apr-2018
Updated: 25-Oct-2021
Aligned Rows:
reactive site
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:reactive site [polypeptide binding site]
  • Comment:the reactive site loop is bounded by two disulfide bridges and is part of the long loop connecting strands beta 1 and beta 2
  • Comment:the reactive site at pH 2.4 closely resembles that of other protease inhibitors, but undergoes a major conformational rearrangement at pH 4.75
  • Citation:PMID 7922043

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                  #    #                    #         #                            
1COU_A          6 CGENekYDSCgskECDkKCKYdgveeeddeepnvPCLvr-----vCHq--dCVCEEGFYRn--kDDKCvsAEDC 70   dog hookworm
PIK58391      152 CPSNmdIDNCs-tACQrTCEAp-----------gICQde-----vCTdgevCFCPDGFFMk---ESDCvpPEQC 205  Japanese sea cucumber
XP_026478959   49 CPENeeFTSCg-tSCSrTCANymnd------lpgPCSr------eCYi--gCKCAEGFVQksaeEKVCvrKEDC 107  cat flea
XP_020623225  512 CPQNrvYTPCk-sSCDeTCQHmn----------nTCTpsp--sqgCNp--gCKCPDGTVFn---GTYCvrPADC 567  Orbicella faveolata
XP_026692580 1106 CSGNmvFSSCm-sQCQaTCSDpd---------rsICEsnldlgthCIe--gCQCPNGFVQss-nNSGCvpQELC 1166 vase tunicate
XP_018083858 1064 CPDNtqYELCv-sSCPeTCNHsl---------plPCLl------pCKe--gCSCKLGYTQs---GDICvlPEDC 1116 African clawed frog
XP_006822490  793 CGINqvYTDCm-sACPpTCENmlh--------nvGCSsa-----iCEa--gCECAEGFVLs---HDGCvePADC 847  Saccoglossus kowale...
XP_015596137   24 CPKNseFKECg-tPCRaTCTYkp----------gICVk------rCEi--gCFCVKGYILknnsTFTCikEEDC 78   wheat stem sawfly
XP_002588162  758 CQANstFSSCa-sACPaTCSDrna--------pnNCAh------kCEe--gCECDPGFVLs---GQDCvpEEQC 811  Florida lancelet
XP_030853969 2656 CDANssFSYCg-pACPtTCYSvrnt-----gddlQCSda-----sCIe--gCFCDPGFVLe---GNGCvpSESC 2713 Strongylocentrotus ...

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