KUBPTI/Kunitz family of serine protease inhibitors. |
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| SMART accession number: | SM00131 |
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| Description: | Serine protease inhibitors. One member of the family is encoded by an alternatively-spliced form of Alzheimer's amyloid beta-protein. |
| Interpro abstract (IPR002223): | The majority of the sequences having this domain belong to the MEROPS inhibitor family I2, clan IB; the Kunitz/bovine pancreatic trypsin inhibitor family, they inhibit proteases of the S1 family [(PUBMED:14705960)] and are restricted to the metazoa with a single exception: Amsacta moorei entomopoxvirus. They are short (~50 residue) alpha/beta proteins with few secondary structures. The fold is constrained by 3 disulphide bonds. The type example for this family is aprotinin (bovine pancreatic trypsin inhibitor) [(PUBMED:1714504)] (or basic protease inhibitor), but the family includes numerous other members [(PUBMED:1703675), (PUBMED:1593645), (PUBMED:8159751), (PUBMED:1304909)], such as snake venom basic protease; mammalian inter-alpha-trypsin inhibitors; trypstatin, a rodent mast cell inhibitor of trypsin; a domain found in an alternatively-spliced form of Alzheimer's amyloid beta-protein; domains at the C-termini of the alpha(1) and alpha(3) chains of type VII and type VI collagens; and tissue factor pathway inhibitor precursor. |
| GO function: | serine-type endopeptidase inhibitor activity (GO:0004867) |
| Family alignment: |
There are 2674 KU domains in 1596 proteins in SMART's nrdb database.
Click on the following links for more information.
- Evolution (species in which this domain is found)
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Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes - Literature (relevant references for this domain)
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Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Salier JP
- Inter-alpha-trypsin inhibitor: emergence of a family within the Kunitz-type protease inhibitor superfamily.
- Trends Biochem Sci. 1990; 15: 435-9
- Display abstract
Plasma inter-alpha-trypsin inhibitor (I alpha TI) is a major representative of the superfamily of Kunitz-type protease inhibitors in mammals. Formerly, I alpha TI was considered to be a single polypeptide, but recent molecular genetic studies have demonstrated an unexpected multipolypeptide chain structure. The newly discovered genes and gene products form the basis of a new family of I alpha TI-related protease inhibitors.
- Ponte P et al.
- A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.
- Nature. 1988; 331: 525-7
- Display abstract
The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta-protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease.
- Tanzi RE, McClatchey AI, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL
- Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.
- Nature. 1988; 331: 528-30
- Display abstract
Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.
- LaskowskiMJ r, Kato I
- Protein inhibitors of proteinases.
- Annu Rev Biochem. 1980; 49: 593-626
- Metabolism (metabolic pathways involving proteins which contain this domain)
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% proteins involved KEGG pathway ID Description 34.48 map05010 Alzheimer's disease 24.14 map04610 Complement and coagulation cascades 20.69 map04512 ECM-receptor interaction 20.69 map04510 Focal adhesion This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with KU domain which could be assigned to a KEGG orthologous group, and not all proteins containing KU domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of KU domains in PDB
PDB code Main view Title 1aal 
Structural effects induced by mutagenesis affected by crystal packing factors: the structure of a 30-51 disulfide mutant of basic pancreatic trypsin inhibitor 1aap 
X-ray crystal structure of the protease inhibitor domain of alzheimer's amyloid beta-protein precursor 1adz 
The solution structure of the second kunitz domain of tissue factor pathway inhibitor, nmr, 30 structures 1b0c 
Evidence of a common decamer in three crystal structures of bpti, crystallized from thiocyanate, chloride or sulfate 1bf0 
Calcicludine (cac) from green mamba dendroaspis angusticeps, nmr, 15 structures 1bhc 
Bovine pancreatic trypsin inhibitor crystallized from thiocyanate 1bik 
X-ray structure of bikunin from the human inter-alpha- inhibitor complex 1bpi 
The structure of bovine pancreatic trypsin inhibitor at 125k: definition of carboxyl-terminal residues glycine-57 and alanine-58 1bpt 
Crevice-forming mutants of bpti: crystal structures of f22a, y23a, n43g, and f45a 1brb 
Crystal structures of rat anionic trypsin complexed with the protein inhibitors appi and bpti 1brc 
Relocating a negative charge in the binding pocket of trypsin 1bth 
Structure of thrombin complexed with bovine pancreatic trypsin inhibitor 1bti 
Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of f22a, y23a, n43g, and f45a 1bun 
Structure of beta2-bungarotoxin: potassium channel binding by kunitz modules and targeted phospholipase action 1bz5 
Evidence of a common decamer in three crystal structures of bpti, crystallize from thiocyanate, chloride or sulfate 1bzx 
The crystal structure of anionic salmon trypsin in complex with bovine pancreatic trypsin inhibitor 1ca0 
Bovine chymotrypsin complexed to appi 1cbw 
Bovine chymotrypsin complexed to bpti 1co7 
R117h mutant rat anionic trypsin complexed with bovine pancreatic trypsin inhibitor (bpti) 1d0d 
Crystal structure of tick anticoagulant protein complexed with bovine pancreatic trypsin inhibitor 1dem 
Proteinase inhibitor homologues as potassium channel blockers 1den 
Proteinase inhibitor homologues as potassium channel blockers 1dtk 
The nmr solution structure of dendrotoxin k from the venom of dendroaspis polylepis polylepis 1dtx 
Crystal structure of alpha-dendrotoxin from the green mamba venom and its comparison with the structure of bovine pancreatic trypsin inhibitor 1eaw 
Crystal structure of the mtsp1 (matriptase)-bpti (aprotinin) complex 1ejm 
Crystal structure of the bpti ala16leu mutant in complex with bovine trypsin 1f5r 
Rat trypsinogen mutant complexed with bovine pancreatic trypsin inhibitor 1f7z 
Rat trypsinogen k15a complexed with bovine pancreatic trypsin inhibitor 1fak 
Human tissue factor complexed with coagulation factor viia inhibited with a bpti-mutant 1fan 
Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of f22a, y23a, n43g, and f45a 1fy8 
Crystal structure of the deltaile16val17 rat anionic trypsinogen-bpti complex 1g6x 
Ultra high resolution structure of bovine pancreatic trypsin inhibitor (bpti) mutant with altered binding loop sequence 1irh 
The solution structure of the third kunitz domain of tissue factor pathway inhibitor 1jc6 
Solution structure of bungarus faciatus ix, a kunitz-type chymotrypsin inhibitor 1jv8 
Nmr structure of bpti mutant g37a 1jv9 
Nmr structure of bpti mutant g37a 1k6u 
Crystal structure of cyclic bovine pancreatic trypsin inhibitor 1knt 
The 1.6 angstroms structure of the kunitz-type domain from the alpha3 chain of the human type vi collagen 1kth 
The anisotropic refinement of kunitz type domain c5 at 0.95 angstrom 1kun 
Solution structure of the human alpha3-chain type vi collagen c-terminal kunitz domain, nmr, 20 structures 1ld5 
Structure of bpti mutant a16v 1ld6 
Structure of bpti_8a mutant 1mtn 
Bovine alpha-chymotrypsin:bpti crystallization 1nag 
Crevice-forming mutants in the rigid core of bovine pancreatic trypsin inhibitor: crystal structures of f22a, y23a, n43g, and f45a 1oa5 
The solution structure of bovine pancreatic trypsin inhibitor at high pressure 1oa6 
The solution structure of bovine pancreatic trypsin inhibitor at high pressure 1p2i 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2j 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2k 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2m 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2n 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2o 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1p2q 
Structural consequences of accommodation of four non- cognate amino-acid residues in the s1 pocket of bovine trypsin and chymotrypsin 1pit 
Determination of a high-quality nuclear magnetic resonance solution structure of the bovine pancreatic trypsin inhibitor and comparison with three crystal structures 1qlq 
Bovine pancreatic trypsin inhibitor (bpti) mutant with altered binding loop sequence 1shp 
The nmr solution structure of a kunitz-type proteinase inhibitor from the sea anemone stichodactyla helianthus 1t7c 
Crystal structure of the p1 glu bpti mutant- bovine chymotrypsin complex 1t8l 
Crystal structure of the p1 met bpti mutant- bovine chymotrypsin complex 1t8m 
Crystal structure of the p1 his bpti mutant- bovine chymotrypsin complex 1t8n 
Crystal structure of the p1 thr bpti mutant- bovine chymotrypsin complex 1t8o 
Crystal structure of the p1 trp bpti mutant- bovine chymotrypsin complex 1taw 
Bovine trypsin complexed to appi 1tfx 
Complex of the second kunitz domain of tissue factor pathway inhibitor with porcine trypsin 1toc 
Structure of serine proteinase 1tpa 
The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors 1uua 
Solution structure of a truncated bovine pancreatic trypsin inhibitor, 3-58 bpti 1uub 
Solution structure of a truncated bovine pancreatic trypsin inhibitor mutant, 3-58 bpti (k15r, r17a, r42s) 1y62 
A 2.4 crystal structure of conkunitzin-s1, a novel kunitz- fold cone snail neurotoxin. 1yc0 
Short form hgfa with first kunitz domain from hai-1 1ykt 
Trypsin/bpti complex mutant 1ylc 
Trypsin/bpti complex mutant 1yld 
Trypsin/bpti complex mutant 1zjd 
Crystal structure of the catalytic domain of coagulation factor xi in complex with kunitz protease inhibitor domain of protease nexin ii 1zr0 
Crystal structure of kunitz domain 1 of tissue factor pathway inhibitor-2 with bovine trypsin 2ca7 
Conkunitzin-s1 is the first member of a new kunitz-type neurotoxin family- structural and functional characterization 2ddi 
Nmr structure of the second kunitz domain of human wfikkn1 2ddj 
Nmr structure of the second kunitz domain of human wfikkn1 2fi3 
Crystal structure of a bpti variant (cys14->ser, cys38- >ser) in complex with trypsin 2fi4 
Crystal structure of a bpti variant (cys14->ser) in complex with trypsin 2fi5 
Crystal structure of a bpti variant (cys38->ser) in complex with trypsin 2ftl 
Crystal structure of trypsin complexed with bpti at 100k 2ftm 
Crystal structure of trypsin complexed with the bpti variant (tyr35->gly) 2hex 
Decamers observed in the crystals of bovine pancreatic trypsin inhibitor 2ijo 
Crystal structure of the west nile virus ns2b-ns3 protease complexed with bovine pancreatic trypsin inhibitor 2j6d 
Conkunitzin-s2 - cone snail neurotoxin - denovo structure 2jot 
Nuclear magnetic resonance studies on huwentoxin-xi from the chinese bird spider ornithoctonus huwena 2kai 
Refined 2.5 angstroms x-ray crystal structure of the complex formed by porcine kallikrein a and the bovine pancreatic trypsin inhibitor. crystallization, patterson search, structure determination, refinement, structure and comparison with its components and with the bovine trypsin- pancreatic trypsin inhibitor complex 2kcr 
Solution structure of anntoxin 2knt 
The 1.2 angstrom structure of kunitz type domain c5 2ody 
Thrombin-bound boophilin displays a functional and accessible reactive-site loop 2ptc 
The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors 2r9p 
Human mesotrypsin complexed with bovine pancreatic trypsin inhibitor(bpti) 2ra3 
Human cationic trypsin complexed with bovine pancreatic trypsin inhibitor (bpti) 2tgp 
The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors 2tpi 
On the disordered activation domain in trypsinogen. chemical labelling and low-temperature crystallography 2w8x 
Structure of the tick ion-channel modulator ra-klp 2zjx 
Bovine pancreatic trypsin inhibitor (bpti) containing only the [5,55] disulfide bond 2zvx 
Structure of a bpti-[5,55] variant containing gly/val at the 14/38th positions 3btd 
The crystal structures of the complexes between the bovine beta-trypsin and ten p1 variants of bpti. 3bte 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti. 3btf 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti. 3btg 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3bth 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3btk 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3btm 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3btq 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3btt 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3btw 
The crystal structures of the complexes between bovine beta- trypsin and ten p1 variants of bpti 3byb 
Crystal structure of textilinin-1, a kunitz-type serine protease inhibitor from the australian common brown snake venom 3ci7 
Crystal structure of a simplified bpti containing 20 alanines 3d65 
Crystal structure of textilinin-1, a kunitz-type serine protease inhibitor from the australian common brown snake venom, in complex with trypsin 3fp6 
Anionic trypsin in complex with bovine pancreatic trypsin inhibitor (bpti) determined to the 1.49 a resolution limit 3fp7 
Anionic trypsin variant s195a in complex with bovine pancreatic trypsin inhibitor (bpti) cleaved at the scissile bond (lys15-ala16) determined to the 1.46 a resolution limit 3fp8 
Anionic trypsin variant s195a in complex with bovine pancreatic trypsin inhibitor (bpti) determined to the 1.46 a resolution limit 3gym 
Structure of prostasin in complex with aprotinin 3tgi 
Wild-type rat anionic trypsin complexed with bovine pancreatic trypsin inhibitor (bpti) 3tgj 
S195a trypsinogen complexed with bovine pancreatic trypsin inhibitor (bpti) 3tgk 
Trypsinogen mutant d194n and deletion of ile 16-val 17 complexed with bovine pancreatic trypsin inhibitor (bpti) 3tpi 
The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors 4pti 
The geometry of the reactive site and of the peptide groups in trypsin, trypsinogen and its complexes with inhibitors 4tpi 
The refined 2.2-angstroms (0.22-nm) x-ray crystal structure of the ternary complex formed by bovine trypsinogen, valine-valine and the arg15 analogue of bovine pancreatic trypsin inhibitor 5pti 
Structure of bovine pancreatic trypsin inhibitor. results of joint neutron and x-ray refinement of crystal form ii 6pti 
Structure of form iii crystals of bovine pancreatic trypsin inhibitor 7pti 
Structural effects induced by removal of a disulfide bridge. the x-ray structure of the c30a(slash)c51a mutant of basic pancreatic trypsin inhibitor at 1.6 angstroms 8pti 
Crystal structure of a y35g mutant of bovine pancreatic trypsin inhibitor 9pti 
Basic pancreatic trypsin inhibitor (met 52 oxidized) - Links (links to other resources describing this domain)
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BLOCKS BPTI_KUNITZ PFAM Kunitz_BPTI INTERPRO IPR002223 PROSITE KU_DOMAIN