Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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KAZAL Kazal type serine protease inhibitors

SMART accession number:	SM00280
Description:	Kazal type serine protease inhibitors and follistatin-like domains.
Interpro abstract (IPR002350):	Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties. This family of Kazal inhibitors, belongs to MEROPS inhibitor family I1, clan IA. They inhibit serine peptidases of the S1 family (IPR001254) [(PUBMED:14705960)]. The members are primarily metazoan, but includes exceptions in the alveolata (apicomplexa), stramenopiles, higher plants and bacteria. Kazal inhibitors, which inhibit a number of serine proteases (such as trypsin and elastase), belong to family of proteins that includes pancreatic secretory trypsin inhibitor; avian ovomucoid; acrosin inhibitor; and elastase inhibitor. These proteins contain between 1 and 7 Kazal-type inhibitor repeats [(PUBMED:6699915), (PUBMED:3828298)]. The structure of the Kazal repeat includes a large quantity of extended chain, 2 short alpha-helices and a 3-stranded anti-parallel beta sheet [(PUBMED:6699915)].The inhibitor makes 11 contacts with its enzyme substrate: unusually, 8 of these important residues are hypervariable [(PUBMED:3828298)]. Altering the enzyme-contact residues, and especially that of the active site bond, affects the the strength of inhibition and specificity of the inhibitor for particular serine proteases [(PUBMED:3828298), (PUBMED:7046785)]. The presence of this Pfam domain is 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 proteinase inhibitors.
GO function:	protein binding (GO:0005515)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 4027 KAZAL domains in 2348 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a KAZAL domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with KAZAL domain is also avaliable.

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  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 40.74 map04610 Complement and coagulation cascades 29.63 map04512 ECM-receptor interaction 29.63 map04350 TGF-beta signaling pathway 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 KAZAL domain which could be assigned to a KEGG orthologous group, and not all proteins containing KAZAL 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 KAZAL domains in PDB

  PDB code	Main view	Title
  1an1		Leech-derived tryptase inhibitor/trypsin complex
  1bmo		Bm-40, fs/ec domain pair
  1bus		Solution conformation of proteinase inhibitor iia from bull seminal plasma by 1h nuclear magnetic resonance and distance geometry
  1cgi		Three-dimensional structure of the complexes between bovine chymotrypsinogen*a and two recombinant variants of human pancreatic secretory trypsin inhibitor (kazal-type)
  1cgj		Three-dimensional structure of the complexes between bovine chymotrypsinogen*a and two recombinant variants of human pancreatic secretory trypsin inhibitor (kazal-type)
  1cho		Crystal and molecular structures of the complex of alpha- *chymotrypsin with its inhibitor turkey ovomucoid third domain at 1.8 angstroms resolution
  1cso		Crystal structure of the omtky3 p1 variant omtky3-ile18i in complex with sgpb
  1ct0		Crystal structure of the omtky3 p1 variant omtky3-ser18i in complex with sgpb
  1ct2		Crystal structure of the omtky3 p1 variant omtky3-thr18i in complex with sgpb
  1ct4		Crystal structure of the omtky3 p1 variant omtky3-val18i in complex with sgpb
  1ds2		Crystal structure of sgpb:omtky3-coo-leu18i
  1ds3		Crystal structure of omtky3-ch2-asp19i
  1h0z		Lekti domain six
  1hja		Lys 18 variant of turkey ovomucoid inhibitor third domain complexed with alpha-chymotrypsin
  1hpt		Three-dimensional structure of a recombinant variant of human pancreatic secretory trypsin inhibitor (kazal type)
  1iy5		Solution structure of wild type omsvp3
  1iy6		Solution structure of omsvp3 variant, p14c/n39c
  1kma		Nmr structure of the domain-i of the kazal-type thrombin inhibitor dipetalin
  1ldt		Complex of leech-derived tryptase inhibitor with porcine trypsin
  1lr7		Crystal structure of fs1, the heparin-binding domain of follistatin, complexed with the heparin analogue sucrose octasulphate (sos)
  1lr8		Crystal structure of fs1, the heparin-binding domain of follistatin, complexed with the heparin analogue d-myo- inositol hexasulphate (ins6s)
  1lr9		Structure of fs1, the heparin-binding domain of follistatin
  1m8b		Solution structure of the c state of turkey ovomucoid at ph 2.5
  1m8c		Solution structure of the t state of turkey ovomucoid at ph 2.5
  1nub		Helix c deletion mutant of bm-40 fs-ec domain pair
  1omt		Solution structure of ovomucoid (third domain) from domestic turkey (298k, ph 4.1) (nmr, 50 structures) (standard noesy analysis)
  1omu		Solution structure of ovomucoid (third domain) from domestic turkey (298k, ph 4.1) (nmr, 50 structures) (refined model using network editing analysis)
  1ovo		Crystallographic refinement of japanese quail ovomucoid, a kazal-type inhibitor, and model building studies of complexes with serine proteases
  1pce		Solution structure and dynamics of pec-60, a protein of the kazal type inhibitor family, determined by nuclear magnetic resonance spectroscopy
  1ppf		X-ray crystal structure of the complex of human leukocyte elastase (pmn elastase) and the third domain of the turkey ovomucoid inhibitor
  1r0r		1.1 angstrom resolution structure of the complex between the protein inhibitor, omtky3, and the serine protease, subtilisin carlsberg
  1sgd		Asp 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 6.5
  1sge		Glu 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 6.5
  1sgn		Asn 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b
  1sgp		Ala 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b
  1sgq		Gly 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b
  1sgr		Leu 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b
  1sgy		Tyr 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 6.5
  1tbq		Crystal structure of insect derived double domain kazal inhibitor rhodniin in complex with thrombin
  1tbr		Crystal structure of insect derived double domain kazal inhibitor rhodniin in complex with thrombin
  1tgs		Three-dimensional structure of the complex between pancreatic secretory inhibitor (kazal type) and trypsinogen at 1.8 angstroms resolution. structure solution, crystallographic refinement and preliminary structural interpretation
  1tur		Solution structure of turkey ovomucoid third domain as determined from nuclear magnetic resonance data
  1tus		Solution structure of reactive-site hydrolyzed turkey ovomucoid third domain by nuclear magnetic resonance and distance geometry methods
  1uvf		Solution structure of the structured part of the 15th domain of lekti
  1uvg		Solution structure of the 15th domain of lekti
  1y1b		Solution structure of anemonia elastase inhibitor
  1y1c		Solution structure of anemonia elastase inhibitor analogue
  1yu6		Crystal structure of the subtilisin carlsberg:omtky3 complex
  1z7k		Crystal structure of trypsin- ovomucoid turkey egg white inhibitor complex
  2arp		Activin a in complex with fs12 fragment of follistatin
  2b0u		The structure of the follistatin:activin complex
  2bus		Solution conformation of proteinase inhibitor iia from bull seminal plasma by 1h nuclear magnetic resonance and distance geometry
  2erw		Crystal structure of infestin 4, a factor xiia inhibitor
  2f3c		Crystal structure of infestin 1, a kazal-type serineprotease inhibitor, in complex with trypsin
  2gkr		Crystal structure of the n-terminally truncated omtky3- del(1-5)
  2gkt		Crystal structure of the p14'-ala32 variant of the n- terminally truncated omtky3-del(1-5)
  2gkv		Crystal structure of the sgpb:p14'-ala32 omtky3-del(1-5) complex
  2jxd		Nmr structure of human serine protease inhibitor kazal type ii (spink2)
  2kcx		Solution nmr structure of kazal-1 domain of human follistatin-related protein 3 (fstl-3). northeast structural genomics target hr6186a.
  2kmo		Solution structure of native leech-derived tryptase inhibitor, ldti
  2kmp		Solution structure of intermeidate iia of leeck-derived tryptase inhibitor, ldti.
  2kmq		Solution structure of intermediate iib of leech-derived tryptase inhibitor, ldti.
  2kmr		Solution structure of intermediate iic of leech-derived tryptase inhibitor, ldti.
  2nu0		Molecular structures of the complexes of sgpb with omtky3 aromatic p1 variants trp18i, his18i, phe18i, and tyr18i
  2nu1		Molecular structures of the complexes of sgpb with omtky3 aromatic p1 variants trp18i, his18i, phe18i and tyr18i
  2nu2		Accommodation of positively-charged residues in a hydrophobic specificity pocket: crystal structures of sgpb in complex with omtky3 variants lys18i and arg18i
  2nu3		Accommodation of positively-charged residues in a hydrophobic specificity pocket: crystal structures of sgpb in complex with omtky3 variants lys18i and arg18i
  2nu4		Accommodation of positively-charged residues in a hydrophobic specificity pocket: crystal structures of sgpb in complex with omtky3 variants lys18i and arg18i
  2ovo		The crystal and molecular structure of the third domain of silver pheasant ovomucoid (omsvp3)
  2p6a		The structure of the activin:follistatin 315 complex
  2sgd		Asp 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 10.7
  2sge		Glu 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 10.7
  2sgf		Phe 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b
  2sgp		Pro 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 6.5
  2sgq		Gln 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 6.5
  2v53		Crystal structure of a sparc-collagen complex
  3b4v		X-ray structure of activin in complex with fstl3
  3hh2		Crystal structure of the myostatin:follistatin 288 complex
  3ovo		Refined x-ray crystal structures of the reactive site modified ovomucoid inhibitor third domains from silver pheasant (omsvp3(asterisk)) and from japanese quail (omjpq3(asterisk))
  3sgb		Structure of the complex of streptomyces griseus protease b and the third domain of the turkey ovomucoid inhibitor at 1.8 angstroms resolution
  3sgq		Gln 18 variant of turkey ovomucoid inhibitor third domain complexed with streptomyces griseus proteinase b at ph 10.7
  4ovo		Refined x-ray crystal structures of the reactive site modified ovomucoid inhibitor third domains from silver pheasant (omsvp3(asterisk)) and from japanese quail (omjpq3(asterisk))

• Links (links to other resources describing this domain)

• PFAM	kazal
  INTERPRO	IPR002350
  PROSITE	KAZAL

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